This project follows up on our recent research implicating the neurotransmitter dopamine signaling as key mediator of circadian timing systems. Our main hypothesis is a subpopulation of dopaminergic neurons send signals to a population of dopamine type 1 receptor 1 (D1r)-expressing neurons in the dorsal striatum, constituting a critical link between food intake and circadian rhythms of daily activity. To address this hypothesis we propose to generate several genetically modified mice and test their behavioral and physiological entrainment to scheduled feeding. These results will expand our understanding of how the downstream targets of dopamine neurons control several important aspects of feeding related behaviors. In addition, since there are numerous dopaminergic drugs available, this research may suggest potential therapeutic strategies to target diseases associated with over- and under-eating.
Disorders associated with over- and under-eating cause many health problems and are costing the United States billions of dollars in medical care. Although hunger-sensing neurons in a part of the brain called the hypothalamus have been identified, we do not know which neurons in the brain regulate the timing of feeding and, in turn, influence activity levels. This proposal seeks to feeding, timing, and the dopaminergic neurotransmitter system.
|Assali, Dina R; Hsu, Cynthia T; Gunapala, Keith M et al. (2018) Food anticipatory activity on a calorie-restricted diet is independent of Sirt1. PLoS One 13:e0199586|