Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex

• Published in: Nature neuroscience Vol. 22; no. 11; pp. 1782 - 1792
• Main Authors: 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, Majewska, Ania K.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-11-2019; Nature Publishing Group
• Subjects: 13/1; 13/31; 14/19; 14/63; 14/69; 631/378/2591; 631/378/2596/1953; 631/378/2613; 631/378/371; 64/60; 82/51; Adrenergic receptors; Analysis; Animal Genetics and Genomics; Animals; Arousal; Behavioral Sciences; Benzylamines - pharmacology; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Brain; Cell Movement - drug effects; Cell Movement - physiology; Circadian Rhythm - physiology; Clenbuterol - pharmacology; CX3C Chemokine Receptor 1 - genetics; Dexmedetomidine - pharmacology; Dominance, Ocular; Female; Fentanyl - pharmacology; Health aspects; Homeostasis; Immune system; Influence; Injury prevention; Locus Coeruleus - drug effects; Male; Mice; Mice, Transgenic; Microglia; Microglia - cytology; Microglia - drug effects; Microglia - physiology; Nadolol - pharmacology; Neurobiology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neurons - metabolism; Neurons - physiology; Neuroplasticity; Neurosciences; Noradrenaline; Norepinephrine; Norepinephrine - metabolism; Norepinephrine - physiology; Parenchyma; Plasticity; Propanolamines - pharmacology; Psychological aspects; Receptor mechanisms; Receptors; Receptors (physiology); Restraint, Physical - physiology; Signaling; Surveillance; Synaptic plasticity; Terbutaline - pharmacology; Variation; Visual cortex; Visual Cortex - physiology; Visual plasticity; Wakefulness; Wounds and Injuries - physiopathology; United States
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/s41593-019-0514-0

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 β
2
-adrenergic receptors recapitulated these observations and disrupted experience-dependent plasticity, and these effects required the presence of β
2
-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.
Stowell, Sipe et al. describe how norepinephrine signaling to microglia during wakefulness influences the dynamic movement of microglial processes, affecting both microglial interactions with neurons and experience-dependent plasticity.