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

Abstract

Microglia are the innate immune cells of the brain with roles in neuroimmunology and synaptic plasticity. Microglial processes continuously survey the brain parenchyma interacting with synaptic elements and maintaining 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, where slow-wave neural activity resembles sleep-like states. We report that microglial surveillance and injury response in awake animals are reduced compared to when animals are anesthetized, suggesting that arousal state profoundly modulates microglial roles in the physiological brain. Stimulating {beta}2-adrenergic receptors recapitulated these observations and also disrupted experience-dependent plasticity only when intact {beta}2-adrenergic receptors were present in microglia specifically. These results indicate that microglial roles in surveillance and synaptic plasticity in the healthy brain are modulated by noradrenergic fluctuations between arousal states and raises new considerations for sleep/wake disruption in neurodevelopment and neuropathology.