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:

Genetic control of instrumental conditioning by striatopallidal neuron–specific S1P receptor Gpr6

Nature Neuroscience volume 10, pages 1395–1397 (2007)Cite this article

Abstract

Instrumental conditioning allows animals to learn about the consequences of their own actions, but the underpinning molecular mechanisms remain elusive. Here we show that the sphingosine-1-phosphate (S1P) receptor Gpr6 is selectively expressed in the striatopallidal neurons in the striatum. Gpr6-deficient mice showed reduced striatal cyclic AMP production in vitro and selective alterations in instrumental conditioning in vivo. Thus, Gpr6 is the first striatopallidal neuron–specific genetic regulator of instrumental conditioning in a mammal.

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: Gpr6 is enriched in the striatopallidal MSNs.
Figure 2: Gpr6 deletion facilitates instrumental conditioning.

Similar content being viewed by others

References

  1. Balleine, B.W. & Dickinson, A. Neuropharmacology 37, 407–419 (1998).

    Article  CAS  PubMed  Google Scholar 

  2. Schultz, W., Dayan, P. & Montague, P.R. Science 275, 1593–1599 (1997).

    CAS  PubMed  Google Scholar 

  3. Balleine, B.W. Physiol. Behav. 86, 717–730 (2005).

    CAS  PubMed  Google Scholar 

  4. Gerfen, C.R. Annu. Rev. Neurosci. 15, 285–320 (1992).

    CAS  PubMed  Google Scholar 

  5. Albin, R.L., Young, A.B. & Penney, J.B. Trends Neurosci. 12, 366–375 (1989).

    CAS  PubMed  Google Scholar 

  6. Lobo, M.K., Karsten, S.L., Gray, M., Geschwind, D.H. & Yang, X.W. Nat. Neurosci. 9, 443–452 (2006).

    CAS  PubMed  Google Scholar 

  7. Uhlenbrock, K., Gassenhuber, H. & Kostenis, E. Cell. Signal. 14, 941–953 (2002).

    CAS  PubMed  Google Scholar 

  8. Ignatov, A., Lintzel, J., Kreienkamp, H.J. & Schaller, H.C. Biochem. Biophys. Res. Commun. 311, 329–336 (2003).

    CAS  PubMed  Google Scholar 

  9. Lein, E.S. et al. Nature 445, 168–176 (2007).

    CAS  PubMed  Google Scholar 

  10. Gong, S. et al. Nature 425, 917–925 (2003).

    CAS  PubMed  Google Scholar 

  11. Day, M. et al. Nat. Neurosci. 9, 251–259 (2006).

    CAS  PubMed  Google Scholar 

  12. Kreitzer, A.C. & Malenka, R.C. Nature 445, 643–647 (2007).

    CAS  PubMed  Google Scholar 

  13. Everitt, B.J. & Robbins, T.W. Nat. Neurosci. 8, 1481–1489 (2005).

    CAS  PubMed  Google Scholar 

  14. Hyman, S.E., Malenka, R.C. & Nestler, E.J. Annu. Rev. Neurosci. 29, 565–598 (2006).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank B. Leung for technical support, C. Evans, N. Maidment and A. Charles for discussions and help in the project, and C. Evans and K. Roberts for met-enkephalin antibody and for assistance in cAMP assays. We also thank Deltagen for the Gpr6−/− mice, and N. Heintz (Rockefeller University) and the US National Institute of Neurological Disorders and Stroke Gene Expression Nervous System Atlas Project and Mutant Mouse Regional Resource Center for the Drd1-, Drd2- and Gpr6-GFP mice. This work was supported in part by pilot grants from the University of California, Los Angeles Hatos Center for Neuropharmacology, grants from the US National Institute on Drug Abuse (P50DA05010) to X.W.Y., grants from the US National Institute on Mental Health (MH56446) to B.W.B., and a University of California, Los Angeles Mental Retardation Research Center training grant from the US National Institute on Child Health and Human Development (5T32HD007032) to M.K.L.

Author information

Authors and Affiliations

  1. Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience & Human Behavior, University of California at Los Angeles, 695 Charles Young Drive South, Los Angeles, 90095, California, USA

    Mary Kay Lobo, Yijun Cui & X William Yang

  2. Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, 695 Charles Young Drive South, Los Angeles, 90095, California, USA

    Mary Kay Lobo, Yijun Cui & X William Yang

  3. Brain Research Institute, University of California at Los Angeles, 695 Charles Young Drive South, Los Angeles, 90095, California, USA

    Mary Kay Lobo, Yijun Cui, Sean B Ostlund, Bernard W Balleine & X William Yang

  4. Department of Psychology, University of California at Los Angeles, 695 Charles Young Drive South, Los Angeles, 90095, California, USA

    Sean B Ostlund & Bernard W Balleine

Authors
  1. Mary Kay Lobo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yijun Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sean B Ostlund
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bernard W Balleine
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. X William Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.K.L. conducted all phases of the experimental work and data analyses, except for the instrumental conditioning studies, and contributed to writing the manuscript. Y.C. contributed to the instrumental conditioning studies. S.B.O. contributed to manuscript preparation and to the data analysis of the instrumental conditioning studies. X.W.Y. and B.W.B. were responsible for the overall design of the project, analyses of the results and writing of the manuscript.

Corresponding authors

Correspondence to Bernard W Balleine or X William Yang.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–5 and Methods (PDF 3586 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lobo, M., Cui, Y., Ostlund, S. et al. Genetic control of instrumental conditioning by striatopallidal neuron–specific S1P receptor Gpr6. Nat Neurosci 10, 1395–1397 (2007). https://doi.org/10.1038/nn1987

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn1987

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