# Determining the shared neuronal network mechanisms of focal epileptic discharges and impaired memory processing in temporal lobe epilepsy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $380,725

## Abstract

ABSTRACT
Memory impairment is a common and devastating comorbidity of temporal lobe epilepsy. The network
mechanisms underlying memory impairments are poorly understood. Micro-electrode recordings from temporal
lobe epilepsy patients reveal frequent focal epileptic discharges (FEDs) that are only detectable with invasive
recordings. Preliminary studies performed in our laboratory in a chronic epileptic mouse model revealed that
mice experience frequent FEDs while they performed a spatial working memory task. Intriguingly, FEDs
occurred robustly at specific locations on the maze, where healthy hippocampus normally generates population
activity (sharp wave ripples, SWR) necessary for working memory. These data support the overall hypothesis
that the cellular networks that normally partake in memory processes are hi-jacked by FEDs. We will test this
hypothesis with three aims. For Aim 1 we will perform large scale tetrode recordings from freely moving mice to
test the hypothesis that neurons active during FEDs overlap with neurons active during working memory SWR
(wm-SWRs). For Aim 2 we will combine high-density linear probe recordings and chemogenetic inhibition to
test the hypothesis that FEDs are generated in the CA3 region of the hippocampus. Finally, in the same
animals as used in Aims 1 and 2, we will perform multi-day 24-hour recordings to test the hypothesis that
FEDS occurring during working memory share cellular and network mechanisms with the early phase of
behavioral seizures. The proposed research could help fill vital gaps in our knowledge about focal epileptic
discharges – both in terms of their mechanisms and how they impact memory processing. We hope to
elucidate which neurons participate in them, develop selective interventions to inhibit them, and determine how
they impact behavioral seizures.

## Key facts

- **NIH application ID:** 10850687
- **Project number:** 5R01NS128222-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Laura Ewell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $380,725
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850687

## Citation

> US National Institutes of Health, RePORTER application 10850687, Determining the shared neuronal network mechanisms of focal epileptic discharges and impaired memory processing in temporal lobe epilepsy (5R01NS128222-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10850687. Licensed CC0.

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