SHANK3 controls maturation of social reward circuits in the VTA

descriptionPublicationkeyboard_double_arrow_right Article 06 Jun 2016 Switzerland, Italy English Publisher:Springer Science and Business Media LLCJournal:Nature Neuroscience, volume 19, pages 926-934 (issn: 1097-6256, eissn: 1546-1726,

Copyright policy )Funded by:SNSF | Role of the reward system..., SNSF | Dopamine receptor associa..., SNSF | Dopamine receptor-associa... +1 projects

Authors: Bariselli, Sebastiano; Tzanoulinou, Stamatina; Glangetas, Christelle; Prévost-Solié, Clément; Pucci, Luca; Viguié, Joanna; Bezzi, Paola; +4 Authors

doi: 10.1038/nn.4319

pmid: 27273769

pmc: PMC4948673

handle: 11573/1405188

SHANK3 controls maturation of social reward circuits in the VTA

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Abstract

Haploinsufficiency of SHANK3, encoding the synapse scaffolding protein SHANK3, leads to a highly penetrant form of autism spectrum disorder. How SHANK3 insufficiency affects specific neural circuits and how this is related to specific symptoms remains elusive. Here we used shRNA to model Shank3 insufficiency in the ventral tegmental area of mice. We identified dopamine (DA) and GABA cell-type-specific changes in excitatory synapse transmission that converge to reduce DA neuron activity and generate behavioral deficits, including impaired social preference. Administration of a positive allosteric modulator of the type 1 metabotropic glutamate receptors mGluR1 during the first postnatal week restored DA neuron excitatory synapse transmission and partially rescued the social preference defects, while optogenetic DA neuron stimulation was sufficient to enhance social preference. Collectively, these data reveal the contribution of impaired ventral tegmental area function to social behaviors and identify mGluR1 modulation during postnatal development as a potential treatment strategy.

Countries

Switzerland, Italy

Related Organizations

University of Geneva
Switzerland
University of Bordeaux
France
centre national de la recherche scientifique
France
Univ Paris
Centre National de la Recherche Scientifique
France

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Keywords

Animals; Autism Spectrum Disorder/metabolism; Behavior, Animal/physiology; Dopamine/metabolism; Dopaminergic Neurons/metabolism; GABAergic Neurons/drug effects; Hippocampus/metabolism; Inhibitory Postsynaptic Potentials/drug effects; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins/metabolism; Patch-Clamp Techniques/methods; Reward; Synapses/metabolism; Synaptic Transmission/physiology; Ventral Tegmental Area/metabolism, 616.8, Patch-Clamp Techniques, Behavior, Animal, Autism Spectrum Disorder, Dopamine, Dopaminergic Neurons, Microfilament Proteins, Ventral Tegmental Area, Mice, Transgenic, Nerve Tissue Proteins, Hippocampus, Synaptic Transmission, Article, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Inhibitory Postsynaptic Potentials, Reward, Synapses, animals; autism spectrum disorder; behavior, animal; dopamine; dopaminergic neurons; gabaergic neurons; hippocampus; inhibitory postsynaptic potentials; mice, inbred c57bl; mice, transgenic; nerve tissue proteins; patch-clamp techniques; synapses; synaptic transmission; ventral tegmental area; reward, Animals, GABAergic Neurons

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