Microglial Regulation of Sleep and Wakefulness

Sleep serves a multitude of roles in brain maturation and function. Although the neural networks involved in sleep regulation have been extensively characterized, it is increasingly recognized that neurons are not the sole conductor orchestrating the rhythmic cycle of sleep and wakefulness. In the central nervous system, microglia have emerged as an important player in sleep regulation. Within the last two decades, microglia have gained substantial attention for carrying out numerous nonimmune tasks that are crucial for brain development and function by co-opting similar mechanisms used in their conventional immune functions. Here, we highlight the importance of microglia in sleep regulation with recent findings reporting an arrhythmic sleep/wake cycle in the absence of microglia. Although the underlying mechanisms for such regulation are still being uncovered, it is likely that microglial contributions to the rhythmic control of the sleep/wake cycle come from their influence on synaptic strength and neuronal activity. We review the current literature to provide speculative signaling pathways and suggest key questions for future research. Advancing our knowledge of the mechanistic contribution of microglia to sleep regulation will not only further our insight into this critical biological process but also be instrumental in providing novel therapeutic strategies for sleep disorders.