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Publisher: Elsevier   (Total: 3157 journals)

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Showing 1 - 200 of 3161 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 9)
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 35, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 24, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 96, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 27, 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: 416, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 10, SJR: 0.18, CiteScore: 1)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.128, CiteScore: 0)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 260, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, 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: 3, 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: 6, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 7)
Acute Pain     Full-text available via subscription   (Followers: 14, 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: 8, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 10, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 23)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 159, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, 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: 10, 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: 14, 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: 33, 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: 4)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, 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: 9, 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: 19, 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: 12)
Advances in Digestive Medicine     Open Access   (Followers: 9)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 25)
Advances in Ecological Research     Full-text available via subscription   (Followers: 44, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 28, 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: 46, 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: 59, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
Advances in Genetics     Full-text available via subscription   (Followers: 16, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 8, 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: 23, 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: 2, 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: 8, 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: 18, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 11, 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: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 2)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
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: 24, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 12)
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: 64)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (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: 404, 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: 11, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 34, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 18)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 14)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 47, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 349, 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: 457, 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: 42, 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: 1, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 10, 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: 51, 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: 53, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 56, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 44, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, 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: 47)
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: 222, 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: 28, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 29, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 38, 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: 18, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription  
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: 42, SJR: 1.512, CiteScore: 5)
Analytical Biochemistry     Hybrid Journal   (Followers: 184, 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: 12)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 23, 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: 203, SJR: 1.58, CiteScore: 3)

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Journal Cover
Journal Prestige (SJR): 10.654
Citation Impact (citeScore): 11
Number of Followers: 222  
  Full-text available via subscription Subscription journal
ISSN (Print) 0896-6273 - ISSN (Online) 1097-4199
Published by Elsevier Homepage  [3157 journals]
  • Long-Range Guidance of Spinal Commissural Axons by Netrin1 and Sonic
           Hedgehog from Midline Floor Plate Cells
    • Abstract: Publication date: Available online 17 January 2019Source: NeuronAuthor(s): Zhuhao Wu, Shirin Makihara, Patricia T. Yam, Shaun Teo, Nicolas Renier, Nursen Balekoglu, Juan Antonio Moreno-Bravo, Olav Olsen, Alain Chédotal, Frédéric Charron, Marc Tessier-LavigneSummaryAn important model for axon pathfinding is provided by guidance of embryonic commissural axons from dorsal spinal cord to ventral midline floor plate (FP). FP cells produce a chemoattractive activity, comprised largely of netrin1 (FP-netrin1) and Sonic hedgehog (Shh), that can attract the axons at a distance in vitro. netrin1 is also produced by ventricular zone (VZ) progenitors along the axons’ route (VZ-netrin1). Recent studies using region-specific netrin1 deletion suggested that FP-netrin1 is dispensable and VZ-netrin1 sufficient for netrin guidance activity in vivo. We show that removing FP-netrin1 actually causes guidance defects in spinal cord consistent with long-range action (i.e., over hundreds of micrometers), and double mutant analysis supports that FP-netrin1 and Shh collaborate to attract at long range. We further provide evidence that netrin1 may guide via chemotaxis or haptotaxis. These results support the model that netrin1 signals at both short and long range to guide commissural axons in spinal cord.Graphical Graphical abstract for this article
  • Synergistic Activity of Floor-Plate- and Ventricular-Zone-Derived Netrin-1
           in Spinal Cord Commissural Axon Guidance
    • Abstract: Publication date: Available online 17 January 2019Source: NeuronAuthor(s): Juan Antonio Moreno-Bravo, Sergi Roig Puiggros, Patrick Mehlen, Alain ChédotalSummaryIn vertebrates, commissural axons extend ventrally toward the floor plate in the spinal cord and hindbrain. Netrin-1, secreted by floor plate cells, was proposed to attract commissural axons at a distance. However, recent genetic studies in mice have shown that netrin-1 is also produced by ventricular zone (VZ) progenitors and that in the hindbrain, it represents the main source of netrin-1 for commissural axons. Here, we show that genetically deleting netrin-1 either from the VZ or the floor plate does not prevent midline crossing in the spinal cord, although axon pathfinding and fasciculation are perturbed. Strikingly, the VZ and floor plate act synergistically, as the simultaneous ablation of netrin-1 from these two sources severely impedes crossing. These results suggest that floor-plate-derived netrin-1 has a distinct impact on commissural axons in the spinal cord and hindbrain.
  • Gut Microbes Join the Social Network
    • Abstract: Publication date: 16 January 2019Source: Neuron, Volume 101, Issue 2Author(s): Helen E. Vuong, Elaine Y. HsiaoThe gut microbiome is increasingly implicated in the regulation of social behavior across model organisms. In this issue of Neuron, Sgritta et al. (2018) examine the role of the gut microbiome in social reward circuits and sociability in three mouse models of autism spectrum disorder.
  • Expectancy-Related Changes in Dopaminergic Error Signals Are Impaired by
           Cocaine Self-Administration
    • Abstract: Publication date: 16 January 2019Source: Neuron, Volume 101, Issue 2Author(s): Yuji K. Takahashi, Thomas A. Stalnaker, Yasmin Marrero-Garcia, Ray M. Rada, Geoffrey SchoenbaumSummaryAddiction is a disorder of behavioral control and learning. While this may reflect pre-existing propensities, drug use also clearly contributes by causing changes in outcome processing in prefrontal and striatal regions. This altered processing is associated with behavioral deficits, including changes in learning. These areas provide critical input to midbrain dopamine neurons regarding expected outcomes, suggesting that effects on learning may result from changes in dopaminergic error signaling. Here, we show that dopamine neurons recorded in rats that had self-administered cocaine failed to suppress firing on omission of an expected reward and exhibited lower amplitude and imprecisely timed increases in firing to an unexpected reward. Learning also appeared to have less of an effect on reward-evoked and cue-evoked firing in the cocaine-experienced rats. Overall, the changes are consistent with reduced fidelity of input regarding the expected outcomes, such as their size, timing, and overall value, because of cocaine use.
  • Crosstalk of Local Translation and Mitochondria: Powering Plasticity in
           Axons and Dendrites
    • Abstract: Publication date: 16 January 2019Source: Neuron, Volume 101, Issue 2Author(s): Wilfried Rossoll, Gary J. BassellTwo papers in Cell uncover reciprocal crosstalk of local translation and mitochondria in neurons. Rangaraju et al. (2019) observe tethered compartments of stable mitochondria in dendrites that provide a local energy supply for mRNA translation at synapses. Cioni et al. (2019) report a novel association of axonal RNA granules with Rab7a-late endosomes that provides a platform for local translation supporting mitochondria.
  • The Puzzling Pulvinar
    • Abstract: Publication date: 16 January 2019Source: Neuron, Volume 101, Issue 2Author(s): Ian C. Fiebelkorn, Sabine KastnerThe functional role of the pulvinar, with its widespread cortical connectivity, has remained elusive. In this issue of Neuron, Jaramillo et al. (2019) provide a computational roadmap for how the pulvinar might influence various cognitive behaviors across multiple large-scale networks.
  • Engram Excitement
    • Abstract: Publication date: 16 January 2019Source: Neuron, Volume 101, Issue 2Author(s): Zimbul Albo, Johannes GräffEngram cells can encode and switch between multiple mnemonic functions, but how they intrinsically do so is unknown. Pignatelli, Ryan, and colleagues show that upon memory recall, the engram’s excitability is transiently elevated, allowing its bearer to adapt to changing environments.
  • A TREK to Translate Genetics to Mechanisms of Migraine
    • Abstract: Publication date: 16 January 2019Source: Neuron, Volume 101, Issue 2Author(s): Rose Z. Hill, Diana M. BautistaIn this issue of Neuron, Royal et al. (2018) find that a mutant form of the TRESK ion channel linked to migraine undergoes alternative translation to produce an inhibitory protein that blocks TREK channels, leading to neuronal hyperexcitability and migraine in rodents.
  • Tau Protein Disrupts Nucleocytoplasmic Transport in Alzheimer’s
    • Abstract: Publication date: 16 January 2019Source: Neuron, Volume 101, Issue 2Author(s): Bahareh Eftekharzadeh, J. Gavin Daigle, Larisa E. Kapinos, Alyssa Coyne, Julia Schiantarelli, Yari Carlomagno, Casey Cook, Sean J. Miller, Simon Dujardin, Ana S. Amaral, Jonathan C. Grima, Rachel E. Bennett, Katharina Tepper, Michael DeTure, Charles R. Vanderburg, Bianca T. Corjuc, Sarah L. DeVos, Jose Antonio Gonzalez, Jeannie Chew, Svetlana Vidensky
  • Cholinergic Interneurons Amplify Thalamostriatal Excitation of Striatal
           Indirect Pathway Neurons in Parkinson’s Disease Models
    • Abstract: Publication date: Available online 15 January 2019Source: NeuronAuthor(s): Asami Tanimura, Yijuan Du, Jyothisri Kondapalli, David L. Wokosin, D. James SurmeierSummaryThe motor symptoms of Parkinson’s disease (PD) are thought to stem from an imbalance in the activity of striatal direct- and indirect-pathway spiny projection neurons (SPNs). Disease-induced alterations in the activity of networks controlling SPNs could contribute to this imbalance. One of these networks is anchored by the parafascicular nucleus (PFn) of the thalamus. To determine the role of the PFn in striatal PD pathophysiology, optogenetic, chemogenetic, and electrophysiological tools were used in ex vivo slices from transgenic mice with region-specific Cre recombinase expression. These studies revealed that in parkinsonian mice, the functional connectivity of PFn neurons with indirect pathway SPNs (iSPNs) was selectively enhanced by cholinergic interneurons acting through presynaptic nicotinic acetylcholine receptors (nAChRs) on PFn terminals. Attenuating this network adaptation by chemogenetic or genetic strategies alleviated motor-learning deficits in parkinsonian mice, pointing to a potential new therapeutic strategy for PD patients.Graphical Graphical abstract for this article
  • Functional Synaptic Architecture of Callosal Inputs in Mouse Primary
           Visual Cortex
    • Abstract: Publication date: Available online 15 January 2019Source: NeuronAuthor(s): Kuo-Sheng Lee, Kaeli Vandemark, Dávid Mezey, Nicole Shultz, David FitzpatrickSummaryCallosal projections are thought to play a critical role in coordinating neural activity between the cerebral hemispheres in placental mammals, but the rules that govern the arrangement of callosal synapses on the dendrites of their target neurons remain poorly understood. Here we describe a high-throughput method to map the functional organization of callosal connectivity by combining in vivo 3D random-access two-photon calcium imaging of the dendritic spines of single V1 neurons with optogenetic stimulation of the presynaptic neural population in the contralateral hemisphere. We find that callosal-recipient spines are more likely to cluster with non-callosal-recipient spines with similar orientation preference. These observations, based on optogenetic stimulation, were confirmed by direct anatomical visualization of callosal synaptic connections using post hoc expansion microscopy. Our results demonstrate, for the first time, that functional synaptic clustering in a short dendritic segment could play a role in integrating distinct neuronal circuits.
  • Ionotropic Receptors Specify the Morphogenesis of Phasic Sensors
           Controlling Rapid Thermal Preference in Drosophila
    • Abstract: Publication date: Available online 14 January 2019Source: NeuronAuthor(s): Gonzalo Budelli, Lina Ni, Cristina Berciu, Lena van Giesen, Zachary A. Knecht, Elaine C. Chang, Benjamin Kaminski, Ana F. Silbering, Aravi Samuel, Mason Klein, Richard Benton, Daniela Nicastro, Paul A. GarritySummaryThermosensation is critical for avoiding thermal extremes and regulating body temperature. While thermosensors activated by noxious temperatures respond to hot or cold, many innocuous thermosensors exhibit robust baseline activity and lack discrete temperature thresholds, suggesting they are not simply warm and cool detectors. Here, we investigate how the aristal Cold Cells encode innocuous temperatures in Drosophila. We find they are not cold sensors but cooling-activated and warming-inhibited phasic thermosensors that operate similarly at warm and cool temperatures; we propose renaming them “Cooling Cells.” Unexpectedly, Cooling Cell thermosensing does not require the previously reported Brivido Transient Receptor Potential (TRP) channels. Instead, three Ionotropic Receptors (IRs), IR21a, IR25a, and IR93a, specify both the unique structure of Cooling Cell cilia endings and their thermosensitivity. Behaviorally, Cooling Cells promote both warm and cool avoidance. These findings reveal a morphogenetic role for IRs and demonstrate the central role of phasic thermosensing in innocuous thermosensation.Graphical Graphical abstract for this article
  • Oligodendrocyte Progenitor Cells Become Regionally Diverse and
           Heterogeneous with Age
    • Abstract: Publication date: Available online 14 January 2019Source: NeuronAuthor(s): Sonia Olivia Spitzer, Sergey Sitnikov, Yasmine Kamen, Kimberley Anne Evans, Deborah Kronenberg-Versteeg, Sabine Dietmann, Omar de Faria, Sylvia Agathou, Ragnhildur Thóra KáradóttirSummaryOligodendrocyte progenitor cells (OPCs), which differentiate into myelinating oligodendrocytes during CNS development, are the main proliferative cells in the adult brain. OPCs are conventionally considered a homogeneous population, particularly with respect to their electrophysiological properties, but this has been debated. We show, by using single-cell electrophysiological recordings, that OPCs start out as a homogeneous population but become functionally heterogeneous, varying both within and between brain regions and with age. These electrophysiological changes in OPCs correlate with the differentiation potential of OPCs; thus, they may underlie the differentiational differences in OPCs between regions and, likewise, differentiation failure with age.Graphical Graphical abstract for this article
  • HCN2 Channels in Cholinergic Interneurons of Nucleus Accumbens Shell
           Regulate Depressive Behaviors
    • Abstract: Publication date: Available online 10 January 2019Source: NeuronAuthor(s): Jia Cheng, Gali Umschweif, Jenny Leung, Yotam Sagi, Paul GreengardSummaryCholinergic interneurons (ChIs) in the nucleus accumbens (NAc) have been implicated in drug addiction, reward, and mood disorders. However, the physiological role of ChIs in depression has not been characterized. Here, we show that the tonic firing rate of ChIs in NAc shell is reduced in chronic stress mouse models and in a genetic mouse model of depression. Chemogenetic inhibition of NAc ChIs renders naive mice susceptible to stress, whereas enhancement of ChI activity reverses depressive phenotypes. As a component of the molecular mechanism, we found that the expression and function of the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) are decreased in ChIs of NAc shell in depressed mice. Overexpression of HCN2 channels in ChIs enhances cell activity and is sufficient to rescue depressive phenotypes. These data suggest that enhancement of HCN2 channel activity in NAc ChIs is a feasible approach for the development of a new class of antidepressants.Graphical Graphical abstract for this article
  • Rostral and Caudal Ventral Tegmental Area GABAergic Inputs to Different
           Dorsal Raphe Neurons Participate in Opioid Dependence
    • Abstract: Publication date: Available online 10 January 2019Source: NeuronAuthor(s): Yue Li, Chun-Yue Li, Wang Xi, Sen Jin, Zuo-Hang Wu, Ping Jiang, Ping Dong, Xiao-Bin He, Fu-Qiang Xu, Shumin Duan, Yu-Dong Zhou, Xiao-Ming LiSummaryBoth the ventral tegmental area (VTA) and dorsal raphe nucleus (DRN) are involved in affective control and reward-related behaviors. Moreover, the neuronal activities of the VTA and DRN are modulated by opioids. However, the precise circuits from the VTA to DRN and how opioids modulate these circuits remain unknown. Here, we found that neurons projecting from the VTA to DRN are primarily GABAergic. Rostral VTA (rVTA) GABAergic neurons preferentially innervate DRN GABAergic neurons, thus disinhibiting DRN serotonergic neurons. Optogenetic activation of this circuit induces aversion. In contrast, caudal VTA (cVTA) GABAergic neurons mainly target DRN serotonergic neurons, and activation of this circuit promotes reward. Importantly, μ-opioid receptors (MOPs) are selectively expressed at rVTA→DRN GABAergic synapses, and morphine depresses the synaptic transmission. Chronically elevating the activity of the rVTA→DRN pathway specifically interrupts morphine-induced conditioned place preference. This opioid-modulated inhibitory circuit may yield insights into morphine reward and dependence pathogenesis.
  • Pioneer Factor NeuroD1 Rearranges Transcriptional and Epigenetic Profiles
           to Execute Microglia-Neuron Conversion
    • Abstract: Publication date: Available online 9 January 2019Source: NeuronAuthor(s): Taito Matsuda, Takashi Irie, Shutaro Katsurabayashi, Yoshinori Hayashi, Tatsuya Nagai, Nobuhiko Hamazaki, Aliya Mari D. Adefuin, Fumihito Miura, Takashi Ito, Hiroshi Kimura, Katsuhiko Shirahige, Tadayuki Takeda, Katsunori Iwasaki, Takuya Imamura, Kinichi NakashimaSummaryMinimal sets of transcription factors can directly reprogram somatic cells into neurons. However, epigenetic remodeling during neuronal reprogramming has not been well reconciled with transcriptional regulation. Here we show that NeuroD1 achieves direct neuronal conversion from mouse microglia both in vitro and in vivo. Exogenous NeuroD1 initially occupies closed chromatin regions associated with bivalent trimethylation of histone H3 at lysine 4 (H3K4me3) and H3K27me3 marks in microglia to induce neuronal gene expression. These regions are resolved to a monovalent H3K4me3 mark at later stages of reprogramming to establish the neuronal identity. Furthermore, the transcriptional repressors Scrt1 and Meis2 are induced as NeuroD1 target genes, resulting in a decrease in the expression of microglial genes. In parallel, the microglial epigenetic signature in promoter and enhancer regions is erased. These findings reveal NeuroD1 pioneering activity accompanied by global epigenetic remodeling for two sequential events: onset of neuronal property acquisition and loss of the microglial identity during reprogramming.Graphical Graphical abstract for this article
  • Differential NOVA2-Mediated Splicing in Excitatory and Inhibitory Neurons
           Regulates Cortical Development and Cerebellar Function
    • Abstract: Publication date: Available online 9 January 2019Source: NeuronAuthor(s): Yuhki Saito, Yuan Yuan, Ilana Zucker-Scharff, John J. Fak, Saša Jereb, Yoko Tajima, Donny D. Licatalosi, Robert B. DarnellSummaryRNA-binding proteins (RBPs) regulate genetic diversity, but the degree to which they do so in individual cell types in vivo is unknown. We developed NOVA2 cTag-crosslinking and immunoprecipitation (CLIP) to generate functional RBP-RNA maps from different neuronal populations in the mouse brain. Combining cell type datasets from Nova2-cTag and Nova2 conditional knockout mice revealed differential NOVA2 regulatory actions on alternative splicing (AS) on the same transcripts expressed in different neurons. This includes functional differences in transcripts expressed in cortical and cerebellar excitatory versus inhibitory neurons, where we find NOVA2 is required for, respectively, development of laminar structure, motor coordination, and synapse formation. We also find that NOVA2-regulated AS is coupled to NOVA2 regulation of intron retention in hundreds of transcripts, which can sequester the trans-acting splicing factor PTBP2. In summary, cTag-CLIP complements single-cell RNA sequencing (RNA-seq) studies by providing a means for understanding RNA regulation of functional cell diversity.Graphical Graphical abstract for this article
  • Layer-Specific Physiological Features and Interlaminar Interactions in the
           Primary Visual Cortex of the Mouse
    • Abstract: Publication date: Available online 8 January 2019Source: NeuronAuthor(s): Yuta Senzai, Antonio Fernandez-Ruiz, György BuzsákiSummaryThe relationship between mesoscopic local field potentials (LFPs) and single-neuron firing in the multi-layered neocortex is poorly understood. Simultaneous recordings from all layers in the primary visual cortex (V1) of the behaving mouse revealed functionally defined layers in V1. The depth of maximum spike power and sink-source distributions of LFPs provided consistent laminar landmarks across animals. Coherence of gamma oscillations (30–100 Hz) and spike-LFP coupling identified six physiological layers and further sublayers. Firing rates, burstiness, and other electrophysiological features of neurons displayed unique layer and brain state dependence. Spike transmission strength from layer 2/3 cells to layer 5 pyramidal cells and interneurons was stronger during waking compared with non-REM sleep but stronger during non-REM sleep among deep-layer excitatory neurons. A subset of deep-layer neurons was active exclusively in the DOWN state of non-REM sleep. These results bridge mesoscopic LFPs and single-neuron interactions with laminar structure in V1.
  • The Costs of Reproducibility
    • Abstract: Publication date: 2 January 2019Source: Neuron, Volume 101, Issue 1Author(s): Russell A. PoldrackImproving the reproducibility of neuroscience research is of great concern, especially to early-career researchers (ECRs). Here I outline the potential costs for ECRs in adopting practices to improve reproducibility. I highlight the ways in which ECRs can achieve their career goals while doing better science and the need for established researchers to support them in these efforts.
  • The NeuroDev Study: Phenotypic and Genetic Characterization of
           Neurodevelopmental Disorders in Kenya and South Africa
    • Abstract: Publication date: 2 January 2019Source: Neuron, Volume 101, Issue 1Author(s): Victoria de Menil, Michelle Hoogenhout, Patricia Kipkemoi, Dorcas Kamuya, Emma Eastman, Alice Galvin, Katini Mwangasha, Jantina de Vries, Symon M. Kariuki, Serini Murugasen, Paul Mwangi, Ilina Singh, Dan J. Stein, Amina Abubakar, Charles R. Newton, Kirsten A. Donald, Elise RobinsonThe NeuroDev study will deeply phenotype cognition, behavior, dysmorphias, and neuromedical traits on an expected cohort of 5,600 Africans (1,800 child cases, 1,800 child controls, and 1,900 parents) and will collect whole blood for exome sequencing and biobanking.
  • Scenes in the Human Brain: Comparing 2D versus 3D Representations
    • Abstract: Publication date: 2 January 2019Source: Neuron, Volume 101, Issue 1Author(s): Iris I.A. Groen, Chris I. BakerThree cortical brain regions are thought to underlie our remarkable ability to perceive and understand visual scenes. In this issue of Neuron, Lescroart and Gallant (2018) use quantitative models of scene processing to reveal 3D representations in these regions.
  • Suppressing Memories by Shrinking the Vesicle Pool
    • Abstract: Publication date: 2 January 2019Source: Neuron, Volume 101, Issue 1Author(s): Ethan B. Richman, Liqun LuoThe cohesin complex regulates cellular functions spanning cell division and neuronal morphogenesis. Now, Phan et al. uncover a role for the cohesin complex in regulating memory acquisition and the size of the synaptic and dense-core vesicle pool.
  • Sodium Is Detected by the OVLT to Regulate Sympathetic Tone
    • Abstract: Publication date: 2 January 2019Source: Neuron, Volume 101, Issue 1Author(s): Patrice G. GuyenetHypernatremia is known to elicit a rise in sympathetic tone and blood pressure. In this issue of Neuron, Nomura et al. (2018) now show that this is mediated via the organum vasculosum laminae terminalis (OVLT). Na+ activates OVLT neurons via a paracrine mechanism involving sodium channel Nax expressed by astrocytes and the ependyma.
  • Interactive Regulation of Neuronal Development by Hippocampal Stem Cell
           Niche Populations
    • Abstract: Publication date: 2 January 2019Source: Neuron, Volume 101, Issue 1Author(s): J.E. Le Belle, H.I. KornblumMicroenvironment cues and cell-to-cell interactions balance stem cell quiescence with proliferation and direct neurogenesis in the adult hippocampal niche. Tang et al. report that hippocampal stem cells release feedback signals that regulate the dendritic complexity and activity of newborn neurons.
  • Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed
           by Deep Single-Cell RNA Sequencing
    • Abstract: Publication date: Available online 31 December 2018Source: NeuronAuthor(s): Qingyun Li, Zuolin Cheng, Lu Zhou, Spyros Darmanis, Norma F. Neff, Jennifer Okamoto, Gunsagar Gulati, Mariko L. Bennett, Lu O. Sun, Laura E. Clarke, Julia Marschallinger, Guoqiang Yu, Stephen R. Quake, Tony Wyss-Coray, Ben A. BarresSummaryMicroglia are increasingly recognized for their major contributions during brain development and neurodegenerative disease. It is currently unknown whether these functions are carried out by subsets of microglia during different stages of development and adulthood or within specific brain regions. Here, we performed deep single-cell RNA sequencing (scRNA-seq) of microglia and related myeloid cells sorted from various regions of embryonic, early postnatal, and adult mouse brains. We found that the majority of adult microglia expressing homeostatic genes are remarkably similar in transcriptomes, regardless of brain region. By contrast, early postnatal microglia are more heterogeneous. We discovered a proliferative-region-associated microglia (PAM) subset, mainly found in developing white matter, that shares a characteristic gene signature with degenerative disease-associated microglia (DAM). Such PAM have amoeboid morphology, are metabolically active, and phagocytose newly formed oligodendrocytes. This scRNA-seq atlas will be a valuable resource for dissecting innate immune functions in health and disease.Graphical Graphical abstract for this article
  • Mechanisms of Spatiotemporal Selectivity in Cortical Area MT
    • Abstract: Publication date: Available online 31 December 2018Source: NeuronAuthor(s): Ambarish S. Pawar, Sergei Gepshtein, Sergey Savel’ev, Thomas D. AlbrightSummaryCortical sensory neurons are characterized by selectivity to stimulation. This selectivity was originally viewed as a part of the fundamental “receptive field” characteristic of neurons. This view was later challenged by evidence that receptive fields are modulated by stimuli outside of the classical receptive field. Here, we show that even this modified view of selectivity needs revision. We measured spatial frequency selectivity of neurons in cortical area MT of alert monkeys and found that their selectivity strongly depends on luminance contrast, shifting to higher spatial frequencies as contrast increases. The changes of preferred spatial frequency are large at low temporal frequency, and they decrease monotonically as temporal frequency increases. That is, even interactions among basic stimulus dimensions of luminance contrast, spatial frequency, and temporal frequency strongly influence neuronal selectivity. This dynamic nature of neuronal selectivity is inconsistent with the notion of stimulus preference as a stable characteristic of cortical neurons.
  • Harnessing Genetic Complexity to Enhance Translatability of Alzheimer’s
           Disease Mouse Models: A Path toward Precision Medicine
    • Abstract: Publication date: Available online 27 December 2018Source: NeuronAuthor(s): Sarah M. Neuner, Sarah E. Heuer, Matthew J. Huentelman, Kristen M.S. O’Connell, Catherine C. KaczorowskiSummaryAn individual’s genetic makeup plays a large role in determining susceptibility to Alzheimer’s disease (AD) but has largely been ignored in preclinical studies. To test the hypothesis that incorporating genetic diversity into mouse models of AD would improve translational potential, we combined a well-established mouse model of AD with a genetically diverse reference panel to generate mice that harbor identical high-risk human mutations but differ across the remainder of their genome. We first show that genetic variation profoundly modifies the impact of human AD mutations on both cognitive and pathological phenotypes. We then validate this complex AD model by demonstrating high degrees of genetic, transcriptomic, and phenotypic overlap with human AD. Overall, work here both introduces a novel AD mouse population as an innovative and reproducible resource for the study of mechanisms underlying AD and provides evidence that preclinical models incorporating genetic diversity may better translate to human disease.
  • A Dendritic Substrate for the Cholinergic Control of Neocortical Output
    • Abstract: Publication date: Available online 26 December 2018Source: NeuronAuthor(s): Stephen R. Williams, Lee N. FletcherSummaryThe ascending cholinergic system dynamically regulates sensory perception and cognitive function, but it remains unclear how this modulation is executed in neocortical circuits. Here, we demonstrate that the cholinergic system controls the integrative operations of neocortical principal neurons by modulating dendritic excitability. Direct dendritic recordings revealed that the optogenetic-evoked release of acetylcholine (ACh) transformed the pattern of dendritic integration in layer 5B pyramidal neurons, leading to the generation of dendritic plateau potentials which powerfully drove repetitive action potential output. In contrast, the synaptic release of ACh did not positively modulate axo-somatic excitability. Mechanistically, the transformation of dendritic integration was mediated by the muscarinic ACh receptor-dependent enhancement of dendritic R-type calcium channel activity, a compartment-dependent modulation which decisively controlled the associative computations executed by layer 5B pyramidal neurons. Our findings therefore reveal a biophysical mechanism by which the cholinergic system controls dendritic computations causally linked to perceptual detection.
  • Circuit Models of Low-Dimensional Shared Variability in Cortical Networks
    • Abstract: Publication date: Available online 20 December 2018Source: NeuronAuthor(s): Chengcheng Huang, Douglas A. Ruff, Ryan Pyle, Robert Rosenbaum, Marlene R. Cohen, Brent DoironSummaryTrial-to-trial variability is a reflection of the circuitry and cellular physiology that make up a neuronal network. A pervasive yet puzzling feature of cortical circuits is that despite their complex wiring, population-wide shared spiking variability is low dimensional. Previous model cortical networks cannot explain this global variability, and rather assume it is from external sources. We show that if the spatial and temporal scales of inhibitory coupling match known physiology, networks of model spiking neurons internally generate low-dimensional shared variability that captures population activity recorded in vivo. Shifting spatial attention into the receptive field of visual neurons has been shown to differentially modulate shared variability within and between brain areas. A top-down modulation of inhibitory neurons in our network provides a parsimonious mechanism for this attentional modulation. Our work provides a critical link between observed cortical circuit structure and realistic shared neuronal variability and its modulation.
  • The Hippocampus and Neocortical Inhibitory Engrams Protect against Memory
    • Abstract: Publication date: Available online 20 December 2018Source: NeuronAuthor(s): Renée S. Koolschijn, Uzay E. Emir, Alexandros C. Pantelides, Hamed Nili, Timothy E.J. Behrens, Helen C. BarronSummaryOur experiences often overlap with each other, yet we are able to selectively recall individual memories to guide decisions and future actions. The neural mechanisms that support such precise memory recall remain unclear. Here, using ultra-high field 7T MRI we reveal two distinct mechanisms that protect memories from interference. The first mechanism involves the hippocampus, where the blood-oxygen-level-dependent (BOLD) signal predicts behavioral measures of memory interference, and representations of context-dependent memories are pattern separated according to their relational overlap. The second mechanism involves neocortical inhibition. When we reduce the concentration of neocortical GABA using trans-cranial direct current stimulation (tDCS), neocortical memory interference increases in proportion to the reduction in GABA, which in turn predicts behavioral performance. These findings suggest that memory interference is mediated by both the hippocampus and neocortex, where the hippocampus separates overlapping but context-dependent memories using relational information, and neocortical inhibition prevents unwanted co-activation between overlapping memories.
  • Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of
           Galen Malformation
    • Abstract: Publication date: Available online 18 December 2018Source: NeuronAuthor(s): Daniel Duran, Xue Zeng, Sheng Chih Jin, Jungmin Choi, Carol Nelson-Williams, Bogdan Yatsula, Jonathan Gaillard, Charuta Gavankar Furey, Qiongshi Lu, Andrew T. Timberlake, Weilai Dong, Michelle A. Sorscher, Erin Loring, Jennifer Klein, August Allocco, Ava Hunt, Sierra Conine, Jason K. Karimy, Mark W. Youngblood, Jinwei ZhangSummaryNormal vascular development includes the formation and specification of arteries, veins, and intervening capillaries. Vein of Galen malformations (VOGMs) are among the most common and severe neonatal brain arterio-venous malformations, shunting arterial blood into the brain’s deep venous system through aberrant direct connections. Exome sequencing of 55 VOGM probands, including 52 parent-offspring trios, revealed enrichment of rare damaging de novo mutations in chromatin modifier genes that play essential roles in brain and vascular development. Other VOGM probands harbored rare inherited damaging mutations in Ephrin signaling genes, including a genome-wide significant mutation burden in EPHB4. Inherited mutations showed incomplete penetrance and variable expressivity, with mutation carriers often exhibiting cutaneous vascular abnormalities, suggesting a two-hit mechanism. The identified mutations collectively account for ∼30% of studied VOGM cases. These findings provide insight into disease biology and may have clinical implications for risk assessment.
  • Migraine-Associated TRESK Mutations Increase Neuronal Excitability through
           Alternative Translation Initiation and Inhibition of TREK
    • Abstract: Publication date: Available online 17 December 2018Source: NeuronAuthor(s): Perrine Royal, Alba Andres-Bilbe, Pablo Ávalos Prado, Clément Verkest, Brigitte Wdziekonski, Sébastien Schaub, Anne Baron, Florian Lesage, Xavier Gasull, Joshua Levitz, Guillaume SandozSummaryIt is often unclear why some genetic mutations to a given gene contribute to neurological disorders and others do not. For instance, two mutations have previously been found to produce a dominant negative for TRESK, a two-pore-domain K+ channel implicated in migraine: TRESK-MT, a 2-bp frameshift mutation, and TRESK-C110R. Both mutants inhibit TRESK, but only TRESK-MT increases sensory neuron excitability and is linked to migraine. Here, we identify a new mechanism, termed frameshift mutation-induced alternative translation initiation (fsATI), that may explain why only TRESK-MT is associated with migraine. fsATI leads to the production of a second protein fragment, TRESK-MT2, which co-assembles with and inhibits TREK1 and TREK2, two other two-pore-domain K+ channels, to increase trigeminal sensory neuron excitability, leading to a migraine-like phenotype in rodents. These findings identify TREK1 and TREK2 as potential molecular targets in migraine and suggest that fsATI should be considered as a distinct class of mutations.Graphical Graphical abstract for this article
  • Tac1-Expressing Neurons in the Periaqueductal Gray Facilitate the
           Itch-Scratching Cycle via Descending Regulation
    • Abstract: Publication date: Available online 13 December 2018Source: NeuronAuthor(s): Zheng-Run Gao, Wen-Zhen Chen, Ming-Zhe Liu, Xiao-Jun Chen, Li Wan, Xin-Yan Zhang, Lei Yuan, Jun-Kai Lin, Meng Wang, Li Zhou, Xiao-Hong Xu, Yan-Gang SunSummaryUncontrollable itch-scratching cycles lead to serious skin damage in patients with chronic itch. However, the neural mechanism promoting the itch-scratching cycle remains elusive. Here, we report that tachykinin 1 (Tac1)-expressing glutamatergic neurons in the lateral and ventrolateral periaqueductal gray (l/vlPAG) facilitate the itch-scratching cycle. We found that l/vlPAG neurons exhibited scratching-behavior-related neural activity and that itch-evoked scratching behavior was impaired after suppressing the activity of l/vlPAG neurons. Furthermore, we showed that the activity of Tac1-expressing glutamatergic neurons in the l/vlPAG was elevated during itch-induced scratching behavior and that ablating or suppressing the activity of these neurons decreased itch-induced scratching behavior. Importantly, activation of Tac1-expressing neurons induced robust spontaneous scratching and grooming behaviors. The scratching behavior evoked by Tac1-expressing neuron activation was suppressed by ablation of spinal neurons expressing gastrin-releasing peptide receptor (GRPR), the key relay neurons for itch. These results suggest that Tac1-expressing neurons in the l/vlPAG promote itch-scratching cycles.Graphical Graphical abstract for this article
  • Engagement of Pulvino-cortical Feedforward and Feedback Pathways in
           Cognitive Computations
    • Abstract: Publication date: Available online 12 December 2018Source: NeuronAuthor(s): Jorge Jaramillo, Jorge F. Mejias, Xiao-Jing WangSummaryComputational modeling of brain mechanisms of cognition has largely focused on the cortex, but recent experiments have shown that higher-order nuclei of the thalamus participate in major cognitive functions and are implicated in psychiatric disorders. Here, we show that a pulvino-cortical circuit model, composed of the pulvinar and two cortical areas, captures several physiological and behavioral observations related to the macaque pulvinar. Effective connections between the two cortical areas are gated by the pulvinar, allowing the pulvinar to shift the operation regime of these areas during attentional processing and working memory and resolve conflict in decision making. Furthermore, cortico-pulvinar projections that engage the thalamic reticular nucleus enable the pulvinar to estimate decision confidence. Finally, feedforward and feedback pulvino-cortical pathways participate in frequency-dependent inter-areal interactions that modify the relative hierarchical positions of cortical areas. Overall, our model suggests that the pulvinar provides crucial contextual modulation to cortical computations associated with cognition.
  • Axoglial Adhesion by Cadm4 Regulates CNS Myelination
    • Abstract: Publication date: Available online 11 December 2018Source: NeuronAuthor(s): Nimrod Elazar, Anya Vainshtein, Neev Golan, Bharath Vijayaragavan, Nicole Schaeren-Wiemers, Yael Eshed-Eisenbach, Elior PelesSummaryThe initiation of axoglial contact is considered a prerequisite for myelination, yet the role cell adhesion molecules (CAMs) play in mediating such interactions remains unclear. To examine the function of axoglial CAMs, we tested whether enhanced CAM-mediated adhesion between OLs and neurons could affect myelination. Here we show that increased expression of a membrane-bound extracellular domain of Cadm4 (Cadm4dCT) in cultured oligodendrocytes results in the production of numerous axoglial contact sites that fail to elongate and generate mature myelin. Transgenic mice expressing Cadm4dCT were hypomyelinated and exhibit multiple myelin abnormalities, including myelination of neuronal somata. These abnormalities depend on specific neuron-glial interaction as they were not observed when these OLs were cultured alone, on nanofibers, or on neurons isolated from mice lacking the axonal receptors of Cadm4. Our results demonstrate that tightly regulated axon-glia adhesion is essential for proper myelin targeting and subsequent membrane wrapping and lateral extension.Graphical Graphical abstract for this article
  • Engram Cell Excitability State Determines the Efficacy of Memory Retrieval
    • Abstract: Publication date: Available online 11 December 2018Source: NeuronAuthor(s): Michele Pignatelli, Tomás J. Ryan, Dheeraj S. Roy, Chanel Lovett, Lillian M. Smith, Shruti Muralidhar, Susumu TonegawaSummaryAnimals need to optimize the efficacy of memory retrieval to adapt to environmental circumstances for survival. The recent development of memory engram labeling technology allows a precise investigation of the processes associated with the recall of a specific memory. Here, we show that engram cell excitability is transiently increased following memory reactivation. This short-term increase of engram excitability enhances the subsequent retrieval of specific memory content in response to cues and is manifest in the animal’s ability to recognize contexts more precisely and more effectively. These results reveal a hitherto unknown transient enhancement of context recognition based on the plasticity of engram cell excitability. They also suggest that recall of a contextual memory is influenced by previous but recent activation of the same engram. The state of excitability of engram cells mediates differential behavioral outcomes upon memory retrieval and may be crucial for survival by promoting adaptive behavior.
  • CaV2.1 α1 Subunit Expression Regulates Presynaptic CaV2.1 Abundance and
           Synaptic Strength at a Central Synapse
    • Abstract: Publication date: Available online 10 December 2018Source: NeuronAuthor(s): Matthias Lübbert, R. Oliver Goral, Christian Keine, Connon Thomas, Debbie Guerrero-Given, Travis Putzke, Rachel Satterfield, Naomi Kamasawa, Samuel M. YoungSummaryThe abundance of presynaptic CaV2 voltage-gated Ca2+ channels (CaV2) at mammalian active zones (AZs) regulates the efficacy of synaptic transmission. It is proposed that presynaptic CaV2 levels are saturated in AZs due to a finite number of slots that set CaV2 subtype abundance and that CaV2.1 cannot compete for CaV2.2 slots. However, at most AZs, CaV2.1 levels are highest and CaV2.2 levels are developmentally reduced. To investigate CaV2.1 saturation states and preference in AZs, we overexpressed the CaV2.1 and CaV2.2 α1 subunits at the calyx of Held at immature and mature developmental stages. We found that AZs prefer CaV2.1 to CaV2.2. Remarkably, CaV2.1 α1 subunit overexpression drove increased CaV2.1 currents and channel numbers and increased synaptic strength at both developmental stages examined. Therefore, we propose that CaV2.1 levels in the AZ are not saturated and that synaptic strength can be modulated by increasing CaV2.1 levels to regulate neuronal circuit output.Graphical Graphical abstract for this article
  • Activity of Prefrontal Neurons Predict Future Choices during Gambling
    • Abstract: Publication date: Available online 6 December 2018Source: NeuronAuthor(s): Johannes Passecker, Nace Mikus, Hugo Malagon-Vina, Philip Anner, Jordane Dimidschstein, Gordon Fishell, Georg Dorffner, Thomas KlausbergerSummaryNeuronal signals in the prefrontal cortex have been reported to predict upcoming decisions. Such activity patterns are often coupled to perceptual cues indicating correct choices or values of different options. How does the prefrontal cortex signal future decisions when no cues are present but when decisions are made based on internal valuations of past experiences with stochastic outcomes' We trained rats to perform a two-arm bandit-task, successfully adjusting choices between certain-small or possible-big rewards with changing long-term advantages. We discovered specialized prefrontal neurons, whose firing during the encounter of no-reward predicted the subsequent choice of animals, even for unlikely or uncertain decisions and several seconds before choice execution. Optogenetic silencing of the prelimbic cortex exclusively timed to encounters of no reward, provoked animals to excessive gambling for large rewards. Firing of prefrontal neurons during outcome evaluation signals subsequent choices during gambling and is essential for dynamically adjusting decisions based on internal valuations.
  • Fractionating Blunted Reward Processing Characteristic of Anhedonia by
           Over-Activating Primate Subgenual Anterior Cingulate Cortex
    • Abstract: Publication date: Available online 4 December 2018Source: NeuronAuthor(s): Laith Alexander, Philip L.R. Gaskin, Stephen J. Sawiak, Tim D. Fryer, Young T. Hong, Gemma J. Cockcroft, Hannah F. Clarke, Angela C. RobertsSummaryAnhedonia is a core symptom of depression, but the underlying neurobiological mechanisms are unknown. Correlative neuroimaging studies implicate dysfunction within ventromedial prefrontal cortex, but the causal roles of specific subregions remain unidentified. We addressed these issues by combining intracerebral microinfusions with cardiovascular and behavioral monitoring in marmoset monkeys to show that over-activation of primate subgenual anterior cingulate cortex (sgACC, area 25) blunts appetitive anticipatory, but not consummatory, arousal, whereas manipulations of adjacent perigenual ACC (pgACC, area 32) have no effect. sgACC/25 over-activation also reduces the willingness to work for reward. 18F-FDG PET imaging reveals over-activation induced metabolic changes in circuits involved in reward processing and interoception. Ketamine treatment ameliorates the blunted anticipatory arousal and reverses associated metabolic changes. These results demonstrate a causal role for primate sgACC/25 over-activity in selective aspects of impaired reward processing translationally relevant to anhedonia, and ketamine’s modulation of an affective network to exert its action.
  • Single-Neuron Correlates of Error Monitoring and Post-Error Adjustments in
           Human Medial Frontal Cortex
    • Abstract: Publication date: Available online 4 December 2018Source: NeuronAuthor(s): Zhongzheng Fu, Daw-An J. Wu, Ian Ross, Jeffrey M. Chung, Adam N. Mamelak, Ralph Adolphs, Ueli RutishauserSummaryHumans can self-monitor errors without explicit feedback, resulting in behavioral adjustments on subsequent trials such as post-error slowing (PES). The error-related negativity (ERN) is a well-established macroscopic scalp EEG correlate of error self-monitoring, but its neural origins and relationship to PES remain unknown. We recorded in the frontal cortex of patients performing a Stroop task and found neurons that track self-monitored errors and error history in dorsal anterior cingulate cortex (dACC) and pre-supplementary motor area (pre-SMA). Both the intracranial ERN (iERN) and error neuron responses appeared first in pre-SMA, and ∼50 ms later in dACC. Error neuron responses were correlated with iERN amplitude on individual trials. In dACC, such error neuron-iERN synchrony and responses of error-history neurons predicted the magnitude of PES. These data reveal a human single-neuron correlate of the ERN and suggest that dACC synthesizes error information to recruit behavioral control through coordinated neural activity.
  • Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in
           Mouse Models of Autism Spectrum Disorder
    • Abstract: Publication date: Available online 3 December 2018Source: NeuronAuthor(s): Martina Sgritta, Sean W. Dooling, Shelly A. Buffington, Eric N. Momin, Michael B. Francis, Robert A. Britton, Mauro Costa-MattioliSummaryCurrently, there are no medications that effectively treat the core symptoms of Autism Spectrum Disorder (ASD). We recently found that the bacterial species Lactobacillus (L.) reuteri reverses social deficits in maternal high-fat-diet offspring. However, whether the effect of L. reuteri on social behavior is generalizable to other ASD models and its mechanism(s) of action remains unknown. Here, we found that treatment with L. reuteri selectively rescues social deficits in genetic, environmental, and idiopathic ASD models. Interestingly, the effects of L. reuteri on social behavior are not mediated by restoring the composition of the host’s gut microbiome, which is altered in all of these ASD models. Instead, L. reuteri acts in a vagus nerve-dependent manner and rescues social interaction-induced synaptic plasticity in the ventral tegmental area of ASD mice, but not in oxytocin receptor-deficient mice. Collectively, treatment with L. reuteri emerges as promising non-invasive microbial-based avenue to combat ASD-related social dysfunction.Graphical Graphical abstract for this article
  • How the Internally Organized Direction Sense Is Used to Navigate
    • Abstract: Publication date: Available online 3 December 2018Source: NeuronAuthor(s): Eun Hye Park, Stephen Keeley, Cristina Savin, James B. Ranck, André A. FentonSummaryHead-direction cells preferentially discharge when the head points in a particular azimuthal direction, are hypothesized to collectively function as a single neural system for a unitary direction sense, and are believed to be essential for navigating extra-personal space by functioning like a compass. We tested these ideas by recording medial entorhinal cortex (MEC) head-direction cells while rats navigated on a familiar, continuously rotating disk that dissociates the environment into two spatial frames: one stationary and one rotating. Head-direction cells degraded directional tuning referenced to either of the externally referenced spatial frames, but firing rates, sub-second cell-pair action potential discharge relationships, and internally referenced directional tuning were preserved. MEC head-direction cell ensemble discharge collectively generates a subjective, internally referenced unitary representation of direction that, unlike a compass, is inconsistently registered to external landmarks during navigation. These findings indicate that MEC-based directional information is subjectively anchored, potentially providing for navigation without a stable externally anchored direction sense.
  • A Neural Circuit Mechanism for Encoding Aversive Stimuli in the Mesolimbic
           Dopamine System
    • Abstract: Publication date: Available online 29 November 2018Source: NeuronAuthor(s): Johannes W. de Jong, Seyedeh Atiyeh Afjei, Iskra Pollak Dorocic, James R. Peck, Christine Liu, Christina K. Kim, Lin Tian, Karl Deisseroth, Stephan LammelSummaryVentral tegmental area (VTA) dopamine (DA) neurons play a central role in mediating motivated behaviors, but the circuitry through which they signal positive and negative motivational stimuli is incompletely understood. Using in vivo fiber photometry, we simultaneously recorded activity in DA terminals in different nucleus accumbens (NAc) subnuclei during an aversive and reward conditioning task. We find that DA terminals in the ventral NAc medial shell (vNAcMed) are excited by unexpected aversive outcomes and to cues that predict them, whereas DA terminals in other NAc subregions are persistently depressed. Excitation to reward-predictive cues dominated in the NAc lateral shell and was largely absent in the vNAcMed. Moreover, we demonstrate that glutamatergic (VGLUT2-expressing) neurons in the lateral hypothalamus represent a key afferent input for providing information about aversive outcomes to vNAcMed-projecting DA neurons. Collectively, we reveal the distinct functional contributions of separate mesolimbic DA subsystems and their afferent pathways underlying motivated behaviors.Graphical Graphical abstract for this article
  • [Na+] Increases in Body Fluids Sensed by Central Nax Induce
           Sympathetically Mediated Blood Pressure Elevations via H+-Dependent
           Activation of ASIC1a
    • Abstract: Publication date: Available online 29 November 2018Source: NeuronAuthor(s): Kengo Nomura, Takeshi Y. Hiyama, Hiraki Sakuta, Takashi Matsuda, Chia-Hao Lin, Kenta Kobayashi, Kazuto Kobayashi, Tomoyuki Kuwaki, Kunihiko Takahashi, Shigeyuki Matsui, Masaharu NodaSummaryIncreases in sodium concentrations ([Na+]) in body fluids elevate blood pressure (BP) by enhancing sympathetic nerve activity (SNA). However, the mechanisms by which information on increased [Na+] is translated to SNA have not yet been elucidated. We herein reveal that sympathetic activation leading to BP increases is not induced by mandatory high salt intakes or the intraperitoneal/intracerebroventricular infusions of hypertonic NaCl solutions in Nax-knockout mice in contrast to wild-type mice. We identify Nax channels expressed in specific glial cells in the organum vasculosum lamina terminalis (OVLT) as the sensors detecting increases in [Na+] in body fluids and show that OVLT neurons projecting to the paraventricular nucleus (PVN) are activated via acid-sensing ion channel 1a (ASIC1a) by H+ ions exported from Nax-positive glial cells. The present results provide an insight into the neurogenic mechanisms responsible for salt-induced BP elevations.
  • Stromalin Constrains Memory Acquisition by Developmentally Limiting
           Synaptic Vesicle Pool Size
    • Abstract: Publication date: Available online 28 November 2018Source: NeuronAuthor(s): Anna Phan, Connon I. Thomas, Molee Chakraborty, Jacob A. Berry, Naomi Kamasawa, Ronald L. DavisSummaryStromalin, a cohesin complex protein, was recently identified as a novel memory suppressor gene, but its mechanism remained unknown. Here, we show that Stromalin functions as a negative regulator of synaptic vesicle (SV) pool size in Drosophila neurons. Stromalin knockdown in dopamine neurons during a critical developmental period enhances learning and increases SV pool size without altering the number of dopamine neurons, their axons, or synapses. The developmental effect of Stromalin knockdown persists into adulthood, leading to strengthened synaptic connections and enhanced olfactory memory acquisition in adult flies. Correcting the SV content in dopamine neuron axon terminals by impairing anterograde SV trafficking motor protein Unc104/KIF1A rescues the enhanced-learning phenotype in Stromalin knockdown flies. Our results identify a new mechanism for memory suppression and reveal that the size of the SV pool is controlled genetically and independent from other aspects of neuron structure and function through Stromalin.Graphical Graphical abstract for this article
  • Assembly Responses of Hippocampal CA1 Place Cells Predict Learned Behavior
           in Goal-Directed Spatial Tasks on the Radial Eight-Arm Maze
    • Abstract: Publication date: Available online 28 November 2018Source: NeuronAuthor(s): Haibing Xu, Peter Baracskay, Joseph O’Neill, Jozsef CsicsvariSummaryHippocampus is needed for both spatial working and reference memories. Here, using a radial eight-arm maze, we examined how the combined demand on these memories influenced CA1 place cell assemblies while reference memories were partially updated. This was contrasted with control tasks requiring only working memory or the update of reference memory. Reference memory update led to the reward-directed place field shifts at newly rewarded arms and to the gradual strengthening of firing in passes between newly rewarded arms but not between those passes that included a familiar-rewarded arm. At the maze center, transient network synchronization periods preferentially replayed trajectories of the next chosen arm in reference memory tasks but the previously visited arm in the working memory task. Hence, reference memory demand was uniquely associated with a gradual, goal novelty-related reorganization of place cell assemblies and with trajectory replay that reflected the animal’s decision of which arm to visit next.
  • High-Density, Long-Lasting, and Multi-region Electrophysiological
           Recordings Using Polymer Electrode Arrays
    • Abstract: Publication date: Available online 27 November 2018Source: NeuronAuthor(s): Jason E. Chung, Hannah R. Joo, Jiang Lan Fan, Daniel F. Liu, Alex H. Barnett, Supin Chen, Charlotte Geaghan-Breiner, Mattias P. Karlsson, Magnus Karlsson, Kye Y. Lee, Hexin Liang, Jeremy F. Magland, Jeanine A. Pebbles, Angela C. Tooker, Leslie F. Greengard, Vanessa M. Tolosa, Loren M. FrankSummaryThe brain is a massive neuronal network, organized into anatomically distributed sub-circuits, with functionally relevant activity occurring at timescales ranging from milliseconds to years. Current methods to monitor neural activity, however, lack the necessary conjunction of anatomical spatial coverage, temporal resolution, and long-term stability to measure this distributed activity. Here we introduce a large-scale, multi-site, extracellular recording platform that integrates polymer electrodes with a modular stacking headstage design supporting up to 1,024 recording channels in freely behaving rats. This system can support months-long recordings from hundreds of well-isolated units across multiple brain regions. Moreover, these recordings are stable enough to track large numbers of single units for over a week. This platform enables large-scale electrophysiological interrogation of the fast dynamics and long-timescale evolution of anatomically distributed circuits, and thereby provides a new tool for understanding brain activity.
  • Neural Stem Cells Behave as a Functional Niche for the Maturation of
           Newborn Neurons through the Secretion of PTN
    • Abstract: Publication date: Available online 26 November 2018Source: NeuronAuthor(s): Changyong Tang, Min Wang, Peijian Wang, Lei Wang, Qingfeng Wu, Weixiang GuoSummaryIn the neurogenic niches, adult neural stem and/or progenitor cells (NSCs) generate functional neurons throughout life, which has been implicated in learning and memory and affective behaviors. During adult neurogenesis, newborn neurons release feedback signals into the niches to regulate NSC proliferation and differentiation. However, whether and how NSCs contribute to the niche governing newborn neuron development is still unknown. Using a combination of cell ablation, retrovirus-mediated single-cell labeling, and signaling pathway modulation, we show that adult hippocampal NSCs continuously supply pleiotrophin factor to the newborn neurons. Without this feedforward signal, the newborn neurons display defective dendritic development and arborization. Thus, our findings reveal that NSCs behave as a functional niche for newly generated newborn neurons to regulate their maturation.
  • Human Scene-Selective Areas Represent 3D Configurations of Surfaces
    • Abstract: Publication date: Available online 26 November 2018Source: NeuronAuthor(s): Mark D. Lescroart, Jack L. GallantSummaryIt has been argued that scene-selective areas in the human brain represent both the 3D structure of the local visual environment and low-level 2D features (such as spatial frequency) that provide cues for 3D structure. To evaluate the degree to which each of these hypotheses explains variance in scene-selective areas, we develop an encoding model of 3D scene structure and test it against a model of low-level 2D features. We fit the models to fMRI data recorded while subjects viewed visual scenes. The fit models reveal that scene-selective areas represent the distance to and orientation of large surfaces, at least partly independent of low-level features. Principal component analysis of the model weights reveals that the most important dimensions of 3D structure are distance and openness. Finally, reconstructions of the stimuli based on the model weights demonstrate that our model captures unprecedented detail about the local visual environment from scene-selective areas.
  • Neocortical Topology Governs the Dendritic Integrative Capacity of Layer 5
           Pyramidal Neurons
    • Abstract: Publication date: Available online 21 November 2018Source: NeuronAuthor(s): Lee N. Fletcher, Stephen R. WilliamsSummaryThe structure of the neocortex varies across the neocortical mantle to govern the physical size of principal neurons. What impact such anatomical variation has on the computational operations of principal neurons remains unknown. Here, we demonstrate within a functionally defined area that neocortical thickness governs the anatomical, electrophysiological, and computational properties of the principal output neurons of the neocortex. We find that neocortical thickness and the size of layer 5B pyramidal neurons changes as a gradient across the rostro-caudal axis of the rat primary visual cortex. Simultaneous somato-dendritic whole-cell recordings and compartmental modeling revealed that the electrical architecture of principal neurons was not preserved; rather, primary visual cortex site-dependent differences in intracellular resistivity accentuated a gradient of the electrical behavior of layer 5B pyramidal neurons to influence the emergence of active dendritic computations. Our findings therefore reveal an exquisite relationship between neocortical structure and neuronal computation.Graphical Graphical abstract for this article
  • Higher-Order Thalamocortical Inputs Gate Synaptic Long-Term Potentiation
           via Disinhibition
    • Abstract: Publication date: Available online 21 November 2018Source: NeuronAuthor(s): Leena E. Williams, Anthony HoltmaatSummarySensory experience and perceptual learning changes receptive field properties of cortical pyramidal neurons (PNs), largely mediated by synaptic long-term potentiation (LTP). The circuit mechanisms underlying cortical LTP remain unclear. In the mouse somatosensory cortex, LTP can be elicited in layer 2/3 PNs by rhythmic whisker stimulation. We dissected the synaptic circuitry underlying this type of plasticity in thalamocortical slices. We found that projections from higher-order, posterior medial thalamic complex (POm) are key to eliciting N-methyl-D-aspartate receptor (NMDAR)-dependent LTP of intracortical synapses. Paired activation of cortical and higher-order thalamocortical inputs increased vasoactive intestinal peptide (VIP) and parvalbumin (PV) interneuron (IN) activity and decreased somatostatin (SST) IN activity, which together disinhibited the PNs. VIP IN-mediated disinhibition was critical for inducing LTP. This study reveals a circuit motif in which higher-order thalamic inputs gate synaptic plasticity via disinhibition. This motif may allow contextual feedback to shape synaptic circuits that process first-order sensory information.Graphical Graphical abstract for this article
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