Cortical zeta-inhibitory peptide injection reduces local sleep need.

Local sleep need within cortical circuits exhibits extensive interregional variability and appears to increase following learning during preceding waking. Although the biological mechanisms responsible for generating sleep need are unclear, this local variability could arise as a consequence of wake-dependent synaptic plasticity. To test whether cortical synaptic strength is a proximate driver of sleep homeostasis, we developed a novel experimental approach to alter local sleep need. One hour prior to light onset, we injected zeta-inhibitory peptide (ZIP), a pharmacological antagonist of protein kinase Mζ, which can produce pronounced synaptic depotentiation, into the right motor cortex of freely behaving rats. When compared with saline control, ZIP selectively reduced slow-wave activity (SWA; the best electrophysiological marker of sleep need) within the injected motor cortex without affecting SWA in a distal cortical site. This local reduction in SWA was associated with a significant reduction in the slope and amplitude of individual slow waves. Local ZIP injection did not significantly alter the amount of time spent in each behavioral state, locomotor activity, or EEG/LFP power during waking or REM sleep. Thus, local ZIP injection selectively produced a local reduction in sleep need; synaptic strength, therefore, may play a causal role in generating local homeostatic sleep need within the cortex.