| First Author | Goff KM | Year | 2019 |
| Journal | Elife | Volume | 8 |
| PubMed ID | 31282864 | Mgi Jnum | J:277694 |
| Mgi Id | MGI:6331429 | Doi | 10.7554/eLife.46846 |
| Citation | Goff KM, et al. (2019) Vasoactive intestinal peptide-expressing interneurons are impaired in a mouse model of Dravet syndrome. Elife 8:e46846 |
| abstractText | Dravet Syndrome (DS) is a severe neurodevelopmental disorder caused by pathogenic loss of function variants in the gene SCN1A which encodes the voltage gated sodium (Na(+)) channel subunit Nav1.1. GABAergic interneurons expressing parvalbumin (PV-INs) and somatostatin (SST-INs) exhibit impaired excitability in DS (Scn1a(+/-)) mice. However, the function of a third major class of interneurons in DS - those expressing vasoactive intestinal peptide (VIP-IN) -is unknown. We recorded VIP-INs in brain slices from Scn1a(+/-)mice and wild-type littermate controls and found prominent impairment of irregular spiking (IS), but not continuous adapting (CA) VIP-INs, in Scn1a(+/-) mice. Application of the Nav1.1-specific toxin Hm1a rescued the observed deficits. The IS vs. CA firing pattern is determined by expression of KCNQ channels; IS VIP-INs switched to tonic firing with both pharmacologic blockade of M-current and muscarinic acetylcholine receptor activation. These results show that VIP-INs express Nav1.1 and are dysfunctional in DS, which may contribute to DS pathogenesis. |
