# Closed-loop Control of Interneuron Spike Timing in Epilepsy

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $525,573

## Abstract

Project Summary/Abstract
Temporal lobe epilepsy (TLE) is a debilitating disorder that includes chronic seizures and pervasive memory
impairments that significantly impact quality of life. In rodent models of TLE, my lab and others have found
dramatic changes in brain synchronization with specific changes in the theta phase locking of individual
interneurons of the dentate gyrus. However, it remains unclear whether this abnormal phase locking is a
causal mediator of seizures and cognitive deficits in epilepsy. In order to test whether the timing of interneuron
activity is directly controlling epileptic phenotypes, we have developed a novel closed-loop optogenetic system
to control the timing of interneuron activity during behavior. In this proposal, we will use our closed-loop
optogenetic system to shift the phase locking of parvalbumin- or somatostatin-expressing interneurons and
determine how the timing of these interneurons alters seizure susceptibility and cognitive performance. In
control mice, we will force an abnormal firing pattern onto the interneurons and determine whether this can
drive increased seizure susceptibility and impair cognition. In epileptic mice, we will use optogenetics to
normalize the timing of interneuron activity and determine whether this can reduce seizure susceptibility and
rescue memory impairments. Together, these experiments will determine how the timing of interneuron activity
mediates seizures and cognitive deficits in epilepsy.

## Key facts

- **NIH application ID:** 10859678
- **Project number:** 1R01NS136590-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Tristan Shuman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $525,573
- **Award type:** 1
- **Project period:** 2024-03-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10859678

## Citation

> US National Institutes of Health, RePORTER application 10859678, Closed-loop Control of Interneuron Spike Timing in Epilepsy (1R01NS136590-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10859678. Licensed CC0.

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