391 Determining the effects of the pathogenic developmental and epileptic encephalopathy patient variant, SCN1B-p.R98C, on neuronal excitability
Year: 2025
Type: article
Abstract: Objectives/Goals: Dravet syndrome is a developmental and epileptic encephalopathy associated with refractory seizures and a high risk of sudden unexpected death in epilepsy. A pathogenic biallelic variant in SCN1B, SCN1B-p.R98C, was identified in three patients with Dravet syndrome. Here we investigate SCN1B-p.R98C on neuronal function in vivo. Methods/Study Population: Scn1b-p.R98C mice were previously generated using CRISPR-Cas9 gene editing. Homozygous animals exhibit increased susceptibility to hyperthermia induced seizures at postnatal day (P) 15, 100% expression of spontaneous generalized seizures by P30, and ~20% undergo SUDEP by approximately P60. Here we examined the neuronal phenotype of P17–28 male and female Scn1b-p.R89C mice. We used whole-cell patch clamp electrophysiology approaches to measure effects of the variant on passive membrane properties, intrinsic excitability, and single action potential properties of parvalbumin positive (PV+) interneurons and pyramidal neurons in layers 5/6 of the somatosensory cortex and CA1 region of the hippocampus. Wild-type littermates were used as controls. Results/Anticipated Results: Our results show no differences between genotypes in any measure for somatosensory cortical PV+ interneurons or pyramidal neurons. In the CA1 region of the hippocampus, we found no differences for any measure in PV+ interneurons. In contrast, CA1 pyramidal neurons were hyperexcitable, however, with no changes in passive membrane properties or single action potential properties. Discussion/Significance of Impact:
Institutions: University of Michigan, Northwestern University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,200
OpenAlex ID: W4408822857