NSWO 18, 2007 59 SLEEP DEPRIVATION RESULTS IN DEPHOSPHORYLATION OF HIPPOCAMPAL AMPA RECEPTORS Robbert Havekes, Roelina Hagewoud, Arianna Novati, Eddy A. van der Zee, Peter Meerlo Department of Molecular Neurobiology, School of Behavioral and Cognitive Neurosciences, University of Groningen, The Netherlands INTRODUCTION A growing body of evidence shows a role for sleep in the regulation of neuronal excitability and neuronal plasticity 1 . Such sleep-mediated neuronal plasticity is thought to be important for proper brain function, in particular for learning and memory formation 2,3 . Support for the importance of sleep for neuronal plasticity and cognitive function comes from studies showing that learning and memory processes are disrupted by sleep deprivation. The effect of sleep loss is most pronounced when tasks require the hippocampus 4,5 . Yet, the neurobiological mechansims underlying sleep deprivation-induced hippocampal dysfunction are not well established. Synaptic plasticity is crucially dependent on glutamate NMDA and AMPA receptors. While several studies have shown that sleep loss may affect hippocampus function via changes in NMDA receptor function 6-9 , little is known regarding effects of sleep loss on AMPA receptors. AMPA receptors consist of different subunits (GluR1 to GluR4) assembled in various combinations 10 . The efficacy of AMPA mediated neurotransmission depends on the incorporation of receptors into the membrane and on receptor channel activity, both of which are regulated by receptor phosphorylation 11,12 . In the present study, we subjected adult mice to sleep deprivation and examined the effects on the phosphorylation state of the AMPA receptor GluR1 subunit, an important determinant of AMPA receptor function. METHODS Sleep deprivation Adult male C57Bl/6J mice were individually housed and maintained under a standard 12h light / 12h dark cycle. The experiment included three groups of animals: a group of control mice (n=8), a group of mice subjected to 6 hours of sleep deprivation (6 h SD, n=7) and another group subjected to 12 hours of sleep deprivation (12 h SD, n=8). For both of the latter groups, sleep deprivation ended at the end of the light phase. Animals were subjected to sleep deprivation by mild stimulation, which involved tapping on the cage, gently shaking the cage or, when this was not sufficient to keep animals awake, disturbing the sleeping nest. The number of stimuli needed to keep the mice awake was recorded.