The Influence of Dopamine Signaling on the Central Circadian Clock: Implications for Jet lag and Obesity

Circadian rhythms, or biological oscillations of approximately twenty-four hours, impact almost all aspects of our lives by regulating the sleep-wake cycle, hormone release, body temperature fluctuation, and timing of food consumption. Circadian entrainment, or temporal synchrony with one’s environment, is essential for survival. In mammals, the central circadian pacemaker resides within the suprachiasmatic nucleus (SCN) and mediates an organism’s entrainment to environmental conditions. While the light-dark cycle is the primary environmental cue, arousal-inducing, non-photic signals such as food consumption, exercise, and social interaction are also potent synchronizers. Many of these stimuli enhance dopaminergic signaling suggesting that a cohesive circadian physiology depends on the relationship between circadian clocks and the dopamine (DA) neuromodulatory circuits that govern motivational behaviors. Here, we identify a direct connection between DA producing neurons of the ventral tegmental area (VTA) and D1 dopamine receptor (Drd1) expressing SCN neurons that mediates resynchronization of activity rhythms to phase-shifted light:dark cycles. Additionally, we discovered that Drd1 null mice are resistant to diet-induced obesity, while rescue of Drd1 expression specifically within the SCN is sufficient to restore obesity, metabolic disease, and circadian disruption associated with an energy-dense diet. From these studies, it is evident that the SCN-Drd1 signaling is essential for adjusting to changes in environmental conditions as experienced during jet lag, shiftwork, and consumption of palatable foods.