A novel circadian output circuit linking sensory input to sleep/wake states

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Sleep is essential for normal nervous system function, and thus normal behaviour, in a wide range of organisms, including species as divergent as humans and fruit flies. When we fall asleep is generally thought to be regulated by two processes. Firstly, an internal timekeeper - the circadian clock. Secondly, a homeostat that measures our level of tiredness. These two processes are largely internal, yet it is an obvious truth that our external environment has a profound impact on our sleep patterns. Pro-arousal drugs, artificial light or uncomfortable temperatures all delay or disrupt our sleep, and poor quality sleep has been linked to both metabolic and psychiatric disease. In non-human species, when to fall asleep is a critical decision, since eating and mating are paused and the organism becomes more vulnerable to predation. Here again, environmental cues must be sensed by an organism, and these cues somehow transmitted to sleep-regulatory regions of the brain. A clearer understanding of how this process occurs at the circuit level is critical to advance our understanding of how sleep is modulated in a variety of species, including humans. We have chosen the fruit fly, Drosophila melanogaster, to investigate this issue. We recently showed that high temperatures in the morning prolong wakefulness in male Drosophila via temperature-sensing neurons signalling to a subset of the circadian clock network called DN1p neurons, which are wake-promoting in the morning at high temperatures. We now identify a novel output circuit downstream of DN1p neurons that mediates this effect. We find that DN1p neurons project to a brain region called the Anterior Optic Tubercle (AOTU). We present data showing that the AOTU contains sleep-promoting neurons that are inhibited by DN1p neurons. We propose experiments to characterise this circuit in detail and to identify additional downstream connections. Through these experiments, we aim to discover how the circadian network in Drosophila is linked to wake/sleep-promoting centres in the fly brain, and how the activity of these circuits is altered by environmental stimuli.