Functional implications of state-dependent regulation of glial cells.
The glymphatic system, regulated by astrocytes, plays a critical role in moving nutrients and metabolites throughout the brain. Recent data demonstrate that this system is highly regulated by brain state, with facilitation of this movement during sleep or anesthesia, and suppression during wakefulness. Both the causal mechanisms and functional consequences of this state-dependent regulation are completely unknown. This proposal is aimed at first clarifying how glyphatic system regulatory processes are activated by state in astrocytes, using a combination of optogenetic, biochemical, and bioinformatics techniques. Additional experiments will employ electrophysiological and behavioral tools to address a second issue: how state-dependent regulation of the glymphatic system mediates the cognitive consequences of sleep vs. sleep loss.