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Distinct roles for direct and indirect pathway striatal neurons in reinforcement


Dopamine signaling is implicated in reinforcement learning, but the neural substrates targeted by dopamine are poorly understood. We bypassed dopamine signaling itself and tested how optogenetic activation of dopamine D1 or D2 receptor–expressing striatal projection neurons influenced reinforcement learning in mice. Stimulating D1 receptor–expressing neurons induced persistent reinforcement, whereas stimulating D2 receptor–expressing neurons induced transient punishment, indicating that activation of these circuits is sufficient to modify the probability of performing future actions.

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Figure 1: dMSN stimulation induces persistent reinforcement, whereas iMSN stimulation induces transient punishment.
Figure 2: Acquisition and expression of trigger preference are not influenced by dopaminergic antagonists.
Figure 3: dMSN and iMSN stimulation modify place preference.


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We thank the Nikon Imaging Center at the University of California San Francisco for assistance with image acquisition, K. Deisseroth for optogenetic constructs and K. Tye for helpful comments on the manuscript. A.C.K. and co-workers are funded by the W.M. Keck Foundation, the Pew Biomedical Scholars Program, the McKnight Foundation and the US National Institutes of Health.

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Authors and Affiliations



A.V.K. and L.D.T. jointly conducted the experiments and analyzed the data. A.V.K. and A.C.K. conceived the study and wrote the manuscript.

Corresponding author

Correspondence to Anatol C Kreitzer.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–5 and Supplementary Tables 1–3 (PDF 517 kb)

Supplementary Video 1

Reinforcement of laser-paired trigger contact in a naïve dMSN-ChR2 mouse. Mouse has never received laser stimulation at start of the video, and gains a strong preference within ~10 minutes of training. Video shows first 15 minutes of the first day of training, sped up 10x. (WMV 5630 kb)

Supplementary Video 2

Punishment of laser-paired trigger contact in a naïve iMSN-ChR2 mouse. Mouse has never received laser stimulation at start of the video, and starts avoiding the laser-paired trigger, as well as exhibiting an “escape response” within 10 minutes of training. Video shows first 15 minutes of the first day of training, sped up 10x. (WMV 5068 kb)

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Kravitz, A., Tye, L. & Kreitzer, A. Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nat Neurosci 15, 816–818 (2012).

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