# Dynamics of Hippocampal Inputs in Alzheimer's Disease

> **NIH NS R00** · UNIVERSITY OF MARYLAND BALTIMORE · 2026 · $248,936

## Abstract

Project Summary
In the US, Alzheimer’s disease (AD) is the sixth leading cause of death, affects 11% of the population over age
65, and costs $355 billion each year. One of the first impairments in AD is spatial memory, which involves the
hippocampal area CA1. CA1 encodes new information, driven by inputs from medial entorhinal cortex (MEC),
and retrieves and consolidates old information, driven by inputs from hippocampal area CA3. Hippocampal
inhibitory neurons, which are lost early in AD, can reduce the influence of, or gate, these inputs. However, we
do not understand how loss or dysfunction of inhibitory neurons in AD affects inputs to CA1 and how this
subsequently disrupts spatial representations and thus memory. This proposal will explore the dynamics of inputs
to CA1, as gated by inhibitory neurons, and its effects on spatial memory, as an avenue for AD treatment. My
central hypothesis is that loss of CA1 somatostatin-expressing inhibitory neurons ungates MEC inputs to CA1
during retrieval and consolidation, destabilizing spatial maps and impairing memory in AD. I will examine this
hypothesis using a chronic recoverable implant design I have developed which enables simultaneous recording
from dozens of neurons in CA1, CA3, and MEC. I will record neural activity while wild type and AD model mice
encode, consolidate, and retrieve memories in a spatial alternation task and spatial contexts. During these three
memory phases, I will measure: CA3 and MEC input drive to CA1 and its dynamics over learning (Aim 1), the
relationship between CA1, CA3, and MEC spatial maps (Aim 2), and the firing patterns of CA1 somatostatin-
expressing and parvalbumin-expressing inhibitory neurons (Aim 3.1). I will then stimulate each inhibitory neuron
type in aged AD model mice during each of the three memory phases to rescue the deficits identified in Aims 1,
2, and 3.1 (Aim 3.2). This research will advance our understanding of how the hippocampus dynamically
encodes, retrieves, and c

## Key facts

- **NIH application ID:** 11190510
- **Project number:** 4R00NS134734-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Emily Aster Aery Jones
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NS
- **Fiscal year:** 2026
- **Award amount:** $248,936
- **Award type:** 4N
- **Project period:** 2023-09-18T00:00:00 → 2028-08-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11190510

## Citation

> US National Institutes of Health, RePORTER application 11190510, Dynamics of Hippocampal Inputs in Alzheimer's Disease (4R00NS134734-03). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/11190510. Licensed CC0.

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