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Publisher: Elsevier   (Total: 3185 journals)

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Showing 1 - 200 of 3185 Journals sorted alphabetically
Academic Pediatrics     Hybrid Journal   (Followers: 37, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 25, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 100, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 28, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 37, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 7)
Acta Astronautica     Hybrid Journal   (Followers: 427, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 28, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 3)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 10, SJR: 0.18, CiteScore: 1)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 292, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 6, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 12, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.307, CiteScore: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1, SJR: 1.793, CiteScore: 6)
Acta Poética     Open Access   (Followers: 4, SJR: 0.101, CiteScore: 0)
Acta Psychologica     Hybrid Journal   (Followers: 27, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access   (Followers: 1)
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, CiteScore: 2)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, CiteScore: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, CiteScore: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 7, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 8)
Acute Pain     Full-text available via subscription   (Followers: 15, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 17, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 9, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 11, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 23)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 179, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 12, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 16, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 28, SJR: 0.126, CiteScore: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 11, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 11, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 24, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 15, SJR: 0.572, CiteScore: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, CiteScore: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 32, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 5)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 14)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 28, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 26, SJR: 1.562, CiteScore: 3)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 20, SJR: 1.977, CiteScore: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, CiteScore: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 15)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 13)
Advances in Digestive Medicine     Open Access   (Followers: 11)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 7)
Advances in Drug Research     Full-text available via subscription   (Followers: 26)
Advances in Ecological Research     Full-text available via subscription   (Followers: 43, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 29, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 8)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 49, SJR: 5.39, CiteScore: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 62, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 17)
Advances in Genetics     Full-text available via subscription   (Followers: 20, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 10, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 24, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 12, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 23)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 3, SJR: 0.193, CiteScore: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.433, CiteScore: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 10, SJR: 1.163, CiteScore: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, CiteScore: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, CiteScore: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.682, CiteScore: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 19, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 12, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 7, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 23)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, CiteScore: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 4)
Advances in Oncobiology     Full-text available via subscription   (Followers: 2)
Advances in Organ Biology     Full-text available via subscription   (Followers: 2)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 17, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.174, CiteScore: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 1.579, CiteScore: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 25, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 17)
Advances in Pharmacology     Full-text available via subscription   (Followers: 16, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.574, CiteScore: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, CiteScore: 1)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 10)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 19)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 66)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (Followers: 1, SJR: 0.263, CiteScore: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, CiteScore: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 6)
Advances in Space Research     Full-text available via subscription   (Followers: 413, SJR: 0.569, CiteScore: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 13, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 36, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 20)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 15)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 51, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 364, SJR: 0.796, CiteScore: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, CiteScore: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, CiteScore: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 11, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 468, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (Followers: 1, SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 17, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 44, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 4)
Agriculture and Natural Resources     Open Access   (Followers: 3)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 57, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 6, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 12, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 11)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 2, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 11, SJR: 1.142, CiteScore: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, CiteScore: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, CiteScore: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, CiteScore: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 10, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 52, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 57, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 62, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 45, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 11)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 13, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 34, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 29, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 35, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 49)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, CiteScore: 2)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 232, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 66, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5, SJR: 0.265, CiteScore: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, CiteScore: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, CiteScore: 1)
American J. of Pathology     Hybrid Journal   (Followers: 30, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 28, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 39, SJR: 1.141, CiteScore: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, CiteScore: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 7)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 63, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 20, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription   (Followers: 1)
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, CiteScore: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 5, SJR: 4.849, CiteScore: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 44, SJR: 1.512, CiteScore: 5)
Analytica Chimica Acta : X     Open Access  
Analytical Biochemistry     Hybrid Journal   (Followers: 200, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 12, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 14)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 24, SJR: 0.683, CiteScore: 2)
Angiología     Full-text available via subscription   (SJR: 0.121, CiteScore: 0)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1, SJR: 0.111, CiteScore: 0)
Animal Behaviour     Hybrid Journal   (Followers: 207, SJR: 1.58, CiteScore: 3)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 6, SJR: 0.937, CiteScore: 2)
Animal Reproduction Science     Hybrid Journal   (Followers: 7, SJR: 0.704, CiteScore: 2)

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Similar Journals
Journal Cover
Neuroscience Research
Journal Prestige (SJR): 1.091
Citation Impact (citeScore): 2
Number of Followers: 9  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0168-0102
Published by Elsevier Homepage  [3185 journals]
    • Abstract: Publication date: Available online 3 April 2019Source: Neuroscience ResearchAuthor(s): Atsuhito Yamagishi, Maya Okada, Masatoshi Masuda, Nobuya Sato The affiliative effect of oxytocin on behavior toward other individuals can be modulated by positive and negative aspects of those individuals. However, the context-dependent effect of oxytocin on helping behavior is still unclear. In this study, we examined the effect of oxytocin administration on helping behavior in rats. The rats learned to open a door to help a cagemate soaked with water. The rats were divided into Pair and Solo groups. The rats in the Pair group were housed with their cagemates and those in the Solo group were housed individually. The rats in both groups received oxytocin (1.0 mg/kg) or saline injections intraperitoneally for 5 consecutive days before starting the experimental sessions. In the rats injected with oxytocin, the Solo group showed helping behavior faster than those in the Pair group. The results suggest that the effects of oxytocin administration on helping behavior are dependent on the social context.
  • Masao Ito (1928–2018)
    • Abstract: Publication date: April 2019Source: Neuroscience Research, Volume 141Author(s):
    • Abstract: Publication date: April 2019Source: Neuroscience Research, Volume 141Author(s):
  • The motor engram as a dynamic change of the cortical network during early
           sequence learning: An fMRI study
    • Abstract: Publication date: Available online 30 March 2019Source: Neuroscience ResearchAuthor(s): Yuki H. Hamano, Sho K. Sugawara, Takaaki Yoshimoto, Norihiro Sadato Neural substrates of motor engrams in the human brain are hard to identify because their dormant states are difficult to discriminate. We utilized eigenvector centrality (EC) to measure the network information that accumulates as an engram during learning. To discriminate engrams formed by emphasis on speed or accuracy, we conducted functional MRI on 58 normal volunteers as they performed a sequential finger-tapping task with the non-dominant left hand. Participants alternated between performing a tapping sequence as quickly as possible (maximum mode) or at a constant speed of 2 Hz, paced by a sequence-specifying visual cue (constant mode). We depicted the formation of the motor engram by characterizing the dormant state as the increase in EC of the resting epoch throughout the training course, and the ecphory, or activated state, as the increment in EC during the task epoch relative to the alternated resting epoch. We found that a network covering the left anterior intraparietal sulcus and inferior parietal lobule represented the engram for the speed of execution, whereas bilateral premotor cortex and right primary motor cortex represented the sequential order of movements. This constitutes the first demonstration of learning-mode specific motor engrams formed by only 30 min of training.
  • Dynamics of memory engrams
    • Abstract: Publication date: Available online 30 March 2019Source: Neuroscience ResearchAuthor(s): Shogo Takamiya, Shoko Yuki, Junya Hirokawa, Hiroyuki Manabe, Yoshio Sakurai In this update article, we focus on “memory engrams”, which are traces of long-term memory in the brain, and emphasizes that they are not static but dynamic. We first introduce the major findings in neuroscience and psychology reporting that memory engrams are sometimes diffuse and unstable, indicating that they are dynamically modified processes of consolidation and reconsolidation. Second, we introduce and discuss the concepts of cell assembly and engram cell, the former has been investigated by psychological experiments and behavioral electrophysiology and the latter is defined by recent combination of activity-dependent cell labelling with optogenetics to show causal relationships between cell population activity and behavioral changes. Third, we discuss the similarities and differences between the cell assembly and engram cell concepts to reveal the dynamics of memory engrams. We also discuss the advantages and problems of live-cell imaging, which has recently been developed to visualize multineuronal activities. The last section suggests the experimental strategy and background assumptions for future research of memory engrams. The former encourages recording of cell assemblies from different brain regions during memory consolidation–reconsolidation processes, while the latter emphasizes the multipotentiality of neurons and regions that contribute to dynamics of memory engrams in the working brain.Graphical abstractGraphical abstract for this article
  • Revisiting a theory of cerebellar cortex
    • Abstract: Publication date: Available online 26 March 2019Source: Neuroscience ResearchAuthor(s): Tadashi Yamazaki, William Lennon Long-term depression at parallel fiber-Purkinje cell synapses plays a principal role in learning in the cerebellum, which acts as a supervised learning machine. Recent experiments demonstrate various forms of synaptic plasticity at different sites within the cerebellum. In this article, we take into consideration synaptic plasticity at parallel fiber-molecular layer interneuron synapses as well as at parallel fiber-Purkinje cell synapses, and propose that the cerebellar cortex performs reinforcement learning, another form of learning that is more capable than supervised learning. We posit that through the use of reinforcement learning, the need for explicit teacher signals for learning in the cerebellum is eliminated; instead, learning can occur via responses from evaluative feedback. We demonstrate the learning capacity of cerebellar reinforcement learning using simple computer simulations of delay eyeblink conditioning and the cart-pole balancing task.Graphical abstractGraphical abstract for this article
  • Adapting terminology Clarifying prism adaptation vocabulary, concepts, and
    • Abstract: Publication date: Available online 22 March 2019Source: Neuroscience ResearchAuthor(s): C Prablanc, F Panico, L Fleury, L Pisella, T Nijboer, S Kitazawa, Y Rossetti When individuals are exposed to a constant change of the interplay with their environment, they are able to develop compensatory alterations of visuo-motor coordination in order to counteract the perturbation. Prism adaptation (PA) is a very simple tool that has been used for several decades to investigate adaptive processes. However, the specific terminology used in PA literature has continuously evolved and is still subjected to broad inconsistency. Growing confusion about the choice of terms used to describe specific processes and methods has yielded the critical need for clarifying the adaptation vocabulary. The aim of this terminology review is to consider and to describe the most common terms used in PA literature in order to ensure more consistent communication in future research. On the basis of a descriptive examination of previous studies on PA, we provide specification for each term, indicating whether it refers to a classical term in PA literature, and whether it is recommended or should be used with particular attention. This terminology represents a useful instrument to both new readers and experts in the field of PA in order to facilitate unambiguous communication and consensual inter-investigations. Recommendations for the use of consistent paradigms and reliable vocabulary are provided for future investigations, in both basic and clinical research.
  • A methodology for discovering novel brain-relevant peptides: Combination
           of ribosome profiling and peptidomics
    • Abstract: Publication date: Available online 9 March 2019Source: Neuroscience ResearchAuthor(s): Ravi Tharakan, Simion Kreimer, Ceereena Ubaida-Mohien, Joelle Lavoie, Volodimir Olexiouk, Gerben Menschaert, Nicholas T. Ingolia, Robert N. Cole, Koko Ishizuka, Akira Sawa, Leslie G. Nucifora Brain derived peptides function as signaling molecules in the brain and regulate various physiological and behavioral processes. The low abundance and atypical fragmentation of these brain derived peptides makes detection using traditional proteomic methods challenging. In this study, we introduce and validate a new methodology for the discovery of novel peptides derived from mammalian brain. This methodology combines ribosome profiling and mass spectrometry-based peptidomics. Using this framework, we have identified a novel peptide in mouse whole brain whose expression is highest in the basal ganglia, hypothalamus and amygdala. Although its functional role is unknown, it has been previously detected in peripheral tissue as a component of the mRNA decapping complex. Continued discovery and studies of novel regulating peptides in mammalian brain may also provide insight into brain disorders.
  • Circuit mechanisms and computational models of REM sleep
    • Abstract: Publication date: March 2019Source: Neuroscience Research, Volume 140Author(s): Charlotte Héricé, Amisha A. Patel, Shuzo Sakata Rapid eye movement (REM) sleep or paradoxical sleep is an elusive behavioral state. Since its discovery in the 1950s, our knowledge of the neuroanatomy, neurotransmitters and neuropeptides underlying REM sleep regulation has continually evolved in parallel with the development of novel technologies. Although the pons was initially discovered to be responsible for REM sleep, it has since been revealed that many components in the hypothalamus, midbrain, pons, and medulla also contribute to REM sleep. In this review, we first provide an up-to-date overview of REM sleep-regulating circuits in the brainstem and hypothalamus by summarizing experimental evidence from neuroanatomical, neurophysiological and gain- and loss-of-function studies. Second, because quantitative approaches are essential for understanding the complexity of REM sleep-regulating circuits and because mathematical models have provided valuable insights into the dynamics underlying REM sleep genesis and maintenance, we summarize computational studies of the sleep-wake cycle, with an emphasis on REM sleep regulation. Finally, we discuss outstanding issues for future studies.
  • Function of local circuits in the hippocampal dentate gyrus-CA3 system
    • Abstract: Publication date: March 2019Source: Neuroscience Research, Volume 140Author(s): Yuta Senzai Anatomical observations, theoretical work and lesioning experiments have supported the idea that the CA3 in the hippocampus is important for encoding, storage and retrieval of memory while the dentate gyrus (DG) is important for the pattern separation of the incoming inputs from the entorhinal cortex. Study of the presumed function of the dentate gyrus in pattern separation has been hampered by the lack of reliable methods to identify different excitatory cell types in the DG. Recent papers have identified different cell types in the DG, in awake behaving animals, with more reliable methods. These studies have revealed each cell type’s spatial representation as well as their involvement in pattern separation. Moreover, chronic electrophysiological recording from sleeping and waking animals also provided more insights into the operation of the DG-CA3 system for memory encoding and retrieval. This article will review the local circuit architectures and physiological properties of the DG-CA3 system and discuss how the local circuit in the DG-CA3 may function, incorporating recent physiological findings in the DG-CA3 system.
  • Circuit architecture for somatotopic action selection in invertebrates
    • Abstract: Publication date: March 2019Source: Neuroscience Research, Volume 140Author(s): Suguru Takagi, Akinao Nose Invertebrate species have significantly contributed to neuroscience owing to the accessibility they provide to cellular- and molecular-level understanding of brain functions. Somatotopic action selection is one of the key features of animal behavior, and studying this process in invertebrates is potentially a sweet spot in understanding the general relationship between neuronal morphology, circuit structure, and animal behavior. In this review, we introduce circuit architectures that realize somatotopic action selection, from simple reflexes to patterned motor outputs, in different invertebrate species. We then discuss future directions towards understanding the general principles underlying the development and evolution of the circuit architecture that enables sensorimotor transformation and action selection in the animal kingdom.
  • Prefrontal circuit organization for executive control
    • Abstract: Publication date: March 2019Source: Neuroscience Research, Volume 140Author(s): Tsukasa Kamigaki The essential role of executive control is to select the most appropriate behavior among other candidates depending on the sensory information (exogenous information) and on the subject’s internal state (endogenous information). Here I review series of the evidence implicating that the rodent prefrontal cortex (PFC) evaluates and compares the expected outcome for candidate actions that are automatically primed by exogenous and endogenous information, and selects the most appropriate action while inhibiting the others, with different PFC subregions contributing to distinct aspects of the computation via differential recruitments of the distributed networks. The recurrent nature of the PFC networks further facilitates the computation by integrating bottom-up signals over a long timescale. I also overview the local circuit organization in the PFC, where vasoactive intestinal peptide-positive (VIP) GABAergic interneurons are tightly linked with the cholinergic system and play significant roles in regulating executive control signals. The empirical evidence inspires the disinhibitory module hypothesis of the PFC organization that a group of pyramidal neurons and interneurons forms a disinhibitory module with similar task-variable selectivity in the PFC, and long-range inputs and neuromodulations in these modules exert a distributed gain modulation of the ongoing executive control signals by adjusting VIP neuron activity.
  • The mouse posterior parietal cortex: Anatomy and functions
    • Abstract: Publication date: March 2019Source: Neuroscience Research, Volume 140Author(s): Dmitry Lyamzin, Andrea Benucci In recent years, the number of studies on decision-making in mice has increased dramatically. Many of these studies focus on the posterior parietal cortex (PPC), an area that has been implicated in sensory and multisensory processing, navigation, motion planning, and decision-making. In this review we summarize recent anatomical and functional studies of mouse PPC. First, we make a note of the existing variability in the nomenclature and its anatomical localization. Based on the commonalities across different studies we then describe the connectivity of PPC and discuss its place within several functional brain networks. In view of the examined connectivity, we go on to discuss the role of PPC for the encoding of single-modality and multimodal stimuli as well as its role in navigation. Finally, we summarize the literature on the choice-related activity: we discuss the variety of behavioral protocols and sensory modalities used in these studies, and we note that the response properties of PPC and its causal involvement in decision-making may depend substantially on these conditions. We conclude that, although more research should be devoted to creating a more complete and consistent image of the mouse PPC, this area should rightfully be considered a convenient model system for a circuit-level understanding of the mammalian parietal cortex.
  • Neuronal, mathematical, and molecular bases of perceptual decision-making
           in C. elegans
    • Abstract: Publication date: March 2019Source: Neuroscience Research, Volume 140Author(s): Yuki Tanimoto, Koutarou D. Kimura Animals process sensory information from the environment to make behavioral decisions. Although environmental information may be ambiguous or gradually changing, animals can still choose one behavioral option among several through perceptual decision-making. Perceptual decision-making has been intensively studied in primates and rodents, and neural activity that accumulates sensory information has been shown to be crucial. However, it remains unclear how the accumulating neural activity is generated, and whether such activity is a conserved decision-making strategy across the animal kingdom. Here, we review the previous perceptual decision-making studies in vertebrates and invertebrates and our recent achievement in an invertebrate model animal, the nematode Caenorhabditis elegans. In the study, we analyzed temporal dynamics of neuronal activity during perceptual decision-making in navigational behavior of C. elegans. We identified neural activity that accumulates sensory information and elucidated the molecular mechanism for the accumulating activity, which may be relevant to decision-making across the animal kingdom.
  • Circuits and neural dynamics underlying behavior
    • Abstract: Publication date: March 2019Source: Neuroscience Research, Volume 140Author(s): Shigeyoshi Fujisawa, Hokto Kazama
    • Abstract: Publication date: March 2019Source: Neuroscience Research, Volume 140Author(s):
  • Neuronal mechanisms regulating the critical period of sensory
           experience-dependent song learning
    • Abstract: Publication date: March 2019Source: Neuroscience Research, Volume 140Author(s): Yoko Yazaki-Sugiyama Neuronal circuits are intensively shaped depending on experiences received during developmental critical periods. How neuronal circuits are sculpted can even affect the later development of higher cognitive functions, such as vocal communication skills. Here, we propose songbirds that learn to sing from early auditory experiences as a model for understanding the neuronal mechanisms underlying the development of multistep vocal learning. By applying the principal concepts of neuronal mechanisms for regulating the timing of critical periods, which have been well investigated by using experience-dependent mammalian cortical plasticity, we review our current understanding of the underlying neuronal mechanism of the song-learning critical period.
  • Adolescent psychosocial stress enhances sensitization to cocaine exposure
           in genetically vulnerable mice
    • Abstract: Publication date: Available online 1 March 2019Source: Neuroscience ResearchAuthor(s): Takatoshi Hikida, Makiko Morita, Mahomi Kuroiwa, Tom Macpherson, Takahide Shuto, Naoki Sotogaku, Minae Niwa, Akira Sawa, Akinori Nishi Development of drug addictive behaviors is modulated by both genetic and environmental risk factors. However, the molecular mechanisms remain unknown. To address the role of adolescent stress in the development of drug addiction, we combined a transgenic mouse model in which a putative dominant-negative form of DISC1 under expressional control of the prion protein promoter is used as a genetic risk factor and adolescent social isolation stress as a gene-environmental interaction (GXE). Repeated cocaine exposure induced greater locomotion in the GXE group than in the other groups. In a conditioned place preference (CPP) test, GXE mice exhibited a significant place preference to the cocaine-conditioned area compared with the other groups. In the nucleus accumbens (NAc) of GXE mice, we found increased enzyme activity of phosphodiesterase-4 (PDE4), predominantly located in NAc D2-receptor-expressing neurons, and enhanced effects of the PDE4 inhibitor rolipram, but not the D1 agonist SKF81297, on the phosphorylation of DARPP-32 and GluA1 at PKA sites. Rolipram injection before cocaine exposure completely inhibited cocaine-induced hyperlocomotion and CPP in the GXE group. These results indicate that GXE enhances sensitivity to repeated cocaine exposure via an increase in PDE4 activity in NAc D2-recptor-expressing neurons, leading to the development of cocaine addictive behaviors.
  • Neural circuits regulating sexual behaviors via the olfactory system in
    • Abstract: Publication date: March 2019Source: Neuroscience Research, Volume 140Author(s): Kentaro K. Ishii, Kazushige Touhara Reproduction is essential for any animal species. Reproductive behaviors, or sexual behaviors, are largely shaped by external sensory cues exchanged during sexual interaction. In many animals, including rodents, olfactory cues play a critical role in regulating sexual behavior. What exactly these olfactory cues are and how they impact animal behavior have been a central question in the field. Over the past few decades, many studies have dedicated to identifying an active compound that elicits sexual behavior from crude olfactory components. The identified substance has served as a tool to dissect the sensory processing mechanisms in the olfactory systems. In addition, recent advances in genetic engineering, and optics and microscopic techniques have greatly expanded our knowledge of the neural mechanisms underlying the control of sexual behavior in mice. This review summarizes our current knowledge about how sexual behaviors are controlled by olfactory cues.
  • Postnatal development of the distribution of nitric oxide-producing
           neurons in the rat corpus callosum
    • Abstract: Publication date: Available online 20 February 2019Source: Neuroscience ResearchAuthor(s): Paolo Barbaresi, Emanuela Mensà, Andrea Sagrati, Laura Graciotti The postnatal development of nitric oxide (NO)-producing intracallosal neurons was studied in rats by nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry from postnatal day 0 (P0) to P30. NADPH-d-positive neurons (NADPH-d+Ns) were detected already at P0, mainly in the rostral region of the corpus callosum (cc). Their location and the intensity of staining allowed them to be classified as type I NO-producing neurons. At P0, tufts of intensely labeled fibers, probably corresponding to the callosal septa described in the monkey and human cc, entered the ventral cc region and reached its dorsal portion. From P5, cell bodies and dendrites were often associated to blood vessels. The number of intracallosal NADPH-d+Ns rose in the first postnatal days to peak at P5, it declined until P10, and then remained almost constant until P30. Their size increased from P0 to P30, dramatically so (>65%) from P0 to P15. From P10 onward their distribution was adult-like, i.e. NADPH-d+Ns were more numerous in the lateral and intermediate portions of the cc and diminished close to the midline. In conjunction with previous data, these findings indicate that intracallosal NADPH-d+Ns could have a role in callosal axon guidance, myelination, refinement processes, and callosal blood flow regulation.
  • Cerebellar transcranial direct current stimulation modulates the effect of
           cerebellar transcranial magnetic stimulation on the excitability of spinal
    • Abstract: Publication date: Available online 19 February 2019Source: Neuroscience ResearchAuthor(s): Akiyoshi Matsugi, Yohei Okada Cerebellar transcranial magnetic stimulation (C-TMS) facilitates the ipsilateral soleus H-reflex, which reflects the excitability of the spinal motoneuron pool. This study aimed to investigate whether this facilitation of the spinal motoneuron pool excitability by C-TMS is affected by cerebellar transcranial direct current stimulation (ctDCS) in a polarity-specific manner. Eleven healthy adults participated in this study. The H-reflex was measured from the right soleus muscle by electrical stimulation of the right tibial nerve. The conditioning TMS over the right cerebellum was delivered 110 ms before tibial nerve stimulation. The H-reflex ratio was calculated as conditioned/unconditioned H-reflex amplitude, and measured for pre- or post-anodal, cathodal, or sham right ctDCS, for 15 min with 2 mA. The results showed that the H-reflex ratio was significantly increased by anodal ctDCS, reduced by cathodal ctDCS, and not affected by sham ctDCS, indicating that the effect of C-TMS on the H-reflex is modulated by ctDCS in a polarity-specific manner. This implies that the effect of C-TMS on the spinal motoneuron pool is affected by the change in excitability of the cerebellum.
  • Confocal and multiphoton calcium imaging of the enteric nervous system in
           anesthetized mice
    • Abstract: Publication date: Available online 18 February 2019Source: Neuroscience ResearchAuthor(s): Yuki Motegi, Masaaki Sato, Kazuhide Horiguchi, Masamichi Ohkura, Keiko Gengyo-Ando, Yuji Ikegaya, Yasuyuki Fusamae, Yoshie Hongo, Minoru Suzuki, Koichi Ogawa, Miyako Takaki, Junichi Nakai Most imaging studies of the enteric nervous system (ENS) that regulates the function of the gastrointestinal tract are so far performed using preparations isolated from animals, thus hindering the understanding of the ENS function in vivo. Here we report a method for imaging the ENS cellular network activity in living mice using a new transgenic mouse line that co-expresses G-CaMP6 and mCherry in the ENS combined with the suction-mediated stabilization of intestinal movements. With confocal or two-photon imaging, our method can visualize spontaneous and pharmacologically-evoked ENS network activity in living animals at cellular and subcellular resolutions, demonstrating the potential usefulness for studies of the ENS function in health and disease.
  • Internal structure of the rat subiculum characterized by diverse
           immunoreactivities and septotemporal differences
    • Abstract: Publication date: Available online 13 February 2019Source: Neuroscience ResearchAuthor(s): Yoshihisa Ishihara, Takaichi Fukuda, Fumi Sato The subiculum is one of output structures of the hippocampal formation and plays a pivotal role in learning and memory. Because its morphological features are less investigated than those of the hippocampus proper, we explored the internal structure of the rat subiculum using immunohistochemistry. The septal subiculum comprised one region, whereas the temporal subiculum consisted of two subregions, the distal subiculum (Sub1) and proximal subiculum (Sub2). The Sub2 contained four layers: (1) molecular layer, (2) superficial cell layer containing three types of pyramidal neurons immunolabeled for either nitric oxide synthase, Purkinje cell protein 4 (PCP4), or calbindin, (3) middle cell layer where boutons labeled for zinc transporter 3 and those for vesicular glutamate transporter 2 accumulated in the proximal and distal part of the Sub2, respectively, and (4) deep cell layer containing PCP4-positive pyramidal cells, apical dendrites of which showed a characteristic bundling pattern. These features were not observed in either the Sub1 or septal subiculum. There were clear species differences between rats and mice in labeling patterns of pyramidal cells. Morphological differences along the septotemporal axis might be the basis of the functional diversity of the subiculum, such as spatial memory and emotional memory processed at different septotemporal levels.
  • Appearance and modulation of a reactive temporal-lobe 8–10-Hz
    • Abstract: Publication date: Available online 12 February 2019Source: Neuroscience ResearchAuthor(s): Koichi Yokosawa, Yui Murakami, Hiroaki Sato Spontaneous 8- to 10-Hz “tau-rhythm” in magnetoencephalographic (MEG) recordings has been reported to originate in the auditory cortex and be suppressed by sound. For unknown reasons however, tau-rhythm is often difficult to detect. In this study, we sought to characterize its emergence and auditory reactivity. Using a 306-channel MEG on 26 right-handed participants, we delivered six-second-long, natural, monaural sounds with pleasant, unpleasant, or neutral emotional valence. In eight participants, a clear, sound-related bilateral suppression of 8–10 Hz tau-rhythm occurred in the temporal areas, close to the source of the 100-ms auditory response. Moreover, these eight “tau subjects” exhibited significantly larger temporal-lobe theta-band (4–8 Hz) power over the entire experimental period compared to the remaining 18 “non-tau subjects”. As it is known that larger theta power is one of signs of drowsiness, this result is consistent with a previously proposed idea that tau-rhythm emerges during drowsiness. Tau-rhythm was furthermore significantly affected by emotional valence in the right hemisphere, where it was respectively suppressed by unpleasant and neutral sounds 8% and 6% more than by pleasant sounds, significantly. Altogether, our results reveal characteristics of tau-rhythm appearance and modulation which have hitherto been difficult to detect non-invasively.
  • miR-1933-3p is upregulated in skeletal muscles of MuSK+ EAMG mice and
           affects Impa1 and Mrpl27
    • Abstract: Publication date: Available online 11 February 2019Source: Neuroscience ResearchAuthor(s): Evgenii Bogatikov, Ida Lindblad, Tanel Punga, Anna Rostedt Punga MuSK antibody seropositive (MuSK+) Myasthenia Gravis (MG) typically affects skeletal muscles of the bulbar area, including the omohyoid muscle, causing focal fatigue, weakness and atrophy. The profile of circulating extracellular microRNA (miRNA) is changed in MuSK + MG, but the intracellular miRNA profile in skeletal muscles of MuSK + MG and MuSK + experimental autoimmune MG (EAMG) remains unknown. This study elucidated the intracellular miRNA profile in the omohyoid muscle of mice with MuSK + EAMG. The levels of eleven mouse miRNAs were elevated and two mouse miRNAs were reduced in muscles of MuSK + EAMG mice. Transient expression of miR-1933-3p and miR-1930-5p in mouse muscle (C2C12) cells revealed several downregulated genes, out of which five had predicted binding sites for miR-1933-3p. The mRNA expression of mitochondrial ribosomal protein L27 (Mrpl27) and Inositol monophosphatase I (Impa1) was reduced in miR-1933-3p transfected C2C12 cells compared to control cells (p = 0.032 versus p = 0.020). Further, transient expression of miR-1933-3p reduced Impa1 protein accumulation in C2C12 cells. These findings provide novel insights of dysregulated miRNAs and their intracellular pathways in muscle tissue afflicted with MuSK + EAMG, providing a possible link to mitochondrial dysfunction and muscle atrophy observed in MuSK + MG.
  • Left, right, or bilateral amygdala activation' How effects of
           smoothing and motion correction on ultra-high field, high-resolution
           functional magnetic resonance imaging (fMRI) data alter inferences
    • Abstract: Publication date: Available online 11 February 2019Source: Neuroscience ResearchAuthor(s): Jerry E. Murphy, Julio A. Yanes, Lauren A.J. Kirby, Meredith A. Reid, Jennifer L. Robinson Given the amygdala’s role in survival mechanisms, and its pivotal contributions to psychological processes, it is no surprise that it is one of the most well-studied brain regions. One of the common methods for understanding the functional role of the amygdala is the use of functional magnetic resonance imaging (fMRI). However, fMRI tends to be acquired using resolutions that are not optimal for smaller brain structures. Furthermore, standard processing includes spatial smoothing and motion correction which further degrade the resolution of the data. Inferentially, this may be detrimental when determining if the amygdalae are active during a task. Indeed, studies using the same task may show differential amygdala(e) activation. Here, we examine the effects of well-accepted preprocessing steps on whole-brain submillimeter fMRI data to determine the impact on activation patterns associated with a robust task known to activate the amygdala(e). We analyzed 7T fMRI data from 30 healthy individuals collected at sub-millimeter in-plane resolution and used a field standard preprocessing pipeline with different combinations of smoothing kernels and motion correction options. Resultant amygdalae activation patterns were altered depending on which combination of smoothing and motion correction were performed, indicating that whole-brain preprocessing steps have a significant impact on the inferences that can be drawn about smaller, subcortical structures like the amygdala.
  • TNFR2 knockdown triggers apoptosis-induced proliferation in primarily
           cultured Schwann cells
    • Abstract: Publication date: Available online 4 February 2019Source: Neuroscience ResearchAuthor(s): Zhongyang Gao, Cuiting Min, Huimin Xie, Jing Qin, Xijing He, Songlin Zhou After sciatic nerve injury, Schwann cells in the distal segments of injury site undergo apoptosis and meanwhile proliferation. Although apoptosis-induced proliferation (AiP) has been characterized in various models, whether the proliferation of Schwann cells in the distal segments is triggered by apoptosis remains unelucidated. In this study, we used small interfering RNA to knock down the expression of TNFR1 and TNFR2 in primarily cultured Schwann cells, respectively and observed its effects on apoptosis and proliferation. The downregulation of TNFR1 or TNFR2 resulted in a remarkable decrease of cell viability and dramatically increased the apoptosis of Schwann cells. In contrast, the cell apoptosis induced by the knockdown of TNFR2, but not TNFR1, promoted the Schwann cell proliferation. Together, these observations indicated that Schwann cells can undergo AiP, and TNFR2 knockdown triggers the process. Additionally, we established the sciatic nerve injury model on TNF-α knock-out (KO) mice, and found that the Schwann cells of KO mice occurred significantly less apoptosis and proliferation than that of wild-type mice in the distal segments, which indicated TNF-α and its receptors were essential in the massive apoptosis and the apoptosis-induced proliferation of Schwann cells after sciatic nerve injury. The finding of AiP in Schwann cells may be beneficial to develop new approaches to promote axon regeneration and thereby improve the functional recovery after peripheral nerve injury.
  • daf-16/FOXO isoform b in AIY neurons is involved in low preference for
           Bifidobacterium infantis in Caenorhabditis elegans
    • Abstract: Publication date: Available online 4 February 2019Source: Neuroscience ResearchAuthor(s): Simo Sun, Akane Ohta, Atsushi Kuhara, Yoshikazu Nishikawa, Eriko Kage-Nakadai The neural and molecular mechanisms underlying food preference have been poorly understood. We previously showed that Bifidobacterium infantis (B. infantis), a well-known probiotic bacterium, extends the lifespan of Caenorhabditis elegans (C. elegans) compared with a standard food, Escherichia coli (E. coli) OP50. In this study, we characterized C. elegans behavior against B. infantis and examined the neural and molecular mechanisms governing that behavior. The majority of the wild-type animals were outside of the B. infantis lawn 10 min after transfer. Although worms did not prefer B. infantis compared to E. coli OP50, they preferred the B. infantis lawn over a lawn containing M9 buffer alone, in which there was no food. Mutant analyses suggested that leaving the B. infantis lawn required daf-16/FOXO. Isoform-specific mutant phenotypes suggested that daf-16 isoform b seemed to be associated with leaving. Genetic rescue experiments demonstrated that the function of daf-16b in AIY interneurons was involved in leaving the B. infantis lawn. The daf-18/PTEN mutants were also defective in leaving. In conclusion, C. elegans showed a low preference for B. infantis, and daf-16b in AIY interneurons and daf-18 had roles in leaving B. infantis.
  • Regulation of cortical blood flow responses by the nucleus basalis of
           Meynert during nociceptive processing
    • Abstract: Publication date: Available online 31 January 2019Source: Neuroscience ResearchAuthor(s): Thierry Paquette, Ryota Tokunaga, Sara Touj, Hugues Leblond, Mathieu Piché Cerebral blood flow (CBF) is essential for neuronal metabolic functions. CBF is partly regulated by cholinergic projections from the nucleus basalis of Meynert (NBM) during cortical processing of sensory information. During pain-related processing, however, this mechanism may be altered by large fluctuations in systemic mean arterial pressure (MAP). The objective of this study was to investigate the contribution of NBM to CBF responses evoked by nociceptive electrical stimuli and how it may be affected by systemic MAP. CBF was recorded in isoflurane-anesthetized rats (n = 8) using laser speckle contrast imaging, in two conditions (intact vs left NBM lesion). Electrical stimulation was applied to the sciatic nerve. Sciatic stimulation produced intensity dependent increases in MAP (p 
  • Regional and temporal regulation and role of somatostatin receptor
           subtypes in the mouse brain following systemic kainate-induced acute
    • Abstract: Publication date: Available online 25 January 2019Source: Neuroscience ResearchAuthor(s): Chizuru Iwasawa, Minoru Narita, Hideki Tamura Somatostatin reduces neuronal excitability via somatostatin receptors (Sst1-Sst5) and inhibits seizure activity. However, the expression status of the Sst subtypes in epileptic mice and their role in the antiepileptic effects of somatostatin remain unclear. Here, we show that the Sst subtypes are regulated differently by epileptic neuronal activity in mice. Systemic kainate injection rapidly and transiently elevated the Sst2 and Sst3 mRNA and reduced Sst1 and Sst4 mRNA in the hippocampus; however, among all the subtypes, only Sst2 mRNA was increased in the excitatory neurons of the basolateral amygdala, accompanied by a decrease in the level of Sst2 protein. Following kainate administration, recovery from seizure was delayed by reduced expression of Sst2 in the basolateral amygdala, but not in the dentate gyrus of the hippocampus; higher expression levels of Bdnf, a neuronal activity marker, were observed in both conditions. These results suggest that Sst2 contributes to seizure termination by feedback inhibition in the amygdala. This could be a potential therapeutic target for acute seizures.
  • The effect of loss of the glucose-monitoring neurons in the anterior
           cingulate cortex: Physiologic challenges induce complex feeding-metabolic
           alterations after local streptozotocin microinjection in rats
    • Abstract: Publication date: Available online 24 January 2019Source: Neuroscience ResearchAuthor(s): Edina Hormay, Bettina László, István Szabó, Tamás Ollmann, Bernadett Nagy, László Péczely, Kitti Mintál, Zoltán Karádi The anterior cingulate cortex (ACC) is interrelated to limbic structures, parts of the central glucose-monitoring (GM) network. GM neurons, postulated to exist here, are hypothesised to participate in regulatory functions, such as the central control of feeding and metabolism. In the present experiments, GM neurons were identified and examined in the ACC by means of the multibarreled microelectrophoretic technique. After bilateral ACC microinjection of streptozotocin (STZ), glucose tolerance tests (GTTs), and determination of relevant plasma metabolite concentrations were performed. Body weights were measured at regular time points during the GTT experiment. Ten percent of the neurons - 30 of 282 recorded cells - responded to the administration of D-glucose, thus, declared to be the GM units. The peak values and dynamics of the GTT blood glucose curves, the plasma metabolite concentrations, and the weight gain were pathologically altered in the STZ treated animals. Our recording experiments revealed the existence of GM neurons in the anterior cingulate cortex. STZ induced selective destruction of these chemosensory cells resulted in feeding and metabolic alterations. The present findings indicate distinguished significance of the cingulate cortical GM neurons in adaptive processes of maintenance of the homeostatic balance.
  • Manganese-enhanced magnetic resonance imaging of the spinal cord in rats
           with formalin-induced pain
    • Abstract: Publication date: Available online 24 January 2019Source: Neuroscience ResearchAuthor(s): Myeounghoon Cha, Kyuhong Lee, Jun Sik Won, Bae Hwan Lee Manganese-enhanced magnetic resonance imaging (MEMRI) is based on neuronal activity-dependent manganese uptake, and provides information about nervous system function. However, systematic studies of pain processing using MEMRI are rare, and few investigations of pain using MEMRI have been performed in the spinal cord. Herein, we investigated the pain dependence of manganese ions administered in the rat spinal cord. MnCl2 was administered into the spinal cord via an intrathecal catheter before formalin injection into the right hind paw (50 μL of 5% formalin). The duration of flinching behavior was recorded and analyzed to measure formalin-induced pain. After the behavioral test, rats were sacrificed with an overdose of urethane (50 mg/kg), and spine samples were extracted and post-fixed in 4% paraformaldehyde solution. The samples were stored in 30% sucrose until molecular resonance (MR) scanning was performed. In axial Mn2+ enhancement images of the spinal cord, Mn2+ levels were found to be significantly elevated on the ipsilateral side of the spinal cord in formalin-injected rats. To confirm pain-dependent Mn enhancement in the spinal cord, c-Fos expression was analyzed, and was found to be increased in the formalin-injected rats. These results indicate that MEMRI is useful for functional analysis of the spinal cord under pain conditions. The gray matter appears to be the focus of intense paramagnetic signals. MEMRI may provide an effective technique for visualizing activity-dependent patterns in the spinal cord.
  • Sex differential effect of dexmedetomidine on fear memory extinction and
           anxiety behavior in adolescent rats
    • Abstract: Publication date: Available online 24 January 2019Source: Neuroscience ResearchAuthor(s): Minji Jang, Taesub Jung, Sung-Hoon Kim, Jihyun Noh Exposure to stressful stimuli, including fear and anxiety, modulates the central noradrenergic system. Dexmedetomidine is a commonly used α2-adrenoreceptor agonist. Because the effect of fear acquisition varies between sexes, the present study was designed to investigate sex-related differences in the effects of dexmedetomidine on fear memory and anxiety-like behavior. We conducted a fear test and an elevated plus maze test in 6–8-week-old male and female rats. Two doses of dexmedetomidine (20 and 40 μg/kg) were injected intraperitoneally three times at 24 h intervals after the tests: after fear expression, extinction 1, and extinction 2. The repeated administration of dexmedetomidine showed significant acceleration of fear memory extinction in female rats but not in male rats; the effect increased proportionally to concentrations of dexmedetomidine. Compared to male rats, female rats treated with both concentrations of dexmedetomidine showed significant anxiolytic behavior after 1 week. Dexmedetomidine accelerated the fear memory extinction and reduced anxiety; it was more effective in female rats than in male rats. Our results suggest that dexmedetomidine may exert protective effects against fear-related and anxiety-like behaviors in rats with fear memory after repeated administration, and the sex-specific effects of dexmedetomidine should be considered.
  • Uridine treatment prevents REM sleep deprivation-induced learning and
           memory impairment
    • Abstract: Publication date: Available online 24 January 2019Source: Neuroscience ResearchAuthor(s): Busra Ocalan, Aysen Cakir, Cansu Koc, Guldal Gulec Suyen, Nevzat Kahveci Previous studies have shown that sleep plays an important role in cognitive functions and sleep deprivation impairs learning and memory. Uridine is the main pyrimidine nucleoside found in human blood circulation and has beneficial effects on cognitive functions. The aim of the present study was to investigate the effects of uridine administration on learning and memory impairment in sleep-deprived rats. Flower pot method was used to induce REM sleep deprivation. Uridine-treated groups received 1 mmol/kg uridine and control groups received 1 ml/kg saline (0.9% NaCl) twice a day for four days and once a day on the 5th day intraperitoneally. Learning and memory performances were measured using Morris water maze (MWM) test. We also measured the ratios of total calcium-calmodulin dependent kinase II (tCaMKII)/β-tubulin and phosphorylated cyclic adenosine monophosphate (cAMP) response element binding protein (pCREB)/β-tubulin, long-term potentiation (LTP) related molecules, using western blot analysis on the hippocampus. The results showed that REM sleep deprivation impaired learning and memory and also decreased the ratios of tCaMKII and pCREB. Uridine treatment enhanced learning and memory parameters in REM sleep-deprived rats. Additionally, decreases in tCaMKII and pCREB were prevented by uridine treatment. These data suggest that administration of uridine for five consecutive days prevents REM sleep deprivation-induced deficits in learning and memory associated with enhanced tCaMKII and pCREB ratios in the hippocampus.Graphical abstractGraphical abstract for this article
  • Monocytes exposed to plasma from patients with Alzheimer’s disease
           undergo metabolic reprogramming
    • Abstract: Publication date: Available online 12 January 2019Source: Neuroscience ResearchAuthor(s): Hannah Wolfe, Virginia Mela, Aedin M. Minogue, Anne-Marie Miller, Chris McGuigan, Laura Williams, Deirdre Lohan, Brian A. Lawlor, Marina A. Lynch The search for a blood-based biomarker that identifies Alzheimer’s disease (AD) and can replace current invasive and expensive diagnostic tests, continues. The most extensively-examined peripheral marker is β-amyloid (Aβ) but the results are inconsistent across studies and do not reflect the changes that take place in the brain. Several studies have assessed possible proteomic signatures but with inconsistent findings, although increases in circulating inflammatory molecules are generally observed. Here, rather than focus on identifying changes in the circulation, we evaluated the effect of plasma from patients with mild cognitive impairment (MCI) and AD on the human monocyte-like cell line, THP-1 cells, and plasma from an AD mouse model on a mouse monocyte-macrophage cell line, J774.2 cells. Plasma from AD patients and the AD mouse model increased inflammatory molecules in the cells and these changes were accompanied by an increase in glycolysis. Interestingly, plasma from MCI patients exerted no significant effect on THP-1 cells. The possibility therefore exists that evaluating the effect of plasma on IL-8 and TNFα mRNA in THP-1 cells combined with analysis of glycolysis in these cells, may be the basis of an indicator that discriminates between AD and MCI and normal controls, but is unlikely to be useful in identifying early pathological changes.
  • Improving working memory and pain inhibition in older persons using
           transcranial direct current stimulation
    • Abstract: Publication date: Available online 4 January 2019Source: Neuroscience ResearchAuthor(s): Zoha Deldar, Nabi Rustamov, Isabelle Blanchette, Mathieu Piché The aim of the present study was to examine whether transcranial Direct Current Stimulation (tDCS) could enhance working memory and pain inhibition in older persons. Fifteen volunteers (7 women, 8 men; mean ± SD: 64 ± 4.4 y.o.) participated in two tDCS sessions during which an n-back task was performed with two levels of working memory load, while painful stimulation was delivered at the ankle. The experiment included five within-subject counterbalanced conditions (pain alone and 0-back or 2-back with or without pain) performed twice during each session. Compared with the pre-tDCS baseline, anodal tDCS decreased response times and improved pain inhibition by working memory in the 2-back condition (p  0.3). These results indicate that working memory and pain inhibition can be improved by tDCS in older persons.
  • Vividness and accuracy: Two independent aspects of motor imagery
    • Abstract: Publication date: Available online 31 December 2018Source: Neuroscience ResearchAuthor(s): Nobuaki Mizuguchi, Marina Suezawa, Kazuyuki Kanosue Motor imagery is the mental execution of an action without any actual movement. Although numerous studies have utilized questionnaires to evaluate the vividness of motor imagery, it remains unclear whether it is related to the accuracy of motor imagery. To examine the relationship between vividness and accuracy, we investigated brain activity during kinesthetic and visual motor imagery, by using a novel sequential finger-tapping task. We estimated accuracy by measuring the fidelity of the actual performance and evaluated vividness by using a visual analog scale. We found that accuracy of visual motor imagery was correlated with the activity in the left visual cortex, as well as with bilateral sensorimotor regions. In contrast, vividness of visual motor imagery was associated with the activity in the right orbitofrontal cortex. However, there was no correlation in the brain activity between the right orbitofrontal cortex and visuomotor regions or between vividness and accuracy of motor imagery. In addition, we did not find any correlation in the kinesthetic imagery condition. We conclude that vividness of visual motor imagery is associated with the right orbitofrontal cortex and is independent of processes occurring in sensorimotor regions, which would be responsible for the accuracy of visual motor imagery.
  • Whisker electromyograms signify awake and anesthetized states in mice
    • Abstract: Publication date: Available online 26 December 2018Source: Neuroscience ResearchAuthor(s): Asako Noguchi, Tetsuya Sakaguchi, Mototsugu Sato, Hide Aikawa, Nobuyoshi Matsumoto, Yuji Ikegaya The behavioral state of animals is essential information for functional recordings of neuronal activity; practically, the exact timing when animals recover from anesthesia is important information. Recordings of cortical local field potentials and dorsal neck electromyograms (EMGs), a widely used method to identify behavioral states, requires at least two recording electrodes, one of which also requires a craniotomy procedure. In the present study, recordings of whisker EMGs alone are sufficient to detect the state switch from anesthesia to awakening in head-fixed mice. This method uses a single electrode and thus is technically simple and demands a less physical burden to animals. Moreover, whisker EMGs recorded under anesthesia reflect respiratory rhythms.
  • l-DOPA+receptor+GPR143,+in+Lewy+bodies&rft.title=Neuroscience+Research&rft.issn=0168-0102&">Immunoreactivity of a G protein-coupled l-DOPA receptor GPR143, in Lewy
    • Abstract: Publication date: Available online 24 December 2018Source: Neuroscience ResearchAuthor(s): Yoshio Goshima, Shuya Watanabe, Erika Seki, Motokazu Koga, Daiki Masukawa, Fumio Nakamura, Takashi Komori, Nobutaka Arai l-3,4-Dihydroxyphenylalanine (l-DOPA) has been believed to be an inert amino acid precursor of dopamine, and is the most effective therapeutic agent in Parkinson’s disease (PD). We proposed l-DOPA as a neurotransmitter in the central nervous system. Recently, the ocular albinism 1 gene product, OA1/GPR143 (GPR143), was identified as a receptor for l-DOPA. In this study, we examined by generating anti-human GPR143 antibody, the localization of GPR143-immunoreactive signals in the brains from control and PD subjects. GPR143-immunoreactive signals were detected throughout the entire midbrain including substantia nigra pars compacta. In the PD brains, we found that GPR143-immunoreactive signals were detected in Lewy bodies and were colocalized with immunoreactive signals with anti-human Ser129 phosphorylated α-synuclein antibody. Although the significance of its occurrence in the inclusion bodies is unknown, our finding suggests possible implications of GPR143 in PD.
  • Evaluation of critical flicker-fusion frequency measurement methods using
           a touchscreen-based visual temporal discrimination task in the behaving
    • Abstract: Publication date: Available online 5 December 2018Source: Neuroscience ResearchAuthor(s): Yuichiro Nomura, Shohei Ikuta, Satoshi Yokota, Junpei Mita, Mami Oikawa, Hiroki Matsushima, Akira Amano, Kazuhiro Shimonomura, Yasuhiro Seya, Chieko Koike The critical flicker-fusion frequency (CFF), defined as the frequency at which a flickering light is indistinguishable from a continuous light, is a useful measure of visual temporal resolution. The mouse CFF has been studied by electrophysiological approaches such as recordings of the electroretinogram (ERG) and the visually evoked potential (VEP), but it has not been measured behaviorally. Here we estimated the mouse CFF by using a touchscreen based operant system. The test with ascending series of frequencies and that with randomized frequencies resulted in about 17 and 14 Hz, respectively, as the frequency which could not be distinguished from steady lights. Since the ascending method of limits tend to overestimate the threshold than the descending method, we estimated the mouse CFF to be about 14 Hz. Our results highlight usefulness of the operant conditioning method in measurement of the mouse visual temporal resolution.
  • Decoding natural scenes based on sounds of objects within scenes using
           multivariate pattern analysis
    • Abstract: Publication date: Available online 1 December 2018Source: Neuroscience ResearchAuthor(s): Xiaojing Wang, Jin Gu, Junhai Xu, Xianglin Li, Junzu Geng, Bin Wang, Baolin Liu Scene recognition plays an important role in spatial navigation and scene classification. It remains unknown whether the occipitotemporal cortex could represent the semantic association between the scenes and sounds of objects within the scenes. In this study, we used the functional magnetic resonance imaging (fMRI) technique and multivariate pattern analysis to assess whether diff ;erent scenes could be discriminated based on the patterns evoked by sounds of objects within the scenes. We found that patterns evoked by scenes could be predicted with patterns evoked by sounds of objects within the scenes in the posterior fusiform area (pF), lateral occipital area (LO) and superior temporal sulcus (STS). The further functional connectivity analysis suggested significant correlations between pF, LO and parahippocampal place area (PPA) except that between STS and other three regions under the scene and sound conditions. A distinct network in processing scenes and sounds was discovered using a seed-to-voxel analysis with STS as the seed. This study may provide a cross-modal channel of scene decoding through the sounds of objects within the scenes in the occipitotemporal cortex, which could complement the single-modal channel of scene decoding based on the global scene properties or objects within the scenes.
  • Oxytocin is indispensable for conspecific-odor preference and controls the
           initiation of female, but not male, sexual behavior in mice
    • Abstract: Publication date: Available online 28 November 2018Source: Neuroscience ResearchAuthor(s): Sunil Dhungel, Dilip Rai, Misao Terada, Chitose Orikasa, Katsuhiko Nishimori, Yasuo Sakuma, Yasuhiko Kondo Oxytocin (OT) has been demonstrated to be involved in various social behaviors in mammals. However, OT gene knockout (OTKO) mice can conceive and deliver successfully, though females cannot rear their pups because of lack of lactation. Here, we investigated the sociosexual behavior of both sexes in two experimental setups: olfactory preference for sexual partner’s odor and direct social interaction in an enriched condition. In the preference test, mice were given a choice of two airborne odors derived from intact male and receptive female mice, or from intact or castrated male mice. Wild-type (WT) mice significantly preferred opposite-sex odors, whereas OTKO mice showed vigorous but equivalent exploration to all stimuli. In social interactions in the enriched condition, no difference in sexual behavior was found between WT and OTKO males. In contrast, WT female initiated sexual behavior at the second week test, while OTKO females required 4 weeks to receive successful mounts. Neuronal activation by odor stimulation was compared between WT and OTKO mice. The numbers of cFos-immunoreactive cells increased in the medial amygdala and the preoptic area after exposure to opposite-sex odors in WT mice, whereas the increase was suppressed in OTKO mice. We conclude that OT plays an important role in the regulation of olfactory-related social behavior in both male and female mice. The influence of OT was greater in female mice, especially during social interactions involving the acquisition of sexual experience.
  • Synaptic topography – Converging connections and emerging function
    • Abstract: Publication date: Available online 20 November 2018Source: Neuroscience ResearchAuthor(s): Naoya Takahashi Brain circuits are constituted of individual neurons that are interconnected with a vast array of synapses. In order to understand how brain function emerges from this complex synaptic network, immense efforts have been made to trace the synaptic topography, i.e. arrangement of synaptic connections, of the network. In addition to anatomically elaborating the synaptic layout at multiple levels across brain regions, recent studies have attempted to elucidate the fundamental wiring principles that govern neural information processing in the brain, establishing a link between anatomy and function. In this review, I will discuss recent discoveries on the topographical organization of synaptic connections at the cell-to-cell and subcellular levels in the cortex and hippocampus. Accumulating evidence leads us to acknowledge the highly structured, non-random synaptic connectivity that emerges together with sensory feature preferences of neurons and synchronous neuronal activity.
  • Gestational stress induced differential expression of HDAC2 in male rat
           offspring hippocampus during development
    • Abstract: Publication date: Available online 16 November 2018Source: Neuroscience ResearchAuthor(s): Libin Liao, Xueqin Wang, Xueping Yao, Bin Zhang, Lihong Zhou, Jufang Huang Accumulating evidence from preclinical and clinical studies indicates prenatal exposure to stress or excess glucocorticoids can affect offspring brain. HDAC2 is an important target of glucocorticoid. Here we detected HDAC2 expression in male offspring hippocampus from gestational restraint stressed rat during development and the relationship between HDAC2 expression and behaviors and neurogenesis in male offspring. Pregnant rats received restrained stress during the last week of pregnancy. Expressions of HDAC2 in offspring hippocampus were detected on postnatal 0 day (P0) and 60 days (P60). Neurogenesis was evaluated by Doublecortin (DCX) staining on P60. Anxiety-like behavior and cognition were detected in open field, elevated plus maze, novel object recognition test, and Barnes maze. We found that HDAC2 expression in the hippocampus of male prenatally stressed offspring (MPSO) was similar to the male control offspring on P0, but significantly lower on P60. Corresponding to the decreased expression of HDAC2 in MPSO hippocampus at P60, neurogenesis in the dentate gyrus of MPSO was significantly lower than the control male offspring. And MPSO also showed greater anxiety and poorer learning and memories abilities than control male offspring. These showed that HDAC2 could partly explain the effects of gestational stress on male offspring behaviors.
  • ADAR2-dependent A-to-I RNA editing in the extracellular linear and
           circular RNAs
    • Abstract: Publication date: Available online 16 November 2018Source: Neuroscience ResearchAuthor(s): Takashi Hosaka, Takenari Yamashita, Sayaka Teramoto, Naoki Hirose, Akira Tamaoka, Shin Kwak Currently, no reliable biomarkers of amyotrophic lateral sclerosis (ALS) exist. In sporadic ALS, RNA editing at the glutamine/arginine site of GluA2 mRNA is specifically reduced in the motor neurons due to the downregulation of adenosine deaminase acting on RNA 2 (ADAR2). Furthermore, TDP-43 pathology, the pathological hallmark of ALS, is observed in the ADAR2-lacking motor neurons in ALS patients and conditional ADAR2 knockout mice, suggesting a pivotal role of ADAR2 downregulation in the ALS pathogenesis. Extracellular RNAs were shown to represent potential disease biomarkers and the editing efficiencies at their ADAR2-dependent sites may reflect cellular ADAR2 activity, suggesting that these RNAs isolated from the body fluids may represent the biomarkers of ALS. We searched for ADAR2-dependent sites in the mouse motor neurons and human-derived cultured cells and found 10 sites in five host RNAs expressed in SH-SY5Y cells and their culture medium. Of these, the arginine/glycine site of SON mRNA was newly identified as an ADAR2-dependent site. Furthermore, we detected a circular RNA with an ADAR2-dependent site in the SH-SY5Y cells and their culture medium. Therefore, the changes in the editing efficiencies at the identified host RNA sites isolated from the body fluids may represent potential biomarkers of ALS.Graphical abstractGraphical abstract for this article
  • Recurrent short-term hypoglycemia and hyperglycemia induce apoptosis and
           oxidative stress via the ER stress response in immortalized adult mouse
           Schwann (IMS32) cells
    • Abstract: Publication date: Available online 13 November 2018Source: Neuroscience ResearchAuthor(s): Ayako Kato, Yasuaki Tatsumi, Hideji Yako, Kazunori Sango, Tatsuhito Himeno, Masaki Kondo, Yoshiro Kato, Hideki Kamiya, Jiro Nakamura, Koichi Kato Hypoglycemia and fluctuating high or low glucose conditions are under-appreciated sources of oxidative stress contributing to diabetic neuropathy. We investigated the effects of recurrent short-term hypoglycemia and hyperglycemia, on apoptosis and oxidative stress in Schwann cells. Immortalized adult mouse Schwann (IMS32) cells were exposed to five different glucose treatments over 3 days: 1) normal glucose (NG), 2) constant low glucose (LG), 3) constant high glucose (HG), 4) intermittent low glucose (ILG; 1 h three times per day), 5) intermittent high glucose (IHG; 1 h three times per day). Cell viability was decreased by all treatment variants, in comparison to NG. Thiobarbituric acid reactive substance (TBARS) levels were increased by HG, LG, IHG, and ILG. High glucose (HG and IHG) and low glucose (LG and ILG) increased the expression of cleaved caspase-3 and reduced that of Bcl-2. In addition, endoplasmic reticulum (ER) stress-responsive transcription factor C/EBP homologous protein (CHOP) expression was increased under low and high glucose conditions. Cell death and oxidative stress induced by HG, LG, IHG, and ILG were significantly reduced by 4-phenyl butyric acid (4-PBA), an ER stress inhibitor. These findings indicate that recurrent short-term hypoglycemia and hyperglycemia induce apoptosis and oxidative stress via the ER stress response in Schwann cells.
  • Non-coding RNA Neat1 and Abhd11os expressions are dysregulated in medium
           spiny neurons of Huntington disease model mice
    • Abstract: Publication date: Available online 2 November 2018Source: Neuroscience ResearchAuthor(s): Hongsun Park, Haruko Miyazaki, Tomoyuki Yamanaka, Nobuyuki Nukina Huntington Disease (HD) is a neurodegenerative disorder caused by expanded CAG repeats in the exon1 of huntingtin gene (HTT). The mutant HTT affects the transcriptional profile of neurons by disrupting the activities of transcriptional machinery and alters expression of many genes. In this study, we identified dysregulated non-coding RNAs (ncRNAs) in medium spiny neurons of 4-week-old HD model mouse. Also, we observed the intracellular localizations of Abhd11os and Neat1 ncRNAs by ViewRNA in situ hybridization, which could provide more precise detection, suggesting that it is a useful method to investigate the expression changes of genes with low expression levels.
  • Insulin growth factor 2 (IGF2) as an emergent target in psychiatric and
           neurological disorders. Review
    • Abstract: Publication date: Available online 31 October 2018Source: Neuroscience ResearchAuthor(s): M. Pardo, Y. Cheng, Y.H. Sitbon, J.A. Lowell, S.F. Grieco, R.J. Worthen, S. Desse, A. Barreda-Diaz Insulin-like growth factor 2 (IGF2) is abundantly expressed in the central nervous system (CNS). Recent evidence highlights the role of IGF2 in the brain, sustained by data showing its alterations as a common feature across a variety of psychiatric and neurological disorders. Previous studies emphasize the potential role of IGF2 in psychiatric and neurological conditions as well as in memory impairments, targeting IGF2 as a pro-cognitive agent. New research on animal models supports that upcoming investigations should explore IGF2′s strong promising role as a memory enhancer. The lack of effective treatments for cognitive disturbances as a result of psychiatric diseases lead to further explore IGF2 as a promising target for the development of new pharmacology for the treatment of memory dysfunctions. In this review, we aim at gathering all recent relevant studies and findings on the role of IGF2 in the development of psychiatric diseases that occur with cognitive problems.Graphical abstractGraphical abstract for this article
  • Comparative neuroanatomy: Integrating classic and modern methods to
    • Abstract: Publication date: Available online 30 October 2018Source: Neuroscience ResearchAuthor(s): Hiromasa Takemura, Franco Pestilli, Kevin S. Weiner Comparative neuroanatomy studies improve understanding of brain structure and function and provide insight regarding brain development, evolution, and also what features of the brain are uniquely human. With modern methods such as diffusion MRI (dMRI) and quantitative MRI (qMRI), we are able to measure structural features of the brain with the same methods across human and non-human primates. In this review article, we discuss how recent dMRI measurements of vertical occipital connections in humans and macaques can be compared with previous findings from invasive anatomical studies that examined connectivity, including relatively forgotten classic strychnine neuronography studies. We then review recent progress in understanding the neuroanatomy of vertical connections within the occipitotemporal cortex by combining modern quantitative MRI and classical histological measurements in human and macaque. Finally, we a) discuss current limitations of dMRI and tractography and b) consider potential paths for future investigations using dMRI and tractography for comparative neuroanatomical studies of white matter tracts between species. While we focus on vertical association connections in visual cortex in the present paper, this same approach can be applied to other white matter tracts. Similar efforts are likely to continue to advance our understanding of the neuroanatomical features of the brain that are shared across species, as well as to distinguish the features that are uniquely human.
  • Pharmacological and proteomic analyses of neonatal polyI:C-treated adult
    • Abstract: Publication date: Available online 26 October 2018Source: Neuroscience ResearchAuthor(s): Kanako Kitagawa, Taku Nagai, Kiyofumi Yamada Perinatal virus infection is an environmental risk factor for neurodevelopmental disorders such as schizophrenia. We previously demonstrated that neonatal treatment with a viral mimetic, polyriboinosinic-polyribocytidilic acid (polyI:C), in mice leads to emotional and cognitive deficits in adolescence. Here, we investigated the effects of antipsychotics on polyI:C-induced behavioral abnormalities. We also performed a proteomic analysis in the hippocampus of polyI:C-treated adult mice using two-dimensional electrophoresis to understand the changes in protein expression following neonatal immune activation. Neonatal mice were subcutaneously injected with polyI:C for 5 days (postnatal day 2–6). At 10 weeks, sensorimotor gating, emotional and cognitive function were analyzed in behavioral tests. Clozapine improved PPI deficit and emotional and cognitive dysfunction in polyI:C-treated mice. However, haloperidol improved only PPI deficit. Proteomic analysis revealed that two candidate proteins were obtained in the hippocampus of polyI:C-treated mice, including aldehyde dehydrogenase family 1 member L1 (ALDH1L1) and collapsin response mediator protein 5 (CRMP5). These data suggest that the neonatal polyI:C-treated mouse model may be useful for evaluating antipsychotic activity of compounds. Moreover, changes in the protein expression of ALDH1L1 and CRMP5 support our previous findings that astrocyte-neuron interaction plays a role in the pathophysiology of neurodevelopmental disorders induced by neonatal immune activation.
  • Optical consequences of a genetically-encoded voltage indicator with a pH
           sensitive fluorescent protein
    • Abstract: Publication date: Available online 18 October 2018Source: Neuroscience ResearchAuthor(s): Bok Eum Kang, Sungmoo Lee, Bradley. J. Baker Genetically-Encoded Voltage Indicators (GEVIs) are capable of converting changes in membrane potential into an optical signal. Here, we focus on recent insights into the mechanism of ArcLight-type probes and the consequences of utilizing a pH-dependent Fluorescent Protein (FP). A negative charge on the exterior of the β-can of the FP combined with a pH-sensitive FP enables voltage-dependent conformational changes to affect the fluorescence of the probe. This hypothesis implies that interaction/dimerization of the FP creates a microenvironment for the probe that is altered via conformational changes. This mechanism explains why a pH sensitive FP with a negative charge on the outside of the β-can is needed, but also suggests that pH could affect the optical signal as well. To better understand the effects of pH on the voltage-dependent signal of ArcLight, the intracellular pH (pHi) was tested at pH 6.8, 7.2, or 7.8. The resting fluorescence of ArcLight gets brighter as the pHi increases, yet only pH 7.8 significantly affected the ΔF/F. ArcLight could also simultaneously report voltage and pH changes during the acidification of a neuron firing multiple action potentials revealing different buffering capacities of the soma versus the processes of the cell.
  • Angiopoietin-1/Tie2 signaling pathway contributes to the therapeutic
           effect of thymosin β4 on diabetic peripheral neuropathy
    • Abstract: Publication date: Available online 13 October 2018Source: Neuroscience ResearchAuthor(s): Lei Wang, Michael Chopp, Alexandra Szalad, XueRong Lu, Mei Lu, Talan Zhang, Zheng Gang Zhang Angiopoietin-1 (Ang1) and its receptor Tie2 regulate vascular function. Our previous study demonstrated that thymosin beta 4 (Tβ4) ameliorates neurological function of diabetic peripheral neuropathy. Mechanisms underlying the therapeutic effect of Tβ4 on diabetic peripheral neuropathy have not been fully investigated. The present in vivo study investigated whether the Ang1/Tie2 signaling pathway is involved in Tβ4-improved neurovascular remodeling in diabetic peripheral neuropathy. Diabetic BKS. Cg-m+/+Leprdb/J (db/db) mice at age 20 weeks were treated with Tβ4 and neutralizing antibody against mouse Tie2 for 4 consecutive weeks. Neurological functional and neurovascular remodeling were measured. Administration of the neutralizing antibody against Tie2 attenuated the therapeutic effect of Tβ4 on improved diabetic peripheral neuropathy as measured by motor and sensory nerve conduction velocity and thermal hypoesthesia compared to diabetic db/db mice treated with Tβ4 only. Histopathological analysis revealed that the neutralizing antibody against Tie2 abolished Tβ4-increased microvascular density in sciatic nerve and intraepidermal nerve fiber density, which were associated with suppression of Tβ4-upregulated occludin expression and Tβ4-reduced protein levels of nuclear factor-κB (NF-κB) and vascular cell adhesion molecule-1 (VCAM1). Our data provide in vivo evidence that the Ang1/Tie2 pathway contributes to the therapeutic effect of Tβ4 on diabetic peripheral neuropathy.
  • Endurance training on rodent brain antioxidant capacity: A meta-analysis
    • Abstract: Publication date: Available online 13 October 2018Source: Neuroscience ResearchAuthor(s): Raphael Fabricio de Souza, Silvia Regina Arruda de Moraes, Ricielle Lopes Augusto, Aristela de Freitas Zanona, Dihogo Matos, Felipe J. Aidar, Belmira Lara da Silveira Andrade-da-Costa The influence of physical exercise on brain antioxidant defense mechanisms has been studied. Nevertheless, the effect of training volume on the brain`s redox balance remains unclear. In this meta-analysis, we compared the effect of training volume on antioxidant enzymatic resource and lipid peroxidation on various brain regions. The activities of the enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and the levels of thiobarbituric acid reactive substances (TBARS) were also evaluated. The effects of training periods (weeks) and exercise duration were compared. Meta-analysis revealed that protocols over 8 weeks were associated with an increase in SOD (p =  0.0008) and CAT activities (p =  0.0001). Exercise durations for 30 and 60 min were associated with higher CAT activity (p =  0.04). Joint analysis revealed that moderate physical exercise over 4 and 8 weeks promoted a healthy enzymatic balance. However, high volumes of exercise over 8 weeks were associated with the increased antioxidant enzymatic activity, indicating higher reactive oxygen species (ROS) levels. The data also indicated that there is still limited research and inaccurate information, on the safety conditions of training periods that simulate tests of ultra resistance in humans.
  • Involvement of IL-6 and GSK3β in impaired sensorimotor gating induced
           by high-fat diet
    • Abstract: Publication date: Available online 13 October 2018Source: Neuroscience ResearchAuthor(s): Chisato Wakabayashi, Hiroshi Kunugi Increased levels of proinflammatory cytokines have been implicated in schizophrenia; however, their pathophysiological roles in abnormal brain dysfunctions remain unclear. We evaluated the effect of proinflammatory cytokines on a high-fat diet (HFD)-induced prepulse inhibition (PPI) deficits in the acoustic startle response. Eight-week-old male C57BL/6J mice were fed a HFD for 3 weeks and then PPI was examined. HFD significantly induced PPI deficits and increased plasma IL-6, but not TNFα, levels. Interestingly, MR16-1 administration during the HFD period ameliorated PPI deficits. Further, in the striatum of HFD-fed mice, phosphorylation of GSK3β, but not GSK3α, was significantly increased; this increase was attenuated by MR16-1, although the protein levels of GSK3α and β were not altered. There were no significant differences in either phosphorylation or protein levels of GSK3α, β in the PFC during the HFD period. These results suggest that increased IL-6 levels during HFD may induce sensorimotor gating deficits, likely through the alteration of striatal GSK3β phosphorylation. MR16-1 might have a beneficial effect on such HFD-induced sensorimotor gating deficits.
  • Performance fatigability does not impact the inhibitory control
    • Abstract: Publication date: Available online 11 October 2018Source: Neuroscience ResearchAuthor(s): Simon Thibault, François Hug, Thibault Deschamps This study explored whether reduction of the maximal voluntary force of finger flexor muscles affects response inhibition processing while performing the flanker “inhibitory reaction time” task. Sixteen participants completed two experimental sessions: each consisted of either a fatiguing exercise (fatigue session) or a control task (control session) followed by a flanker task. When responding to 32 compatible and 32 incompatible trials, the participants were asked to respond to a right-facing arrow by pressing a button beneath their middle finger, and to a left-facing arrow by pressing a button beneath their index finger. During the fatigue session, the participants were instructed to sustain 50% of their maximal voluntary isometric force during a handgrip force task with their wrist in a neutral position. In the control session, this exercise was replaced by a 7-min period of rest. The results showed that the handgrip task was effective at inducing a significant decrease in maximal force (-25.2 ± 9.1%, p < 0.001). However, this performance fatigability did not affect either the reaction time or the error rate. Similarly, it did not alter the conflict-monitoring function involved in the settings of response override. A functional robustness of the inhibition function under fatigue effect is assumed, at least in young healthy adults.
  • Na+, K+-ATPase inhibition causes hyperactivity and impulsivity in mice via
           dopamine D2 receptor-mediated mechanism
    • Abstract: Publication date: Available online 6 October 2018Source: Neuroscience ResearchAuthor(s): Yuki Kurauchi, Yuko Yoshimaru, Yuto Kajiwara, Taishi Yamada, Keigo Matsuda, Akinori Hisatsune, Takahiro Seki, Hiroshi Katsuki Hyperactivity and impulsivity are common symptoms in several psychiatric disorders. Although dysfunction of Na+, K+-ATPase has been reported to be associated with the psychiatric disorders, it is not clear whether inhibition of Na+, K+-ATPase causes behavioral effects, including hyperactivity and impulsivity, in mice. Here, we evaluated the effect of intracerebroventricular (icv) injection of ouabain, an inhibitor of Na+, K+-ATPase, on hyperactivity and impulsivity in mice. At seven days after icv injection, ouabain-injected mice displayed the increase in the distance traveled in the open field arena in the open field test and the increase in the number of head-dipping behavior in the cliff avoidance test. Chlorpromazine or haloperidol, typical antipsychotics, reduced the hyperactivity and impulsivity in ouabain-injected mice. On the other hand, neither lithium carbonate nor valproate, established mood-stabilizing drugs, improved hyperactivity and impulsivity in our mouse model. Furthermore, ouabain-injected mice exhibited the increase in the number of c-fos-positive cells in the nucleus accumbens and the prefrontal cortex but not in the ventral tegmental area, which was reduced by haloperidol. These results suggest that the dysfunction of Na+, K+-ATPase causes hyperactivity and impulsivity via hyperactivation of dopamine D2 receptor-mediated signaling pathway, causing disturbed neuronal circuits in mice.
  • The organization of tyrosine hydroxylase-immunopositive cells in the
           sparrow retina
    • Abstract: Publication date: Available online 20 September 2018Source: Neuroscience ResearchAuthor(s): Joo-Yeong Jeon, Eun-Shil Lee, Eun-Bee Park, Chang-Jin Jeon The purpose of this study was to identify tyrosine hydroxylase-immunopositive (TH+) cells in the sparrow retina using immunocytochemistry and quantitative analysis. All TH+ cells were conventional amacrine cells. Based on dendritic morphology, at least two types were observed. The first type had a single thick primary process that descended from the cell body and many densely beaded processes in substrata (s) 1, less beaded processes in s3, and spiny processes in s4/5 of the inner plexiform layer. The dendrites of the second type appeared similar in each layer, but it displayed several primary processes that spread laterally away from the soma before descending to the inner plexiform layer. The average density of TH+ cells was 37.48 ± 1.97 cells/mm2 (mean ± standard deviation; n = 4), and the estimated total number of TH+ cells was 3,061.25 ± 192.79. The highest and lowest densities of TH+ cells were located in the central dorsotemporal retina and periphery of the ventronasal retina, respectively. TH+ cells did not express calbindin-D28 K, calretinin, or parvalbumin. These results suggest that all TH+ cells in specific amacrine cell subpopulations are involved in retinal information processing in both the ON and OFF sublaminae in sparrow retina.
  • GABAergic inhibition reduces the impact of synaptic excitation on somatic
    • Abstract: Publication date: Available online 20 September 2018Source: Neuroscience ResearchAuthor(s): Chiaki Kobayashi, Kazuki Okamoto, Yasuhiro Mochizuki, Hidetoshi Urakubo, Kenta Funayama, Tomoe Ishikawa, Tetsuhiko Kashima, Ayako Ouchi, Agnieszka F. Szymanska, Shin Ishii, Yuji Ikegaya The effect of excitatory synaptic input on the excitation of the cell body is believed to vary depending on where and when the synaptic activation occurs in dendritic trees and the spatiotemporal modulation by inhibitory synaptic input. However, few studies have examined how individual synaptic inputs influence the excitability of the cell body in spontaneously active neuronal networks mainly because of the lack of an appropriate method. We developed a calcium imaging technique that monitors synaptic inputs to hundreds of spines from a single neuron with millisecond resolution in combination with whole-cell patch-clamp recordings of somatic excitation. In rat hippocampal CA3 pyramidal neurons ex vivo, a fraction of the excitatory synaptic inputs were not detectable in the cell body against background noise. These synaptic inputs partially restored their somatic impact when a GABAA receptor blocker was intracellularly perfused. Thus, GABAergic inhibition reduces the influence of some excitatory synaptic inputs on the somatic excitability. Numerical simulation using a single neuron model demonstrates that the timing and locus of a dendritic GABAergic input are critical to exert this effect. Moreover, logistic regression analyses suggest that the GABAergic inputs sectionalize spine activity; that is, only some subsets of synchronous synaptic activity seemed to be preferably passed to the cell body. Thus, dendrites actively sift inputs from specific presynaptic cell assemblies.
  • Fragile X mental retardation protein regulates accumulation of the active
           zone protein Munc18-1 in presynapses via local translation in axons during
    • Abstract: Publication date: Available online 19 September 2018Source: Neuroscience ResearchAuthor(s): Shumaia Parvin, Renoma Takeda, Yu Sugiura, Makiko Neyazaki, Terukazu Nogi, Yukio Sasaki Fragile X mental retardation protein (FMRP), a causative gene (FMR1) product of Fragile X syndrome (FXS), is an RNA-binding protein to regulate local protein synthesis in dendrites for postsynaptic functions. However, involvement of FMRP in local protein synthesis in axons for presynaptic functions remains unclear. Here we investigated role of FMRP in local translation of the active zone protein Munc18-1 during presynapse formation. We found that leucine-rich repeat transmembrane neuronal 2 (LRRTM2)-conjugated beads, which promotes synchronized presynapse formation, induced simultaneous accumulation of FMRP and Munc18-1 in presynapses of axons of mouse cortical neurons in neuronal cell aggregate culture. The LRRTM2-induced accumulation of Munc18-1 in presynapses was observed in axons protein-synthesis-dependently, even physically separated from cell bodies. The accumulation of Munc18-1 was enhanced in Fmr1-knockout (KO) axons as compared to wild type (WT), suggesting FMRP-regulated suppression for local translation of Munc18-1 in axons during presynapse formation. Using naturally formed synapses of dissociated culture, structured illumination microscope revealed that accumulation of Munc18-1 puncta in Fmr1-KO neurons increased significantly at 19 days in vitro, as compared to WT. Our findings lead the possibility that excessive accumulation of Munc18-1 in presynapses at early stage of synaptic development in Fmr1-KO neurons may have a critical role in impaired presynaptic functions in FXS.Graphical abstractGraphical abstract for this article
  • Three-dimensional analysis of the vestibulo-ocular reflex and the ability
           to distinguish the direction of centripetal acceleration in humans during
           eccentric rotation with the right ear facing downwards
    • Abstract: Publication date: Available online 12 September 2018Source: Neuroscience ResearchAuthor(s): Xiuwen Jiang, Takao Imai, Tomoko Okumura, Yumi Ohta, Yasuhiro Osaki, Takashi Sato, Hidenori Inohara This study was conducted to evaluate the linear vestibulo-ocular reflex (lVOR) mediated by the saccule, and to investigate the relationship between the lVOR and the ability to distinguish the direction of centripetal acceleration during centric and eccentric rotation. Participants sat on a chair in darkness, with the right ear facing downwards, either directly above the center of rotation, or with their nose out, nose in, right shoulder out, or left shoulder out against the center of rotation (eccentric rotation). Participants were given no information about the chair position, and were rotated sinusoidally at 0.1–0.7 Hz. Three-dimensional eye movements during rotation were analyzed. Participants were asked to describe the position of the chair after rotation. Correctly reporting the five possible chair positions requires recognition of the direction of centripetal acceleration. We analyzed the rate of correct answers to assess participants’ ability to identify the direction of centripetal acceleration. lVOR mediated by the saccule was observed only at high rotational frequencies. The rate of correct answers was higher at high rotational frequencies than that at low rotational frequencies. These results indicate that high rotational frequency is important for both lVOR mediated by the saccule and distinguishing the direction of centripetal acceleration.
  • Respect and admiration differentially activate the anterior temporal lobe
    • Abstract: Publication date: Available online 9 September 2018Source: Neuroscience ResearchAuthor(s): Hironori Nakatani, Sera Muto, Yulri Nonaka, Tomoya Nakai, Tomomi Fujimura, Kazuo Okanoya Admiration and respect are positive social emotions often experienced when recognizing excellent behavior in another person. Although both strongly rely on appraisal of behavior, admiration focuses on the admirable behavior of a person, while respect focuses on the person as a whole. The evaluation and interpretation of the social behavior of another person are dependent on semantic memory. Social semantic knowledge is represented in the anterior temporal lobe (ATL), and ATL activity is modulated by conceptual details of semantic knowledge. As respect requires evaluation of not only excellent behavior but also of the person as a whole, we hypothesized that the ATL is differentially activated by admiration and respect. To test our hypothesis, we conducted functional magnetic resonance imaging experiments. We presented participants with vignettes describing admirable behavior of fictitious characters and asked them to imagine and report how they would normally feel when encountering the situation described in the vignettes, i.e., admiration or respect and its intensity. A part of the left ATL was more strongly modulated by the intensity of respect than of admiration. Although admiration and respect are often considered to be closely related, our results indicate that the neural substrates underlying these emotions are different.
  • Proposal for an accurate TMS-MRI co-registration process via 3D laser
    • Abstract: Publication date: Available online 28 August 2018Source: Neuroscience ResearchAuthor(s): Naruhito Hironaga, Takahiro Kimura, Takako Mitsudo, Atsuko Gunji, Makoto Iwata An important technical issue in transcranial magnetic stimulation (TMS) usage is how accurately the specific brain areas activated by TMS are assessed. However, in practice, electric field induced in TMS is dispersed and therefore actual estimation is still difficult. As a preliminary step, the projection line which is perpendicular to the TMS stimulation coil beneath the center of the coil must be accurately estimated into the brain. Therefore, we have developed a new TMS-MRI co-registration procedure that employs a 3D laser-scanner system that is very useful for general hand-manipulated TMS, and which easily estimates the TMS projection point onto the brain. The proposed system accurately captures the positional relationship between the TMS coil and anatomical images. The results of 3D image processing revealed that the registration error at each stage was kept within the submillimeter level. In addition, a motor evoked potential experiment examining the right finger motor area revealed that understandable responses were obtained when stimulation was targeted to the three different motor areas according to Penfield’s map. 3D laser scanning is a technique of substantial recent interest for anatomical co-registration. The proposed method demonstrated submillimeter level accuracy of TMS-MRI co-registration.
  • Being a leader in a rhythmic interaction activates reward-related brain
    • Abstract: Publication date: Available online 25 August 2018Source: Neuroscience ResearchAuthor(s): Hiroka Sabu, Tomoyo Morita, Hideyuki Takahashi, Eiichi Naito, Minoru Asada Interpersonal rhythmic interaction is one of the fundamental behaviors that allow humans to socially interact with others. In this study, we provide novel neuroimaging evidence that being followed by other agents in such an interaction is pleasant for humans. Using functional magnetic resonance imaging, we measured the brain activity of 17 participants while they performed a virtual drum-hitting task, in one of the following conditions: a) alternating with a virtual agent that would always copy their hitting pace, or b) alternating with a virtual agent that would randomly hit the drum. The participants reported a significantly higher subjective feeling of being followed by the agent in the first condition. Moreover, almost all participants preferred the agent that followed their drum-hitting rhythm. The activity of the caudate nucleus, which is one of the reward-related brain structures, was found to be associated with the subjective feeling of being followed, suggesting that the sense of being the leader, in an interpersonal rhythmic interaction, creates a pleasant feeling.
  • Radioprotective effect of epimedium on neurogenesis and cognition after
           acute radiation exposure
    • Abstract: Publication date: Available online 23 August 2018Source: Neuroscience ResearchAuthor(s): Si Wei Wang, Bo Xu Ren, Feng Qian, Xue Zhi Luo, Xi Tang, Xiao Chun Peng, Jiang Rong Huang, Feng Ru Tang The radioprotective effect of herb epimedium (or yin yang huo) extract (5 g/kg, oral administration daily for 4 weeks) on neurogenesis and cognition after acute radiation exposure with 5.5 Gy was evaluated in Balb/c mice by behavioral tests and immunohistochemical study. The results indicated that epimedium extract could improve animal weight loss, locomotor activity and spatial learning and memory which are similar to pre-irradiation intraperitoneal injection (100 mg/kg) of amifostine phosphate, a well- known radioprotective drug. Immunohistochemical study showed that epimedium extract prevented the loss of proliferation cells, newly generated neurons, and interneurons in the hilus, in particular, the subgranular zone of the dentate gyrus. It suggests that herb epimedium may be a promising radio-neuro-protective drug to prevent radiation-induced neuropsychological disorders.
  • Comparative effects of implanted electrodes with differing contact
           patterns on peripheral nerve regeneration and functional recovery
    • Abstract: Publication date: Available online 17 August 2018Source: Neuroscience ResearchAuthor(s): Ai-Ping Yu, Yan-Qun Qiu, Jie Li, Yun-Dong Shen, Xiao-Min Wang, Meng Cong, Qian-Ru He, Qing-zhong Chen, Fei Ding, Yu-Dong Gu, Jian-Guang Xu, Su Jiang, Wen-Dong Xu Electrical stimulation could enhance nerve regeneration and functional recovery. The objective of this study was to evaluate the regenerative effects of implanted electrodes with different contacts in resected sciatic nerve. Sciatic nerve resection and microsurgical repair models were established and randomly divided into four groups (point contact, 1/4 circle contact; whole-circle contact; no electrodes as control). Electrical stimulation was performed and electrophysiological, morphological and histological exams (of the sciatic nerve and muscle) were conducted at 4 and 10 weeks post-implantation. Point and 1/4 circle contact groups showed significantly higher scores in the sciatic functional index (SFI), increased amplitude of compound muscle action potential (AMP) and motor nerve conduction velocity (MNCV) compared to the control group at both 4 and 10 weeks post-implantation. Point and 1/4 circle contact morphologically promoted sciatic nerve regeneration and reduced muscular atrophy with less mechanical injury to the nerve trunk observed compared with the whole-circle contact group at both 4 and 10 weeks post-implantation. Electrodes with point and 1/4 circle contacts represented an alternatively portable and effective method of electrical stimulation to facilitate injured sciatic nerve regeneration and reduce subsequent muscular atrophy, which might offer a promising approach for treating peripheral nerve injuries.
  • Top-down control: A unified principle of cortical learning
    • Abstract: Publication date: Available online 17 August 2018Source: Neuroscience ResearchAuthor(s): Hiroshi Makino Cognitive control of the brain flexibly maps incoming sensory information onto execution of actions appropriate for the current goal. Learning is a process that enables the brain to estimate current states of the world by extracting its spatiotemporal structure and generate goal-directed motor outputs through selective association of events or movement refinement. Accumulating evidence suggests that top-down control from higher-order brain areas modulates downstream neural activity and changes local computations that are critical for the execution of learned behavior. Recent technological advances in multi-site recordings and optogenetic approaches are beginning to reveal more direct evidence of top-down cognitive control by monitoring and perturbing activity of top-down inputs and observing its causal consequences on behavior and downstream neural dynamics. Here I highlight that learning-related changes in neural circuits in distinct domains of learning converge onto a unified principle; namely recruitment of top-down control whether it involves sensory, motor or offline learning. Recruitment of top-down control may reflect experience-dependent adaptation and integration of internal models for refined state estimation and goal-directed optimal behavior.
  • The subiculum: Unique hippocampal hub and more
    • Abstract: Publication date: Available online 16 August 2018Source: Neuroscience ResearchAuthor(s): Nobuyoshi Matsumoto, Takuma Kitanishi, Kenji Mizuseki The hippocampal formation, which comprises the hippocampus proper, dentate gyrus, and subiculum, is crucial for learning, memory, and spatial navigation. Historically, most studies have focused on the hippocampus proper and dentate gyrus; however, recent evidence has highlighted the substantial contribution of the subiculum to interregional communication and behavioral performance. Moreover, various network oscillations in the subiculum appear to be crucial for cognitive functions. The subiculum shows complicated spatial representation during exploratory behavior, suggesting that the subiculum does not simply relay hippocampal information to the target regions but it functions as a unique computational unit. The network mechanism underlying the uniqueness of the subiculum awaits further investigation.
  • Single unit activity of subthalamic nucleus of patients with Parkinson’s
           disease under local and generalized anaesthesia: Multifactor analysis
    • Abstract: Publication date: Available online 16 August 2018Source: Neuroscience ResearchAuthor(s): Vladislav Myrov, Alexey Sedov, Ekaterina Salova, Alexey Tomskiy, Elena Belova The analysis of neuronal activity in human brain is a complicated task as it meets several limitations, including small sample sizes, dependent variables in the dataset and the short duration of recordings that entangles the analysis procedure. Here, we present the comparative research of neuronal activity in subthalamic nucleus (STN) of 8 Parkinsonian patients undergoing DBS surgery in awake state and under propofol anaesthesia using different statistical approaches. We studied 25 parameters of single unit activity and performed a direct comparison of the parameters between the groups to characterise the changes in STN activity under anaesthesia. We found a significant decrease in firing rate and a prominent increase in bursting of neurons in the anaesthetised state. Also, these data were used to determine the most important parameters for classification. We revealed the differences between parametric and nonparametric approaches regarding the identification of the most important spike train features. The random forest trees algorithm showed a greater accuracy of classification (91.7 ± 1.8%) compared to generalised linear models (82.4 ± 3.8%). The lists of the features important for classification according to F-scores and random forest trees also differed markedly. Our results indicate that feature interactions play a key role in neuronal activity analysis and must be taken into account.
  • Annexin 1 inhibits remifentanil-induced hyperalgesia and NMDA receptor
           phosphorylation via regulating spinal CXCL12/CXCR4 in rats
    • Abstract: Publication date: Available online 16 August 2018Source: Neuroscience ResearchAuthor(s): Tang Li, Haiyun Wang, Jinxin Wang, Yimeng Chen, Chenyi Yang, Mingshu Zhao, Guolin Wang, Zhuo Yang Chemokines related neuroinflammation and N-methyl-d-aspartate receptor (NMDAR) mediated nociceptive transmission are pivotal determinants in the pathogenesis of opioid-induced hyperalgesia (OIH), but little is known about specific mechanism and treatment. Chemokine CXCL12 with its receptor CXCR4 is implicated in different pathological pain, moreover, neurotoxicity of CXCL12 is associated with NMDAR activation. Recent studies recapitulate the anti-nociception of Annexin 1 (ANXA1) in inflammatory pain. This study examined whether ANXA1 prevented remifentanil-caused OIH through modulating CXCL12 and NMDAR pathway in rats. Acute exposure to remifentanil induced mechanical allodynia and thermal hyperalgesia, which was accompanied by the increase of spinal ANXA1 and CXCL12/CXCR4 expression. Central injection of Anxa12-26 attenuated behavioral OIH in a dose-dependent manner, facilitated ANXA1 production, and inhibited up-regulation of CXCL12/CXCR4 level and NR2B-containing NMDAR phosphorylation. Moreover, pretreatment with AMD3100 reduced hyperalgesia and NR2B-containing NMDAR phosphorylation. Also, exogenous CXCL12 elicited pain hypersensitivity and NMDAR activation in naïve rats, which was reversed by the supplemental delivery of Anxa12-26. These current findings indicate the participation of spinal CXCL12/CXCR4 and NR2B-containing NMDAR pathway in anti-hyperalgesic action of ANXA1 in OIH.
  • Progression of Alzheimer’s disease, tau propagation, and its
           modifiable risk factors
    • Abstract: Publication date: Available online 16 August 2018Source: Neuroscience ResearchAuthor(s): Shuko Takeda The number of patients with Alzheimer's disease (AD) has been increasing exponentially side by side with aging societies worldwide. Symptoms of AD worsen over time due to progressive neurodegeneration, requiring institutional care at the later stage and resulting in a heavy burden on patients, caregivers, and the public-health system. AD neuropathology is characterized by cerebral accumulation and aggregation of amyloid-β (Aβ) and tau proteins. For decades, Aβ has been a leading target in the therapeutic development for AD, and many drug candidates have been tested in clinical trials; however, most medications have failed to slow the progression of the disease. Tau pathology currently is attracting more attention as an alternate target for developing disease-modifying therapy. Tau is known to spread in a hierarchical pattern in AD brain, likely by trans-synaptic tau transfer between neurons. Extracellular tau may mediate tau spreading and serve as biomarker for AD. AD pathogenesis is multifactorial, and many genetic- and non-genetic factors are known to contribute to Aβ- and tau-related pathology. Recent studies indicate an association between vascular risk factors and AD. Identifying modifiable risk factors for AD and understanding their contributory mechanisms could be key in tackling this devastating disease.
  • The sleep network organization during slow-wave sleep is more stable with
           age and has small-world characteristics more marked than during REM sleep
           in healthy men
    • Abstract: Publication date: Available online 16 August 2018Source: Neuroscience ResearchAuthor(s): Matthieu Hein, Jean-Pol Lanquart, Gwénolé Loas, Philippe Hubain, Paul Linkowski Sleep plays an important role in cognitive functioning. However, few studies have investigated the sleep network organization. The aim of our study was to empirically investigate the presence and the stability with age of a small-world network organization during REM and slow-wave sleep using the effective connectivity measured by the Granger causality. Polysomnographic data from 30 healthy men recruited prospectively were analysed. To obtain the 19 × 19 connectivity matrix of all possible pairwise combinations of electrodes by the Granger causality method from our EEG data, we used the Toolbox MVGC multivariate Granger causality. The computation of the network measures was realised by importing these connectivity matrices into the EEGNET Toolbox. Even if all small-world coefficients obtained are compatible with a small-world network organization during REM and slow-wave sleep, slow-wave sleep seems to have a small-world network organization more marked than REM sleep. Moreover, the sleep network organization is affected greater by age during REM sleep than during slow-wave sleep. In healthy individuals, the highlighting of a sleep network organization during slow-wave sleep more stable with age and with small-world characteristics more marked than during REM sleep may help to better understand the global and local processing of information during sleep.
  • Dissecting executive control circuits with neuron types
    • Abstract: Publication date: Available online 12 August 2018Source: Neuroscience ResearchAuthor(s): Tsukasa Kamigaki Executive control supports our ability to behave flexibly in accordance with a given situation. In order to fully understand how cortical circuits achieve this task, we need to determine the intrinsic physiological and connection profiles of neuron types and analyze their functional roles during behavior. This article introduces current knowledge regarding neuron type classification in the cortex and reviews our understanding of how each neuron type is incorporated in the functional cortical circuit to implement executive control. Recent work using neuron-type specific imaging/recording has begun to reveal significant functional organizations of pyramidal neurons and their subtypes depending on the layers and long-range projection targets. GABAergic interneurons also make crucial contributions to executive control in a subtype-specific manner. Vasoactive intestinal peptide (VIP)-positive interneurons are preferentially recruited by top-down inputs from higher-order cortical regions and amplify the signals in pyramidal neurons by inhibiting other interneuron subtypes. Particularly in the prefrontal cortex, one of the hierarchically highest cortices, executive control signals are regulated by the VIP neuron-mediated disinhibition and robustly maintained through recurrent connections at a long time scale. The differences and commonalities in the functional organization between sensory areas and the prefrontal cortex are discussed.
  • Inter-subject correlation of temporoparietal junction activity is
           associated with conflict patterns during flexible decision-making
    • Abstract: Publication date: Available online 11 August 2018Source: Neuroscience ResearchAuthor(s): Shisei Tei, Jukka-Pekka Kauppi, Junya Fujino, Kathryn F. Jankowski, Ryosaku Kawada, Toshiya Murai, Hidehiko Takahashi Although behavioral flexibility and conflict regulation may rely on executive function, the mechanism underlying these relationships remains obscure. We studied whether subjects’ conflict ratings were associated with right dorsolateral prefrontal cortex (rDLPFC) and temporoparietal junction (rTPJ) activity during flexible decision-making in a moral dilemma task using inter-subject correlation (ISC)-based approach (i.e., brain-behavior correlation matrices analysis). We observed a statistically significant positive correlation between the ISC matrix of rTPJ and conflict-scores. This implies that similar rTPJ activity patterns across subjects were associated with similar conflict-rating patterns across subjects. Our findings suggest that rTPJ activity may be also related to conflicting experience.
  • Potential biomarkers for distinguishing people with Alzheimer’s disease
           from cognitively intact elderly based on the rich-club hierarchical
           structure of white matter networks
    • Abstract: Publication date: Available online 11 August 2018Source: Neuroscience ResearchAuthor(s): Suping Cai, Kexin Huang, Yafei Kang, Yuanyuan Jiang, Karen M. von Deneen, Liyu Huang The aim of this study is to identify potential biomarkers that may distinguish people with Alzheimer’s disease (AD) from cognitively intact elderly. We analyzed the features of rich-club hierarchical network between the AD and a control group by diffusion tensor imaging. We detected that the changes between the two groups were located mainly in the feeder and local connections. Then, we calculated the betweenness centrality of the rich nodes and the strength values of all feeder connections, and we chose the nodes and connections that showed the most significant differences as features. We found that 1) Feeder and local connections were changed in the AD group; 2) Rich nodes of the left putamen and precuneus had significant differences in betweenness centrality between the AD and control groups; 3) Three connections showed significant differences. The obtained features were fed into a linear discriminant analysis for classifying AD from cognitively intact elderly. The classification accuracy is superior to that of traditional biomarkers (hippocampal volume and clinical scores). Our results suggested that rich-club hierarchical network analysis is a viable tool for finding potential biomarkers. The obtained features can be applied as potential biomarkers for distinguishing AD patients from cognitively intact elderly.
  • Genome editing in the mammalian brain using the CRISPR–Cas system
    • Abstract: Publication date: Available online 1 August 2018Source: Neuroscience ResearchAuthor(s): Jun Nishiyama Recent advances in genome editing technologies such as the clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease Cas9 have enabled the rapid and efficient modification of endogenous genomes in a variety of cell types, accelerating biomedical research. In particular, precise genome editing in somatic cells in vivo allows for the rapid generation of genetically modified cells in living animals and holds great promise for the possibility of directly correcting genetic defects associated with human diseases. However, because of the limited efficiency and suitability of these technologies in the brain, especially in postmitotic neurons, the practical application of genome editing technologies has been largely limited in the field of neuroscience. Recent technological advances overcome significant challenges facing genome editing in the brain and have enabled us to precisely edit the genome in both mitotic cells and mature postmitotic neurons in vitro and in vivo, providing powerful means for studying gene function and dysfunction in the brain. This review highlights the development of genome editing technologies for the brain and discusses their applications, limitations, and future challenges.
  • Brain mechanisms of visual long-term memory retrieval in primates
    • Abstract: Publication date: Available online 30 June 2018Source: Neuroscience ResearchAuthor(s): Masaki Takeda Memorizing events or objects and retrieving them from memory are essential for daily life. Historically, memory processing was studied in neuropsychology, in which patients provided us with insights into the brain mechanisms underlying memory. Psychological hypotheses about memory processing have been further investigated using neuroscience techniques, such as functional imaging and electrophysiology. In this article, I briefly summarize recent findings on multi-scale neural circuitry for memory at the scale of single neurons and cortical layers as well as inter-area and whole-brain interactions. The key idea which connects multi-scale neural circuits is how neuronal assemblies utilize the frequency of communication between neurons, cortical layers, and brain areas. Using findings and ideas from other cognitive function studies, I discuss the plausible communication between neurons involved in memory.
  • Cell death cascade and molecular therapy in ADAR2-deficient motor neurons
           of ALS
    • Abstract: Publication date: Available online 23 June 2018Source: Neuroscience ResearchAuthor(s): Takenari Yamashita, Shin Kwak TAR DNA-binding protein (TDP-43) pathology in the motor neurons is the most reliable pathological hallmark of amyotrophic lateral sclerosis (ALS), and motor neurons bearing TDP-43 pathology invariably exhibit failure in RNA editing at the GluA2 glutamine/arginine (Q/R) site due to down-regulation of adenosine deaminase acting on RNA 2 (ADAR2). Conditional ADAR2 knockout (AR2) mice display ALS-like phenotype, including progressive motor dysfunction due to loss of motor neurons. Motor neurons devoid of ADAR2 express Q/R site-unedited GluA2, and AMPA receptors with unedited GluA2 in their subunit assembly are abnormally permeable to Ca2+, which results in progressive neuronal death. Moreover, analysis of AR2 mice has demonstrated that exaggerated Ca2+ influx through the abnormal AMPA receptors overactivates calpain, a Ca2+-dependent protease, that cleaves TDP-43 into aggregation-prone fragments, which serve as seeds for TDP-43 pathology. Activated calpain also disrupts nucleo-cytoplasmic transport and gene expression by cleaving molecules involved in nucleocytoplasmic transport, including nucleoporins. These lines of evidence prompted us to develop molecular targeting therapy for ALS by normalization of disrupted intracellular environment due to ADAR2 down-regulation. In this review, we have summarized the work from our group on the cell death cascade in sporadic ALS and discussed a potential therapeutic strategy for ALS.Graphical abstractGraphical abstract for this article
  • Systemic administration of α-lipoic acid suppresses excitability of
           nociceptive wide-dynamic range neurons in rat spinal trigeminal nucleus
    • Abstract: Publication date: Available online 6 June 2018Source: Neuroscience ResearchAuthor(s): S. Hidaka, Y. Kanai, S. Takehana, Y. Syoji, Y. Kubota, N. Uotsu, K. Yui, Y. Shimazu, M. Takeda Although a modulatory role has been reported for α-lipoic acid (LA) on T-type Ca2+ channels in the nervous system, the acute effects of LA in vivo, particularly on nociceptive transmission in the trigeminal system, remain to be determined. The aim of the present study was to investigate whether acute intravenous LA administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from seventeen SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. The mean firing frequency of SpVc WDR neurons in response to both non-noxious and noxious mechanical stimuli was significantly and dose-dependently inhibited by LA (1–100 mM, i.v.) and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 5 min. These inhibitory effects lasted for approximately 10 min. These results suggest that acute intravenous LA administration suppresses trigeminal sensory transmission, including nociception, via possibly blocking T-type Ca2+ channels. LA may be used as a therapeutic agent for the treatment of trigeminal nociceptive pain.
  • Acceleration of NLRP3 inflammasome by chronic cerebral hypoperfusion in
           Alzheimer’s disease model mouse
    • Abstract: Publication date: Available online 6 June 2018Source: Neuroscience ResearchAuthor(s): Jingwei Shang, Toru Yamashita, Yun Zhai, Yumiko Nakano, Ryuta Morihara, Xianghong Li, Feng Tian, Xia Liu, Yong Huang, Xiaowen Shi, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe Cerebral neuroinflammation defines a novel pathway for progressing Alzheimer’s disease (AD) pathology. We investigated immunohistological changes of neuroinflammation with nucleotide-binding domain and leucine-rich repeat (NLR)-protein 3 (NLRP3), activated caspase-1 and interleukin-1 beta (IL-1β) in a novel AD (APP23) mice with chronic cerebral hypoperfusion (CCH) model from 4 months (M) of age, moreover, examined protective effect of galantamine. CCH strongly enhanced NLRP3, activated caspase-1 and IL-1β expressions in hippocampus and thalamus at age 12 M of AD mice. CCH also exaggerated amyloid-beta (Aβ) 40 depositions in cerebral cortex. Furthermore, CCH exacerbated a marked dissociation of neurovascular unit (NVU). These pathological changes were ameliorated by galantamine treatment. The present study demonstrated that CCH strongly enhanced primary AD pathology including neuroinflammation, Aβ accumulations and NVU dissociation in AD mice, which was greatly protected by an allosterically potentiating ligand galantamine.Graphical abstractChronic cerebral hypoperfusion (CCH) strongly exaggerated Aβ accumulations. CCH greatly exacerbated neuroinflammation and NVU dissociation in AD mice. Primary AD pathology was greatly protected by galantamine.Graphical abstract for this article
  • Effect of orexin-A in the arcuate nucleus on cisplatin-induced gastric
           side effects in rats
    • Abstract: Publication date: Available online 4 June 2018Source: Neuroscience ResearchAuthor(s): Feifei Guo, Luo Xu, Shengli Gao, Xiangrong Sun, Nana Zhang, Yanling Gong The most common side effects of the cancer chemotherapy drug cisplatin are nausea and vomiting. These effects are heavily influenced by orexigenic and anorexigenic peptides. We explored the effects of orexin-A on the cisplatin-treated rats and a possible mechanism for its effects on cisplatin-induced side effects. Quantitative real-time PCR was used to measure the change of prepro-orexin mRNA in the hypothalamus following cisplatin treatment. The effect of orexin-A and cisplatin on the firing rate of arcuate nucleus neurons was recorded. The effect of administration of orexin-A and a neuropeptide Y1 receptor antagonist to the arcuate nucleus on food intake, pica, and gastric motility on cisplatin treated rats were also measured. The relative expression of prepro-orexin mRNA in the hypothalamus was reduced by cisplatin. Exogenous orexin-A altered cisplatin-induced changes to the neuronal firing of gastric distension-responsive neurons, alleviated the cisplatin-induced anorexia, pica and improves the weakened gastric motility in the arcuate nucleus of rats. These effects could be partially blocked by intracerebroventricular injection (i.c.v.) of a neuropeptide Y1 receptor antagonist. These results suggest that orexin-A signaling ameliorates the gastric disorder induced by cisplatin in rats, and may act through neuropeptide Y neurons in the arcuate nucleus.
  • Np95/Uhrf1 regulates tumor suppressor gene expression of neural
           stem/precursor cells, contributing to neurogenesis in the adult mouse
    • Abstract: Publication date: Available online 31 May 2018Source: Neuroscience ResearchAuthor(s): Naoya Murao, Shuzo Matsubara, Taito Matsuda, Hirofumi Noguchi, Tetsuji Mutoh, Masahiro Mutoh, Haruhiko Koseki, Masakazu Namihira, Kinichi Nakashima Adult neurogenesis is a process of generating new neurons from neural stem/precursor cells (NS/PCs) in restricted adult brain regions throughout life. It is now generally known that adult neurogenesis in the hippocampal dentate gyrus (DG) and subventricular zone participates in various higher brain functions, such as learning and memory formation, olfactory discrimination and repair after brain injury. However, the mechanisms underlying adult neurogenesis remain to be fully understood. Here, we show that Nuclear protein 95 KDa (Np95, also known as UHRF1 or ICBP90), which is an essential protein for maintaining DNA methylation during cell division, is involved in multiple processes of adult neurogenesis. Specific ablation of Np95 in adult NS/PCs (aNS/PCs) led to a decrease in their proliferation and an impairment of neuronal differentiation and to suppression of neuronal maturation associated with the impairment of dendritic formation in the hippocampal DG. We also found that deficiency of Np95 in NS/PCs increased the expression of tumor suppressor genes p16 and p53, and confirmed that expression of these genes in NS/PCs recapitulates the phenotype of Np95-deficient NS/PCs. Taken together, our findings suggest that Np95 plays an essential role in proliferation and differentiation of aNS/PCs through the regulation of tumor suppressor gene expression in adult neurogenesis.
  • In utero electroporation-based translating ribosome affinity purification
           identifies age-dependent mRNA expression in cortical pyramidal neurons
    • Abstract: Publication date: Available online 29 May 2018Source: Neuroscience ResearchAuthor(s): Tianxiang Huang, Lena H. Nguyen, Tiffany V. Lin, Xuan Gong, Longbo Zhang, Gi Bum Kim, Matthew R. Sarkisian, Joshua J. Breunig, Angelique Bordey We combined translating ribosome affinity purification (TRAP) with in utero electroporation (IUE), called iTRAP to identify the molecular profile of specific neuronal populations during neonatal development without the need for viral approaches and FACS sorting. We electroporated a plasmid encoding EGFP-tagged ribosomal protein L10a at embryonic day (E) 14–15 to target layer 2–4 cortical neurons of the somatosensory cortex. At three postnatal (P) ages—P0, P7, and P14—when morphogenesis occurs and synapses are forming, TRAP and molecular profiling was performed from electroporated regions. We found that ribosome bound (Ribo)-mRNAs from ∼7300 genes were significantly altered over time and included classical neuronal genes known to decrease (e.g., Tbr1, Dcx) or increase (e.g., Eno2, Camk2a, Syn1) as neurons mature. This approach led to the identification of specific developmental patterns for Ribo-mRNAs not previously reported to be developmentally regulated in neurons, providing rationale for future examination of their role in selective biological processes. These include upregulation of Lynx1, Nrn1, Cntnap1 over time; downregulation of St8sia2 and Draxin; and bidirectional changes to Fkbp1b. iTRAP is a versatile approach that allows researchers to easily assess the molecular profile of specific neuronal populations in selective brain regions under various conditions, including overexpression and knockdown of target genes, and in disease settings.
  • Non-structured spike sequences of hippocampal neuronal ensembles in awake
    • Abstract: Publication date: Available online 26 May 2018Source: Neuroscience ResearchAuthor(s): Takuya Sasaki The hippocampal network generates synchronized spikes of a large population of pyramidal neurons associated with sharp-wave ripples in local field potential signals. Ample evidence demonstrates that the synchronized spikes are created by sequential activation of hippocampal place cells that correspond to the animal’s past or future trajectories and are hypothesized to play instrumental roles in mnemonic functions. However, not all place-cell spike sequences are precisely organized, and some sequences are composed of spikes from non-spatial cells, implying that not all hippocampal synchronized events directly replicate learned behavioral episodes. While less attention has been given to such non-ordered spike sequences, variable and dynamic selection of active neuronal assemblies may be optimal mechanisms for rapidly reorganizing functional circuits and self-developing novel representations to enable flexible decision-making processes. We recently showed that specific neurons, including both spatial and non-spatial cells, are preferentially recruited in synchronous events for particular time periods, suggesting that there are temporally fluctuating background states of the hippocampal network that determine active neuronal ensembles. Based on recent reports, this review discusses potential roles of the low-fidelity, heterogeneous repertoire of synchronized spike sequences of hippocampal neurons.
  • Serotonergic projections to the ventral respiratory column from raphe
           nuclei in rats
    • Abstract: Publication date: Available online 24 May 2018Source: Neuroscience ResearchAuthor(s): Ryosuke Morinaga, Nobuaki Nakamuta, Yoshio Yamamoto The ventral respiratory column (VRC) generates rhythmical respiration and is divided into four compartments: the Bötzinger complex (BC), pre-Bötzinger complex (PBC), rostral ventral respiratory group (rVRG), and caudal ventral respiratory group (cVRG). Serotonergic nerve fibers are densely distributed in the rostral to caudal VRC and serotonin would be one of the important modulators for the respiratory control in the VRC. In the present study, to elucidate detailed distribution of serotonergic neurons in raphe nuclei projecting to the various rostrocaudal levels of VRC, we performed combination of retrograde tracing technique by cholera toxin B subunit (CTB) with immunohistochemistry for tryptophan hydroxylase 2 (TPH2). The double-immunoreactive neurons with CTB and TPH2 were distributed in the both rostral and caudal raphe nuclei, i.e. dorsal raphe nucleus, raphe magnus nucleus, gigantocellular reticular nucleus alpha and ventral parts, lateral paragigantocellular nucleus, parapyramidal area, raphe obscurus nucleus, and raphe pallidus nucleus. The distributions of double-immunoreactive neurons were similar among injection groups of BC, PBC, anterior rVRG, and posterior rVRG/cVRG. In conclusion, serotonergic neurons in both rostral and caudal raphe nuclei projected throughout the VRC and these serotonergic projections may contribute to respiratory responses to various environmental and vital changes.
  • Effects of propofol on IPSCs in CA1 and dentate gyrus cells of rat
           hippocampus: Propofol effects on hippocampal cells’ IPSCs
    • Abstract: Publication date: Available online 17 May 2018Source: Neuroscience ResearchAuthor(s): Masanori Ishiguro, Suguru Kobayashi, Kiyoji Matsuyama, Takashi Nagamine Propofol (2, 6-diisopropylphenol) is one of the most popular intravenous anesthetic agents. In this study, we compared the effects of propofol on inhibitory postsynaptic currents (IPSCs) induced by single and paired electrical stimulations in CA1 pyramidal cells (CA1-PCs) and dentate gyrus granule cells (DG-GCs) in rat hippocampal slices using the whole cell patch-clamp technique. In the absence of propofol, the amplitude of evoked IPSC by single stimulation and decay time constants were stable in both CA1-PCs and DG-GCs for 30 min. Propofol (1 μM and 10 μM) increased both IPSC amplitude in CA1-PCs, but not in DG-GCs. Further, using a paired pulse stimulation protocol, the ratio of IPSC amplitudes (the second response: A2/the first response: A1) was increased by propofol in CA1, but not in DG-GCs. These results suggest that propofol selectively affects IPSCs in CA1-PCs, which is similar to previously reported actions of benzodiazepines.
  • Effects of SC99 on cerebral ischemia-perfusion injury in rats: Selective
           modulation of microglia polarization to M2 phenotype via inhibiting
           JAK2-STAT3 pathway
    • Abstract: Publication date: Available online 12 May 2018Source: Neuroscience ResearchAuthor(s): Yiping Ding, Jinhong Qian, Haiying Li, Haitao Shen, Xiang Li, Yan Kong, Zhuan Xu, Gang Chen Inhibition of Janus kinases 2-Signal transducers and activators of transcription3 (JAK2-STAT3) pathway has been shown to exert anti-inflammatory actions. SC99, a novel specific inhibitor targeting JAK2-STAT3 pathway, has been verified to negatively modulate platelet activation and aggregation in vitro. In current study, a middle cerebral artery occlusion and reperfusion (MCAO/R) model was established in Sprague Dawley rats and primary cultured microglia was exposed to oxygen and glucose deprivation (OGD/R) in vitro. Different dosages were employed to detect the effects of SC99 on cerebral ischemia-perfusion (I/R) injury and evaluate the underlying mechanisms. Our results showed that intracerebroventricular injection of SC99 (10 mmol/L, 15 μL) produced an effective inhibitory effect on the phosphorylation of JAK2 and STAT3. Correspondingly, SC99 ameliorated neuronal apoptosis and degeneration, neurobehavioral deficits, inflammatory response and brain edema. And SC99 promoted microglia polarization to an anti-inflammatory M2 phenotype. We concluded that SC99 could alleviate brain damage and play an anti-inflammatory action by promoting microglia polarization to an anti-inflammatory phenotype after I/R injury, which provides an emerging and promising alternative to protect the brain against MCAO/R injury in the future investigations.
  • Vascular endothelial growth factor improves the cognitive decline of
           Alzheimer’s disease via concurrently inducing the expression of ADAM10
           and reducing the expression of β-site APP cleaving enzyme 1 in Tg2576
    • Abstract: Publication date: Available online 24 April 2018Source: Neuroscience ResearchAuthor(s): Hongwei Guo, Deyu Xia, Shaohua Liao, Bing Niu, Jigang Tang, Huaiqiang Hu, Hairong Qian, Bingzhen Cao Alzheimer’s disease (AD) is primarily characterized by the production and deposit of β-amyloid protein (Aβ) in β-amyloid plaques (APs). On this basis, we investigated whether vascular endothelial growth factor (VEGF), a growth factor with important neuroprotective activity, may provide a therapeutic opportunity for treating AD. We initially found that the expression and production of VEGF was downregulated in the brains of Tg2576 mice during the course of AD development and progression. Restoring VEGF in the brains of Tg2576 mice antagonized the production and deposit of Aβ in Tg2576 mice. The addition of VEGF concurrently increased the expression of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and decreased the expression of β-site APP cleaving enzyme 1 (BACE1), which contributes to the enhanced clearance of Aβ in vivo. By decreasing the production and deposit of Aβ, VEGF improved the cognitive decline of Tg2576 mice. These observations provide a novel implication for VEGF as a therapeutic approach for the treatment of AD.Graphical abstractGraphical abstract for this article
  • Upregulation of Cav3.2 T-type calcium channels in adjacent intact L4
           dorsal root ganglion neurons in neuropathic pain rats with L5 spinal nerve
    • Abstract: Publication date: Available online 21 April 2018Source: Neuroscience ResearchAuthor(s): Qing-Ying Liu, Wen Chen, Shuang Cui, Fei-Fei Liao, Ming Yi, Feng-Yu Liu, You Wan Besides the injured peripheral dorsal root ganglion (DRG) neurons, the adjacent intact DRG neurons also have important roles in neuropathic pain. Ion channels including Cav3.2 T-type calcium channel in the DRG neurons are important in the development of neuropathic pain. In the present study, we aimed to examine the expression of Cav3.2 T-type calcium channels in the intact DRG neurons in neuropathic pain. A neuropathic pain model of rat with lumbar 5 (L5) spinal nerve ligation (SNL) was established, in which the L4 DRG was separated from the axotomized L5 DRG, and the molecular, morphological and electrophysiological changes of Cav3.2 T-type calcium channels in L4 DRG neurons were investigated. Western blotting showed that total and membrane protein levels of Cav3.2 in L4 DRG neurons increased, and voltage-dependent patch clamp recordings revealed an increased T-type current density with a curve shift to the left in steady-state activation in the acutely isolated L4 DRG neurons in neuropathic pain rats. Immunofluorescent staining further showed that the membrane expression of Cav3.2 increased in CGRP-, IB4-positive small neurons and NF200-positive large ones. In conclusion, the membrane expression and the function of Cav3.2 T-type calcium channels are increased in the intact L4 DRG neurons in neuropathic pain rats with peripheral nerve injury like SNL.
  • Local traction force in the proximal leading process triggers nuclear
           translocation during neuronal migration
    • Abstract: Publication date: Available online 5 April 2018Source: Neuroscience ResearchAuthor(s): Hiroki Umeshima, Ken-ichi Nomura, Shuhei Yoshikawa, Marcel Hörning, Motomu Tanaka, Shinya Sakuma, Fumihito Arai, Makoto Kaneko, Mineko Kengaku Somal translocation in long bipolar neurons is regulated by actomyosin contractile forces, yet the precise spatiotemporal sites of force generation are unknown. Here we investigate the force dynamics generated during somal translocation using traction force microscopy. Neurons with a short leading process generated a traction force in the growth cone and counteracting forces in the leading and trailing processes. In contrast, neurons with a long leading process generated a force dipole with opposing traction forces in the proximal leading process during nuclear translocation. Transient accumulation of actin filaments was observed at the dipole center of the two opposing forces, which was abolished by inhibition of myosin II activity. A swelling in the leading process emerged and generated a traction force that pulled the nucleus when nuclear translocation was physically hampered. The traction force in the leading process swelling was uncoupled from somal translocation in neurons expressing a dominant negative mutant of the KASH protein, which disrupts the interaction between cytoskeletal components and the nuclear envelope. Our results suggest that the leading process is the site of generation of actomyosin-dependent traction force in long bipolar neurons, and that the traction force is transmitted to the nucleus via KASH proteins.
  • Therapeutic time window of anti-high mobility group box-1 antibody
           administration in mouse model of spinal cord injury
    • Abstract: Publication date: Available online 28 March 2018Source: Neuroscience ResearchAuthor(s): Masahide Nakajo, Naohiro Uezono, Hideyuki Nakashima, Hidenori Wake, Setsuro Komiya, Masahiro Nishibori, Kinichi Nakashima Spinal cord injury (SCI) is a devastating neurologic disorder that often leads to permanent disability, and there is no effective treatment for it. High mobility group box-1 (HMGB1) is a damage-associated molecular protein that triggers sterile inflammation upon injuries. We have previously shown that two administrations of neutralizing monoclonal antibody (mAb) against HMGB1 (immediately after (0 h) and 6 h after) SCI dramatically improves functional recovery after SCI in mice. However, when considering clinical application, 0 h after SCI is not practical. Therefore, in this study, we examined the therapeutic time window of the mAb administration. Injection at 3 h after SCI significantly improved the functional recovery comparably to injection immediately after SCI, while injection at 6 h was less effective, and injection at 9 or 12 h had no therapeutic effect. We also found beneficial effects of injection at 3 h after injury on blood-spinal cord barrier maintenance, inflammatory-related gene expression and preservation of the damaged spinal cord tissue. Taken together, our results suggest that a single administration of anti-HMGB1 mAb within a proper time window could be a novel and potential therapeutic strategy for SCI.
  • Neuroimaging correlates of narcolepsy with cataplexy: A systematic review
    • Abstract: Publication date: Available online 23 March 2018Source: Neuroscience ResearchAuthor(s): Masataka Wada, Masaru Mimura, Yoshihiro Noda, Shotaro Takasu, Eric Plitman, Makoto Honda, Akiyo Natsubori, Kamiyu Ogyu, Ryosuke Tarumi, Ariel Graff-Guerrero, Shinichiro Nakajima Recent developments in neuroimaging techniques have advanced our understanding of biological mechanisms underpinning narcolepsy. We used MEDLINE to retrieve neuroimaging studies to compare patients with narcolepsy and healthy controls. Thirty-seven studies were identified and demonstrated several replicated abnormalities: (1) gray matter reductions in superior frontal, superior and inferior temporal, and middle occipital gyri, hypothalamus, amygdala, insula, hippocampus, cingulate cortex, thalamus, and nucleus accumbens, (2) decreased fractional anisotropy in white matter of fronto-orbital and cingulate area, (3) reduced brain metabolism or cerebral blood flow in middle and superior frontal, and cingulate cortex (4) increased activity in inferior frontal gyri, insula, amygdala, and nucleus accumbens, and (5) N-acetylaspartate/creatine-phosphocreatine level reduction in hypothalamus. In conclusion, all the replicated findings are still controversial due to the limitations such as heterogeneity or size of the samples and lack of multimodal imaging or follow-up. Thus, future neuroimaging studies should employ multimodal imaging methods in a large sample size of patients with narcolepsy and consider age, duration of disease, age at onset, severity, human leukocyte antigen type, cerebrospinal fluid hypocretin levels, and medication intake in order to elucidate possible neuroimaging characteristic of narcolepsy and identify therapeutic targets.
  • Characterization of mouse chorda tympani responses evoked by stimulation
           of anterior or posterior fungiform taste papillae
    • Abstract: Publication date: Available online 23 March 2018Source: Neuroscience ResearchAuthor(s): Stuart A. McCaughey Different gustatory papilla types vary in their locations on the tongue. Distinctions have often made between types, but variation within fungiform papillae has seldom been explored. Here, regional differences in fungiform papillae were investigated by flowing solutions selectively over either an anterior fungiform (AF, tongue tip) or a posterior fungiform (PF, middle third) region as taste-evoked activity was measured in the chorda tympani nerve of C57BL/6J (B6) mice. Significantly larger responses were evoked by NaCl applied to the AF than PF region, and the ENaC blocker amiloride reduced the NaCl response size only for the former. Umami synergy, based on co-presenting MSG and IMP, was larger for the AF than PF region. The regions did not differ in response size to sour chemicals, but responses to l-lysine, l-arginine, sucrose, and tetrasodium pyrophosphate were larger for the AF than PF region. Thus, fungiform papillae on the tongue tip differed from those found further back in their transduction mechanisms for salty and umami compounds. Gustatory sensitivity also showed regional variation, albeit with a complex relationship to palatability and taste quality. Overall, the data support a regional organization for the mouse tongue, with different functional zones for the anterior, middle, and posterior thirds.
  • Behavioral evaluation of auditory stream segregation in rats
    • Abstract: Publication date: Available online 23 March 2018Source: Neuroscience ResearchAuthor(s): Takahiro Noda, Hirokazu Takahashi Perceptual organization of sound sequences into separate sound sources or streams is called auditory stream segregation. Neural substrates for this process in both the spectral and temporal domains remain to be elucidated. Despite abundant knowledge about their auditory physiology, behavioral evidence for auditory streaming in rodents is still limited. We provided behavioral evidence for auditory streaming in the go/no-go discrimination task, but not in the two-alternative choice task. In the go/no-go discrimination phase, rats were able to discriminate different rhythms corresponding to segregated or integrated tone sequences in both short inter-tone interval (ITI) and long ITI conditions. Nevertheless, performance was poorer in the long ITI group. In probe testing, which assessed the ability to discriminate one of the segregated tone sequences from ABA- tone sequences, the detection rate increased with the difference in frequency (ΔF) for short (100 ms), but not long (200 ms) ITIs. Our results indicate that auditory streaming in rats on both the spectral and temporal features in the ABA- tone paradigm is qualitatively analogous to that observed in human psychophysics studies. This suggests that rodents are a valuable model for investigating the neural substrates of auditory streaming.
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