Bidirectional modulation of sleep and wakefulness via prefrontal cortical chemogenetics
The cortex is now recognised as a key regulator of sleep. It remains unclear, however, how sleep is affected by changes in cortical activity over different spatial scales. For instance, sleep states are associated with global changes in activity across cortex, but sleep pressure is associated with local variations in cortical activity. Here we use chemogenetic manipulations of a single neuronal population to determine how sleep reflects the spatial scale of cortical activity. Global inhibition of Rbp4-Cre+ neurons increases sleep, but also produces abnormal brief-awakenings and reduces electroencephalogram slow-wave activity, a marker of sleep intensity. In contrast, local inhibition/excitation of Rbp4-Cre+ neurons in the prefrontal but not occipital cortex increases sleep/wake, respectively, whilst preserving normal sleep architecture and electrophysiological features. We conclude that globally altering cortical activity may induce unphysiological sleep due to conflicting sleep-regulatory signals, while locally modulating prefrontal cortex affords bidirectional sleep regulation that leaves naturalistic features intact.