Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex
Name
nihms-1539793.pdf
Description
Accepted version
Size
2.69 MB
Format
Unknown
Checksum (MD5)
ae703e2cb47813427000f67fc2a1cc2d
Author(s)
Stowell, Rianne D.
Sipe, Grayson O.
Dawes, Ryan P.
Batchelor, Hanna N.
Lordy, Katheryn A.
Whitelaw, Brendan S.
Stoessel, Mark B.
Bidlack, Jean M.
Brown, Edward
Sur, Mriganka
Date Issued
October 2019
Journal
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Version
Author's final manuscript
Abstract
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. Microglia are the brain’s resident innate immune cells and also have a role in synaptic plasticity. Microglial processes continuously survey the brain parenchyma, interact with synaptic elements and maintain tissue homeostasis. However, the mechanisms that control surveillance and its role in synaptic plasticity are poorly understood. Microglial dynamics in vivo have been primarily studied in anesthetized animals. Here we report that microglial surveillance and injury response are reduced in awake mice as compared to anesthetized mice, suggesting that arousal state modulates microglial function. Pharmacologic stimulation of β2-adrenergic receptors recapitulated these observations and disrupted experience-dependent plasticity, and these effects required the presence of β2-adrenergic receptors in microglia. These results indicate that microglial roles in surveillance and synaptic plasticity in the mouse brain are modulated by noradrenergic tone fluctuations between arousal states and emphasize the need to understand the effect of disruptions of adrenergic signaling in neurodevelopment and neuropathology.
MIT Department
Picower Institute for Learning and Memory
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/s41593-019-0514-0
