Illuminating subcortical GABAergic and glutamatergic circuits for reward and aversion

Reinforcement, reward, and aversion are fundamental processes for guiding appropriate behaviors. Longstanding theories have pointed to dopaminergic neurons of the ventral tegmental area (VTA) and the limbic systems’ descending pathways as crucial systems for modulating these behaviors. The application of optogenetic techniques in neurotransmitter- and projection-specific circuits has supported and enhanced many preexisting theories but has also revealed many unexpected results. Here, we review the past decade of optogenetic experiments to study the neural circuitry of reinforcement and reward/aversion with a focus on the mesolimbic dopamine system and brain areas along the medial forebrain bundle (MFB). The cumulation of these studies to date has revealed generalizable findings across molecularly defined cell types in areas of the basal forebrain and anterior hypothalamus. Optogenetic stimulation of GABAergic neurons in these brain regions drives reward and can support positive reinforcement and optogenetic stimulation of glutamatergic neurons in these regions drives aversion. We also review studies of the activity dynamics of neurotransmitter defined populations in these areas which have revealed varied response patterns associated with motivated behaviors.