# Deconstructing epileptic circuits in a mouse model of SLC6A1 syndrome

> **NIH NIH F32** · J. DAVID GLADSTONE INSTITUTES · 2022 · $67,582

## Abstract

PROJECT SUMMARY & ABSTRACT
 The SLC6A1 gene has been recently implicated in a spectrum of neurodevelopmental disorders including
epilepsy, autism, and intellectual and motor disability, collectively named SLC6A1 syndrome. SLC6A1 encodes
the GABA transporter GAT1, but the cellular and circuit mechanisms by which SLC6A1 mutations cause SLC6A1
syndrome remain unknown, thus hampering the development of effective treatments. To fill this gap, I propose
to dissect the mechanisms that cause epilepsy in a new mouse model carrying a human SLC6A1 mutation.
 My preliminary data show that Slc6a1 S295L/+ mutation leads to state-dependent seizures in
thalamocortical circuits, disrupting sleep. Motivated by these findings, I will test the central hypothesis that
thalamic circuits are key regulators of epileptic seizures associated with SLC6A1 syndrome. To test this
hypothesis, I will determine the impact of S295L mutation on synaptic and intrinsic properties of thalamocortical
neurons and thalamic circuit excitability in brain slices, and on thalamocortical function in vivo. I will also
investigate whether thalamic targeting with optogenetic tools can treat epileptic seizures.
 The proposed work will harness in vitro and in vivo electrophysiological and optogenetic circuit dissection
techniques. These results will elucidate our basic understanding of GAT1 dysfunction and assess how the
subsequent increased tonic GABA current might impact the thalamocortical circuit in SLC6A1 syndrome.
Ultimately, this work will help identify potential therapeutic targets to treat SLC6A1-related epilepsy.

## Key facts

- **NIH application ID:** 10508480
- **Project number:** 1F32NS127998-01
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Yuliya Voskobiynyk
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 1
- **Project period:** 2023-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10508480

## Citation

> US National Institutes of Health, RePORTER application 10508480, Deconstructing epileptic circuits in a mouse model of SLC6A1 syndrome (1F32NS127998-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10508480. Licensed CC0.

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