Microglial calcium signaling is attuned to neuronal activity in awake mice
- Mayo Clinic, United States
Abstract
Microglial calcium signaling underlies a number of key physiological 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 physiological 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) trigger increased microglial process calcium signaling, often concomitant with process extension. Additionally, hypoactive shifts in neuronal activity (isoflurane anesthesia and CaMKIIa Gi DREADD activation) also trigger microglial process calcium signaling. Under hypoactive neuronal conditions, microglia also exhibit process extension and outgrowth with high 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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All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Anthony D Umpierre
Funding
National Institute of Neurological Disorders and Stroke (NS114040)
- Anthony D Umpierre
National Institute of Neurological Disorders and Stroke (NS112144)
- Gregory Worrell
- Long-Jun Wu
National Institute of Neurological Disorders and Stroke (NS088627)
- Long-Jun Wu
National Institute of Neurological Disorders and Stroke (NS110825)
- Long-Jun Wu
National Institute of Neurological Disorders and Stroke (NS110949)
- Long-Jun Wu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental procedures were approved by the Mayo Clinic's Institutional Animal Care and Use Committee (IACUC, protocol #2731-17) and were conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals.
Copyright
© 2020, Umpierre et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Microglial calcium signaling is attuned to neuronal activity in awake mice
eLife 9:e56502.
https://doi.org/10.7554/eLife.56502
