UC San Diego

The mesolimbic dopaminergic system consists of interconnected brain regions that include the nucleus accumbens (NAc), ventral tegmental area (VTA), ventral pallidum (VP) and lateral habenula (LHb). These circuits have each been implicated in processes that underlie reward and motivation. The VP is a highly heterogeneous structure with varying cell types, projection targets, and functional roles that are only recently being appreciated. Indeed, recent work has revealed a possible opponent role of VP GABA and glutamate neurons in motivated behavior. Specifically, activation of VP GABA neurons, mainly through their projections to the VTA, induced positive reinforcement; while stimulation of VP glutamate neurons, particularly their projection to the LHb, triggered avoidance. In this work, I further elucidated the mechanism by which VP GABA neurons elicit reward. Particularly, I studied the VP to VTA pathway and assessed the potential for VP GABA terminal stimulation in VTA to trigger dopamine release in the NAc. I showed that stimulation of VP GABA terminals elicits an increase in dopamine release upon both behavior-contingent and non-contingent stimulation. However, both amplitude and duration of dopamine release appeared to be modulated by whether stimulation was contingent on behavior, suggesting a role for motivational or other components in gating the ability of VP GABA inputs to VTA to influence dopamine signaling. These studies provide a foundation for further testing of associated pathways that correlate with reward, learning, and ultimately addiction.