# Molecular and Cellular Basis of Spiking and Seizures in Neocortical Epilepsy

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $457,496

## Abstract

Summary:
 Epilepsy is a disease of recurrent seizures that affects up to 1% of the world's population. At present
time, we understand very little about how regions of the human brain become epileptic and produce seizures.
We also have no medications that cure or prevent epilepsy from forming, a process known as epileptogenesis.
Current medications can suppress seizures, but have not been shown to prevent or cure the disease, so that
epileptic patients who stop taking their medications continue to have seizures. One approach that can lead to
a permanent reduction in seizures is epilepsy surgery to remove focal regions of the brain where seizures start.
Long term intracranial recordings that are often performed as part of these surgeries reveal extremely frequent
epileptic discharges or 'spikes' often at or near regions of the brain where seizures start, suggesting that these
'interictal' (between seizures) spikes are highly associated with epileptic brain regions. In fact interictal spikes
appear before seizures in some animal models of epileptogenesis. However, the exact relationship between
interictal spiking and seizures is not known nor is it clear whether treatments that block seizures block spiking or
vice versa.
 Here, we plan to extend our work that has taken an unbiased approach to identify new therapeutic targets
for epilepsy based on high throughput genomic studies from precisely localized human neocortical regions from
patients who have undergone epilepsy surgery. We will use data acquired from gene expression studies in
human epileptic brain to identify genes and molecular pathways associated with interictal spiking and compare
these to brain regions that produce seizures. We have also developed a novel computational approach to
differentiate tissue regions where interictal spiking is generated versus where it spreads. The spatial
organization of specific cell types, genes, and signaling intermediates will be mapped to specific laminar regions
as well as to recently discovered >microlesions= in deeper cortical layers that are present only in high spiking
regions. Finally, an in vivo animal model that separates interictal spiking from seizures will be used to test the
specific functions of MAP Kinase signaling on interictal spiking and seizures as potential therapeutics for both
epileptogenesis and established epilepsy.

## Key facts

- **NIH application ID:** 10142548
- **Project number:** 5R01NS109515-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** JEFFREY A LOEB
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $457,496
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142548

## Citation

> US National Institutes of Health, RePORTER application 10142548, Molecular and Cellular Basis of Spiking and Seizures in Neocortical Epilepsy (5R01NS109515-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10142548. Licensed CC0.

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