Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Distinct roles for direct and indirect pathway striatal neurons in reinforcement

Nature Neuroscience volume 15, pages 816–818 (2012)Cite this article

Subjects

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. Azrin, N.H. & Holz, W.C. Punishment. in Operant Behavior: Areas of Research and Application (ed. Honig, W.K.) 380–447 (Appleton-Century-Crofts, New York, 1966).

  2. Skinner, B.F. Science and Human Behavior (Macmillan, New York, 1953).

  3. Koob, G.F. & Volkow, N.D. Neuropsychopharmacology 35, 217–238 (2010).

    Article  Google Scholar 

  4. Eshel, N. & Roiser, J.P. Biol. Psychiatry 68, 118–124 (2010).

    Article  Google Scholar 

  5. Bromberg-Martin, E.S., Matsumoto, M. & Hikosaka, O. Neuron 68, 815–834 (2010).

    Article  CAS  Google Scholar 

  6. Lobo, M.K. et al. Science 330, 385–390 (2010).

    Article  CAS  Google Scholar 

  7. Ferguson, S.M. et al. Nat. Neurosci. 14, 22–24 (2011).

    Article  CAS  Google Scholar 

  8. Hikida, T., Kimura, K., Wada, N., Funabiki, K. & Nakanishi, S. Neuron 66, 896–907 (2010).

    Article  CAS  Google Scholar 

  9. Frank, M.J., Seeberger, L.C. & O'Reilly, R.C. Science 306, 1940–1943 (2004).

    Article  CAS  Google Scholar 

  10. Kravitz, A.V. et al. Nature 466, 622–626 (2010).

    Article  CAS  Google Scholar 

  11. Balleine, B.W., Delgado, M.R. & Hikosaka, O. J. Neurosci. 27, 8161–8165 (2007).

    Article  CAS  Google Scholar 

  12. Nakatani, Y. et al. Neurobiol. Learn. Mem. 92, 370–380 (2009).

    Article  Google Scholar 

  13. Abe, M. et al. Curr. Biol. 21, 557–562 (2011).

    Article  CAS  Google Scholar 

  14. Kreitzer, A.C. & Malenka, R.C. Neuron 60, 543–554 (2008).

    Article  CAS  Google Scholar 

  15. Schultz, W. Annu. Rev. Neurosci. 30, 259–288 (2007).

    Article  CAS  Google Scholar 

  16. Sohal, V.S., Zhang, F., Yizhar, O. & Deisseroth, K. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459, 698–702 (2009).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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.

Author information

Author notes

  1. Alexxai V Kravitz and Lynne D Tye: These authors contributed equally to this work.

Authors and Affiliations

  1. Gladstone Institute of Neurological Disease, University of California San Francisco, San Francisco, California, USA

    Alexxai V Kravitz, Lynne D Tye & Anatol C Kreitzer

  2. Departments of Physiology and Neurology, University of California San Francisco, San Francisco, California, USA

    Lynne D Tye & Anatol C Kreitzer

  3. Neuroscience Graduate Program, University of California San Francisco, San Francisco, California, USA

    Anatol C Kreitzer

Authors
  1. Alexxai V Kravitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lynne D Tye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anatol C Kreitzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Ethics declarations

Competing interests

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)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kravitz, A., Tye, L. & Kreitzer, A. Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nat Neurosci 15, 816–818 (2012). https://doi.org/10.1038/nn.3100

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.3100

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing