Key aspects of the synaptic homeostasis hypothesis of sleep function will be tested in the first 3 projects ofthis center application, including that: i) brain plasticity during wakefulness leads to molecular,electrophysiological and metabolic 'traces' reflecting the occurrence of synaptic potentiation; ii) synapticpotentiation, in turn, is responsible for higher levels of slow waves during subsequent sleep; and iii) sleepslow waves are necessary for the renormalization of cortical circuits after learning and for the enhancementof performance after sleep. This project will test the synaptic homeostasis hypothesis in a clinicalpopulation subjects with major depressive disorder. About half of depressives show an acuteantidepressant response to sleep deprivation. Many of the same molecular markers of synaptic potentiationthat are induced by sleep deprivation are also induced by antidepressant drugs, suggesting that sleepdeprivation and antidepressants both act by the induction of plasticity-related genes. According to thehypothesis, activation of such genes should be associated with increased sleep slow waves.
Aim 1 of thisstudy will confirm that depressives can be subdivided into those who show a normal decline of slow waveactivity (SWA) across the night and those who do not, and extend our preliminary findings that depressivescan also be subdivided into those who show normal vs. abnormal topography and local homeostaticregulation of SWA.
Aim 2 will employ the same visuomotor task as Projects II and III to demonstrate that thesubgroup of depressives with abnormal SWA homeostasis will show impaired local homeostasis anddecreased sleep-dependent learning in comparison to the subgroup with more normal SWA homeostasis.Finally, Aim 3 will test the hypothesis' prediction that sleep deprivation will produce an antidepressantresponse only in depressed subjects with a normal time course and topography of SWA during the night, aswell a normal SWA activity response to the homeostatic challenge of sleep deprivation.
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