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      Prefrontal parvalbumin interneurons require juvenile social experience to establish adult social behavior

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          Abstract

          Social isolation during the juvenile critical window is detrimental to proper functioning of the prefrontal cortex (PFC) and establishment of appropriate adult social behaviors. However, the specific circuits that undergo social experience-dependent maturation to regulate social behavior are poorly understood. We identify a specific activation pattern of parvalbumin-positive interneurons (PVIs) in dorsal-medial PFC (dmPFC) prior to an active bout, or a bout initiated by the focal mouse, but not during a passive bout when mice are explored by a stimulus mouse. Optogenetic and chemogenetic manipulation reveals that brief dmPFC-PVI activation triggers an active social approach to promote sociability. Juvenile social isolation decouples dmPFC-PVI activation from subsequent active social approach by freezing the functional maturation process of dmPFC-PVIs during the juvenile-to-adult transition. Chemogenetic activation of dmPFC-PVI activity in the adult animal mitigates juvenile isolation-induced social deficits. Therefore, social experience-dependent maturation of dmPFC-PVI is linked to long-term impacts on social behavior.

          Abstract

          Isolation during critical periods of development prevents development of normal social behaviours in mice, and this is thought to involve the prefrontal cortex. Here, the authors identify an activation pattern in parvalbumin-positive interneurons in the dorsal medial prefrontal cortex that when activated promotes sociability behaviours in mice.

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          Most cited references32

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          Neocortical excitation/inhibition balance in information processing and social dysfunction.

          Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.
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            Behavioural phenotyping assays for mouse models of autism.

            Autism is a heterogeneous neurodevelopmental disorder of unknown aetiology that affects 1 in 100-150 individuals. Diagnosis is based on three categories of behavioural criteria: abnormal social interactions, communication deficits and repetitive behaviours. Strong evidence for a genetic basis has prompted the development of mouse models with targeted mutations in candidate genes for autism. As the diagnostic criteria for autism are behavioural, phenotyping these mouse models requires behavioural assays with high relevance to each category of the diagnostic symptoms. Behavioural neuroscientists are generating a comprehensive set of assays for social interaction, communication and repetitive behaviours to test hypotheses about the causes of autism. Robust phenotypes in mouse models hold great promise as translational tools for discovering effective treatments for components of autism spectrum disorders.
              • Record: found
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              • Article: not found

              Cortical inhibitory neurons and schizophrenia.

              Impairments in certain cognitive functions, such as working memory, are core features of schizophrenia. Convergent findings indicate that a deficiency in signalling through the TrkB neurotrophin receptor leads to reduced GABA (gamma-aminobutyric acid) synthesis in the parvalbumin-containing subpopulation of inhibitory GABA neurons in the dorsolateral prefrontal cortex of individuals with schizophrenia. Despite both pre- and postsynaptic compensatory responses, the resulting alteration in perisomatic inhibition of pyramidal neurons contributes to a diminished capacity for the gamma-frequency synchronized neuronal activity that is required for working memory function. These findings reveal specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.

                Author and article information

                Contributors
                hirofumi.morishita@mssm.edu
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                21 February 2020
                21 February 2020
                2020
                : 11
                : 1003
                Affiliations
                [1 ]ISNI 0000 0001 0670 2351, GRID grid.59734.3c, Department of Psychiatry, , Icahn School of Medicine at Mount Sinai, ; One Gustave L. Levy Place, New York, NY 10029 USA
                [2 ]ISNI 0000 0001 0670 2351, GRID grid.59734.3c, Department of Neuroscience, , Icahn School of Medicine at Mount Sinai, ; One Gustave L. Levy Place, New York, NY 10029 USA
                [3 ]ISNI 0000 0001 0670 2351, GRID grid.59734.3c, Department of Ophthalmology, , Icahn School of Medicine at Mount Sinai, ; One Gustave L. Levy Place, New York, NY 10029 USA
                [4 ]ISNI 0000 0001 0670 2351, GRID grid.59734.3c, Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, ; One Gustave L. Levy Place, New York, NY 10029 USA
                [5 ]ISNI 0000 0001 0670 2351, GRID grid.59734.3c, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, ; One Gustave L. Levy Place, New York, NY 10029 USA
                Author information
                http://orcid.org/0000-0002-9884-0133
                http://orcid.org/0000-0002-0632-4538
                http://orcid.org/0000-0002-2112-8682
                http://orcid.org/0000-0002-6470-1805
                http://orcid.org/0000-0001-7700-0891
                http://orcid.org/0000-0002-1045-1337
                Article
                14740
                10.1038/s41467-020-14740-z
                7035248
                32081848
                6d30a115-1c15-4bdc-a91d-c3a55dedcdc2
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 2 July 2019
                : 22 January 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000025, U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH);
                Award ID: R01MH119523
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100000893, Simons Foundation;
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                cellular neuroscience,development of the nervous system,social behaviour
                Uncategorized
                cellular neuroscience, development of the nervous system, social behaviour

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