# Circuits driving spatial coding deficits in epilepsy

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $510,618

## Abstract

Project Summary/Abstract
Temporal lobe epilepsy (TLE) is a debilitating disorder that includes pervasive memory impairments that
significantly impact quality of life. In rodent models of TLE, my lab and others have found major deficits in
learning and memory as well as in the precision and stability of CA1 place cells. However, it remains unclear
whether impaired spatial coding in CA1 is primarily due to local processing deficits in hippocampus or rather is
influenced by impaired spatial coding and synchronization from upstream inputs. In fact, there is significant
evidence that upstream inputs into the hippocampus from the medial entorhinal cortex (MEC) may be altered in
epilepsy. This proposal will test the hypothesis that both MEC inputs into the hippocampus have altered spatial
coding and synchronization. To test this hypothesis, we will first use calcium imaging with miniature
microscopes to characterize how chronic epilepsy alters spatial coding in MECII stellate cells and MECIII
neurons, which directly input into hippocampus. Next, we will use silicon probes to record single unit firing and
LFPs simultaneously in MECII, MECIII, DG, and CA1 and determine how synchronization throughout the
entorhinal-hippocampal circuit is altered in epileptic mice. Finally, we will use excitatory and inhibitory
DREADDs to modulate MEC neurons in control and epileptic mice and determine how each input into
hippocampus alters synchronization of hippocampal circuits and spatial memory. Together, these aims will use
state-of-the-art recording and manipulation techniques to determine precisely where and how spatial coding
and synchronization breaks down in epileptic mice and gain new insights into the cause of cognitive deficits.

## Key facts

- **NIH application ID:** 10335883
- **Project number:** 5R01NS116357-02
- **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:** 2022
- **Award amount:** $510,618
- **Award type:** 5
- **Project period:** 2021-02-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335883

## Citation

> US National Institutes of Health, RePORTER application 10335883, Circuits driving spatial coding deficits in epilepsy (5R01NS116357-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10335883. Licensed CC0.

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