Sleep Homeostasis and Synaptic Plasticity

After a busy day we are sleepy. Yet, how the brain translates this accumulated wake experience into sleep drive and eventually forces us to fall asleep remains a mystery. In this proposal, we aim to identify the neural circuitry that regulates this homeostatic sleep drive by mapping where in the brain sleep need is encoded and where it is translated into sleep drive. Sleep pressure the internal drive to sleep is proposed to be regulated by the interaction of circadian and homeostatic processes. In this two-process model, circadian mechanisms synchronize sleep drive to the day-nightcycle while homeostatic sleep pressure responds to wake experience, increasing in parallel with wakefulness and dissipating again during sleep. The homeostatic regulation of sleep remains shrouded in mystery. One of the most exciting recent hypotheses concerning the function of sleep homeostasis is thesynaptic homeostasis hypothesis. The basic idea is as follows everyday behavior and learning produce a net increase in synaptic weights in the brain, meaning that the chemical connections between neurons are strengthened. One function of sleep is therefore to downscale or normalize all synapses in the brain, the relative synaptic strength differences that have accrued through learning.But how is wake experience translated into sleep drive Where in the brain does this occur Is there a discrete sleep drive circuit a homeostat that operates in concert with the circadian circuitry or does sleep drive accumulate everywhere in the brain To answer these questions we need to study a brain that is highly accessible while still being similar enough to man to be a valuable model organism.