Alterations in endogenous circadian rhythm and debilitating sleep disorders represent an unsolved medical problem. The circadian clock regulates the sleep/wake cycle and is complemented by homeostatic sleep pressure factors. Surprisingly, why we sleep and how the clock synchronizes rhythmic behavior, remain a mystery. Intriguing hypotheses suggest that the role of sleep is to maintain synaptic homeostasis or to reactivate specific circuits that are important to memory and learning. Also, it is postulated that clock-controlled genes affect behavior through the remodelling of synapses throughout the day and night. Therefore, it is important to isolate and characterize specific circuits that demonstrate rhythmic synaptic plasticity and to understand how they affect behavior in a live vertebrate. In this proposal, the transparent and diurnal zebrafish model will be used to examine patterns of synaptic plasticity and behavior during the day and night. The zebrafish is ideally suited to study sleep and circadian rhythms, and the neuronal networks are largely conserved with mammals. We recently showed, for the first time, circadian and homeostatic sleep control of rhythmic structural synaptic plasticity in zebrafish. The goal of this proposal is to identify and characterize new functional circuits involved in circadian, sleep, and memory regulation. We will use in-vivo imaging techniques to visualize rhythmic synapses during the day and night, and after sleep deprivation in multiple neuronal circuits. Loss- and gain-of-function approaches will be used to understand how specific circuits regulate synaptic plasticity and behavioral performance. These data should provide important evidence for the role of the circadian clock and sleep in regulating synaptic plasticity and behavior. This study is expected to provide a critical framework to understand the function of sleep, and may help in the treatment of sleep disorders.
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