# The role of CA2 in epilepsy and social comorbidity

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $524,203

## Abstract

PROJECT ABSTRACT
A key challenge in temporal lobe epilepsy (TLE) is to determine the neural mechanisms contributing to
seizures because current drugs fail to treat all seizures and usually come with debilitating side effects.
Moreover, current drugs do not treat alterations in social behavior often manifest by individuals with epilepsy,
including increased social aggression. This project will challenge current dogma as to the pathophysiological
bases of how the hippocampus contributes to seizures in TLE, which has focused on three major regions of the
hippocampus: dentate gyrus, CA3 and CA1. Instead, we examine area CA2, a relatively small region of
hippocampus that has received little attention but is known to survive relatively intact in TLE patients and
rodent models, and may serve as a seizure focus or facilitate seizure propagation. Experimental tools
developed in the laboratories of the two Principal Investigators now enable the direct investigation of the
importance of CA2 in mouse TLE models by employing a mouse line that expresses Cre recombinase
relatively selectively in CA2 principal neurons. Cre-dependent viral vectors will be used to express genetically
encoded tools in CA2 principal neurons to examine both alterations in CA2 circuitry in TLE and the effects of
CA2 acute or chronic silencing on seizures. Thus, we will determine whether CA2 controls the pharmacological
induction of acute seizures in the healthy brain and/or chronic seizures in the epileptic brain. We will also
determine the importance of CA2 in reported deficits in social cognition and social aggression in mouse models
of acquired TLE, as we find that CA2 is required for social recognition memory and is implicated in social
aggression. As the social hormone arginine vasopressin promotes social memory and social aggression by
enhancing CA2 input and output, and has been shown to regulate seizures in animals, we will examine the role
of CA2 regulation by this hormone on social behavioral alterations in epileptic mice. By evaluating the role of
CA2 in epilepsy, this project offers the promise of providing both basic mechanistic insight into seizures and
social behavioral comorbidity, and may validate novel drug targets highly enriched in CA2 neurons.

## Key facts

- **NIH application ID:** 9928131
- **Project number:** 5R01NS106983-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** STEVEN A SIEGELBAUM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $524,203
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928131

## Citation

> US National Institutes of Health, RePORTER application 9928131, The role of CA2 in epilepsy and social comorbidity (5R01NS106983-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9928131. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*