# Main Research Component 2: Binge-type alcohol exposure during adolescence alters the septohippocampal circuit during advanced aging

> **NIH NIH P50** · STATE UNIVERSITY OF NY,BINGHAMTON · 2020 · $296,962

## Abstract

PROJECT SUMMARY/ABSTRACT
MAIN RESEARCH COMPONENT 2
Converging data from human studies and preclinical animal models have revealed that alcohol binge
drinking/exposure during early adolescence is associated with changes in brain structure and connectivity.
Persistent brain damage after adolescent intermittent ethanol exposure (AIE) in rodents, a model of binge
drinking, entails reduced hippocampal neurogenesis and a loss of cholinergic neurons in the medial septum
and diagonal band of Broca (MS/DB). The circuit formed between those regions, the septohippocampal
pathway, is critical for learning and memory. The cholinergic projections from the MS/DB to the hippocampus
are arranged in a highly topographical pattern, but pilot data suggest a loss of neurogenesis in the
hippocampus disrupts the unique somatotopic organization during the aging process. Furthermore, we
observed that as rats aged following AIE, a spatial memory impairment emerged, which was paralleled by a
reduction in activity-related acetylcholine release within the hippocampus. The goal of this proposal is to reveal
how heavy intermittent alcohol exposure during adolescence alters brain connectivity, neural plasticity and
behavioral function across the lifespan. Specifically, we will determine how aging following AIE (a) alters the
topographical organization of the cholinergic septohippocampal pathway and impedes the expression of
cholinergic neural phenotypes within the MS/DB, which modulate activity-dependent hippocampal
acetylcholine release (Aim 1); (b) disrupts the neurophysiological profile of cholinergic septohippocampal
pathway and leads to behavioral and acetylcholine dysfunction across septotemporal axis of the hippocampus
(Aim 2). Finally, given that the septohippocampal circuit is extremely pliable to environmental conditions, we
will use exercise as a tool to restore hippocampal neurogenesis, prevent MS/DB cholinergic atrophy/cell loss,
and halt dysfunctional remapping to the hippocampus, caused by aging with AIE, which we hypothesized leads
to impaired spatial behavior and blunted activity-dependent acetylcholine release (Aim 3). Our preliminary data
revealed a profile of septohippocampal dysfunction that resembled alcohol-related dementia as rats exposed to
AIE begin to age, and the goal of this proposal is to understand this complex process so it can be corrected to
reduce the risk of cognitive dysfunction and unsuccessful aging.

## Key facts

- **NIH application ID:** 10006504
- **Project number:** 5P50AA017823-12
- **Recipient organization:** STATE UNIVERSITY OF NY,BINGHAMTON
- **Principal Investigator:** Lisa M Savage
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $296,962
- **Award type:** 5
- **Project period:** 2009-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006504

## Citation

> US National Institutes of Health, RePORTER application 10006504, Main Research Component 2: Binge-type alcohol exposure during adolescence alters the septohippocampal circuit during advanced aging (5P50AA017823-12). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10006504. Licensed CC0.

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