# Hippocampal interneurons in novel memory formation in health and Alzheimer's disease

> **NIH NIH RF1** · GEORGIA INSTITUTE OF TECHNOLOGY · 2022 · $1,513,656

## Abstract

Remembering precise locations of importance is a key component of spatial memory. Over the
past few decades, extensive prior work has shown that excitatory pyramidal cells in hippocampus
code for various spatially relevant cues. Hippocampal inhibitory interneurons have been ascribed
important roles in generating oscillations and maintaining optimal levels of excitatory activity, but
their role in spatial memory formation is unclear. Understanding the role of interneurons in
memory formation processes is crucial because several studies have revealed deficits in inhibition
due to Alzheimer’s disease (AD) pathology such as elevated amyloid beta. Among other types of
inhibitory interneurons, parvalbumin-positive (PV) interneurons are especially susceptible to AD
pathology and directly inhibit excitatory cells. Spatial navigation deficits and hippocampal
dysfunction occur early in AD but exactly how hippocampal PV inhibitory deficits contribute to
impaired memory remains uncertain. Thus, there is an urgent unmet need to understand the role
of hippocampal inhibitory interneurons in forming representations of new experiences and to
determine how this process fails due to AD pathology. Elucidating the role of PV inhibition in
memory formation requires causal manipulations to record and stimulate PV activity in a cell-type
specific and temporally precise manner. Accordingly, these studies will record the electrical
activity of many inhibitory and excitatory neurons simultaneously and selectively stimulate PV
interneurons in mice acquiring novel spatial memory. The proposed research will use closed-loop
optogenetic stimulation to specifically abolish or generate particular patterns of PV activity in
healthy mice and in mouse models of Aβ pathology. With these approaches, the planned studies
will test the hypothesis that intact inhibitory activity is necessary for normal memory formation and
altered inhibitory activity disrupts memory formation in mouse models of Aβ pathology. This
research will show how vulnerability of PV interneurons to AD pathology leads to impaired spatial
learning and memory formation. These findings will lead to new stimulation and pharmacological
treatments for AD based on restoring PV function.

## Key facts

- **NIH application ID:** 10512199
- **Project number:** 1RF1AG078736-01
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Annabelle Catherine Singer
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,513,656
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10512199

## Citation

> US National Institutes of Health, RePORTER application 10512199, Hippocampal interneurons in novel memory formation in health and Alzheimer's disease (1RF1AG078736-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10512199. Licensed CC0.

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