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Nf1 functions in sleep homeostasis neurons for circadian rhythms and memory

Abstract

The sleep/wake cycle is thought to be controlled by two main processes: a circadian clock that regulates timing of arousal and a sleep homeostat that regulates duration of arousal according to sleep need. It is unknown though how these two processes work together: whether they work in parallel or functionally interact with each other. This gap in conceptual understanding is due in part to the dearth of information about the nature of the sleep homeostat as well as the neuroanatomy responsible for transmitting time-of-day information from the circadian clock network to the rest of the brain.In unpublished data, my lab has shown that a cluster of neurons in the antennal mechanosensory and motor center (AMMC) functions in both processes. In this thesis I describe the contribution that expression of the Neurofibromatosis 1 (Nf1) gene within these neurons makes to the sleep/wake cycle. By utilizing various Gal4>RNAi combinations, I found that Nf1 is required AMMC neurons for aversive associative memory and required in a GABAergic subset of these neurons for circadian locomotor rhythmicity. In genetic epistasis experiments I also found that deficits in both behaviors can be rescued by suppressing Insulin Receptor-Ras signaling. Collectively, my results illustrate a specific molecular pathway for the circadian and memory functions controlled by Nf1 and indicate that sleep need, circadian timing, and memory are linked by neurons in the AMMC.

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