VIP interneuron impairment promotes in vivo circuit dysfunction and autism-related behaviors in Dravet syndrome.

ABSTRACT: Dravet syndrome (DS) is a severe neurodevelopmental disorder caused by loss-of-function variants in SCN1A, which encodes the voltage-gated sodium channel subunit Nav1.1. We recently showed that neocortical vasoactive intestinal peptide interneurons (VIP-INs) express Nav1.1 and are hypoexcitable in DS (Scn1a^+/-) mice. Here, we investigate VIP-IN function at the circuit and behavioral level by performing in vivo 2-photon calcium imaging in awake wild-type (WT) and Scn1a^+/- mice. VIP-IN and pyramidal neuron activation during behavioral transition from quiet wakefulness to active running is diminished in Scn1a^+/- mice, and optogenetic activation of VIP-INs restores pyramidal neuron activity to WT levels during locomotion. VIP-IN selective Scn1a deletion reprodu

SUBMITTER: Goff KM 

PROVIDER: S-EPMC10592464 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature