Arousal-circadian interactions: Circadian and photic regulation of the tuberal hypothalamus

Abstract

In mammals, physiological and behavioural rhythms (e.g., hormone secretion, body temperature, and the sleep-wake cycle) are controlled by the central pacemaker in the hypothalamus: the suprachiasmatic nucleus (SCN). The sleep-wake cycle is also under direct influence from recently discovered neuropeptides, the orexins. Orexins are fundamental for arousal and their activity demonstrates circadian rhythmicity. Nevertheless, environmental light modulates SCN- orchestrated rhythms, but how this may affect orexin neuronal activity is poorly understood. This study sought to establish whether orexin cells reveal a pattern in activity across the sleep-wake cycle as well as a circadian activation pattern in constant environmental lighting conditions (constant darkness) in CD-1 mice. CD-1 mice were subjected to constant darkness and levels of orexin activation were assessed at various time points throughout the ~24-hour cycle. Further, some animals were subjected to a 1-hour light pulse, as this resets the circadian clock and promotes sleep, which may feedback to silence the wake-promoting orexin cells. Analysis of orexin activity, using cFos as a marker of cellular activity within orexin immunoreactive cells, indicated that there was no statistically significant difference between cull times in constant darkness or between controls and light pulsed CD-1 mice. However, differences were observed in levels of orexin activation under light-dark conditions. It was demonstrated that orexin activity increased before the transition from the light (inactive) to dark (active) phase. This increase in activation then decreased soon after this transition before increasing again during the middle of the animal‟s active phase.

Date of Award	1 Aug 2011
Original language	English
Awarding Institution	The University of Manchester
Supervisor	John Gigg (Supervisor) & Hugh Piggins (Supervisor)