Hypothalamic versus neocortical control of sleep

Purpose of review Regions of the neocortex most strongly activated during waking exhibit increased sleep intensity during subsequent sleep. The novel concept that aspects of sleep homeostasis are determined locally in the cortex contrasts with the established views that global changes in neocortical activity during sleep are achieved through inhibition of ascending arousal systems that originate in the brainstem and hypothalamus. Recent findings Experiments in animals and humans document asymmetries in neocortical electroencephalogram (EEG) slow-wave activity (SWA), a marker of homeostatic sleep need, as a result of functional activity during waking. In addition to local, use-dependent augmentation of EEG SWA and evoked potentials, expression of plasticity-related genes and of sleep-regulatory cytokines and neuromodulators have been shown to be elevated in a use-dependent manner in neocortex. The functional consequences of local sleep are hypothesized to involve regulation of synaptic plasticity, synaptic homeostasis and energy balance. Summary The evidence for use-dependent modulation of neocortical activity during sleep is compelling and provides novel insights into sleep function. However, local changes in neocortex are generally expressed on a background of global sleep. It remains to be determined if events initiated in the cortex have global sleep-promoting effects and how neocortical and hypothalamic mechanisms of sleep control interact.