Abstract
Microglial calcium signaling underlies a number of key physiological and pathological processes in situ, but has not been studied in vivo in awake mice. Using multiple GCaMP6 variants targeted to microglia, we assessed how microglial calcium signaling responds to alterations in neuronal activity across a wide range. We find that only a small subset of microglial somata and processes exhibited spontaneous calcium transients in a chronic window preparation. However, hyperactive shifts in neuronal activity (kainate status epilepticus and CaMKIIa Gq DREADD activation) triggered increased microglial process calcium signaling, often concomitant with process extension. Additionally, hypoactive shifts in neuronal activity (isoflurane anesthesia and CaMKIIa Gi DREADD activation) also increased microglial process calcium signaling. Under hypoactive neuronal conditions, microglia also exhibited process extension and outgrowth with greater calcium signaling. Our work reveals that microglia have highly distinct microdomain signaling, and that processes specifically respond to bi-directional shifts in neuronal activity through increased calcium signaling.
Highlights
Microglia are resident immune cells of the CNS, which are specialized to respond to both immunological and neuronal stimuli
Microglial calcium activity has been frequently described in situ, with limited studies performed in vivo
Microglial calcium activity was present in both the Lck-GCaMP6f mouse and the cytosolic GCaMP6s mouse (Figure 1B and C)
Summary
Microglia are resident immune cells of the CNS, which are specialized to respond to both immunological and neuronal stimuli. More recent in vivo studies have demonstrated that spontaneous calcium signaling is nearly absent in microglia (Brawek et al, 2017; Eichhoff et al, 2011; Pozner et al, 2015). Such observations downplay the potential utility of calcium signaling for microglial function. Microglial processes have not been extensively evaluated for their calcium activity in vivo, nor has any assessment been performed in the awake animal. We evaluated microglial soma and process calcium signaling in awake mice using two-photon microscopy
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