Microglial calcium signaling is attuned to neuronal activity in awake mice

Male Neurons 0301 basic medicine status epilepticus 0303 health sciences Kainic Acid Isoflurane QH301-705.5 Science Q R GCaMP 3. Good health Mice 03 medical and health sciences Status Epilepticus DREADD Medicine Animals Calcium Female Calcium Signaling Microglia Biology (General) Neuroscience
DOI: 10.7554/elife.56502 Publication Date: 2020-07-27T12:00:26Z
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.
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