# Inhibitory Neural Circuits in Dentate Function

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $410,964

## Abstract

The dentate gyrus contributes to hippocampal memory encoding by transforming dense cortical patterns of
sensory and spatial information into sparse neural representations of specific contexts. Diverse local inhibitory
circuits are essential for this process, maintaining low levels of neural activity wherein only small fractions of
principal neurons are active at any given time. The dentate gyrus also continually generates new neurons
throughout life, providing a substrate for adult brain plasticity through experience-dependent construction of
new circuits. It is well established that GABA receptor-mediated mechanisms tightly regulate proliferation and
functional integration of adult-born neurons. Thus, GABAergic interneurons provide both inhibitory control of
mature dentate neurons and regulate the production of adult-born neurons. The goal of this project is to
determine how a highly abundant subtype of GABAergic interneuron contributes to both inhibitory and
neurogenic functions in the dentate gyrus. This family of interneurons called Ivy/Neurogliaform cells (INGs) has
been relatively neglected due to the inability to selectively target them using genetic approaches. We will
address this roadblock by validating new tools to identify and manipulate INGs, and compare their functions
with the highly-studied parvalbumin (PV)- expressing fast-spiking interneurons. These fast and slow-spiking
interneuron subtypes have highly divergent anatomical, intrinsic and synaptic properties, suggesting that they
play distinct roles in dentate inhibition and neurogenesis. Based on our preliminary data, we hypothesize that
slow-spiking INGs use GABAA and GABAB receptor activation to enforce sparse yet high-fidelity
spiking of mature GCs as well as regulate early stages of dentate neurogenesis. We will combine cellular
and circuit level analysis with optogenetic approaches to assess the role of slow spiking interneurons in both
inhibition and neurogenesis. After understanding the cellular properties of slow-spiking interneurons subtypes,
we will dissect their role in controlling GC inhibition and spike timing, comparing with results from fast-spiking
interneurons. We will use optogenetic silencing to determine the respective interneuron contributions to
dentate excitability with a focus on GABAB mediated-inhibition and interactions between slow and fast-spiking
subtypes. Finally, we will test the role of slow-spiking interneurons in stem cell proliferation, and the
contribution of GABAB receptor-mediating inhibition in differential excitability of young and mature GCs. The
results of these studies will provide fundamental insight into the function of slow-spiking interneurons in dentate
excitability and neurogenesis.

## Key facts

- **NIH application ID:** 10152690
- **Project number:** 5R01NS105438-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Linda Overstreet-Wadiche
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $410,964
- **Award type:** 5
- **Project period:** 2018-06-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152690

## Citation

> US National Institutes of Health, RePORTER application 10152690, Inhibitory Neural Circuits in Dentate Function (5R01NS105438-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10152690. Licensed CC0.

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