Unlocking the Metabolic Mysteries of Sleep

Dr. Amita Seghal is a professor of Neuroscience at the University of Pennsylvania.

Why we spend ~a third of our lives sleeping and what it is that makes us sleepy are major questions about sleep that lack satisfactory answers. There is universal agreement that lack of sleep impairs performance, especially cognitive ability, during waking hours and considerable evidence supports adverse effects of sleep loss on other physiological parameters as well.  Thus, sleep may be regarded as important for waking function.  However, what happens during sleep to facilitate wake performance and promote health?

Driven by the successful use of Drosophila for deciphering molecular mechanisms of the circadian clock, we developed a Drosophila model to address molecular and cellular underpinnings of sleep.  Through the use of forward genetic screens, we have identified genes and tissues that affect sleep amount.  Coupled with our efforts to understand the fundamental basis of sleep, we are getting a handle on the regulation and function of sleep that may be broadly relevant for the brain, and perhaps even the body.  We find that sleep is important for metabolic, in particular energetic, homeostasis in the brain. This includes the clearance of metabolic waste, which can be accomplished in different ways.  For instance, we find that autophagy and endocytosis through the blood brain barrier (BBB), both of which facilitate clearance, are regulated by sleep.  Our ongoing work implicates sleep in lipid metabolism, in particular.  We find that specific lipids accumulate under conditions of high sleep need e.g. when endocytosis through the BBB is blocked. And lipids are transferred from neurons to glia in a daily cycle that helps to maintain mitochondrial homeostasis in neurons.  Together this work is leading to an understanding of cellular/molecular processes that underlie sleep.

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Hosted by Dr. Laura Colgin

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