# Roles of glycinergic neurons in Dravet syndrome-associated disordered breathing and mortality

> **NIH NIH F31** · UNIVERSITY OF CONNECTICUT STORRS · 2023 · $44,681

## Abstract

Summary
Dravet syndrome (DS) is a severe form of epilepsy with a high rate of SUPEP. Respiratory
failure is a leading cause of SUDEP, and DS patients' frequently exhibit disordered breathing.
However, mechanisms underlying respiratory dysfunction in DS are unknown. Evidence
suggests cortical seizures activate inhibitory projections to suppress brainstem function and
result in death; however, a yet unexplored possibility is that DS-associated mutations directly
affect brainstem respiratory centers and serve as a common substrate for both seizure and
respiratory dysfunction. We recently showed that Scn1a transcript is highly expressed in
brainstem inhibitory neurons, and expression of a DS-associated Scn1a mutation (A1783V) in
inhibitory neurons resulted in cell autonomous loss of neural activity and disruption of
respiratory function at the cellular and whole-animal levels. Therefore, I hypothesize that loss of
Scn1a function directly impacts brainstem respiratory control. To test this, I will disrupt Scn1a
function globally (Scn1a-/+), specifically in all VGAT+ inhibitory neurons and only in glycinergic
neurons (GlyT2:A1783V) and determine whether these animals exhibit disordered breathing,
seizures or premature death (Aim 1), and altered cellular activity of respiratory neurons (Aim 2).
This work will provide novel insight into roles of glycinergic neurons in DS, and determine the
extent to which loss of Scn1a function directly affect brainstem function.

## Key facts

- **NIH application ID:** 10532702
- **Project number:** 5F31NS120467-03
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Brenda Milla
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $44,681
- **Award type:** 5
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10532702

## Citation

> US National Institutes of Health, RePORTER application 10532702, Roles of glycinergic neurons in Dravet syndrome-associated disordered breathing and mortality (5F31NS120467-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10532702. Licensed CC0.

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