The Role of Transient Striatal Dopamine Release Events in Negative Reinforcement Processes

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Evaluating and avoiding negative outcomes is critical for optimal decision-making and, ultimately, animal survival. A chemical in the brain called dopamine is well known to promote advantageous behavior when animals are pursuing reward; however, little is known regarding the role of dopamine when animals are avoiding harm. The principal investigator's lab is able to measure real-time dopamine levels in the brain of behaving animals using a tool called voltammetry, and turn dopamine neurons on/off using a tool called optogenetics. Using these tools, the investigator's research team will perform a thorough assessment of how dopamine levels within the brains of behaving rats are involved in the avoidance of footshock. Additional experiments serve to determine whether dopamine is involved in assessing the value of avoiding different intensities of footshock. It is predicted that dopamine levels will change over the course of learning in a manner that promotes successful footshock avoidance and scale with the value of the footshock avoided. All aspects of the proposed project will involve undergraduate trainees, especially trainees from underrepresented populations. By using cutting-edge technologies to investigate the role of dopamine in the avoidance of harm, the principal investigator and his students will uncover novel information about the neurobiological mechanisms underlying behavior while simultaneously developing a future, diverse population of scientists.The principal investigator recently demonstrated that a warning signal predicting the avoidance of an aversive event evokes transient surges in dopamine concentration within the ventral striatum. This finding suggests that the transient dopamine signal represents environmental stimuli predicting the avoidance of something bad similarly to those predicting the receipt of something good. Furthermore, preliminary optogenetics data reveal that facilitating midbrain dopamine neural activity during warning signal presentation promotes avoidance outcomes in well-trained rats. Despite these important advances, the precise role(s) that transient dopamine release events play in negative reinforcement processes remains unknown. In this project, the investigator and his research team will use fast-scan cyclic voltammetry and optogenetics to assess the role of transient dopamine release events in the nucleus accumbens core, dorsomedial striatum, and dorsolateral striatum during: 1) avoidance learning, 2) maintenance and extinction of avoidance, and 3) positive vs. negative reinforcement value assessment. The collection of these data will generate presently unknown mechanistic detail regarding how the brain processes negative reinforcement-- information that may contribute to a more nuanced understanding of the role of dopamine in animal behavior. To accomplish these goals, the investigator will involve undergraduate students, particularly those from underrepresented backgrounds, in all aspects of data collection and dissemination. In addition, the investigator will develop an international neuroscience conference experience program for undergraduate students from underrepresented minorities and a neuroscience outreach program in which undergraduate students from underrepresented minorities visit Denver city museums and schools to teach the general public about the brain.