Neural circuit regulation of ramping activity in dopamine neurons

Project Summary Ventral striatal dopamine progressively rises as rodents navigate toward spatially distant rewards, a surprising recent finding that was not anticipated by temporal difference learning models of dopamine function. Ramping dopamine release in the ventral striatum reflects the value and proximity of goals, scaling by the value of the reward and stretching or compressing in different environments to span the distance between start and goal locations. Activity in ventral tegmental area (VTA) dopamine neurons also ramps up as animals approach goals, but the strength and persistence of ramping activity in dopamine neurons depends on both the use of an internal model of goal proximity and on the amount of task experience. Ramping activity in dopamine neurons appears immediately when naïve mice run toward newly-discovered rewards in spatial environments, and ramps gradually fade away over several days of training if sensory information about reward proximity is available. When an internal representation of progress toward the goal is required, however, robust ramping activity in dopamine neurons persists indefinitely. These findings suggest the hypothesis that ramping activity in VTA dopamine neurons depends on the use of brain regions that represent an internal model of the environment and current progress toward goals. We propose to test this overarching hypothesis by addressing the following specific aims: 1) Test the hypothesis that neural activity in the ventral hippocampus contributes to ramping activity in midbrain dopamine neurons. 2) Compare the evolution of ramping activity in VTA dopamine neurons with the evolution of ramping dopamine release in the ventral striatum. 3) Characterize neural activity in VTA GABA neurons during spatial and non-spatial navigation to rewards. Understanding the neural mechanisms that underlie ramping activity in dopamine neurons will have relevance for the neural basis of cognitive control, goal-directed behavior, perseverance, and spatial learning. Our findings will provide valuable information relevant for mental disorders associated with dysfunction in these abilities including attention deficit hyperactivity disorder, obsessive compulsive disorder, depression, and addiction.