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Publisher: Elsevier   (Total: 3162 journals)

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Showing 1 - 200 of 3162 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: 33, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 23, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 97, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 26, 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: 412, 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: 254, 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: 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: 28, 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: 6)
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: 16, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 8, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 153, 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: 12, 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: 32, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 8, 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: 3)
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: 10, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 29, 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: 24)
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: 7)
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: 58, 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: 22)
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: 7, 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: 6, 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: 1)
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: 9)
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: 18)
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   (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: 399, 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: 17)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 46, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 342, 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: 453, 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: 3)
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: 11, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 10)
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: 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: 9, 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: 50, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 54, 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: 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: 27, 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: 211, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 64, 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: 28, 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: 62, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 17, 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: 177, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 11, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
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: 197, SJR: 1.58, CiteScore: 3)

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Journal Cover
Neuron
Journal Prestige (SJR): 10.654
Citation Impact (citeScore): 11
Number of Followers: 215  
 
  Full-text available via subscription Subscription journal
ISSN (Print) 0896-6273 - ISSN (Online) 1097-4199
Published by Elsevier Homepage  [3162 journals]
  • A Brain Module for Scalable Control of Complex, Multi-motor Threat
           Displays
    • Abstract: Publication date: Available online 8 November 2018Source: NeuronAuthor(s): Brian J. Duistermars, Barret D. Pfeiffer, Eric D. Hoopfer, David J. AndersonSummaryThreat displays are a universal feature of agonistic interactions. Whether threats are part of a continuum of aggressive behaviors or separately controlled remains unclear. We analyze threats in Drosophila and show they are triggered by male cues and visual motion, and comprised of multiple motor elements that can be flexibly combined. We isolate a cluster of ∼3 neurons whose activity is necessary for threat displays but not for other aggressive behaviors, and whose artificial activation suffices to evoke naturalistic threats in solitary flies, suggesting that the neural control of threats is modular with respect to other aggressive behaviors. Artificially evoked threats suffice to repel opponents from a resource in the absence of contact aggression. Depending on its level of artificial activation, this neural threat module can evoke different motor elements in a threshold-dependent manner. Such scalable modules may represent fundamental “building blocks” of neural circuits that mediate complex multi-motor behaviors.
       
  • Primate Nigrostriatal Dopamine System Regulates Saccadic Response
           Inhibition
    • Abstract: Publication date: Available online 8 November 2018Source: NeuronAuthor(s): Takaya Ogasawara, Masafumi Nejime, Masahiko Takada, Masayuki MatsumotoSummaryAnimals need to inhibit inappropriate actions that would lead to unwanted outcomes. Although this ability, called response inhibition, is impaired in neurological/psychiatric disorders with dopaminergic dysfunctions, how dopamine regulates response inhibition remains unclear. Here we investigated neuronal signals of the nigrostriatal dopamine system in monkeys performing a saccadic countermanding task. Subsets of dopamine neurons in the substantia nigra and striatal neurons receiving the dopaminergic input were activated when the monkey was required to cancel a planned saccadic eye movement. These activations were stronger when canceling the eye movements was successful compared with failed and were enhanced in demanding trials. The activated dopamine neurons were distributed mainly in the dorsolateral, but not in the ventromedial, part of the nigra. Furthermore, pharmacological blockade of dopaminergic neurotransmission in the striatum dampened the performance of canceling saccadic eye movements. The present findings indicate that disruption of nigrostriatal dopamine signaling causes impairments in response inhibition.
       
  • Merkel Cells Activate Sensory Neural Pathways through Adrenergic Synapses
    • Abstract: Publication date: Available online 8 November 2018Source: NeuronAuthor(s): Benjamin U. Hoffman, Yoshichika Baba, Theanne N. Griffith, Eugene V. Mosharov, Seung-Hyun Woo, Daniel D. Roybal, Gerard Karsenty, Ardem Patapoutian, David Sulzer, Ellen A. LumpkinSummaryEpithelial-neuronal signaling is essential for sensory encoding in touch, itch, and nociception; however, little is known about the release mechanisms and neurotransmitter receptors through which skin cells govern neuronal excitability. Merkel cells are mechanosensory epidermal cells that have long been proposed to activate neuronal afferents through chemical synaptic transmission. We employed a set of classical criteria for chemical neurotransmission as a framework to test this hypothesis. RNA sequencing of adult mouse Merkel cells demonstrated that they express presynaptic molecules and biosynthetic machinery for adrenergic transmission. Moreover, live-cell imaging directly demonstrated that Merkel cells mediate activity- and VMAT-dependent release of fluorescent catecholamine neurotransmitter analogs. Touch-evoked firing in Merkel-cell afferents was inhibited either by pre-synaptic silencing of SNARE-mediated vesicle release from Merkel cells or by neuronal deletion of β2-adrenergic receptors. Together, these results identify both pre- and postsynaptic mechanisms through which Merkel cells excite mechanosensory afferents to encode gentle touch.Graphical Graphical abstract for this article
       
  • Visual Control of Walking Speed in Drosophila
    • Abstract: Publication date: Available online 8 November 2018Source: NeuronAuthor(s): Matthew S. Creamer, Omer Mano, Damon A. ClarkSummaryAn animal’s self-motion generates optic flow across its retina, and it can use this visual signal to regulate its orientation and speed through the world. While orientation control has been studied extensively in Drosophila and other insects, much less is known about the visual cues and circuits that regulate translational speed. Here, we show that flies regulate walking speed with an algorithm that is tuned to the speed of visual motion, causing them to slow when visual objects are nearby. This regulation does not depend strongly on the spatial structure or the direction of visual stimuli, making it algorithmically distinct from the classic computation that controls orientation. Despite the different algorithms, the visual circuits that regulate walking speed overlap with those that regulate orientation. Taken together, our findings suggest that walking speed is controlled by a hierarchical computation that combines multiple motion detectors with distinct tunings.
       
  • Segregated Subnetworks of Intracortical Projection Neurons in Primary
           Visual Cortex
    • Abstract: Publication date: Available online 8 November 2018Source: NeuronAuthor(s): Mean-Hwan Kim, Petr Znamenskiy, Maria Florencia Iacaruso, Thomas D. Mrsic-FlogelSummaryThe rules by which neurons in neocortex choose their synaptic partners are not fully understood. In sensory cortex, intermingled neurons encode different attributes of sensory inputs and relay them to different long-range targets. While neurons with similar responses to sensory stimuli make connections preferentially, the relationship between synaptic connectivity within an area and long-range projection target remains unclear. We examined the local connectivity and visual responses of primary visual cortex neurons projecting to anterolateral (AL) and posteromedial (PM) higher visual areas in mice. Although the response properties of layer 2/3 neurons projecting to different targets were often similar, they avoided making connections with each other. Thus, projection target, in addition to response similarity, constrains local synaptic connectivity of AL and PM projection neurons. We propose that reduced crosstalk between different populations of projection neurons permits independent function of these output channels.
       
  • Complement C3aR Inactivation Attenuates Tau Pathology and Reverses an
           Immune Network Deregulated in Tauopathy Models and Alzheimer’s Disease
    • Abstract: Publication date: Available online 8 November 2018Source: NeuronAuthor(s): Alexandra Litvinchuk, Ying-Wooi Wan, Dan B. Swartzlander, Fading Chen, Allysa Cole, Nicholas E. Propson, Qian Wang, Bin Zhang, Zhandong Liu, Hui ZhengSummaryStrong evidence implicates the complement pathway as an important contributor to amyloid pathology in Alzheimer’s disease (AD); however, the role of complement in tau modulation remains unclear. Here we show that the expression of C3 and C3a receptor (C3aR1) are positively correlated with cognitive decline and Braak staging in human AD brains. Deletion of C3ar1 in PS19 mice results in the rescue of tau pathology and attenuation of neuroinflammation, synaptic deficits, and neurodegeneration. Through RNA sequencing and cell-type-specific transcriptomic analysis, we identify a C3aR-dependent transcription factor network that regulates a reactive glial switch whose inactivation ameliorates disease-associated microglia and neurotoxic astrocyte signatures. Strikingly, this C3aR network includes multiple genes linked to late-onset AD. Mechanistically, we identify STAT3 as a direct target of C3-C3aR signaling that functionally mediates tau pathogenesis. All together our findings demonstrate a crucial role for activation of the C3-C3aR network in mediating neuroinflammation and tau pathology.Graphical Graphical abstract for this article
       
  • Dendritic Inhibition in Layer 1 Cortex Gates Associative Memory
    • Abstract: Publication date: 7 November 2018Source: Neuron, Volume 100, Issue 3Author(s): Wen-Hsien Hou, Marco CapognaLearning-related plasticity is critical for emotional memory. In this issue of Neuron,Abs et al., (2018) describe novel dynamics mediated by neurogliaform cells in layer 1 neocortex of mouse that are associated with aversive memory.
       
  • Vascular and Neurogenic Rejuvenation in Aging Mice by Modulation of ASM
    • Abstract: Publication date: 7 November 2018Source: Neuron, Volume 100, Issue 3Author(s): Min Hee Park, Ju Youn Lee, Kang Ho Park, In Kyung Jung, Kyoung-Tae Kim, Yong-Seok Lee, Hyun-Hee Ryu, Yong Jeong, Minseok Kang, Markus Schwaninger, Erich Gulbins, Martin Reichel, Johannes Kornhuber, Tomoyuki Yamaguchi, Hee-Jin Kim, Seung Hyun Kim, Edward H. Schuchman, Hee Kyung Jin, Jae-sung Bae
       
  • Noninvasive Ultrasonic Drug Uncaging Maps Whole-Brain Functional Networks
    • Abstract: Publication date: 7 November 2018Source: Neuron, Volume 100, Issue 3Author(s): Jeffrey B. Wang, Muna Aryal, Qian Zhong, Daivik B. Vyas, Raag D. AiranSummaryBeing able to noninvasively modulate brain activity, where and when an experimenter desires, with an immediate path toward human translation is a long-standing goal for neuroscience. To enable robust perturbation of brain activity while leveraging the ability of focused ultrasound to deliver energy to any point of the brain noninvasively, we have developed biocompatible and clinically translatable nanoparticles that allow ultrasound-induced uncaging of neuromodulatory drugs. Utilizing the anesthetic propofol, together with electrophysiological and imaging assays, we show that the neuromodulatory effect of ultrasonic drug uncaging is limited spatially and temporally by the size of the ultrasound focus, the sonication timing, and the pharmacokinetics of the uncaged drug. Moreover, we see secondary effects in brain regions anatomically distinct from and functionally connected to the sonicated region, indicating that ultrasonic drug uncaging could noninvasively map the changes in functional network connectivity associated with pharmacologic action at a particular brain target.
       
  • Global and Multiplexed Dendritic Computations under
           In Vivo-like Conditions
    • Abstract: Publication date: 7 November 2018Source: Neuron, Volume 100, Issue 3Author(s): Balázs B. Ujfalussy, Judit K. Makara, Máté Lengyel, Tiago BrancoSummaryDendrites integrate inputs nonlinearly, but it is unclear how these nonlinearities contribute to the overall input-output transformation of single neurons. We developed statistically principled methods using a hierarchical cascade of linear-nonlinear subunits (hLN) to model the dynamically evolving somatic response of neurons receiving complex, in vivo-like spatiotemporal synaptic input patterns. We used the hLN to predict the somatic membrane potential of an in vivo-validated detailed biophysical model of a L2/3 pyramidal cell. Linear input integration with a single global dendritic nonlinearity achieved above 90% prediction accuracy. A novel hLN motif, input multiplexing into parallel processing channels, could improve predictions as much as conventionally used additional layers of local nonlinearities. We obtained similar results in two other cell types. This approach provides a data-driven characterization of a key component of cortical circuit computations: the input-output transformation of neurons during in vivo-like conditions.Graphical Graphical abstract for this article
       
  • The Calyx of Held: A Hypothesis on the Need for Reliable Timing in an
           Intensity-Difference Encoder
    • Abstract: Publication date: 7 November 2018Source: Neuron, Volume 100, Issue 3Author(s): Philip X. Joris, Laurence O. TrussellThe calyx of Held is the preeminent model for the study of synaptic function in the mammalian CNS. Despite much work on the synapse and associated circuit, its role in hearing remains enigmatic. We propose that the calyx is one of the key adaptations that enables an animal to lateralize transient sounds. The calyx is part of a binaural circuit that is biased toward high sound frequencies and is sensitive to intensity differences between the ears. This circuit also shows marked sensitivity to interaural time differences, but only for brief sound transients (“clicks”). In a natural environment, such transients are rare except as adventitious sounds generated by other animals moving at close range. We argue that the calyx, and associated temporal specializations, evolved to enable spatial localization of sound transients, through a neural code congruent with the circuit’s sensitivity to interaural intensity differences, thereby conferring a key benefit to survival.
       
  • Christopher A. Walsh
    • Abstract: Publication date: 7 November 2018Source: Neuron, Volume 100, Issue 3Author(s): Christopher Walsh studies how the human brain develops with an appreciation for how basic science is informed and enriched by patients. In this interview, Dr. Walsh shares how mapping a genetic mutation united his scientific passion with his clinical training and advises that ideas are cheap but experiments are golden.
       
  • Spike Time Synchrony in the Absence of Continuous Oscillations
    • Abstract: Publication date: 7 November 2018Source: Neuron, Volume 100, Issue 3Author(s): John B. Trimper, Laura Lee ColginEliav et al., (2018) recently reported hippocampal-entorhinal spiking in bats occurring preferentially at specific phases of nonrhythmic extracellular voltage fluctuations. This disentanglement of phase coding from continuous oscillations raises new questions about the importance of rhythms for neuronal coordination.
       
  • Unlocking the Potential for Endogenous Repair to Restore Sight
    • Abstract: Publication date: 7 November 2018Source: Neuron, Volume 100, Issue 3Author(s): Rachael A. Pearson, Robin R. AliThe eye often leads the way in the development of novel strategies for treating neurodegenerative disorders. Here, we highlight an exciting new study examining the potential for reactivating endogenous repair mechanisms and enabling the mammalian retina to repair itself.
       
  • The Thalamostriatal Pathway and the Hierarchical Control of Action
    • Abstract: Publication date: 7 November 2018Source: Neuron, Volume 100, Issue 3Author(s): Laura A. Bradfield, Miriam Matamales, Jesus Bertran-GonzalezSequential ordering of motor commands is required for the simplest of our daily activities. In this issue of Neuron, Díaz-Hernández et al. (2018) show that distinct thalamic inputs to different regions of the dorsal striatum critically modulate the initiation and execution of action sequences.
       
  • Seeing Order and Disorder in the Behaving Brain
    • Abstract: Publication date: 7 November 2018Source: Neuron, Volume 100, Issue 3Author(s): Ann KennedyThe medial prefrontal cortex (mPFC) is important for control of social behavior and is commonly studied in disorders of social dysfunction. Here, Liang et al. (2018) perform calcium imaging in the mPFC of freely behaving mice, elucidating the complex dynamics of mPFC neurons during social behavior and changes in activity after pharmacological disruption.
       
  • Circadian and Sleep Circuits Ring Together
    • Abstract: Publication date: 7 November 2018Source: Neuron, Volume 100, Issue 3Author(s): Cynthia T. Hsu, Amita SehgalProlonged wakefulness stimulates the homeostatic need to sleep, but transition to sleep also depends on the circadian time of day. However, links between circadian and homeostatic influences are not well understood. Guo et al. (2018) identify a Drosophila circuit connecting circadian clock neurons to sleep-promoting ring neurons in the ellipsoid body.
       
  • Inflamed Astrocytes: A Path to Depression Led by Menin
    • Abstract: Publication date: 7 November 2018Source: Neuron, Volume 100, Issue 3Author(s): Fernanda Neutzling Kaufmann, Caroline MenardIncreasing evidence supports a role for inflammation in the development of mood disorders. In this issue of Neuron, Leng et al. (2018) show that reduction of menin expression in astrocytes of stress-related brain regions exacerbates neuroinflammation, promoting the establishment of depression-like behaviors in mice.
       
  • h-Channels Contribute to Divergent Intrinsic Membrane Properties of
           Supragranular Pyramidal Neurons in Human versus Mouse Cerebral Cortex
    • Abstract: Publication date: Available online 1 November 2018Source: NeuronAuthor(s): Brian E. Kalmbach, Anatoly Buchin, Brian Long, Jennie Close, Anirban Nandi, Jeremy A. Miller, Trygve E. Bakken, Rebecca D. Hodge, Peter Chong, Rebecca de Frates, Kael Dai, Zoe Maltzer, Philip R. Nicovich, C. Dirk Keene, Daniel L. Silbergeld, Ryder P. Gwinn, Charles Cobbs, Andrew L. Ko, Jeffrey G. Ojemann, Christof KochSummaryGene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single-cell/nucleus RNA sequencing revealed ubiquitous HCN1-subunit expression in excitatory neurons in human, but not mouse, supragranular layers. Using patch-clamp recordings, we found stronger h-channel-related membrane properties in supragranular pyramidal neurons in human temporal cortex, compared to mouse supragranular pyramidal neurons in temporal association area. The magnitude of these differences depended upon cortical depth and was largest in pyramidal neurons in deep L3. Additionally, pharmacologically blocking h-channels produced a larger change in membrane properties in human compared to mouse neurons. Finally, using biophysical modeling, we provide evidence that h-channels promote the transfer of theta frequencies from dendrite-to-soma in human L3 pyramidal neurons. Thus, h-channels contribute to between-species differences in a fundamental neuronal property.
       
  • Food Sensation Modulates Locomotion by Dopamine and Neuropeptide Signaling
           in a Distributed Neuronal Network
    • Abstract: Publication date: Available online 1 November 2018Source: NeuronAuthor(s): Alexandra Oranth, Christian Schultheis, Oleg Tolstenkov, Karen Erbguth, Jatin Nagpal, David Hain, Martin Brauner, Sebastian Wabnig, Wagner Steuer Costa, Rebecca D. McWhirter, Sven Zels, Sierra Palumbos, David M. Miller III, Isabel Beets, Alexander GottschalkSummaryFinding food and remaining at a food source are crucial survival strategies. We show how neural circuits and signaling molecules regulate these food-related behaviors in Caenorhabditis elegans. In the absence of food, AVK interneurons release FLP-1 neuropeptides that inhibit motorneurons to regulate body posture and velocity, thereby promoting dispersal. Conversely, AVK photoinhibition promoted dwelling behavior. We identified FLP-1 receptors required for these effects in distinct motoneurons. The DVA interneuron antagonizes signaling from AVK by releasing cholecystokinin-like neuropeptides that potentiate cholinergic neurons, in response to dopaminergic neurons that sense food. Dopamine also acts directly on AVK via an inhibitory dopamine receptor. Both AVK and DVA couple to head motoneurons by electrical and chemical synapses to orchestrate either dispersal or dwelling behavior, thus integrating environmental and proprioceptive signals. Dopaminergic regulation of food-related behavior, via similar neuropeptides, may be conserved in mammals.Graphical Graphical abstract for this article
       
  • Scale-Invariant Visual Capabilities Explained by Topographic
           Representations of Luminance and Texture in Primate V1
    • Abstract: Publication date: Available online 1 November 2018Source: NeuronAuthor(s): Giacomo Benvenuti, Yuzhi Chen, Charu Ramakrishnan, Karl Deisseroth, Wilson S. Geisler, Eyal SeidemannSummaryHumans have remarkable scale-invariant visual capabilities. For example, our orientation discrimination sensitivity is largely constant over more than two orders of magnitude of variations in stimulus spatial frequency (SF). Orientation-selective V1 neurons are likely to contribute to orientation discrimination. However, because at any V1 location neurons have a limited range of receptive field (RF) sizes, we predict that at low SFs V1 neurons will carry little orientation information. If this were the case, what could account for the high behavioral sensitivity at low SFs' Using optical imaging in behaving macaques, we show that, as predicted, V1 orientation-tuned responses drop rapidly with decreasing SF. However, we reveal a surprising coarse-scale signal that corresponds to the projection of the luminance layout of low-SF stimuli to V1’s retinotopic map. This homeomorphic and distributed representation, which carries high-quality orientation information, is likely to contribute to our striking scale-invariant visual capabilities.
       
  • Topography of a Visuomotor Transformation
    • Abstract: Publication date: Available online 1 November 2018Source: NeuronAuthor(s): Thomas O. Helmbrecht, Marco dal Maschio, Joseph C. Donovan, Styliani Koutsouli, Herwig BaierSummaryThe brain converts perceptual information into appropriate patterns of muscle activity depending on the categorization and localization of sensory cues. Sensorimotor information might either be encoded by distributed networks or by “labeled lines” connecting sensory channels to dedicated behavioral pathways. Here we investigate, in the context of natural behavior, how the tectum of larval zebrafish can inform downstream premotor areas. Optogenetic mapping revealed a tectal motor map underlying locomotor maneuvers for escape and approach. Single-cell reconstructions and high-resolution functional imaging showed that two spatially segregated and uncrossed descending axon tracts selectively transmit approach and escape signals to the hindbrain. Moreover, the approach pathway conveys information about retinotopic target coordinates to specific premotor ensembles via spatially ordered axonal projections. This topographic organization supports a tectum-generated space code sufficient to steer orienting movements. We conclude that specific labeled lines guide object-directed behavior in the larval zebrafish brain.Graphical Graphical abstract for this article
       
  • Polarity Acquisition in Cortical Neurons Is Driven by Synergistic Action
           of Sox9-Regulated Wwp1 and Wwp2 E3 Ubiquitin Ligases and Intronic miR-140
           
    • Abstract: Publication date: Available online 1 November 2018Source: NeuronAuthor(s): Mateusz C. Ambrozkiewicz, Manuela Schwark, Mika Kishimoto-Suga, Ekaterina Borisova, Kei Hori, Andrea Salazar-Lázaro, Alexandra Rusanova, Bekir Altas, Lars Piepkorn, Paraskevi Bessa, Theres Schaub, Xin Zhang, Tamara Rabe, Silvia Ripamonti, Marta Rosário, Haruhiko Akiyama, Olaf Jahn, Tatsuya Kobayashi, Mikio Hoshino, Victor TarabykinSummaryThe establishment of axon-dendrite polarity is fundamental for radial migration of neurons during cortex development of mammals. We demonstrate that the E3 ubiquitin ligases WW-Containing Proteins 1 and 2 (Wwp1 and Wwp2) are indispensable for proper polarization of developing neurons. We show that knockout of Wwp1 and Wwp2 results in defects in axon-dendrite polarity in pyramidal neurons, and their aberrant laminar cortical distribution. Knockout of miR-140, encoded in Wwp2 intron, engenders phenotypic changes analogous to those upon Wwp1 and Wwp2 deletion. Intriguingly, transcription of the Wwp1 and Wwp2/miR-140 loci in neurons is induced by the transcription factor Sox9. Finally, we provide evidence that miR-140 supervises the establishment of axon-dendrite polarity through repression of Fyn kinase mRNA. Our data delineate a novel regulatory pathway that involves Sox9–[Wwp1/Wwp2/miR-140]-Fyn required for axon specification, acquisition of pyramidal morphology, and proper laminar distribution of cortical neurons.Graphical Graphical abstract for this article
       
  • FOXG1 Orchestrates Neocortical Organization and Cortico-Cortical
           Connections
    • Abstract: Publication date: Available online 1 November 2018Source: NeuronAuthor(s): Francesca Cargnin, Ji-Sun Kwon, Sol Katzman, Bin Chen, Jae W. Lee, Soo-Kyung LeeSummaryThe hallmarks of FOXG1 syndrome, which results from mutations in a single FOXG1 allele, include cortical atrophy and corpus callosum agenesis. However, the etiology for these structural deficits and the role of FOXG1 in cortical projection neurons remain unclear. Here we demonstrate that Foxg1 in pyramidal neurons plays essential roles in establishing cortical layers and the identity and axon trajectory of callosal projection neurons. The neuron-specific actions of Foxg1 are achieved by forming a transcription complex with Rp58. The Foxg1-Rp58 complex directly binds and represses Robo1, Slit3, and Reelin genes, the key regulators of callosal axon guidance and neuronal migration. We also found that inactivation of one Foxg1 allele specifically in cortical neurons was sufficient to cause cerebral cortical hypoplasia and corpus callosum agenesis. Together, this study reveals a novel gene regulatory pathway that specifies neuronal characteristics during cerebral cortex development and sheds light on the etiology of FOXG1 syndrome.
       
  • Light Prior to Eye Opening Promotes Retinal Waves and Eye-Specific
           Segregation
    • Abstract: Publication date: Available online 1 November 2018Source: NeuronAuthor(s): Alexandre Tiriac, Benjamin E. Smith, Marla B. FellerSummaryRetinal waves are bursts of correlated activity that occur prior to eye opening and provide a critical source of activity that drives the refinement of retinofugal projections. Retinal waves are thought to be initiated spontaneously with their spatiotemporal features dictated by immature neural circuits. Here we demonstrate that, during the second postnatal week in mice, changes in light intensity dictate where and when a subset of retinal waves are triggered via activation of conventional photoreceptors. Propagation properties of triggered waves are indistinguishable from spontaneous waves, indicating that they are activating the same retinal circuits. Using whole-brain imaging techniques, we demonstrate that light deprivation prior to eye opening diminishes eye-specific segregation of the retinal projections to the dorsolateral geniculate nucleus of the thalamus, but not other retinal targets. These data indicate that light that passes through the closed eyelids plays a critical role in the development of the image-forming visual system.Graphical Graphical abstract for this article
       
  • Changes in the Synaptic Proteome in Tauopathy and Rescue of Tau-Induced
           Synapse Loss by C1q Antibodies
    • Abstract: Publication date: Available online 1 November 2018Source: NeuronAuthor(s): Borislav Dejanovic, Melanie A. Huntley, Ann De Mazière, William J. Meilandt, Tiffany Wu, Karpagam Srinivasan, Zhiyu Jiang, Vineela Gandham, Brad A. Friedman, Hai Ngu, Oded Foreman, Richard A.D. Carano, Ben Chih, Judith Klumperman, Corey Bakalarski, Jesse E. Hanson, Morgan ShengSummarySynapse loss and Tau pathology are hallmarks of Alzheimer’s disease (AD) and other tauopathies, but how Tau pathology causes synapse loss is unclear. We used unbiased proteomic analysis of postsynaptic densities (PSDs) in Tau-P301S transgenic mice to identify Tau-dependent alterations in synapses prior to overt neurodegeneration. Multiple proteins and pathways were altered in Tau-P301S PSDs, including depletion of a set of GTPase-regulatory proteins that leads to actin cytoskeletal defects and loss of dendritic spines. Furthermore, we found striking accumulation of complement C1q in the PSDs of Tau-P301S mice and AD patients. At synapses, C1q decorated perisynaptic membranes, accumulated in correlation with phospho-Tau, and was associated with augmented microglial engulfment of synapses and decline of synapse density. A C1q-blocking antibody inhibited microglial synapse removal in cultured neurons and in Tau-P301S mice, rescuing synapse density. Thus, inhibiting complement-mediated synapse removal by microglia could be a potential therapeutic target for Tau-associated neurodegeneration.
       
  • Dissecting the Synapse- and Frequency-Dependent Network Mechanisms of
           In Vivo Hippocampal Sharp Wave-Ripples
    • Abstract: Publication date: Available online 25 October 2018Source: NeuronAuthor(s): Juan F. Ramirez-Villegas, Konstantin F. Willeke, Nikos K. Logothetis, Michel BesserveSummaryHippocampal ripple oscillations likely support reactivation of memory traces that manifest themselves as temporally organized spiking of sparse neuronal ensembles. However, the network mechanisms concurring to achieve this function are largely unknown. We designed a multi-compartmental model of the CA3-CA1 subfields to generate biophysically realistic ripple dynamics from the cellular level to local field potentials. Simulations broadly parallel in vivo observations and support that ripples emerge from CA1 pyramidal spiking paced by recurrent inhibition. In addition to ripple oscillations, key coordination mechanisms involve concomitant aspects of network activity. Recurrent synaptic interactions in CA1 exhibit slow-gamma band coherence with CA3 input, thus offering a way to coordinate CA1 activities with CA3 inducers. Moreover, CA1 feedback inhibition controls the content of spontaneous replay during CA1 ripples, forming new mnemonic representations through plasticity. These insights are consistent with slow-gamma interactions and interneuronal circuit plasticity observed in vivo, suggesting a multifaceted ripple-related replay phenomenon.Graphical Graphical abstract for this article
       
  • A Population of Navigator Neurons Is Essential for Olfactory Map Formation
           during the Critical Period
    • Abstract: Publication date: Available online 25 October 2018Source: NeuronAuthor(s): Yunming Wu, Limei Ma, Kyle Duyck, Carter C. Long, Andrea Moran, Hayley Scheerer, Jillian Blanck, Allison Peak, Andrew Box, Anoja Perera, C. Ron YuSummaryIn the developing brain, heightened plasticity during the critical period enables the proper formation of neural circuits. Here, we identify the “navigator” neurons, a group of perinatally born olfactory sensory neurons, as playing an essential role in establishing the olfactory map during the critical period. The navigator axons project circuitously in the olfactory bulb and traverse multiple glomeruli before terminating in perspective glomeruli. These neurons undergo a phase of exuberant axon growth and exhibit a shortened lifespan. Single-cell transcriptome analyses reveal distinct molecular signatures for the navigators. Extending their lifespan prolongs the period of exuberant growth and perturbs axon convergence. Conversely, a genetic ablation experiment indicates that, despite postnatal neurogenesis, only the navigators are endowed with the ability to establish a convergent map. The presence and the proper removal of the navigator neurons are both required to establish tight axon convergence into the glomeruli.
       
  • Brain-wide Organization of Neuronal Activity and Convergent Sensorimotor
           Transformations in Larval Zebrafish
    • Abstract: Publication date: Available online 25 October 2018Source: NeuronAuthor(s): Xiuye Chen, Yu Mu, Yu Hu, Aaron T. Kuan, Maxim Nikitchenko, Owen Randlett, Alex B. Chen, Jeffery P. Gavornik, Haim Sompolinsky, Florian Engert, Misha B. AhrensSummarySimultaneous recordings of large populations of neurons in behaving animals allow detailed observation of high-dimensional, complex brain activity. However, experimental approaches often focus on singular behavioral paradigms or brain areas. Here, we recorded whole-brain neuronal activity of larval zebrafish presented with a battery of visual stimuli while recording fictive motor output. We identified neurons tuned to each stimulus type and motor output and discovered groups of neurons in the anterior hindbrain that respond to different stimuli eliciting similar behavioral responses. These convergent sensorimotor representations were only weakly correlated to instantaneous motor activity, suggesting that they critically inform, but do not directly generate, behavioral choices. To catalog brain-wide activity beyond explicit sensorimotor processing, we developed an unsupervised clustering technique that organizes neurons into functional groups. These analyses enabled a broad overview of the functional organization of the brain and revealed numerous brain nuclei whose neurons exhibit concerted activity patterns.
       
  • Large-Scale Cortical Networks for Hierarchical Prediction and Prediction
           Error in the Primate Brain
    • Abstract: Publication date: Available online 25 October 2018Source: NeuronAuthor(s): Zenas C. Chao, Kana Takaura, Liping Wang, Naotaka Fujii, Stanislas DehaeneSummaryAccording to predictive-coding theory, cortical areas continuously generate and update predictions of sensory inputs at different hierarchical levels and emit prediction errors when the predicted and actual inputs differ. However, predictions and prediction errors are simultaneous and interdependent processes, making it difficult to disentangle their constituent neural network organization. Here, we test the theory by using high-density electrocorticography (ECoG) in monkeys during an auditory “local-global” paradigm in which the temporal regularities of the stimuli were controlled at two hierarchical levels. We decomposed the broadband data and identified lower- and higher-level prediction-error signals in early auditory cortex and anterior temporal cortex, respectively, and a prediction-update signal sent from prefrontal cortex back to temporal cortex. The prediction-error and prediction-update signals were transmitted via γ (>40 Hz) and α/β (
       
  • Imaging Cortical Dynamics in GCaMP Transgenic Rats with a Head-Mounted
           Widefield Macroscope
    • Abstract: Publication date: Available online 25 October 2018Source: NeuronAuthor(s): Benjamin B. Scott, Stephan Y. Thiberge, Caiying Guo, D. Gowanlock R. Tervo, Carlos D. Brody, Alla Y. Karpova, David W. TankSummaryWidefield imaging of calcium dynamics is an emerging method for mapping regional neural activity but is currently limited to restrained animals. Here we describe cScope, a head-mounted widefield macroscope developed to image large-scale cortical dynamics in rats during natural behavior. cScope provides a 7.8 × 4 mm field of view and dual illumination paths for both fluorescence and hemodynamic correction and can be fabricated at low cost using readily attainable components. We also report the development of Thy-1 transgenic rat strains with widespread neuronal expression of the calcium indicator GCaMP6f. We combined these two technologies to image large-scale calcium dynamics in the dorsal neocortex during a visual evidence accumulation task. Quantitative analysis of task-related dynamics revealed multiple regions having neural signals that encode behavioral choice and sensory evidence. Our results provide a new transgenic resource for calcium imaging in rats and extend the domain of head-mounted microscopes to larger-scale cortical dynamics.
       
  • A Self-Regulating Gap Junction Network of Amacrine Cells Controls Nitric
           Oxide Release in the Retina
    • Abstract: Publication date: Available online 25 October 2018Source: NeuronAuthor(s): Jason Jacoby, Amurta Nath, Zachary F. Jessen, Gregory W. SchwartzSummaryNeuromodulators regulate circuits throughout the nervous system, and revealing the cell types and stimulus conditions controlling their release is vital to understanding their function. The effects of the neuromodulator nitric oxide (NO) have been studied in many circuits, including in the vertebrate retina, where it regulates synaptic release, gap junction coupling, and blood vessel dilation, but little is known about the cells that release NO. We show that a single type of amacrine cell (AC) controls NO release in the inner retina, and we report its light responses, electrical properties, and calcium dynamics. We discover that this AC forms a dense gap junction network and that the strength of electrical coupling in the network is regulated by light through NO. A model of the network offers insights into the biophysical specializations leading to auto-regulation of NO release within the network.Graphical Graphical abstract for this article
       
  • Astrocytes Integrate Behavioral State and Vascular Signals during
           Functional Hyperemia
    • Abstract: Publication date: Available online 25 October 2018Source: NeuronAuthor(s): Cam Ha T. Tran, Govind Peringod, Grant R. GordonSummaryDynamic changes in astrocyte free Ca2+ regulate synaptic signaling and local blood flow. Although astrocytes are poised to integrate signals from synapses and the vasculature to perform their functional roles, it remains unclear what dictates astrocyte responses during neurovascular coupling under realistic conditions. We examined peri-arteriole and peri-capillary astrocytes in the barrel cortex of active mice in response to sensory stimulation or volitional behaviors. We observed an AMPA and NMDA receptor-dependent elevation in astrocyte endfoot Ca2+ that followed functional hyperemia onset. This delayed astrocyte Ca2+ signal was dependent on the animal’s action at the time of measurement as well as a neurovascular pathway that linked to endothelial-derived nitric oxide. A similar elevation in endfoot Ca2+ was evoked using vascular chemogenetics or optogenetics, and opto-stimulated dilation recruited the same nitric oxide pathway as functional hyperemia. These data show that behavioral state and microvasculature influence astrocyte Ca2+ in active mice.
       
  • Alcohol Activates Scabrous-Notch to Influence Associated Memories
    • Abstract: Publication date: Available online 25 October 2018Source: NeuronAuthor(s): Emily Petruccelli, Michael Feyder, Nicolas Ledru, Yanabah Jaques, Edward Anderson, Karla R. KaunSummaryDrugs of abuse, like alcohol, modulate gene expression in reward circuits and consequently alter behavior. However, the in vivo cellular mechanisms through which alcohol induces lasting transcriptional changes are unclear. We show that Drosophila Notch/Su(H) signaling and the secreted fibrinogen-related protein Scabrous in mushroom body (MB) memory circuitry are important for the enduring preference of cues associated with alcohol’s rewarding properties. Alcohol exposure affects Notch responsivity in the adult MB and alters Su(H) targeting at the dopamine-2-like receptor (Dop2R). Alcohol cue training also caused lasting changes to the MB nuclear transcriptome, including changes in the alternative splicing of Dop2R and newly implicated transcripts like Stat92E. Together, our data suggest that alcohol-induced activation of the highly conserved Notch pathway and accompanying transcriptional responses in memory circuitry contribute to addiction. Ultimately, this provides mechanistic insight into the etiology and pathophysiology of alcohol use disorder.Graphical Graphical abstract for this article
       
  • Spatial and Temporal Organization of the Individual Human Cerebellum
    • Abstract: Publication date: Available online 25 October 2018Source: NeuronAuthor(s): Scott Marek, Joshua S. Siegel, Evan M. Gordon, Ryan V. Raut, Caterina Gratton, Dillan J. Newbold, Mario Ortega, Timothy O. Laumann, Babatunde Adeyemo, Derek B. Miller, Annie Zheng, Katherine C. Lopez, Jeffrey J. Berg, Rebecca S. Coalson, Annie L. Nguyen, Donna Dierker, Andrew N. Van, Catherine R. Hoyt, Kathleen B. McDermott, Scott A. NorrisSummaryThe cerebellum contains the majority of neurons in the human brain and is unique for its uniform cytoarchitecture, absence of aerobic glycolysis, and role in adaptive plasticity. Despite anatomical and physiological differences between the cerebellum and cerebral cortex, group-average functional connectivity studies have identified networks related to specific functions in both structures. Recently, precision functional mapping of individuals revealed that functional networks in the cerebral cortex exhibit measurable individual specificity. Using the highly sampled Midnight Scan Club (MSC) dataset, we found the cerebellum contains reliable, individual-specific network organization that is significantly more variable than the cerebral cortex. The frontoparietal network, thought to support adaptive control, was the only network overrepresented in the cerebellum compared to the cerebral cortex (2.3-fold). Temporally, all cerebellar resting state signals lagged behind the cerebral cortex (125–380 ms), supporting the hypothesis that the cerebellum engages in a domain-general function in the adaptive control of all cortical processes.Graphical Graphical abstract for this article
       
  • Uncovering the Cells and Circuits of Touch in Normal and Pathological
           Settings
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Francie Moehring, Priyabrata Halder, Rebecca P. Seal, Cheryl L. StuckyThe sense of touch is fundamental as it provides vital, moment-to-moment information about the nature of our physical environment. Primary sensory neurons provide the basis for this sensation in the periphery; however, recent work demonstrates that touch transduction mechanisms also occur upstream of the sensory neurons via non-neuronal cells such as Merkel cells and keratinocytes. Within the spinal cord, deep dorsal horn circuits transmit innocuous touch centrally and also transform touch into pain in the setting of injury. Here non-neuronal cells play a key role in the induction and maintenance of persistent mechanical pain. This review highlights recent advances in our understanding of mechanosensation, including a growing appreciation for the role of non-neuronal cells in both touch and pain.
       
  • Activity-Regulated Transcription: Bridging the Gap between Neural Activity
           and Behavior
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Ee-Lynn Yap, Michael E. GreenbergSummaryGene transcription is the process by which the genetic codes of organisms are read and interpreted as a set of instructions for cells to divide, differentiate, migrate, and mature. As cells function in their respective niches, transcription further allows mature cells to interact dynamically with their external environment while reliably retaining fundamental information about past experiences. In this Review, we provide an overview of the field of activity-dependent transcription in the vertebrate brain and highlight contemporary work that ranges from studies of activity-dependent chromatin modifications to plasticity mechanisms underlying adaptive behaviors. We identify key gaps in knowledge and propose integrated approaches toward a deeper understanding of how activity-dependent transcription promotes the refinement and plasticity of neural circuits for cognitive function.
       
  • The AMPA Receptor Code of Synaptic Plasticity
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Graham H. Diering, Richard L. HuganirSummaryChanges in the properties and postsynaptic abundance of AMPA-type glutamate receptors (AMPARs) are major mechanisms underlying various forms of synaptic plasticity, including long-term potentiation (LTP), long-term depression (LTD), and homeostatic scaling. The function and the trafficking of AMPARs to and from synapses is modulated by specific AMPAR GluA1–GluA4 subunits, subunit-specific protein interactors, auxiliary subunits, and posttranslational modifications. Layers of regulation are added to AMPAR tetramers through these different interactions and modifications, increasing the computational power of synapses. Here we review the reliance of synaptic plasticity on AMPAR variants and propose “the AMPAR code” as a conceptual framework. The AMPAR code suggests that AMPAR variants will be predictive of the types and extent of synaptic plasticity that can occur and that a hierarchy exists such that certain AMPARs will be disproportionally recruited to synapses during LTP/homeostatic scaling up, or removed during LTD/homeostatic scaling down.
       
  • Development and Functional Diversification of Cortical Interneurons
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Lynette Lim, Da Mi, Alfredo Llorca, Oscar MarínIn the cerebral cortex, GABAergic interneurons have evolved as a highly heterogeneous collection of cell types that are characterized by their unique spatial and temporal capabilities to influence neuronal circuits. Current estimates suggest that up to 50 different types of GABAergic neurons may populate the cerebral cortex, all derived from progenitor cells in the subpallium, the ventral aspect of the embryonic telencephalon. In this review, we provide an overview of the mechanisms underlying the generation of the distinct types of interneurons and their integration in cortical circuits. Interneuron diversity seems to emerge through the implementation of cell-intrinsic genetic programs in progenitor cells, which unfold over a protracted period of time until interneurons acquire mature characteristics. The developmental trajectory of interneurons is also modulated by activity-dependent, non-cell-autonomous mechanisms that influence their ability to integrate in nascent circuits and sculpt their final distribution in the adult cerebral cortex.
       
  • Towards an Understanding of Synapse Formation
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Thomas C. SüdhofSynapses are intercellular junctions specialized for fast, point-to-point information transfer from a presynaptic neuron to a postsynaptic cell. At a synapse, a presynaptic terminal secretes neurotransmitters via a canonical release machinery, while a postsynaptic specialization senses neurotransmitters via diverse receptors. Synaptic junctions are likely organized by trans-synaptic cell-adhesion molecules (CAMs) that bidirectionally orchestrate synapse formation, restructuring, and elimination. Many candidate synaptic CAMs were described, but which CAMs are central actors and which are bystanders remains unclear. Moreover, multiple genes encoding synaptic CAMs were linked to neuropsychiatric disorders, but the mechanisms involved are unresolved. Here, I propose that engagement of multifarious synaptic CAMs produces parallel trans-synaptic signals that mediate the establishment, organization, and plasticity of synapses, thereby controlling information processing by neural circuits. Among others, this hypothesis implies that synapse formation can be understood in terms of inter- and intracellular signaling, and that neuropsychiatric disorders involve an impairment in such signaling.
       
  • Looking Forward to the Next 30
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s):
       
  • Navigating Social Space
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Matthew Schafer, Daniela SchillerCognitive maps are encoded in the hippocampal formation and related regions and range from the spatial to the purely conceptual. Neural mechanisms that encode information into relational structures, up to an arbitrary level of abstraction, may explain such a broad range of representation. Research now indicates that social life can also be mapped by these mechanisms: others’ spatial locations, social memory, and even a two-dimensional social space framed by social power and affiliation. The systematic mapping of social life onto a relational social space facilitates adaptive social decision making, akin to social navigation. This emerging line of research has implications for cognitive mapping research, clinical disorders that feature hippocampal dysfunction, and the field of social cognitive neuroscience.
       
  • What Is a Cognitive Map' Organizing Knowledge for Flexible Behavior
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Timothy E.J. Behrens, Timothy H. Muller, James C.R. Whittington, Shirley Mark, Alon B. Baram, Kimberly L. Stachenfeld, Zeb Kurth-NelsonIt is proposed that a cognitive map encoding the relationships between entities in the world supports flexible behavior, but the majority of the neural evidence for such a system comes from studies of spatial navigation. Recent work describing neuronal parallels between spatial and non-spatial behaviors has rekindled the notion of a systematic organization of knowledge across multiple domains. We review experimental evidence and theoretical frameworks that point to principles unifying these apparently disparate functions. These principles describe how to learn and use abstract, generalizable knowledge and suggest that map-like representations observed in a spatial context may be an instance of general coding mechanisms capable of organizing knowledge of all kinds. We highlight how artificial agents endowed with such principles exhibit flexible behavior and learn map-like representations observed in the brain. Finally, we speculate on how these principles may offer insight into the extreme generalizations, abstractions, and inferences that characterize human cognition.
       
  • Perceptual Decision-Making: A Field in the Midst of a Transformation
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Farzaneh Najafi, Anne K. ChurchlandMajor changes are underway in the field of perceptual decision-making. Single-neuron studies have given way to population recordings with identified cell types, traditional analyses have been extended to accommodate these large and diverse collections of neurons, and novel methods of neural disruption have provided insights about causal circuits. Further, the field has expanded to include multiple new species: rodents and invertebrates, for example, have been instrumental in demonstrating the importance of internal state on neural responses. Finally, a renewed interest in ethological stimuli prompted development of new behaviors, frequently analyzed by new, automated movement tracking methods. Taken together, these advances constitute a seismic shift in both our approach and understanding of how incoming sensory signals are used to guide decisions.
       
  • Neural Circuit Motifs in Valence Processing
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Kay M. TyeHow do our brains determine whether something is good or bad' How is this computational goal implemented in biological systems' Given the critical importance of valence processing for survival, the brain has evolved multiple strategies to solve this problem at different levels. The psychological concept of “emotional valence” is now beginning to find grounding in neuroscience. This review aims to bridge the gap between psychology and neuroscience on the topic of emotional valence processing. Here, I highlight a subset of studies that exemplify circuit motifs that repeatedly appear as implementational systems in valence processing. The motifs I identify as being important in valence processing include (1) Labeled Lines, (2) Divergent Paths, (3) Opposing Components, and (4) Neuromodulatory Gain. Importantly, the functionality of neural substrates in valence processing is dynamic, context-dependent, and changing across short and long timescales due to synaptic plasticity, competing mechanisms, and homeostatic need.
       
  • Predictive Processing: A Canonical Cortical Computation
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Georg B. Keller, Thomas D. Mrsic-FlogelThis perspective describes predictive processing as a computational framework for understanding cortical function in the context of emerging evidence, with a focus on sensory processing. We discuss how the predictive processing framework may be implemented at the level of cortical circuits and how its implementation could be falsified experimentally. Lastly, we summarize the general implications of predictive processing on cortical function in healthy and diseased states.
       
  • Lost in Translation: Traversing the Complex Path from Genomics to
           Therapeutics in Autism Spectrum Disorder
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Nenad Sestan, Matthew W. StateRecent progress in the genomics of non-syndromic autism spectrum disorder (nsASD) highlights rare, large-effect, germline, heterozygous de novo coding mutations. This distinguishes nsASD from later-onset psychiatric disorders where gene discovery efforts have predominantly yielded common alleles of small effect. These differences point to distinctive opportunities for clarifying the neurobiology of nsASD and developing novel treatments. We argue that the path ahead also presents key challenges, including distinguishing human pathophysiology from the potentially pleiotropic neurobiology mediated by established risk genes. We present our view of some of the conceptual limitations of traditional studies of model organisms, suggest a strategy focused on investigating the convergence of multiple nsASD genes, and propose that the detailed characterization of the molecular and cellular landscapes of developing human brain is essential to illuminate disease mechanisms. Finally, we address how recent advances are leading to novel strategies for therapeutics that target various points along the path from genes to behavior.
       
  • Working Memory 2.0
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Earl K. Miller, Mikael Lundqvist, André M. BastosWorking memory is the fundamental function by which we break free from reflexive input-output reactions to gain control over our own thoughts. It has two types of mechanisms: online maintenance of information and its volitional or executive control. Classic models proposed persistent spiking for maintenance but have not explicitly addressed executive control. We review recent theoretical and empirical studies that suggest updates and additions to the classic model. Synaptic weight changes between sparse bursts of spiking strengthen working memory maintenance. Executive control acts via interplay between network oscillations in gamma (30–100 Hz) in superficial cortical layers (layers 2 and 3) and alpha and beta (10–30 Hz) in deep cortical layers (layers 5 and 6). Deep-layer alpha and beta are associated with top-down information and inhibition. It regulates the flow of bottom-up sensory information associated with superficial layer gamma. We propose that interactions between different rhythms in distinct cortical layers underlie working memory maintenance and its volitional control.
       
  • Building Models of Brain Disorders with Three-Dimensional Organoids
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Neal D. Amin, Sergiu P. PaşcaDisorders of the nervous system are challenging to study and treat due to the relative inaccessibility of functional human brain tissue for research. Stem cell-derived 3D human brain organoids have the potential to recapitulate features of the human brain with greater complexity than 2D models and are increasingly being applied to model diseases affecting the central nervous system. Here, we review the use of human brain organoids to investigate neurological and psychiatric (neuropsychiatric) disorders and how this technology may ultimately advance our biological understanding of these conditions.
       
  • The Meningeal Lymphatic System: A New Player in Neurophysiology
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Sandro Da Mesquita, Zhongxiao Fu, Jonathan KipnisThe nature of fluid dynamics within the brain parenchyma is a focus of intensive research. Of particular relevance is its participation in diseases associated with protein accumulation and aggregation in the brain, such as Alzheimer’s disease (AD). The meningeal lymphatic vessels have recently been recognized as an important player in the complex circulation and exchange of soluble contents between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF). In aging mammals, for example, impaired functioning of the meningeal lymphatic vessels can lead to accelerated accumulation of toxic amyloid beta protein in the brain parenchyma, thus aggravating AD-related pathology. Given that meningeal lymphatic vessels are functionally linked to paravascular influx/efflux of the CSF/ISF, and in light of recent findings that certain cytokines, classically perceived as immune molecules, exert neuromodulatory effects, it is reasonable to suggest that the activity of meningeal lymphatics could alter the accessibility of CSF-borne immune neuromodulators to the brain parenchyma, thereby altering their effects on the brain. Accordingly, in this Perspective we propose that the meningeal lymphatic system can be viewed as a novel player in neurophysiology.
       
  • Connecting Circuits for Supraspinal Control of Locomotion
    • Abstract: Publication date: 24 October 2018Source: Neuron, Volume 100, Issue 2Author(s): Manuel J. Ferreira-Pinto, Ludwig Ruder, Paolo Capelli, Silvia ArberLocomotion is regulated by distributed circuits and achieved by the concerted activation of body musculature. While the basic properties of executive circuits in the spinal cord are fairly well understood, the precise mechanisms by which the brain impacts locomotion are much less clear. This Review discusses recent work unraveling the cellular identity, connectivity, and function of supraspinal circuits. We focus on their involvement in the regulation of the different phases of locomotion and their interaction with spinal circuits. Dedicated neuronal populations in the brainstem carry locomotor instructions, including initiation, speed, and termination. To align locomotion with behavioral needs, brainstem output structures are recruited by midbrain and forebrain circuits that compute and infer volitional, innate, and context-dependent locomotor properties. We conclude that the emerging logic of supraspinal circuit organization helps to understand how locomotor programs from exploration to hunting and escape are regulated by the brain.
       
  • The Thalamostriatal Projections Contribute to the Initiation and Execution
           of a Sequence of Movements
    • Abstract: Publication date: Available online 18 October 2018Source: NeuronAuthor(s): Edgar Díaz-Hernández, Rubén Contreras-López, Asai Sánchez-Fuentes, Luis Rodríguez-Sibrían, Josué O. Ramírez-Jarquín, Fatuel TecuapetlaSummaryOne of the main inputs driving striatal activity is the thalamostriatal projection. While the hypothesis postulating that the different thalamostriatal projections contribute differentially to shape the functions of the striatum is largely accepted, existing technical limitations have hampered efforts to prove it. Here, through the use of electrophysiological recordings of antidromically photo-identified thalamostriatal neurons and the optogenetic inhibition of thalamostriatal terminals, we identify that the thalamostriatal projections from the parafascicular and the ventroposterior regions of the thalamus contribute to the smooth initiation and the appropriate execution of a sequence of movements. Our results support a model in which both thalamostriatal projections have specific contributions to the initiation and execution of sequences, highlighting the specific contribution of the ventroposterior thalamostriatal connection for the repetition of actions.
       
  • Parsing Hippocampal Theta Oscillations by Nested Spectral Components
           during Spatial Exploration and Memory-Guided Behavior
    • Abstract: Publication date: Available online 18 October 2018Source: NeuronAuthor(s): Vítor Lopes-dos-Santos, Gido M. van de Ven, Alexander Morley, Stéphanie Trouche, Natalia Campo-Urriza, David DupretSummaryTheta oscillations reflect rhythmic inputs that continuously converge to the hippocampus during exploratory and memory-guided behavior. The theta-nested operations that organize hippocampal spiking could either occur regularly from one cycle to the next or be tuned on a cycle-by-cycle basis. To resolve this, we identified spectral components nested in individual theta cycles recorded from the mouse CA1 hippocampus. Our single-cycle profiling revealed theta spectral components associated with different firing modulations and distinguishable ensembles of principal cells. Moreover, novel co-firing patterns of principal cells in theta cycles nesting mid-gamma oscillations were the most strongly reactivated in subsequent offline sharp-wave/ripple events. Finally, theta-nested spectral components were differentially altered by behavioral stages of a memory task; the 80-Hz mid-gamma component was strengthened during learning, whereas the 22-Hz beta, 35-Hz slow gamma, and 54-Hz mid-gamma components increased during retrieval. We conclude that cycle-to-cycle variability of theta-nested spectral components allows parsing of theta oscillations into transient operating modes with complementary mnemonic roles.
       
  • A Neural Population Mechanism for Rapid Learning
    • Abstract: Publication date: Available online 18 October 2018Source: NeuronAuthor(s): Matthew G. Perich, Juan A. Gallego, Lee E. MillerSummaryLong-term learning of language, mathematics, and motor skills likely requires cortical plasticity, but behavior often requires much faster changes, sometimes even after single errors. Here, we propose one neural mechanism to rapidly develop new motor output without altering the functional connectivity within or between cortical areas. We tested cortico-cortical models relating the activity of hundreds of neurons in the premotor (PMd) and primary motor (M1) cortices throughout adaptation to reaching movement perturbations. We found a signature of learning in the “output-null” subspace of PMd with respect to M1 reflecting the ability of premotor cortex to alter preparatory activity without directly influencing M1. The output-null subspace planning activity evolved with adaptation, yet the “output-potent” mapping that captures information sent to M1 was preserved. Our results illustrate a population-level cortical mechanism to progressively adjust the output from one brain area to its downstream structures that could be exploited for rapid behavioral adaptation.Graphical Graphical abstract for this article
       
  • Molecular Interface of Neuronal Innate Immunity, Synaptic Vesicle
           Stabilization, and Presynaptic Homeostatic Plasticity
    • Abstract: Publication date: Available online 18 October 2018Source: NeuronAuthor(s): Nathan Harris, Richard D. Fetter, Daniel J. Brasier, Amy Tong, Graeme W. DavisSummaryWe define a homeostatic function for innate immune signaling within neurons. A genetic analysis of the innate immune signaling genes IMD, IKKβ, Tak1, and Relish demonstrates that each is essential for presynaptic homeostatic plasticity (PHP). Subsequent analyses define how the rapid induction of PHP (occurring in seconds) can be coordinated with the life-long maintenance of PHP, a time course that is conserved from invertebrates to mammals. We define a novel bifurcation of presynaptic innate immune signaling. Tak1 (Map3K) acts locally and is selective for rapid PHP induction. IMD, IKKβ, and Relish are essential for long-term PHP maintenance. We then define how Tak1 controls vesicle release. Tak1 stabilizes the docked vesicle state, which is essential for the homeostatic expansion of the readily releasable vesicle pool. This represents a mechanism for the control of vesicle release, and an interface of innate immune signaling with the vesicle fusion apparatus and homeostatic plasticity.
       
  • Parabrachial CGRP Neurons Establish and Sustain Aversive Taste Memories
    • Abstract: Publication date: Available online 18 October 2018Source: NeuronAuthor(s): Jane Y. Chen, Carlos A. Campos, Brooke C. Jarvie, Richard D. PalmiterSummaryFood aversions develop when the taste of a novel food is associated with sickness, which often occurs after food poisoning or chemotherapy treatment. We identified calcitonin-gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) as sufficient and necessary for establishing a conditioned taste aversion (CTA). Photoactivating projections from CGRPPBN neurons to either the central nucleus of the amygdala or the bed nucleus of the stria terminalis can also induce robust CTA. CGRPPBN neurons undergo plasticity following CTA, and inactivation of either Arc or Grin1 (genes involved in memory consolidation) prevents establishment of a strong CTA. Calcium imaging reveals that the novel food re-activates CGRPPBN neurons after conditioning. Inhibition of these neurons or inactivation of the Grin1 gene after conditioning attenuates CTA expression. Our results indicate that CGRPPBN neurons not only play a key role for learning food aversions but also contribute to the maintenance and expression of those memories.
       
  • ALS/FTD-Linked Mutation in FUS Suppresses Intra-axonal Protein Synthesis
           and Drives Disease Without Nuclear Loss-of-Function of FUS
    • Abstract: Publication date: Available online 18 October 2018Source: NeuronAuthor(s): Jone López-Erauskin, Takahiro Tadokoro, Michael W. Baughn, Brian Myers, Melissa McAlonis-Downes, Carlos Chillon-Marinas, Joshua N. Asiaban, Jonathan Artates, Anh T. Bui, Anne P. Vetto, Sandra K. Lee, Ai Vy Le, Ying Sun, Mélanie Jambeau, Jihane Boubaker, Deborah Swing, Jinsong Qiu, Geoffrey G. Hicks, Zhengyu Ouyang, Xiang-Dong FuSummaryThrough the generation of humanized FUS mice expressing full-length human FUS, we identify that when expressed at near endogenous murine FUS levels, both wild-type and ALS-causing and frontotemporal dementia (FTD)-causing mutations complement the essential function(s) of murine FUS. Replacement of murine FUS with mutant, but not wild-type, human FUS causes stress-mediated induction of chaperones, decreased expression of ion channels and transporters essential for synaptic function, and reduced synaptic activity without loss of nuclear FUS or its cytoplasmic aggregation. Most strikingly, accumulation of mutant human FUS is shown to activate an integrated stress response and to inhibit local, intra-axonal protein synthesis in hippocampal neurons and sciatic nerves. Collectively, our evidence demonstrates that human ALS/FTD-linked mutations in FUS induce a gain of toxicity that includes stress-mediated suppression in intra-axonal translation, synaptic dysfunction, and progressive age-dependent motor and cognitive disease without cytoplasmic aggregation, altered nuclear localization, or aberrant splicing of FUS-bound pre-mRNAs.Graphical Graphical abstract for this article
       
  • Chd2 Is Necessary for Neural Circuit Development and Long-Term Memory
    • Abstract: Publication date: Available online 18 October 2018Source: NeuronAuthor(s): Young J. Kim, Sattar Khoshkhoo, Jan C. Frankowski, Bingyao Zhu, Saad Abbasi, Sunyoung Lee, Ye Emily Wu, Robert F. HuntSummaryConsiderable evidence suggests loss-of-function mutations in the chromatin remodeler CHD2 contribute to a broad spectrum of human neurodevelopmental disorders. However, it is unknown how CHD2 mutations lead to impaired brain function. Here we report mice with heterozygous mutations in Chd2 exhibit deficits in neuron proliferation and a shift in neuronal excitability that included divergent changes in excitatory and inhibitory synaptic function. Further in vivo experiments show that Chd2+/− mice displayed aberrant cortical rhythmogenesis and severe deficits in long-term memory, consistent with phenotypes observed in humans. We identified broad, age-dependent transcriptional changes in Chd2+/− mice, including alterations in neurogenesis, synaptic transmission, and disease-related genes. Deficits in interneuron density and memory caused by Chd2+/− were reproduced by Chd2 mutation restricted to a subset of inhibitory neurons and corrected by interneuron transplantation. Our results provide initial insight into how Chd2 haploinsufficiency leads to aberrant cortical network function and impaired memory.
       
  • A Feedforward Mechanism Mediated by Mechanosensitive Ion Channel PIEZO1
           and Tissue Mechanics Promotes Glioma Aggression
    • Abstract: Publication date: Available online 18 October 2018Source: NeuronAuthor(s): Xin Chen, Siyi Wanggou, Ankur Bodalia, Min Zhu, Weifan Dong, Jerry J. Fan, Wen Chi Yin, Hyun-Kee Min, Malini Hu, Diana Draghici, Wenkun Dou, Feng Li, Fiona J. Coutinho, Heather Whetstone, Michelle M. Kushida, Peter B. Dirks, Yuanquan Song, Chi-chung Hui, Yu Sun, Lu-Yang WangSummaryAlteration of tissue mechanical properties is a physical hallmark of solid tumors including gliomas. How tumor cells sense and regulate tissue mechanics is largely unknown. Here, we show that mechanosensitive ion channel Piezo regulates mitosis and tissue stiffness of Drosophila gliomas, but not non-transformed brains. PIEZO1 is overexpressed in aggressive human gliomas and its expression inversely correlates with patient survival. Deleting PIEZO1 suppresses the growth of glioblastoma stem cells, inhibits tumor development, and prolongs mouse survival. Focal mechanical force activates prominent PIEZO1-dependent currents from glioma cell processes, but not soma. PIEZO1 localizes at focal adhesions to activate integrin-FAK signaling, regulate extracellular matrix, and reinforce tissue stiffening. In turn, a stiffer mechanical microenvironment elevates PIEZO1 expression to promote glioma aggression. Therefore, glioma cells are mechanosensory in a PIEZO1-dependent manner, and targeting PIEZO1 represents a strategy to break the reciprocal, disease-aggravating feedforward circuit between tumor cell mechanotransduction and the aberrant tissue mechanics.
       
  • Astrocyte-Secreted Chordin-like 1 Drives Synapse Maturation and Limits
           Plasticity by Increasing Synaptic GluA2 AMPA Receptors
    • Abstract: Publication date: Available online 18 October 2018Source: NeuronAuthor(s): Elena Blanco-Suarez, Tong-Fei Liu, Alex Kopelevich, Nicola J. AllenSummaryIn the developing brain, immature synapses contain calcium-permeable AMPA glutamate receptors (AMPARs) that are subsequently replaced with GluA2-containing calcium-impermeable AMPARs as synapses stabilize and mature. Here, we show that this essential switch in AMPARs and neuronal synapse maturation is regulated by astrocytes. Using biochemical fractionation of astrocyte-secreted proteins and mass spectrometry, we identified that astrocyte-secreted chordin-like 1 (Chrdl1) is necessary and sufficient to induce mature GluA2-containing synapses to form. This function of Chrdl1 is independent of its role as an antagonist of bone morphogenetic proteins (BMPs). Chrdl1 expression is restricted to cortical astrocytes in vivo, peaking at the time of the AMPAR switch. Chrdl1 knockout (KO) mice display reduced synaptic GluA2 AMPARs, altered kinetics of synaptic events, and enhanced remodeling in an in vivo plasticity assay. Studies have shown that humans with mutations in Chrdl1 display enhanced learning. Thus astrocytes, via the release of Chrdl1, promote GluA2-dependent synapse maturation and thereby limit synaptic plasticity.
       
  • Long-Term Potentiation Requires a Rapid Burst of Dendritic Mitochondrial
           Fission during Induction
    • Abstract: Publication date: Available online 11 October 2018Source: NeuronAuthor(s): Sai Sachin Divakaruni, Adam M. Van Dyke, Ramesh Chandra, Tara A. LeGates, Minerva Contreras, Poorna A. Dharmasri, Henry N. Higgs, Mary Kay Lobo, Scott M. Thompson, Thomas A. BlanpiedSummarySynaptic transmission is bioenergetically demanding, and the diverse processes underlying synaptic plasticity elevate these demands. Therefore, mitochondrial functions, including ATP synthesis and Ca2+ handling, are likely essential for plasticity. Although axonal mitochondria have been extensively analyzed, LTP is predominantly induced postsynaptically, where mitochondria are understudied. Additionally, though mitochondrial fission is essential for their function, signaling pathways that regulate fission in neurons remain poorly understood. We found that NMDAR-dependent LTP induction prompted a rapid burst of dendritic mitochondrial fission and elevations of mitochondrial matrix Ca2+. The fission burst was triggered by cytosolic Ca2+ elevation and required CaMKII, actin, and Drp1, as well as dynamin 2. Preventing fission impaired mitochondrial matrix Ca2+ elevations, structural LTP in cultured neurons, and electrophysiological LTP in hippocampal slices. These data illustrate a novel pathway whereby synaptic activity controls mitochondrial fission and show that dynamic control of fission regulates plasticity induction, perhaps by modulating mitochondrial Ca2+ handling.
       
  • Rbfox1 Mediates Cell-type-Specific Splicing in Cortical Interneurons
    • Abstract: Publication date: Available online 11 October 2018Source: NeuronAuthor(s): Brie Wamsley, Xavier Hubert Jaglin, Emilia Favuzzi, Giulia Quattrocolo, Maximiliano José Nigro, Nusrath Yusuf, Alireza Khodadadi-Jamayran, Bernardo Rudy, Gord FishellSummaryCortical interneurons display a remarkable diversity in their morphology, physiological properties, and connectivity. Elucidating the molecular determinants underlying this heterogeneity is essential for understanding interneuron development and function. We discovered that alternative splicing differentially regulates the integration of somatostatin- and parvalbumin-expressing interneurons into nascent cortical circuits through the cell-type-specific tailoring of mRNAs. Specifically, we identified a role for the activity-dependent splicing regulator Rbfox1 in the development of cortical interneuron-subtype-specific efferent connectivity. Our work demonstrates that Rbfox1 mediates largely non-overlapping alternative splicing programs within two distinct but related classes of interneurons.Graphical Graphical abstract for this article
       
  • Precise Synaptic Balance in the Zebrafish Homolog of Olfactory Cortex
    • Abstract: Publication date: Available online 11 October 2018Source: NeuronAuthor(s): Peter Rupprecht, Rainer W. FriedrichSummaryNeuronal computations critically depend on the connectivity rules that govern the convergence of excitatory and inhibitory synaptic signals onto individual neurons. To examine the functional synaptic organization of a distributed memory network, we performed voltage clamp recordings in telencephalic area Dp of adult zebrafish, the homolog of olfactory cortex. In neurons of posterior Dp, odor stimulation evoked large, recurrent excitatory and inhibitory inputs that established a transient state of high conductance and synaptic balance. Excitation and inhibition in individual neurons were co-tuned to different odors and correlated on slow and fast timescales. This precise synaptic balance implies specific connectivity among Dp neurons, despite the absence of an obvious topography. Precise synaptic balance stabilizes activity patterns in different directions of coding space and in time while preserving high bandwidth. The coordinated connectivity of excitatory and inhibitory subnetworks in Dp therefore supports fast recurrent memory operations.
       
  • Gamma Synchronization between V1 and V4 Improves Behavioral Performance
    • Abstract: Publication date: Available online 11 October 2018Source: NeuronAuthor(s): Gustavo Rohenkohl, Conrado Arturo Bosman, Pascal FriesSummaryBehavior is often driven by visual stimuli, relying on feedforward communication from lower to higher visual areas. Effective communication depends on enhanced interareal coherence, but it remains unclear whether this coherence occurs at an optimal phase relation that actually improves stimulus transmission to behavioral report. We recorded local field potentials from V1 and V4 of macaques performing an attention task during which they reported changes in the attended stimulus. V1-V4 gamma synchronization immediately preceding the stimulus change partly predicted subsequent reaction times (RTs). RTs slowed systematically as trial-by-trial interareal gamma phase relations deviated from the phase relation at which V1 and V4 synchronized on average. V1-V4 gamma phase relations accounted for RT differences of 13–31 ms. Effects were specific to the attended stimulus and not explained by local power or phase. Thus, interareal gamma synchronization occurs at the optimal phase relation for transmission of sensory inputs to motor responses.
       
  • Somatostatin Interneurons Facilitate Hippocampal-Prefrontal Synchrony and
           Prefrontal Spatial Encoding
    • Abstract: Publication date: Available online 11 October 2018Source: NeuronAuthor(s): Atheir I. Abbas, Marina J.M. Sundiang, Britt Henoch, Mitchell P. Morton, Scott S. Bolkan, Alan J. Park, Alexander Z. Harris, Christoph Kellendonk, Joshua A. GordonSummaryDecreased hippocampal-prefrontal synchrony may mediate cognitive deficits in schizophrenia, but it remains unclear which cells orchestrate this long-range synchrony. Parvalbumin (PV)- and somatostatin (SOM)-expressing interneurons show histological abnormalities in individuals with schizophrenia and are hypothesized to regulate oscillatory synchrony within the prefrontal cortex. To examine the relationship between interneuron function, long-range hippocampal-prefrontal synchrony, and cognition, we optogenetically inhibited SOM and PV neurons in the medial prefrontal cortex (mPFC) of mice performing a spatial working memory task while simultaneously recording neural activity in the mPFC and the hippocampus (HPC). We found that inhibiting SOM, but not PV, interneurons during the encoding phase of the task impaired working memory accuracy. This behavioral impairment was associated with decreased hippocampal-prefrontal synchrony and impaired spatial encoding in mPFC neurons. These findings suggest that interneuron dysfunction may contribute to cognitive deficits associated with schizophrenia by disrupting long-range synchrony between the HPC and PFC.
       
  • Intermingled Ensembles in Visual Association Cortex Encode Stimulus
           Identity or Predicted Outcome
    • Abstract: Publication date: Available online 11 October 2018Source: NeuronAuthor(s): Rohan N. Ramesh, Christian R. Burgess, Arthur U. Sugden, Michael Gyetvan, Mark L. AndermannSummaryThe response of a cortical neuron to a motivationally salient visual stimulus can reflect a prediction of the associated outcome, a sensitivity to low-level stimulus features, or a mix of both. To distinguish between these alternatives, we monitored responses to visual stimuli in the same lateral visual association cortex neurons across weeks, both prior to and after reassignment of the outcome associated with each stimulus. We observed correlated ensembles of neurons with visual responses that either tracked the same predicted outcome, the same stimulus orientation, or that emerged only following new learning. Visual responses of outcome-tracking neurons encoded “value,” as they demonstrated a response bias to salient, food-predicting cues and sensitivity to reward history and hunger state. Strikingly, these attributes were not evident in neurons that tracked stimulus orientation. Our findings suggest a division of labor between intermingled ensembles in visual association cortex that encode predicted value or stimulus identity.Graphical Graphical abstract for this article
       
  • Dopamine Neurons Reflect the Uncertainty in Fear Generalization
    • Abstract: Publication date: Available online 11 October 2018Source: NeuronAuthor(s): Yong S. Jo, Gabriel Heymann, Larry S. ZweifelSummaryGeneralized fear is a maladaptive behavior in which non-threatening stimuli elicit a fearful response. Here, we demonstrate that discrimination between predictive and non-predictive threat stimuli is highly sensitive to probabilistic discounting and increasing threat intensity in mice. We find that dopamine neurons of the ventral tegmental area (VTA) encode both the negative valence of threat-predictive cues and the certainty of threat prediction. As fear generalization emerges, the dopamine neurons that are activated by a threat predictive cue (CS+) decrease the amplitude of activation and an equivalent signal emerges to a non-predictive cue (CS–). Temporally precise enhancement of dopamine neurons during threat conditioning to high threat levels or uncertain threats can prevent generalization. Moreover, phasic enhancement of genetically captured dopamine neurons activated by threat cues can reverse fear generalization. These findings demonstrate the dopamine neurons reflect the certainty of threat prediction that can be used to inform and update the fear engram.
       
  • Neonatal Tbr1 Dosage Controls Cortical Layer 6 Connectivity
    • Abstract: Publication date: Available online 11 October 2018Source: NeuronAuthor(s): Siavash Fazel Darbandi, Sarah E. Robinson Schwartz, Qihao Qi, Rinaldo Catta-Preta, Emily Lin-Ling Pai, Jeffrey D. Mandell, Amanda Everitt, Anna Rubin, Rebecca A. Krasnoff, Sol Katzman, David Tastad, Alex S. Nord, A. Jeremy Willsey, Bin Chen, Matthew W. State, Vikaas S. Sohal, John L.R. RubensteinSummaryAn understanding of how heterozygous loss-of-function mutations in autism spectrum disorder (ASD) risk genes, such as TBR1, contribute to ASD remains elusive. Conditional Tbr1 deletion during late mouse gestation in cortical layer 6 neurons (Tbr1layer6 mutants) provides novel insights into its function, including dendritic patterning, synaptogenesis, and cell-intrinsic physiology. These phenotypes occur in heterozygotes, providing insights into mechanisms that may underlie ASD pathophysiology. Restoring expression of Wnt7b largely rescues the synaptic deficit in Tbr1layer6 mutant neurons. Furthermore, Tbr1layer6 heterozygotes have increased anxiety-like behavior, a phenotype seen ASD. Integrating TBR1 chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) data from layer 6 neurons and activity of TBR1-bound candidate enhancers provides evidence for how TBR1 regulates layer 6 properties. Moreover, several putative TBR1 targets are ASD risk genes, placing TBR1 in a central position both for ASD risk and for regulating transcriptional circuits that control multiple steps in layer 6 development essential for the assembly of neural circuits.
       
  • Ephaptic Coupling Promotes Synchronous Firing of Cerebellar Purkinje Cells
    • Abstract: Publication date: Available online 4 October 2018Source: NeuronAuthor(s): Kyung-Seok Han, Chong Guo, Christopher H. Chen, Laurens Witter, Tomas Osorno, Wade G. RegehrSummaryCorrelated neuronal activity at various timescales plays an important role in information transfer and processing. We find that in awake-behaving mice, an unexpectedly large fraction of neighboring Purkinje cells (PCs) exhibit sub-millisecond synchrony. Correlated firing usually arises from chemical or electrical synapses, but, surprisingly, neither is required to generate PC synchrony. We therefore assessed ephaptic coupling, a mechanism in which neurons communicate via extracellular electrical signals. In the neocortex, ephaptic signals from many neurons summate to entrain spiking on slow timescales, but extracellular signals from individual cells are thought to be too small to synchronize firing. Here we find that a single PC generates sufficiently large extracellular potentials to open sodium channels in nearby PC axons. Rapid synchronization is made possible because ephaptic signals generated by PCs peak during the rising phase of action potentials. These findings show that ephaptic coupling contributes to the prevalent synchronization of nearby PCs.Graphical Graphical abstract for this article
       
  • Neural Coding of Leg Proprioception in Drosophila
    • Abstract: Publication date: Available online 4 October 2018Source: NeuronAuthor(s): Akira Mamiya, Pralaksha Gurung, John C. TuthillSummaryAnimals rely on an internal sense of body position and movement to effectively control motor behavior. This sense of proprioception is mediated by diverse populations of mechanosensory neurons distributed throughout the body. Here, we investigate neural coding of leg proprioception in Drosophila, using in vivo two-photon calcium imaging of proprioceptive sensory neurons during controlled movements of the fly tibia. We found that the axons of leg proprioceptors are organized into distinct functional projections that contain topographic representations of specific kinematic features. Using subclass-specific genetic driver lines, we show that one group of axons encodes tibia position (flexion/extension), another encodes movement direction, and a third encodes bidirectional movement and vibration frequency. Overall, our findings reveal how proprioceptive stimuli from a single leg joint are encoded by a diverse population of sensory neurons, and provide a framework for understanding how proprioceptive feedback signals are used by motor circuits to coordinate the body.Graphical Graphical abstract for this article
       
  • Oxytocin Transforms Firing Mode of CA2 Hippocampal Neurons
    • Abstract: Publication date: Available online 4 October 2018Source: NeuronAuthor(s): Natasha N. Tirko, Katherine W. Eyring, Ioana Carcea, Mariela Mitre, Moses V. Chao, Robert C. Froemke, Richard W. TsienSummaryOxytocin is an important neuromodulator in the mammalian brain that increases information salience and circuit plasticity, but its signaling mechanisms and circuit effect are not fully understood. Here we report robust oxytocinergic modulation of intrinsic properties and circuit operations in hippocampal area CA2, a region of emerging importance for hippocampal function and social behavior. Upon oxytocin receptor activation, CA2 pyramidal cells depolarize and fire bursts of action potentials, a consequence of phospholipase C signaling to modify two separate voltage-dependent ionic processes. A reduction of potassium current carried by KCNQ-based M channels depolarizes the cell; protein kinase C activity attenuates spike rate of rise and overshoot, dampening after-hyperpolarizations. These actions, in concert with activation of fast-spiking interneurons, promote repetitive firing and CA2 bursting; bursting then governs short-term plasticity of CA2 synaptic transmission onto CA1 and, thus, efficacy of information transfer in the hippocampal network.
       
  • Distinct and Dynamic ON and OFF Neural Ensembles in the Prefrontal Cortex
           Code Social Exploration
    • Abstract: Publication date: Available online 27 September 2018Source: NeuronAuthor(s): Bo Liang, Lifeng Zhang, Giovanni Barbera, Wenting Fang, Jing Zhang, Xiaochun Chen, Rong Chen, Yun Li, Da-Ting LinSummaryThe medial prefrontal cortex (mPFC) is important for social behavior, but the mechanisms by which mPFC neurons code real-time social exploration remain largely unknown. Here we utilized miniScopes to record calcium activities from hundreds of excitatory neurons in the mPFC while mice freely explored restrained social targets in the absence or presence of the psychedelic drug phencyclidine (PCP). We identified distinct and dynamic ON and OFF neural ensembles that displayed opposing activities to code real-time behavioral information. We further illustrated that ON and OFF ensembles tuned to social exploration carried information of salience and novelty for social targets. Finally, we showed that dysfunctions in these ensembles were associated with abnormal social exploration elicited by PCP. Our findings underscore the importance of mPFC ON and OFF neural ensembles for proper exploratory behavior, including social exploration, and pave the way for future studies elucidating neural circuit dysfunctions in psychiatric disorders.Graphical Graphical abstract for this article
       
  • Learning-Related Plasticity in Dendrite-Targeting Layer 1 Interneurons
    • Abstract: Publication date: Available online 27 September 2018Source: NeuronAuthor(s): Elisabeth Abs, Rogier B. Poorthuis, Daniella Apelblat, Karzan Muhammad, M. Belen Pardi, Leona Enke, Dahlia Kushinsky, De-Lin Pu, Max Ferdinand Eizinger, Karl-Klaus Conzelmann, Ivo Spiegel, Johannes J. LetzkusSummaryA wealth of data has elucidated the mechanisms by which sensory inputs are encoded in the neocortex, but how these processes are regulated by the behavioral relevance of sensory information is less understood. Here, we focus on neocortical layer 1 (L1), a key location for processing of such top-down information. Using Neuron-Derived Neurotrophic Factor (NDNF) as a selective marker of L1 interneurons (INs) and in vivo 2-photon calcium imaging, electrophysiology, viral tracing, optogenetics, and associative memory, we find that L1 NDNF-INs mediate a prolonged form of inhibition in distal pyramidal neuron dendrites that correlates with the strength of the memory trace. Conversely, inhibition from Martinotti cells remains unchanged after conditioning but in turn tightly controls sensory responses in NDNF-INs. These results define a genetically addressable form of dendritic inhibition that is highly experience dependent and indicate that in addition to disinhibition, salient stimuli are encoded at elevated levels of distal dendritic inhibition.
       
  • A Circadian Output Circuit Controls Sleep-Wake Arousal in
           Drosophila
    • Abstract: Publication date: Available online 27 September 2018Source: NeuronAuthor(s): Fang Guo, Meghana Holla, Madelen M. Díaz, Michael RosbashSummaryThe Drosophila core circadian circuit contains distinct groups of interacting neurons that give rise to diurnal sleep-wake patterns. Previous work showed that a subset of dorsal neurons 1 (DN1s) are sleep-promoting through their inhibition of activity-promoting circadian pacemakers. Here we show that these anterior-projecting DNs (APDNs) also “exit” the circadian circuitry and communicate with the homeostatic sleep center in higher brain regions to regulate sleep and sleep-wake arousal. These APDNs connect to a small, discrete subset of tubercular-bulbar neurons, which are connected in turn to specific sleep-centric ellipsoid body (EB)-ring neurons of the central complex. Remarkably, activation of the APDNs produces sleep-like oscillations in the EB and affects arousal. The data indicate that this APDN-TuBusup-EB circuit temporally regulates sleep-wake arousal in addition to the previously defined role of the TuBu-EB circuit in vision, navigation, and attention.
       
  • Single Neurons in the Human Brain Encode Numbers
    • Abstract: Publication date: Available online 20 September 2018Source: NeuronAuthor(s): Esther F. Kutter, Jan Bostroem, Christian E. Elger, Florian Mormann, Andreas NiederSummaryOur human-specific symbolic number skills that underpin science and technology spring from nonsymbolic set size representations. Despite the significance of numerical competence, its single-neuron mechanisms in the human brain are unknown. We therefore recorded from single neurons in the medial temporal lobe of neurosurgical patients that performed a calculation task. We found that distinct groups of neurons represented either nonsymbolic or symbolic number, but not both number formats simultaneously. Numerical information could be decoded robustly from the population of neurons tuned to nonsymbolic number and with lower accuracy also from the population of neurons selective to number symbols. The tuning characteristics of selective neurons may explain why set size is represented only approximately in behavior, whereas number symbols allow exact assessments of numerical values. Our results suggest number neurons as neuronal basis of human number representations that ultimately give rise to number theory and mathematics.
       
  • Circuit Robustness to Temperature Perturbation Is Altered by
           Neuromodulators
    • Abstract: Publication date: Available online 20 September 2018Source: NeuronAuthor(s): Sara A. Haddad, Eve MarderSummaryIn the ocean, the crab Cancer borealis is subject to daily and seasonal temperature changes. Previous work, done in the presence of descending modulatory inputs, had shown that the pyloric rhythm of the crab increases in frequency as temperature increases but maintains its characteristic phase relationships until it “crashes” at extremely high temperatures. To study the interaction between neuromodulators and temperature perturbations, we studied the effects of temperature on preparations from which the descending modulatory inputs were removed. Under these conditions, the pyloric rhythm was destabilized. We then studied the effects of temperature on preparations in the presence of oxotremorine, proctolin, and serotonin. Oxotremorine and proctolin enhanced the robustness of the pyloric rhythm, whereas serotonin made the rhythm less robust. These experiments reveal considerable animal-to-animal diversity in their crash stability, consistent with the interpretation that cryptic differences in many cell and network parameters are revealed by extreme perturbations.
       
  • Communication from Learned to Innate Olfactory Processing Centers Is
           Required for Memory Retrieval in Drosophila
    • Abstract: Publication date: Available online 20 September 2018Source: NeuronAuthor(s): Michael-John Dolan, Ghislain Belliart-Guérin, Alexander Shakeel Bates, Shahar Frechter, Aurélie Lampin-Saint-Amaux, Yoshinori Aso, Ruairí J.V. Roberts, Philipp Schlegel, Allan Wong, Adnan Hammad, Davi Bock, Gerald M. Rubin, Thomas Preat, Pierre-Yves Plaçais, Gregory S.X.E. JefferisSummaryThe behavioral response to a sensory stimulus may depend on both learned and innate neuronal representations. How these circuits interact to produce appropriate behavior is unknown. In Drosophila, the lateral horn (LH) and mushroom body (MB) are thought to mediate innate and learned olfactory behavior, respectively, although LH function has not been tested directly. Here we identify two LH cell types (PD2a1 and PD2b1) that receive input from an MB output neuron required for recall of aversive olfactory memories. These neurons are required for aversive memory retrieval and modulated by training. Connectomics data demonstrate that PD2a1 and PD2b1 neurons also receive direct input from food odor-encoding neurons. Consistent with this, PD2a1 and PD2b1 are also necessary for unlearned attraction to some odors, indicating that these neurons have a dual behavioral role. This provides a circuit mechanism by which learned and innate olfactory information can interact in identified neurons to produce appropriate behavior.
       
  • Probing Sensory Readout via Combined Choice-Correlation Measures and
           Microstimulation Perturbation
    • Abstract: Publication date: Available online 20 September 2018Source: NeuronAuthor(s): Xuefei Yu, Yong GuSummaryIt is controversial whether covariation between neuronal activity and perceptual choice (i.e., choice correlation) reflects the functional readout of sensory signals. Here, we combined choice-correlation measures and electrical microstimulation on a site-to-site basis in the medial superior temporal area (MST), middle temporal area (MT), and ventral intraparietal area (VIP) when macaques discriminated between motion directions in both fine and coarse tasks. Microstimulation generated comparable effects between tasks but heterogeneous effects across and within brain regions. Within the MST and MT, microstimulation significantly biased an animal’s choice toward the sensory preference instead of choice-related signals of the stimulated units. This was particularly evident for sites with conflict preference of sensory and choice-related signals. In the VIP, microstimulation failed to produce significant effects in either task despite strong choice correlations presented in this area. Our results suggest that sensory readout may not be inferred from choice-related signals during perceptual decision-making tasks.
       
  • Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating
           Astrocyte-Mediated Neuroinflammation
    • Abstract: Publication date: Available online 13 September 2018Source: NeuronAuthor(s): Lige Leng, Kai Zhuang, Zeyue Liu, Changquan Huang, Yuehong Gao, Guimiao Chen, Hui Lin, Yu Hu, Di Wu, Meng Shi, Wenting Xie, Hao Sun, Zhicheng Shao, Huifang Li, Kunkun Zhang, Wei Mo, Timothy Y. Huang, Maoqiang Xue, Zengqiang Yuan, Xia ZhangSummaryAstrocyte dysfunction and inflammation are associated with the pathogenesis of major depressive disorder (MDD). However, the mechanisms underlying these effects remain largely unknown. Here, we found that multiple endocrine neoplasia type 1 (Men1; protein: menin) expression is attenuated in the brain of mice exposed to CUMS (chronic unpredictable mild stress) or lipopolysaccharide. Astrocyte-specific reduction of Men1 (GcKO) led to depressive-like behaviors in mice. We observed enhanced NF-κB activation and IL-1β production with menin deficiency in astrocytes, where depressive-like behaviors in GcKO mice were restored by NF-κB inhibitor or IL-1β receptor antagonist. Importantly, we identified a SNP, rs375804228, in human MEN1, where G503D substitution is associated with a higher risk of MDD onset. G503D substitution abolished menin-p65 interactions, thereby enhancing NF-κB activation and IL-1β production. Our results reveal a distinct astroglial role for menin in regulating neuroinflammation in depression, indicating that menin may be an attractive therapeutic target in MDD.
       
 
 
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