Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Circadian rhythms have evolved to anticipate and adapt animals to the constraints of the earth's 24-hour light cycle. Notably, they can provide anticipatory benefits, such as promoting water intake prior to sleep to mitigate the impact of reduced water intake during sleep. Most circadian rhythms are orchestrated by the body's mater circadian clock, the suprachiasmatic nucleus; however, little is known about how pathophysiological perturbations might alter the activity of clock neurons to beneficially adapt rhythms to new physiological conditions. The vascular organ of the lamina terminalis (OVLT) is a specialized brain area that is capable of detecting dehydration and the presence of molecules present in the blood during systemic infection. Owing to these characteristics, the OVLT is in a prime position to inform the clock of changes in physiological status, and drive changes in clock neuron activity that can adapt central rhythms to the new condition. My preliminary data shows that clock neurons are inhibited when OVLT neurons are excited by hypertonicity (as in dehydration). Since the electrical activity of clock neurons is low during the awake-period and high during the sleep-period, I hypothesize that dehydration will inhibit the activity of clock neurons via OVLT neurons that release the inhibitory neurotransmitter GABA and prolong the awake-period in mice to promote water-seeking behaviour. Conversely, I hypothesize that bacterial endotoxin (an infection molecule) will excite clock neurons via OVLT neurons that release the excitatory transmitter glutamate to promote sickness behaviour (e.g. sleep). Gaining a specific understanding of the mechanisms regulating circadian rhythms could provide important targets for therapeutic intervention in diurnal disorders or for adaptation to shift-work or jet-lag.