Reward and aversion in a heterogeneous midbrain dopamine system

•Midbrain dopamine neurons have heterogeneous molecular and physiological properties.•DA neurons may have distinct behavioral functions based on their projection targets.•Inputs to the ventral tegmental area synapse on different neuron subpopulations.•DA neurons participate in distinct circuits mediating partially distinct functions.

The ventral tegmental area (VTA) is a heterogeneous brain structure that serves a central role in motivation and reward processing. Abnormalities in the function of VTA dopamine (DA) neurons and the targets they influence are implicated in several prominent neuropsychiatric disorders including addiction and depression. Recent studies suggest that the midbrain DA system is composed of anatomically and functionally heterogeneous DA subpopulations with different axonal projections. These findings may explain a number of previously confusing observations that suggested a role for DA in processing both rewarding as well as aversive events. Here we will focus on recent advances in understanding the neural circuits mediating reward and aversion in the VTA and how stress as well as drugs of abuse, in particular cocaine, alter circuit function within a heterogeneous midbrain DA system.This article is part of a Special Issue entitled ‘NIDA 40th Anniversary Issue’.