Date of Graduation

2026

Degree Type

Dissertation/Thesis

Degree Name

Bachelor of Science (BS)

Advisor(s)

Kaoutsar Nasrallah

Abstract

Epilepsy, a neurological disorder characterized by recurrent seizures, is often driven by hyperexcitable neural circuits that result from an imbalance between excitatory and inhibitory signaling. Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system and is essential for maintaining neuronal excitability. One mechanism through which GABA exerts inhibitory control is via δ-subunit–containing γ-aminobutyric acid type A receptors (δ-GABAARs), which mediate tonic inhibition by providing steady background suppression of neuronal activity. δ-GABAARs are particularly enriched in the DG, where they help regulate the excitability of granule neurons and preserve the DG’s gating function. This project will test the hypothesis that dysregulation of δ-GABAAR-mediated tonic inhibition is implicated in temporal lobe epilepsy (TLE), with previous studies suggesting that reduced inhibition contributes to worsened seizure outcomes. However, the specific contribution of DG δ-GABAARs to seizure severity and neuronal activation remains incompletely understood.

To test our hypothesis, we will evaluate whether selective removal of δ-GABAARs from DG neurons exacerbates seizures, by promoting overactivation of DG neurons. Two aims are proposed: (1) quantify seizure severity in DG-δ-GABAAR conditional knockout (cKO) mice versus controls after kainic-acid-induced seizures, a well established model of TLE; and (2) assess neuronal activation using a marker of neural activity (c-Fos) visualized with fluorescence microscopy following immunostaining. This research could reveal how δ-GABAARs regulate seizures, providing mechanistic insights into tonic inhibition in epilepsy and identifying potential therapeutic targets for mitigating seizure progression and cognitive dysfunction.

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