# Epilepsy related cell loss and cognitive dysfunction

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $412,129

## Abstract

Project Summary
Temporal lobe epilepsy is often associated with significant cognitive dysfunction, but the mechanisms
underlying such dysfunction are not understood. In both human temporal lobe epilepsy and related models,
neuronal loss occurs in selected populations of hippocampal neurons, and this cell loss could be associated
with the learning and memory deficits. The effects of loss of each of the most vulnerable groups of neurons
are of particular interest, and these neurons include mossy cells in the hilus of the dentate gyrus, hilar
somatostatin (SOM) neurons, and SOM neurons in stratum oriens of CA1, the majority of which are oriens
lacunosum-moleculare (OLM) neurons. It remains unclear how the loss of each cell type contributes to the
reorganization of synaptic connections and alters the in vivo function of hippocampal circuits. The broad goal
of this proposal is to determine the effects of selective ablation of each of these three groups of
hippocampal neurons and associated axonal reorganization on electrophysiological and behavioral
measures of cognitive function. To determine the effects of loss of each cell population, the neurons will be
ablated separately through adeno-associated virus (AAV) expression of Cre-dependent diphtheria toxin A in
mice with cell-type specific expression of Cre. Specific Aim 1 will test the hypothesis that selective ablation of
each of the vulnerable groups of neurons will lead to unique patterns of reorganization of remaining
populations of neurons. Cre-dependent transfection of eYFP in Cre-expressing mice will be used to identify
changes in the axonal arborizations of remaining neurons and determine if aberrant synaptic circuits are
created. Specific Aim 2 will test the hypothesis that mossy cell or hilar SOM neuron deletion, but not OLM
neuron deletion, will induce desynchronization of dentate hilar neuron firing during locomotion. Silicon probe
recordings of theta oscillations and multiple single-unit recordings of dentate hilar neurons will be used to
determine whether mossy cell, hilar SOM interneuron, or SOM OLM deletion induces this desynchronization of
dentate hilar neurons. Specific Aim 3 will test the hypothesis that OLM deletion, but not mossy cell or hilar
SOM neuron deletion, will cause less precise (broadened) place related firing of CA1 pyramidal neurons.
These studies will use calcium imaging of large populations of CA1 neurons in freely moving animals with
custom-made miniaturized microscopes to determine which cell type is sufficient for degrading the precision of
place field firing. This proposal combines the mutually complementary expertise of two laboratories to
determine if loss of specific groups of neurons and related reorganization of hippocampal circuits can lead to
changes in how large groups of neurons become synchronized and encode information, and thus contribute to
cognitive dysfunction in epilepsy and related disorders.

## Key facts

- **NIH application ID:** 9844083
- **Project number:** 5R01NS099137-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Peyman Golshani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,129
- **Award type:** 5
- **Project period:** 2017-06-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844083

## Citation

> US National Institutes of Health, RePORTER application 9844083, Epilepsy related cell loss and cognitive dysfunction (5R01NS099137-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9844083. Licensed CC0.

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