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

Abstract

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.

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Figure 1: Odour-outcome association task in mice.
Figure 2: VTA neurons show three distinct response types.
Figure 3: Identifying dopaminergic and GABAergic neurons.
Figure 4: Response variability based on CS–US preference, reward omission and air puffs.

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Acknowledgements

We thank M. Meister, V. N. Murthy, J. D. Schall and R. P. Heitz for comments, C. Dulac for sharing resources, C. I. Moore, J. Ritt and J. Siegle for advice about microdrives, K. Deisseroth for the AAV-FLEX-ChR2 construct, and E. Soucy and J. Greenwood for technical support. This work was supported by a Howard Hughes Medical Institute Fellowship from the Helen Hay Whitney Foundation (J.Y.C.); the Human Frontiers Science Program (S.H.); a Howard Hughes Medical Institute Collaborative Innovation Award, a Smith Family New Investigator Award, the Alfred Sloan Foundation, the Milton Fund (N.U.); F32 DK078478, P30 DK046200 (L.V.); and R01 DK075632, R01 DK089044, P30 DK046200, P30 DK057521 (B.B.L.).

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J.Y.C. and S.H. collected and analysed data. J.Y.C., S.H. and N.U. designed experiments and wrote the paper. L.V. and B.B.L. generated Vgat-Cre mice.

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Correspondence to Naoshige Uchida.

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Cohen, J., Haesler, S., Vong, L. et al. Neuron-type-specific signals for reward and punishment in the ventral tegmental area. Nature 482, 85–88 (2012). https://doi.org/10.1038/nature10754

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