Neuron-type-specific signals for reward and punishment in the ventral tegmental area

Abstract

Dopaminergic neurons in the mouse ventral tegmental area signal the difference between received and expected reward, whereas GABAergic neurons signal expected reward. The ventral tegmental area (VTA), a part of the brain involved in reward and addiction, contains both dopaminergic and GABAergic signals, but the role of the subpopulations in reward representation and processing is unclear. Using optogenetics to identify dopaminergic and GABAergic neurons, this study characterizes VTA responses to rewarding and aversive stimuli. The two neuronal types are shown to have distinct responses to reward: dopaminergic neurons signal reward prediction errors, whereas GABAergic neurons signal reward expectation. Dopamine has a central role in motivation and reward. Dopaminergic neurons in the ventral tegmental area (VTA) signal the discrepancy between expected and actual rewards (that is, reward prediction error)1,2,3, but how they compute such signals is unknown. We recorded the activity of VTA neurons while mice associated different odour cues with appetitive and aversive outcomes. We found three types of neuron based on responses to odours and outcomes: approximately half of the neurons (type I, 52%) showed phasic excitation after reward-predicting odours and rewards in a manner consistent with reward prediction error coding; the other half of neurons showed persistent activity during the delay between odour and outcome that was modulated positively (type II, 31%) or negatively (type III, 18%) by the value of outcomes. Whereas the activity of type I neurons was sensitive to actual outcomes (that is, when the reward was delivered as expected compared to when it was unexpectedly omitted), the activity of type II and type III neurons was determined predominantly by reward-predicting odours. We ‘tagged’ dopaminergic and GABAergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to optical stimulation while recording. All identified dopaminergic neurons were of type I and all GABAergic neurons were of type II. These results show that VTA GABAergic neurons signal expected reward, a key variable for dopaminergic neurons to calculate reward prediction error.