|
|
@@ -0,0 +1,38 @@
|
|
|
+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
|
