A significant portion of our life is spent asleep and we still do not know why. Chronic sleep deprivation and sleep disorders are experienced by millions of people in our society, and sleep loss has profound effects on brain activity and cognitive functions. Surprisingly, we still do not know what happens in the brain after sleep deprivation that makes us feel tired and impaired even in simple tasks. The objective of this project is to provide an understanding of neuronal mechanisms underlying behavioural, sensory and cognitive changes incurred after sleep deprivation, through a suite of state-of-the-art neurophysiological techniques and methodologies. We hypothesize that prior waking experience results in specific changes in the activity of cortical neuronal networks that in turn directly results in an impaired cognition and necessitates sleep. In order to address this hypothesis we will use visual stimulation, sensory gating and ‘oddball’ paradigms, spatial navigation and reaction time tasks in rats and mice in vivo. Furthermore, we will exploit conventional and conditional knock-out mouse models to investigate global and local effects of metabotropic glutamate and GABA receptors on wake- and experience-dependent changes in cortical neuronal activity during sleep deprivation. This work will not only help to explain specific mechanisms underlying behavioural and sensory deficits after sleep deprivation, but by doing so will pave the way towards more focused innovative research relevant for public health and safety.