# The role of hippocampal neurogenesis in alcohol withdrawal seizure and cognition

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $494,202

## Abstract

Abstract
Alcohol withdrawal (AW) after chronic alcohol exposure produces a series of symptoms. Among
them, generalized tonic-clonic seizures and impairments in cognition and emotion are the most
severe and dangerous symptoms. Despite alcohol’s aversive effects, alcohol’s positive-
reinforcing effects of euphoria, anxiolysis, and reduction in pain and seizures dramatically
increase the vulnerability to relapse and alcohol abuse. The severity and susceptibility to relapse
and perpetuation of alcohol abuse underscore the urgent need to understand mechanisms
underlying alcohol dependence and withdrawal in order to develop new therapeutic strategies to
intervene and treat AW-associated syndromes. In this application, we will test the novel
hypothesis that structural and functional changes in hippocampal newborn dentate granule cells
(DGCs) underlie the development and maintenance of AW-associated physiological and
psychological dysfunctions. DGCs are continuously produced and integrate into hippocampal
neural circuits, and this process has been implicated in seizures, as well as cognitive and
emotional function. The central goal of this proposal is to use novel, genetic methods for mapping
and understanding hippocampal neural circuits that are responsible for maladaptation during
alcohol exposure and withdrawal. In Aim 1, we will determine whether AW alters synaptic,
neuronal, and functional connectivity of DGCs by using structural, electrophysiological, and rabies
virus-mediated mapping methods. In Aim 2, to test the essential role of newborn DGCs in AW-
induced seizure expression, we will use a DREADD (Designer Receptors Exclusively Activated
by Designer Drugs) method and produce models with gain-of-function and loss-of-function in
newborn DGCs. Using this method, we will assess whether specific activation and inhibition of
newborn DGCs will enhance and decrease AW seizures, respectively. In Aim 3, we will determine
whether altered activity of newborn DGCs is responsible for deficits in cognition and emotion
during abstinence. Our studies will unveil the essential function of hippocampal newborn DGCs
in AW syndromes at the level of neural circuits and provide a critical foundation for understanding
and treating AW-induced physiological and psychological dysfunctions.

## Key facts

- **NIH application ID:** 10817897
- **Project number:** 5R01AA027766-05
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Hoonkyo Suh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $494,202
- **Award type:** 5
- **Project period:** 2020-04-10 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817897

## Citation

> US National Institutes of Health, RePORTER application 10817897, The role of hippocampal neurogenesis in alcohol withdrawal seizure and cognition (5R01AA027766-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10817897. Licensed CC0.

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