Circadian rhythms are fundamental to living organisms. The mammalian circadian system, which controls daily rhythms of behavior and physiology, is a multi-oscillatory system composed of a master pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) and many other oscillators in peripheral organs. However, the SCN is not the only pacemaker. When arousing stimuli are present, circadian behavior rhythms are observed even when circadian clocks in the SCN and peripheral tissues are disabled. The molecular mechanisms, anatomical loci, and functional significance of these extra-SCN pacemakers are not known. We have assembled molecular and imaging toolsets and technologies to identify the neural circuitry and physiological outputs of those extra-SCN pacemakers. The proposed studies will uncover the functional significance of the enigmatic extra-SCN circadian pacemakers in mammals. The discovery of the loci and physiological roles of the extra-SCN pacemakers will expand our understanding of the molecular and physiological processes of the circadian system. Importantly, our studies will investigate how the SCN and extra-SCN pacemakers interact to regulate feeding and sleep. Disruption of circadian rhythms and sleep by shiftwork and exposure to artificial light at night increases the risk of human diseases. In addition, sleep and circadian rhythms are impaired in several neurological disorders and in persons with drug addictions. Therefore, understanding how extra-SCN pacemakers control circadian rhythms will elucidate novel processes that could be manipulated to manage circadian disruption in humans.
Mammalian pacemakers located outside of the suprachiasmatic nucleus have not been studied in-depth. The goals of this project are to discover the neural circuitry and functional significance of these under-studied circadian pacemakers. Understanding how these enigmatic circadian pacemakers augment our current model of the circadian system will provide new ways to prevent, diagnose, and treat human disorders that are caused by, or lead to, circadian disruption.
