# Behavioral state-dependent microglia Ca2+ dynamics

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2024 · $193,750

## Abstract

We propose to investigate a novel form of microglia Ca2+ signal that we have discovered in awake behaving
mice. It is the first microglia Ca2+ signal identified so far that represents a direct response to active, vigilant
behavior and neuronal activity within short latency (<10 seconds). Due to the complexity of experimental
procedures and the paucity of available data very little is known about microglia Ca2+ dynamics in awake
behaving mice. This is in striking contrast to the expected importance of Ca2+ signaling for microglia function.
From work on cultured microglia it is known that basic cellular processes such as cytoskeletal rearrangements,
which are a prerequisite for cell motility and phagocytosis, as well as most mechanisms underlying the secretion
of signaling molecules such as cytokines depend on intracellular fluctuations of Ca2+. Microglia express
numerous membrane proteins to potentially translate extracellular signals into intracellular Ca2+ elevations.
Among these are purinergic receptors, immune system-related receptors as well as ion channels. Specifically,
microglia express L-type Ca2+ channels (LTCCs). LTCCs have attracted special attention because antagonists
of this class of ion channels, traditionally applied to control blood pressure, have demonstrated therapeutic
potential for limiting neuroinflammation and cognitive impairments accompanying neurodegenerative diseases.
The contribution of microglia LTCCs to this therapeutic potential is not yet well established and it is not clear
when these ion channels become normally activated. For this proposal we will employ two-photon microscopy
on transgenic mice with microglia-specific expression of the genetically-encoded Ca2+ indicator GCaMP6f. The
mice will be head-fixed on a motorized linear treadmill for precise control over speed and duration of enforced
locomotion events in addition to the monitoring of voluntary locomotion events. Locomotion represents a reliable
means to induce moderate arousal, a behavioral state of heightened vigilance. To avoid a bias by the
experimental conditions the studies will include imaging of microglia through chronic cranial windows several
weeks following surgery as well as acute surgery experiments for topical pharmacology. Our preliminary
pharmacological experiments suggest that locomotion-induced microglia Ca2+ elevations depend on LTCCs. In
Aim 1 we will conduct a systematic characterization of the newly discovered locomotion-induced microglia Ca2+
elevations. We will investigate the kinetic constraints of the responses and test whether V1 microglia Ca2+
responses are affected by visual stimulation. In Aim 2 we will combine microglia-selective gene deletion and
pharmacological experiments to determine which LTCC subtype predominantly contributes to the responses.
Upon successful completion of the proposed experiments we will have established a rigorous foundation for
rational design of future studies aimed at unraveling the consequences ...

## Key facts

- **NIH application ID:** 10757921
- **Project number:** 5R21MH129960-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Martin Paukert
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $193,750
- **Award type:** 5
- **Project period:** 2023-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757921

## Citation

> US National Institutes of Health, RePORTER application 10757921, Behavioral state-dependent microglia Ca2+ dynamics (5R21MH129960-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10757921. Licensed CC0.

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