# The role of the septo-hippocampal cholinergic circuit in regulating hippocampal function

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $34,376

## Abstract

Project Summary
As our population ages, the number of people inflicted with Alzheimer’s disease (AD) will continue to grow.
One of the major problems associated with AD, a neurodegenerative disorder, is progressive memory decline
that arises as a result of defective hippocampal functions including hippocampal neurogenesis and
hippocampal network activity. A major regulatory circuit of broad hippocampal function is known as the Septo-
Hippocampal Circuit (SHC), which is susceptible to degeneration in AD. Ample evidence has shown
degeneration of the cholinergic component of the SHC correlates positively with the severity of dementia and
memory dysfunction. Hippocampal neurogenesis and hippocampal network dynamics play a crucial role in
regulating proper memory function. Our findings suggest that modulating the SHC can increase hippocampal
neurogenesis and that DG network dynamics are impaired at the 3 month stage in AD mice, highlighting the
importance of this critical time period. I will test the hypothesis that SHC cholinergic regulation of adult
neurogenesis and DG dynamics is impaired in AD and that stimulation of the cholinergic circuit can restore
neurogenesis levels and DG dynamics. I will use a mouse model that harbors 5 AD related transgenes
(5xFAD) and test the early stage of the disease (3 months) for 1) SHC cholinergic control of adult
neurogenesis in AD mice and 2) SHC cholinergic control of dentate gyrus dynamics in AD mice. Completion of
proposed work will establish a circuit specific mechanism that regulates hippocampal neurogenesis and
hippocampal network dynamics in AD. Ultimately, mimicking basic features of identified circuitry mechanisms
may constitute a novel strategy to repair the degenerated brain.

## Key facts

- **NIH application ID:** 10290303
- **Project number:** 5F31AG067718-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Luis Quintanilla
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $34,376
- **Award type:** 5
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10290303

## Citation

> US National Institutes of Health, RePORTER application 10290303, The role of the septo-hippocampal cholinergic circuit in regulating hippocampal function (5F31AG067718-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10290303. Licensed CC0.

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