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+authors:
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+ -
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+ firstname: Kevin
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+ lastname: Goff
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+ affiliation: 'The University of Pennsylvania School of Medicine'
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+ id: 'ORCID:0000-0001-5862-0219'
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+ -
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+ firstname: Ala
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+ lastname: Somarowthu
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+ affiliation: 'The Children''s Hospital of Philadelphia'
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+ -
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+ firstname: Ethan
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+ lastname: Goldberg
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+ affiliation: 'The Children''s Hospital of Philadelphia'
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+ id: 'ORCID:0000-0002-7404-735X'
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+title: 'Goff-et-al-2023 VIP interneuron impairment promotes in vivo circuit dysfunction and autism-related behaviors in Dravet syndrome'
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+description: "Dravet Syndrome (DS) is a\nsevere neurodevelopmental disorder caused by loss of function variants in SCN1A\nwhich encodes the voltage-gated sodium channel subunit Nav1.1. We recently\nshowed that neocortical vasoactive intestinal peptide interneurons (VIP-INs)\nexpress Nav1.1 and are hypoexcitable in DS (Scn1a+/-) mice. Here,\nwe investigated VIP-IN function at the circuit and behavioral level by\nperforming in vivo 2-photon calcium imaging in awake WT and Scn1a+/-\nmice. VIP-IN and pyramidal neuron activation during behavioral transition from\nquiet wakefulness to active running was diminished in Scn1a+/-\nmice, and optogenetic activation of VIP-INs restored pyramidal neuron activity\nto WT levels during locomotion. VIP-IN selective Scn1a deletion reproduced\ncore autism spectrum disorder-related behaviors in addition to cellular- and\ncircuit-level deficits in VIP-IN function, but without epilepsy, sudden death, or\navoidance behaviors seen in the global model. Hence, VIP-INs are impaired in\nvivo and may underlie non-seizure cognitive and behavioral comorbidities in\nDS."
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+keywords:
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+ - 'Dravet syndrome'
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+ - SCN1A
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+ - 'VIP Interneuron'
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+ - Autism
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+ - Optogenetics
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+ - 'Two-photon imaging'
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+license:
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+ name: 'Creative Commons CC0 1.0 Public Domain Dedication'
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+ url: 'https://creativecommons.org/publicdomain/zero/1.0/'
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+funding:
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+ - 'NIH NINDS, F31 NS111803'
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+ - 'NIH NINDS, R01 NS110869'
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+ - 'The Dana Foundation, David Mahoney Neuroimaging Program'
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+ - 'Burroughs Wellcome Fund, Career Award for Medical Scientists'
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+references:
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+ -
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+ reftype: IsSupplementTo
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+ citation: 'Goff, K. M. & Goldberg, E. M. VIP interneuron impairment promotes in vivo circuit dysfunction and autism-related behaviors in Dravet syndrome. Cell Reports (Accepted, 2023).'
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+resourcetype: Dataset
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+templateversion: 1.2
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