# Circadian changes in network excitability and Alzheimer disease pathogenesis

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $50,686

## Abstract

Project Summary
In AD, network hyperexcitability in the form of epileptic activity has a clear diurnal pattern and is more common
at night and during sleep. Our work focuses on the molecular circadian clock as a source of AD-related
hyperexcitability, as it is the mechanism responsible for regulating neurophysiology and excitability in a cell
type-specific manner. The molecular clock regulates excitability through oscillating expression of clock genes
and clock-controlled genes in the neocortex and hippocampus. Inhibitory interneurons, such as parvalbumin
(PV+) interneurons in the hippocampus and cortex, play a critical role in AD-related hyperexcitability, with PV+
cells being the most abundant in the hippocampus and cortex.
Our working model posits that circadian dysfunction in PV+ interneurons contributes to the diurnal prominence
of AD-related hyperexcitability in the inactive/rest phase. The experiments outlined here will test the hypothesis
that AD-related disruption of the cell-autonomous molecular clock in PV+ interneurons disrupt daily changes in
clock-controlled gene expression in a mouse model of AD. In Aim 1 we will measure changes in clock gene
and clock-controlled gene expression in PV+ hippocampal and cortical interneurons. In Aim 2 we will measure
naturalistic behaviors in mouse models of Alzheimer’s using machine learning.

## Key facts

- **NIH application ID:** 10835173
- **Project number:** 3R01AG061785-03S1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Karen L Gamble
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $50,686
- **Award type:** 3
- **Project period:** 2021-09-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835173

## Citation

> US National Institutes of Health, RePORTER application 10835173, Circadian changes in network excitability and Alzheimer disease pathogenesis (3R01AG061785-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10835173. Licensed CC0.

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