Sleep Homeostasis and Synaptic Plasticity

In this proposal, we aim to identify the neural circuitry that regulates homeostatic sleep drive by mapping where in the brain sleep need is encoded and where it is translated into sleep drive. Our initial attempt of using RNAi to knock down genes proposed to be involved in sleep homeostasis in discrete circuits was not successful. We also had difficulty replicating published methods that quantify synapse formation. We are now using a thermogenetic approach to activate discrete circuits in the brain to find brain regions that encode sleep homeostasis. To date, we have screened about 200 lines and have found a number of interesting effectors. Perhaps the most compelling finding is that prolonged wakefulness is not necessarily a strong driver of homeostatic buildup. Likewise, prolonged sleep does not necessarily dissipate sleep drive. As a result, we now have access to a unique tool set of drivers to manipulate acute behavioral state as well as homeostatic drive, which we can use to dissociate sleepwakefulness from subsequent rebound ie. homeostatic drive.