authors:
  -
    firstname: Kevin
    lastname: Goff
    affiliation: 'The University of Pennsylvania School of Medicine'
    id: 'ORCID:0000-0001-5862-0219'
  -
    firstname: Ala
    lastname: Somarowthu
    affiliation: 'The Children''s Hospital of Philadelphia'
  -
    firstname: Ethan
    lastname: Goldberg
    affiliation: 'The Children''s Hospital of Philadelphia'
    id: 'ORCID:0000-0002-7404-735X'
title: 'Goff-et-al-2023 VIP interneuron impairment promotes in vivo circuit dysfunction and autism-related behaviors in Dravet syndrome'
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."
keywords:
  - 'Dravet syndrome'
  - SCN1A
  - 'VIP Interneuron'
  - Autism
  - Optogenetics
  - 'Two-photon imaging'
license:
  name: 'Creative Commons CC0 1.0 Public Domain Dedication'
  url: 'https://creativecommons.org/publicdomain/zero/1.0/'
funding:
  - 'NIH NINDS, F31 NS111803'
  - 'NIH NINDS, R01 NS110869'
  - 'The Dana Foundation, David Mahoney Neuroimaging Program'
  - 'Burroughs Wellcome Fund, Career Award for Medical Scientists'
references:
  -
    reftype: IsSupplementTo
    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).'
resourcetype: Dataset
templateversion: 1.2