PROJECT SUMMARY A critical issue for understanding sleep function is whether and how it impacts the accuracy of neuronal network computations to improve behavioral performance. Indeed, studies over the past several decades have shown that even brief periods of rest are correlated with subsequent improved perceptual and cognitive performance. However, despite the prevalence and beneficial impact of sleep on behavioral performance, little is known about the neural mechanisms of this improvement. We propose new studies to explore unchartered territory: we will explore the beneficial impact of sleep on information coding across cortical circuits and on perceptual performance. We propose to use multiple-electrode recordings simultaneously in three cortical areas, early and mid-level visual cortex (areas V1 and V4) and dorsolateral prefrontal cortex (area dlPFC) to examine, for the first time, the dynamics and coding in neuronal populations before, during, and after sleep, and their impact on behavioral performance. In Aim 1, we will investigate whether the low-frequency synchronization of network activity ubiquitously observed during slow-wave sleep is associated with a post- sleep reduction in the degree of synchronized fluctuations of population activity in visual and prefrontal cortex. In Aim 2, we will use electrical stimulation during quiet wakefulness to emulate the restorative effects of sleep in the absence of sleep, and causally test our hypothesis in Aim 1 that slow-wave population activity during sleep causes a reduction in synchronized fluctuations in population activity after sleep. This Aim will provide proof of concept for invasive stimulation procedures to improve perceptual performance in the absence of sleep, and will set the stage for future noninvasive procedures in humans. In Aim 3, we will use optogenetic stimulation to test the mechanism of the sleep-dependent improvement in neuronal and behavioral performance. We hypothesize that sleep is associated with increased synaptic efficacy in local circuits that persists during post-sleep wakefulness. We further hypothesize that this increase in synaptic efficacy elevates firing rates and spike timing coordination between neurons after sleep to improve the accuracy of encoding information in population activity. Our research has the potential to advance our understanding of the neural mechanisms underlying sleep and thus provide future solutions to ameliorate the detrimental effects of sleep disorder on cognitive performance, including practical applications for non-invasive neuronal prosthetic devices.