Effects of arousal on the cicadian clock

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How does the brain track the passage of time? Behavioural neuroscientists believe that a circadian clock located in the hypothalamus coordinates the temporal patterns in physiology and behaviour, and maintains synchrony between these endogenous rhythms and the external day-night cycle. Understanding how this circadian clock functions has become my main research interest. The circadian clock is located in the suprachiasmatic nucleus (SCN). This heterogeneous structure receives input from the eye and various other brain regions, and projects directly to other hypothalamic and thalamic areas. Further more, the SCN appears to regulate many important areas involved in sleep and wake through multisynaptic pathways. While the role that the circadian clock plays in regulating arousal is well studied, the effects of arousal on the circadian clock are less well understood. I have previously shown that enforced arousal during the sleep period can reset the circadian clock. Furthermore, my students and I have shown that such arousal inhibits gene expression and biochemical pathways in SCN cells. The pathway by which arousal affects the clock remains unknown. The goal of this proposal is to examine how the various brain areas and neurotransmitters known to participate in arousal (acetylcholine from the basal forebrain and mesopontine tegmentum; norepinephrine from the locus coeruleus; serotonin from the raphe) affect circadian responses at the molecular, tissue and behavioural levels. The present proposal has the short-term goal of understanding how arousal affects the circadian clock.