| First Author | Kaneko K | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 13 | Pages | 110580 |
| PubMed ID | 35354025 | Mgi Jnum | J:328767 |
| Mgi Id | MGI:7286378 | Doi | 10.1016/j.celrep.2022.110580 |
| Citation | Kaneko K, et al. (2022) Developmentally regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome. Cell Rep 38(13):110580 |
| abstractText | Dravet syndrome is a neurodevelopmental disorder characterized by epilepsy, intellectual disability, and sudden death due to pathogenic variants in SCN1A with loss of function of the sodium channel subunit Nav1.1. Nav1.1-expressing parvalbumin GABAergic interneurons (PV-INs) from young Scn1a(+/-) mice show impaired action potential generation. An approach assessing PV-IN function in the same mice at two time points shows impaired spike generation in all Scn1a(+/-) mice at postnatal days (P) 16-21, whether deceased prior or surviving to P35, with normalization by P35 in surviving mice. However, PV-IN synaptic transmission is dysfunctional in young Scn1a(+/-) mice that did not survive and in Scn1a(+/-) mice >/= P35. Modeling confirms that PV-IN axonal propagation is more sensitive to decreased sodium conductance than spike generation. These results demonstrate dynamic dysfunction in Dravet syndrome: combined abnormalities of PV-IN spike generation and propagation drives early disease severity, while ongoing dysfunction of synaptic transmission contributes to chronic pathology. |
