Hypothalamic neuron circuits underlying interplay between biological clock and metabolism

Generally all creatures on this planet attain a circadian system, which impacts almost all aspects of living by regulating daily rhythmic physical processes and behaviors. In mammals, the central pacemaker, suprachiasmatic nucleus (SCN), is located in the hypothalamus, right above optic chiasm. Receiving light information from the environment from the retina, SCN synchronizes the circadian rhythms of the entire body in coordination to the sunrise and sunset cycle, to maximize survival. While light entrained circadian clocks regulate daily behavioral patterns of feeding, availability of food is also an important salient environmental cue that is able to alter the circadian machinery. However, less is known about the mechanism of how food alters the biological clock. In this dissertation, using mouse (mus musculus) as model organism, with a focus in the hypothalamus, we investigated the mechanisms of the interplay between biological clock and metabolism. We demonstrated that dopamine signaling in the SCN enables energy-dense food induced alteration of the daily eating pattern and consequential obesity. We also identified a leptin responsive neuron circuit from dorsal medial hypothalamus (DMH) to the SCN that behaves as an integration hub for food to entrain the circadian system.