In Vivo Imaging of Microglial Calcium Signaling in Brain Inflammation and Injury

Microglia, the innate immune sentinels of the central nervous system, are the most dynamic cells in the brain parenchyma. They are the first responders to insult and mediate neuroinflammation. Following cellular damage, microglia extend their processes towards the lesion, modify their morphology, release cytokines and other mediators, and eventually migrate towards the damaged area and remove cellular debris by phagocytosis. Intracellular Ca(2+) signaling plays important roles in many of these functions. However, Ca(2+) in microglia has not been systematically studied in vivo. Here we review recent findings using genetically encoded Ca(2+) indicators and two-photon imaging, which have enabled new insights into Ca(2+) dynamics and signaling pathways in large populations of microglia in vivo. These new approaches will help to evaluate pre-clinical interventions and immunomodulation for pathological brain conditions such as stroke and neurodegenerative diseases.