# Closed-loop control of dentate inhibitory timing in healthy and epileptic mice

> **NIH NIH F32** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $33,195

## Abstract

Project Summary/Abstract
Temporal lobe epilepsy is a debilitating and pervasive disorder that is characterized not only by seizures which
typically emerge from the hippocampus but also by severe memory impairments. Patients with TLE report that
the potential for memory problems is of greatest concern to them. The relationship between seizures
themselves and the memory deficits associated with temporal lobe epilepsy is complex and nuanced. Though
the cause of seizures and memory deficits is unknown, rodent models can be used to study this complicated
relationship. This proposal will investigate a breakdown that occurs in the spike timing of a subset of
interneurons in the dentate gyrus of epileptic animals. Prior literature strongly supports the notion that altered
dentate inhibition may contribute to seizures and to memory deficits, but this has not been directly shown. In
this proposal, I will test the hypothesis that this breakdown in dentate inhibitory timing contributes directly to the
memory deficits seen in epilepsy and, separately, contributes to seizures. To test this hypothesis, I will use in
vivo silicon probes to record LFPs and single-units simultaneously in CA1 and the dentate gyrus and will apply
a closed-loop optogenetic stimulation protocol to control dentate parvalbumin-expressing interneuron firing.
This closed-loop optogenetic stimulation protocol is innovative and exciting, as it will alter the firing patterns of
specific inhibitory neurons in the dentate gyrus relative to various phases of the CA1 theta cycle, rather than
manipulate cell firing at the time of seizures themselves. These manipulations will be done in epileptic and
healthy animals so that we will not only determine the effects of precise interneuron firing in the pathological
hippocampus, but also in the healthy hippocampus. Together, these aims will use state-of-the-art recording
and manipulation techniques to gain new insights into the cause of cognitive deficits and seizures.

## Key facts

- **NIH application ID:** 10395865
- **Project number:** 3F32NS116416-02S1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Zoé Christenson Wick
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,195
- **Award type:** 3
- **Project period:** 2020-05-22 → 2023-11-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395865

## Citation

> US National Institutes of Health, RePORTER application 10395865, Closed-loop control of dentate inhibitory timing in healthy and epileptic mice (3F32NS116416-02S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10395865. Licensed CC0.

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