Our circadian clocks have evolved to synchronize behavioral and physiological activities to a specific time of the day in order to optimize survival. Although Darwinian pressures have declined for humans, many of the emergent stresses of modern society burdens our ancient circuitry governing circadian synchrony. As such, new pathologies are emerging including mental, cardiovascular, metabolic disorders and cancer. The synchronization process of biological rhythms, termed entrainment, requires environmental cues (zeitgebers) that are able to reset the molecular clock machinery. For mammals, the most dominant daily zeitgeber is light. During photoentrainment, the ambient light levels that are detected by photoreceptors are conveyed to the central circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus to permit synchrony to day/night cycles. However, other cues such as availability of food, social interactions or physical exercise also influence the phase of the SCN. Many of these cues also increase dopamine (DA) neurotransmission. We hypothesize that increased DA signaling in the SCN allows the central oscillator to enter a more ?entrainment susceptible? state where new cues are able to adjust the circadian clock more readily. In the parent grant, we proposed to delineate this circuit and, thus far, have made significant advances during the funding period. With the proposed supplement grant application, we are seeking to purchase a fiber photometry system which will allow us to determine whether reward signaling midbrain dopaminergic neurons increase the period and reduce the amplitude of the SCN molecular and neuronal activity rhythms. The proposed experiments will demonstrate how entrainment cues are integrated in the SCN in vivo.
Necessities of modern society put immense pressure on human physiology by forcing incongruity between endogenous circadian rhythms and environmental cycles, which leads to a range of health issues including psychological abnormalities, cardiovascular diseases, cancer and obesity. This project aims to identify novel neural circuits that govern biological rhythms in the brain and therefore provide unique therapeutic targets to circumvent these pathologies.
