Morphotype-specific calcium signaling in human microglia

Key functions of Ca 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 Ca dyshomeostasis is a disease hallmark in many mouse models of neurological disorders but the Ca signal properties of human microglia remain unknown. We developed a novel genetically-encoded ratiometric Ca indicator, targeting microglial cells in the freshly resected human tissue, organotypically cultured tissue slices and analyzed in situ ongoing Ca signaling of decades-old microglia dwelling in their native microenvironment. The data revealed marked compartmentalization of Ca signals, with signal properties differing across the compartments and resident morphotypes. The basal Ca levels were low in ramified and high in ameboid microglia. The fraction of cells with ongoing Ca signaling, the fraction and the amplitude of process Ca signals and the duration of somatic Ca signals decreased when moving from ramified via hypertrophic to ameboid microglia. In contrast, the size of active compartments, the fraction and amplitude of somatic Ca signals and the duration of process Ca signals increased along this pathway.