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Updated: Jun 6, 2026
Simultaneous Imaging of Microglial Dynamics and Neuronal Activity in Awake Mice
Published on: August 23, 2022
Microglial calcium signal acts as a rapid sensor of single neuron damage in vivo
Gerhard Eichhoff1, Bianca Brawek, Olga Garaschuk
1Institute of Physiology II, University of Tübingen, Keplerstr. 15, 72074 Tübingen, Germany.
Abstract:
In the healthy adult brain microglia, the main immune-competent cells of the CNS, have a distinct (so-called resting or surveying) phenotype. Resting microglia can only be studied in vivo since any isolation of brain tissue inevitably triggers microglial activation. Here we used in vivo two-photon imaging to obtain a first insight into Ca(2+) signaling in resting cortical microglia. The majority (80%) of microglial cells showed no spontaneous Ca(2+) transients at rest and in conditions of strong neuronal activity. However, they reliably responded with large, generalized Ca(2+) transients to damage of an individual neuron. These damage-induced responses had a short latency (0.4-4s) and were localized to the immediate vicinity of the damaged neuron (< 50 μm cell body-to-cell body distance). They were occluded by the application of ATPγS as well as UDP and 2-MeSADP, the agonists of metabotropic P2Y receptors, and they required Ca(2+) release from the intracellular Ca(2+) stores. Thus, our in vivo data suggest that microglial Ca(2+) signals occur mostly under pathological conditions and identify a Ca(2+) store-operated signal, which represents a very sensitive, rapid, and highly localized response of microglial cells to brain damage. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
Insights
Resting microglia, the brain's immune cells, rarely show calcium signals. However, they rapidly and locally respond to neuronal damage via a store-operated calcium signal, indicating a sensitive pathway for detecting brain injury.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells in the central nervous system (CNS), exhibiting a resting phenotype in healthy adult brains.
- Studying resting microglia in vivo is crucial as tissue isolation triggers their activation.
- Calcium (Ca2+) signaling is fundamental to cellular function, but its role in resting microglia remains largely unexplored.
Purpose of the Study:
- To investigate Ca2+ signaling dynamics in resting cortical microglia in vivo.
- To characterize the microglial response to neuronal damage under physiological conditions.
- To identify the mechanisms underlying microglial Ca2+ signaling during brain injury.
Main Methods:
- Utilized in vivo two-photon imaging to observe Ca2+ transients in resting microglia.
- Assessed microglial responses under basal conditions, during strong neuronal activity, and following targeted neuronal damage.
- Employed pharmacological agents (ATPγS, UDP, 2-MeSADP) and manipulated intracellular Ca2+ stores to probe signaling pathways.
Main Results:
- The majority of resting microglia (80%) exhibited no spontaneous Ca2+ transients.
- Microglia responded robustly to individual neuronal damage with rapid, localized Ca2+ transients (0.4-4s latency, <50 μm).
- These responses were mediated by P2Y receptors and required Ca2+ release from intracellular stores, indicating a store-operated Ca2+ signal.
Conclusions:
- Microglial Ca2+ signaling is predominantly observed under pathological conditions rather than during normal brain function.
- A novel store-operated Ca2+ signal in microglia acts as a highly sensitive and rapid detector of localized brain damage.
- This finding elucidates a critical mechanism for microglial surveillance and response to injury in the CNS.
