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Updated: Jun 20, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Morphotype-specific calcium signaling in human microglia
Sofia Nevelchuk1, Bianca Brawek1, Niklas Schwarz2
1Department of Neurophysiology, Institute of Physiology, Eberhard Karls University of Tübingen, Keplerstr. 15, 72074, Tübingen, Germany.
Background:
Key functions of Ca2+ signaling in rodent microglia include monitoring the brain state as well as the surrounding neuronal activity and sensing the danger or damage in their vicinity. Microglial Ca2+ dyshomeostasis is a disease hallmark in many mouse models of neurological disorders but the Ca2+ signal properties of human microglia remain unknown.
Methods:
We developed a novel genetically-encoded ratiometric Ca2+ indicator, targeting microglial cells in the freshly resected human tissue, organotypically cultured tissue slices and analyzed in situ ongoing Ca2+ signaling of decades-old microglia dwelling in their native microenvironment.
Results:
The data revealed marked compartmentalization of Ca2+ signals, with signal properties differing across the compartments and resident morphotypes. The basal Ca2+ levels were low in ramified and high in ameboid microglia. The fraction of cells with ongoing Ca2+ signaling, the fraction and the amplitude of process Ca2+ signals and the duration of somatic Ca2+ signals decreased when moving from ramified via hypertrophic to ameboid microglia. In contrast, the size of active compartments, the fraction and amplitude of somatic Ca2+ signals and the duration of process Ca2+ signals increased along this pathway.
Insights
Human microglia exhibit compartmentalized calcium (Ca2+) signals, with distinct properties varying by cell shape and location. This reveals crucial differences from rodent models, impacting brain health research.
Area of Science:
- Neuroscience
- Cell Biology
- Neuroimmunology
Background:
- Microglia, the brain's immune cells, use calcium (Ca2+) signaling to monitor neural activity and detect damage.
- Ca2+ dyshomeostasis is implicated in neurological disorders in mice, but human microglial Ca2+ signaling remains uncharacterized.
Purpose of the Study:
- To investigate the in situ Ca2+ signaling properties of human microglia within their native microenvironment.
- To characterize the differences in Ca2+ signal compartmentalization and properties across human microglial morphotypes.
Main Methods:
- Development of a novel genetically-encoded ratiometric Ca2+ indicator for human microglia.
- Analysis of Ca2+ signaling in freshly resected human brain tissue and organotypic slice cultures.
- In situ monitoring of Ca2+ signaling in aged human microglia.
Main Results:
- Human microglial Ca2+ signals are compartmentalized, with distinct properties in different cellular compartments and morphotypes.
- Basal Ca2+ levels are lower in ramified microglia and higher in ameboid microglia.
- Signal dynamics (fraction of active cells, signal amplitude/duration) vary significantly across microglial morphotypes (ramified, hypertrophic, ameboid).
Conclusions:
- Human microglia display unique, compartmentalized Ca2+ signaling patterns not previously observed.
- Differences in Ca2+ signaling across morphotypes suggest functional specialization within the human microglia population.
- These findings provide a foundation for understanding human microglial roles in health and disease.
