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This chapter reviews different approaches and their findings in pursuit of sleep genes, with a highlight on the complex nature of sleep genetics revealed by those approaches. The polygenic nature of sleep can be appreciated even in studies using single-gene approaches. A branch of forward genetics, quantitative trait locus (QTL) analysis is the choice for comprehensively elucidating the genetic landscape of complex phenotypes such as sleep. The systems genetics approach, on the other hand, identifies genes whose expression affects sleep-wake phenotypes, and thus the genes identified are likely components of the sleep regulatory machinery and not simply a response to changes in sleep-wake states. Using multiple genetic approaches over the last few decades, researchers have begun to elucidate the genetic basis of sleep, and in particular, have established multigenic nature of sleep.
We propose that sleep is linked to synaptic homeostasis. Specifically, we propose that: (1) Wakefulness is associated with synaptic potentiation in cortical circuits; (2) synaptic potentiation is tied to the homeostatic regulation of slow wave activity; (3) slow wave activity is associated with synaptic downscaling; and (4) synaptic downscaling is tied to several beneficial effects of sleep, including performance enhancement.
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