# The role of P2Y6 receptors in microglial calcium signaling:  Investigations in the awake animal during the basal state and epilepsy development

> **NIH NIH F32** · MAYO CLINIC ROCHESTER · 2021 · $33,919

## Abstract

Project Summary/Abstract
[This is the original document submitted in the F32 application. It is unchanged by this supplement.]
Microglia are the resident immune cells of the central nervous system (CNS). In the CNS, calcium signaling is
an essential secondary messenger system in astrocytes and neurons. However, in microglia, calcium signaling
is not completely understood. In this proposal, we investigate microglial calcium signaling in health and disease.
In our first aim, we explore whether microglial calcium signaling occurs in the awake mouse and whether that
signaling is neuronal activity dependent using in vivo two-photon microscopy. Activity-dependent calcium
signaling in microglia would suggest that this cell type could critically sense and respond to neuronal changes.
The ability to sense neuronal activity may be particularly important during epilepsy development. In our second
aim, we explore whether and how microglial calcium activity changes in a model of epilepsy development. In
aim 2, we use in vivo, longitudinal two-photon imaging to study changes in calcium signaling during
epileptogenesis. We hypothesize that the purinergic receptor, P2Y6, is essential for microglial calcium signaling
in both health and disease. Our training plan utilizes selective pharmacology and gene knockout strategies to
understand the mechanisms of microglial calcium signaling.
Our proposed research is an important first step in understanding a critical secondary messenger system and
its role in microglial-neuron interactions. Successful completion of these aims will advance our understanding
of the epileptogenic process (NINDS Benchmark II for Epilepsy Research). Research will be performed at the
Mayo Clinic, a renowned center for translational research and clinical care. Project mentors are experts in
microglial physiology/pathophysiology (Dr. Long-Jun Wu), and mechanisms of epileptogenesis (Dr. Greg
Worrell).

## Key facts

- **NIH application ID:** 10377815
- **Project number:** 3F32NS114040-02S1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Anthony David Umpierre
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,919
- **Award type:** 3
- **Project period:** 2019-09-17 → 2021-09-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377815

## Citation

> US National Institutes of Health, RePORTER application 10377815, The role of P2Y6 receptors in microglial calcium signaling:  Investigations in the awake animal during the basal state and epilepsy development (3F32NS114040-02S1). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10377815. Licensed CC0.

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