# CMA: Network plasticity in acquired epileptogenesis

> **NIH VA I01** · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · 2021 · —

## Abstract

Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and a major source of disability in
the veteran population as it is frequently caused by war-time head injuries. More than 1/3 of TLE patients do not
respond to anticonvulsant medications and many are not candidates for epilepsy surgery. Therefore, new
treatments are needed to prevent the development of epilepsy after the initial insult. Yet, the mechanisms that
lead to the development of epilepsy during the period directly after status epilepticus (SE) are still poorly
understood. A deep and precise understanding of these mechanisms is critical for development of interventions
that can treat temporal epilepsy without the side-effects of medications and potential disability from large surgical
resections. To determine the network dynamic changes in specific cell types during the earliest period after SE,
we have developed a miniaturized microscope that is completely integrated with a high channel
extracellular electrophysiology recording device (E-Scope). We hypothesize that hypersynchronous firing
of parvalbumin positive (PV+) and progressive decreased engagement of somatostatin+ (SOM+) interneurons
emerge during the epileptogenic period after the insult. We also hypothesize that these pathological circuit
dynamics in both excitatory and inhibitory neurons will be readily observed during 200-400 Hz high frequency
oscillations (HFOs) have been shown to be a biomarker for hyper-excitable epileptic circuit. In Aim 1 we will
measure how PV+ and SOM+ neurons become activated during pathological fast ripples and physiological
sharp-wave ripples through the epileptogenic period. In Aim 2, we will measure the precision of spatial coding
by excitatory neurons and the reactivation of ensembles during physiological sharp-wave ripples and
pathological fast ripples through the epileptogenic period. This information will be critical for identifying the cell
specific targets for interventions to prevent epileptogenesis. Overall Strategy: The overall goal of our
collaborative merit proposal is to determine the key changes in hippocampal and neocortical circuitry that
promotes the development of epilepsy and cognitive dysfunction after the initial insult. Aims of Other Proposals:
1. Wasterlain will use immunocytochemical techniques, including EM immunocytochemistry, to quantify changes
in the GABA receptor expression at the synapse and in the peri-synaptic space. 2. Naylor will use in-vitro slice
patch clamp recordings, optogenetics, and computational modeling to understand how the functional connectivity
of different interneuron types changes during this key period. 3. Smirnakis will use a combination of
electrophysiological techniques and in-vivo mesoscopic two-photon calcium imaging to track the activity patterns
of neocortical neurons during this period, to understand how hippocampal-cortical communication changes and
drives the development of epilepsy. All studies are independent, ye...

## Key facts

- **NIH application ID:** 10013745
- **Project number:** 1I01BX005202-01
- **Recipient organization:** VA GREATER LOS ANGELES HEALTHCARE SYSTEM
- **Principal Investigator:** Peyman Golshani
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013745

## Citation

> US National Institutes of Health, RePORTER application 10013745, CMA: Network plasticity in acquired epileptogenesis (1I01BX005202-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10013745. Licensed CC0.

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