# Controlling epilepsy symptoms with precisely timed inhibition and circuit editing

> **NIH NS F32** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2026 · $75,880

## Abstract

PROJECT SUMMARY/ABSTRACT
Temporal lobe epilepsy (TLE) is a complex neurological disorder that is characterized by spontaneous,
reoccurring seizures and often presents with debilitating cognitive comorbidities including learning and memory
deficits. Current treatments for TLE are ineffective at managing cognitive comorbidities and often exacerbate
these symptoms. The mechanisms underlying cognitive impairments in TLE are poorly understood, but
learning and memory deficits are thought to arise when TLE pathologies disrupt the normal function of
hippocampal circuits that support these cognitive processes. Circuits in the hippocampal dentate gyrus (DG)
are known to support learning and memory and have been shown to be disrupted in TLE patients and in
animal models of TLE. Recently, Dr. Shuman showed that the spike timing of DG interneurons is disrupted in
TLE. Additionally, he showed that restoring proper spike timing of DG interneurons with closed-loop
optogenetic stimulation decreased seizure susceptibility in TLE mice. Because proper spike timing in the
hippocampus is an important mechanism that supports learning and memory computations, I hypothesize that
DG interneuron spike timing is also important for behavior. In aim 1, I will test this hypothesis by using closed-
loop optogenetic stimulation to alter the spike timing of DG interneurons relative to ongoing theta oscillations. I
predict that disrupting DG interneuron spike timing in non-epileptic mice will impair learning and memory while
restoring the disrupted spike timing of DG interneurons in TLE mice will restore learning and memory deficits.
While optogenetic approaches are great for assessing the causal relationships between physiological
processes and behavior, there are a number of barriers that limit the translational potential of optogenetics. In
aim 2, I will employ a novel circuit-editing tool to increase connectivity between DG interneurons and their
upstream inputs in the medial entorhinal cortex (

## Key facts

- **NIH application ID:** 11281358
- **Project number:** 1F32NS146143-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Christopher David Adam
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NS
- **Fiscal year:** 2026
- **Award amount:** $75,880
- **Award type:** 1
- **Project period:** 2026-03-05T00:00:00 → 2029-03-04T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11281358

## Citation

> US National Institutes of Health, RePORTER application 11281358, Controlling epilepsy symptoms with precisely timed inhibition and circuit editing (1F32NS146143-01). Retrieved via AI Analytics 2026-07-04 from https://api.ai-analytics.org/grant/nih/11281358. Licensed CC0.

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