Serotonin and dopamine An updated investigation of neurochemical signals surrounding appetitive and aversive stimuli

Many people believe that dopamine and serotonin are key players in experiencing reward and happiness, but this understanding oversimplifies the complex roles these neuromodulators play in influencing behavior. Our current understanding of dopamine and serotonin signaling remains incomplete, limiting the development of effective treatments for neuropsychiatric disorders such as obsessive-compulsive disorder (OCD), addiction, depression, and Parkinson’s disease. In this thesis, we employed high-precision techniques with high specificity, sensitivity, and temporal resolution to better characterize dopamine and serotonin signaling. By utilizing fast-scan cyclic voltammetry (FSCV) to measure real-time serotonin and dopamine release and optogenetics to selectively activate serotonergic neurons, we investigated how these neuromodulators respond to appetitive and aversive stimuli on behaviorally-relevant timescales. We found dopamine release is differentially regulated across striatal subregions and that, within the ventromedial striatum (VMS), value-based changes in dopamine signaling in response to rewards occur rapidly and incorporate both model-based and model-free reinforcement learning mechanisms. Additionally, we found that VMS dopamine tracks aversive stimulus duration and prediction but not value or prediction error. Lastly, we observed that serotonin mildly promotes voluntary actions and ongoing movement but does not influence instinctive or compulsive behaviors. Together, our findings provide new insights into how dopamine and serotonin influence behavior in response to appetitive and aversive stimuli. These insights offer promising avenues for improving therapeutic strategies for neuropsychiatric disorders.