Circadian Encoding of Reward-Seeking Behavior in the Mesolimbic Dopamine Pathway - Project Summary The primary objective of this research project is to elucidate how circadian rhythms are integrated into neural circuitry important for reward-seeking behavior. Circadian timekeeping is an evolutionarily conserved system essential for the proper function of reward-seeking behavior. By aligning reward behaviors with optimal times of day, animals can seek food, mates, and safety in a manner that enhances survival. Investigating the circadian modulation of reward neural circuitry is therefore necessary to understand the fundamental properties that comprise the neural encoding of reward behavior. This research also has broad implications for human health, as maladaptive reward behaviors underlie various neuropsychiatric diseases, including addiction, bipolar disorder, and depression. Advancing the neuroscience of reward behavior has significant potential for informing the development of therapeutic and diagnostic tools for disorders affecting the brain's reward system. This study aims to determine how circadian rhythms are integrated within the brain's reward system by investigating the bidirectional relationship between rhythms in the ventral tegmental area (VTA) and nucleus accumbens (NAc), two key regions in the dopamine reward pathway. Aim 1 will examine how circadian clock gene expression in the VTA drives rhythms in the NAc, dopamine release, and reward-seeking behavior by selectively ablating critical circadian clock genes in the VTA and measuring downstream effects using long- term fiber photometry and behavioral assays. Aim 2 will investigate the reciprocal relationship, assessing how circadian clock gene expression in the NAc affects circadian clock gene expression in the VTA, dopamine release, and behavior using a similar approach. If these regions operate through a reinforcing feedback loop, it would suggest that circadian rhythms in reward behavior arise from coordinated communication rather than a unidirectional flow of circadian information. These findings could reshape the understanding of neural timekeeping in reward circuits and provide insight into how circadian disruptions manifest at the neural circuit level. This fellowship would support invaluable training opportunities toward the trainee's growth as a neuroscientist. Specializing in both circadian neuroscience and cutting edge tools like long-term fiber photometry, the Jones lab provides the ideal environment to conduct the proposed methodology. Additionally, this research plan will help develop expertise in the dopamine dynamics of reward through collaboration with Co-Sponsor, Dr. Rachel Smith, therefore preparing the trainee for a career at the intersection of circadian and reward neuroscience.
