Abstracts

Rationale: Stress is a well-recognized seizure precipitant in individuals with epilepsy. Individuals with Dravet Syndrome (DS) exhibit a high prevalence of neuropsychiatric comorbidities and respond differently to stress compared to other childhood epilepsies. In our previous work, we observed that Scn1a⁺/⁻ (DS) mice exhibit altered baseline synaptic transmission in the bed nucleus of the stria terminalis (BNST) neurons. The BNST is a critical region for processing stress signals and modulating the hypothalamic-pituitary-adrenal axis, which regulates corticosterone (CORT) levels in rodents.

Our goal was to investigate how stress impacts DS mice. To do this, we determined how chronic restraint stress (CRS) alters body weight, serum CORT levels, and synaptic transmission in the BNST of DS mice compared to wild-type (WT) littermates. We hypothesize that prolonged CORT exposure will exacerbate the existing circuit dysregulation in DS mice, leading to maladaptive physiological and synaptic adaptations. We further investigate these changes in corticotropin-releasing-factor (CRF⁺) BNST neurons, given their role in stress responses.

Methods: Male and female Scn1a⁺/⁻ (DS; n=19) and WT (n=13) littermates (P18–P26) were assigned to either no handling (control) or 2 h/day restraint for 8 days. Body weight was recorded daily, and tail-snip blood was collected on day 1 and day 8 to measure serum CORT levels. On day 9, coronal slices containing the anterior BNST were prepared for whole-cell voltage-clamp recordings. We recorded spontaneous excitatory postsynaptic currents (sEPSCs) at –65 mV and inhibitory postsynaptic currents (sIPSCs) at +10 mV. Data were analyzed by two-way ANOVA.

Results: Under control conditions, DS mice weighed less than WT mice (genotype effect: F(1,7)=11.0,p=0.01). CRS reduced weight in WT mice (treatment effect: F(1,16)=6.46,p=0.02), but not in DS mice. CRS significantly elevated CORT levels in both genotypes (treatment effect: F(2,37)=12.3,p< 0.0001).