# Dissecting microcircuit alterations in the epileptic dentate gyrus with functional imaging

> **NIH NIH F31** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $46,036

## Abstract

Temporal lobe epilepsy (TLE) is a common neurological disorder affecting up to 1 in 100 people and
characterized by recurrent focal seizures. These seizures are driven by synchronous neuronal activity originating
in the mesial temporal lobe, most commonly the hippocampal formation. The dentate gyrus region of the
hippocampal formation is highly reorganized in chronic TLE; disease-associated remodeling of the “dentate gate”
is thought to open up pathological conduction pathways for synchronous discharges and seizures to propagate
through the mesial temporal lobe. However, this pathophysiological understanding lacks a mechanistic
explanation of how macroscale synchronous dynamics emerge from alterations of the dentate gyrus at the
microcircuit level. In particular, how the collective activity of the four principal populations of the dentate gyrus,
i.e., adult-born and mature granule cells, mossy cells, and interneurons, gives rise to epileptiform network-level
events remains unknown. This proposal aims to characterize the activity of these populations during interictal
events and seizures, and test a theoretical model of the emergence of macrolevel network events from the
activity of microlevel ensembles.
 To address this question, I will use simultaneous in vivo two-photon calcium imaging and local field
potential recordings in behaving mice in the intrahippocampal kainic acid model of epilepsy to optically record
activity dynamics of genetically identified populations in the dentate gyrus in mice with chronic TLE, and correlate
them with macrolevel features of the local field potential. In Aim 1, I will characterize these four populations in
the interictal period, during pathological interictal events, and during seizures. Recent work in vitro work has
shown that distinct ensembles of dentate gyrus neurons fire during interictal events. In Aim 2, I propose a
mechanistic generative model for the recruitment of microcircuits by macroscale epileptiform events. This model
predicts that network activity during interictal events provides a series of snapshots of the pathological structure
that allows the chronically epileptic network to support seizures. The experiments and modeling described here
will provide the first in vivo characterization of activity dynamics of the principal neuronal populations of the
epileptic dentate gyrus, and have the potential to unify microscopic and macroscopic narratives of the disease.

## Key facts

- **NIH application ID:** 10316991
- **Project number:** 5F31NS120783-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Zhenrui Liao
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2020-09-30 → 2023-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316991

## Citation

> US National Institutes of Health, RePORTER application 10316991, Dissecting microcircuit alterations in the epileptic dentate gyrus with functional imaging (5F31NS120783-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10316991. Licensed CC0.

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