# Regulation of Adult Hippocampal Neural Stem Cells by Glutamate Transport

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2021 · $420,021

## Abstract

A unique neurogenic niche in the adult hippocampus hosts neural-lineage stem cells (NSCs) that generate new
neurons in a wide range of adult mammals. This process of adult neurogenesis is essential for optimal
hippocampal cognitive-emotional function and suggests an avenue for regenerating tissue in the adult brain.
However, adult neurogenesis is sensitive to local niche signals, and depending on local signaling, it can fluctuate
dramatically in quantity and net contribution to hippocampal function. Better understanding of the key regulatory
components of stem cell-niche interactions is critically needed to advance efforts to support hippocampal function
and repair. A major niche signal known to modulate adult neurogenesis in both healthy and diseased or injured
states is the neurotransmitter glutamate. Excess glutamate stimulation is common in injuries and illnesses that
differentially impact the hippocampus, including trauma, stroke, seizure, and neurodegeneration. Our objective
in this application is to examine the mechanisms by which the excitatory neurotransmitter glutamate stimulates
adult neurogenesis. Previous work on glutamatergic regulation of adult neurogenesis focuses on the role of
glutamate receptor stimulation. Our preliminary data, in contrast, suggest an unexpected role for glutamate
transporters from the excitatory amino acid transporter (EAAT) family in glutamate-induced stimulation of NSC
proliferation. NSCs are widely known to express large quantities of EAATs yet their functional role has received
little attention. The proposed experiments will investigate the central hypothesis that glutamate transport through
EAAT1 promotes NSC activation and subsequent neurogenesis via cell depolarization. In Aim 1, we will use
novel in vivo knockdown models to test the working hypothesis that NSC EAAT1 facilitates NSC proliferation
and thereby stimulates adult neurogenesis. In Aim 2, we will use chemogenetic manipulation of NSC membrane
potential and electrophysiology to test the working hypothesis that depolarization via EAAT1 drives NSC
activation. These results of the proposed studies are expected to have a positive impact because they will
introduce a novel molecular mechanism by which a major niche signal—glutamate—contributes to neurogenesis
in the adult brain. The expected findings will have relevance both to fundamental understanding of hippocampal
homeostasis and to design of therapeutic approaches that seek to capitalize on NSCs to support tissue repair.

## Key facts

- **NIH application ID:** 10286497
- **Project number:** 1R21NS123797-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Elizabeth Diana Kirby
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $420,021
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10286497

## Citation

> US National Institutes of Health, RePORTER application 10286497, Regulation of Adult Hippocampal Neural Stem Cells by Glutamate Transport (1R21NS123797-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10286497. Licensed CC0.

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