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Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance

Nature Neuroscience volume 15, pages 1105–1107 (2012)Cite this article

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Abstract

Lateral habenula (LHb) projections to the ventral midbrain, including the rostromedial tegmental nucleus (RMTg), convey negative reward–related information, but the behavioral ramifications of selective activation of this pathway remain unexplored. We found that exposure to aversive stimuli in mice increased LHb excitatory drive onto RMTg neurons. Furthermore, optogenetic activation of this pathway promoted active, passive and conditioned behavioral avoidance. Thus, activity of LHb efferents to the midbrain is aversive but can also serve to negatively reinforce behavioral responding.

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Figure 1: Acute unpredictable foot shock exposure enhances LHb-to-RMTg glutamate release.
Figure 2: Activation of LHb inputs to the RMTg produces passive and conditioned behavioral avoidance.
Figure 3: Activation of LHb inputs to the RMTg produces active behavioral avoidance and disrupts positive reinforcement.

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References

  1. Shin, L.M. & Liberzon, I. Neuropsychopharmacology 35, 169–191 (2010).

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Brischoux, F., Chakraborty, S., Brierley, D.I. & Ungless, M.A. Proc. Natl. Acad. Sci. USA 106, 4894–4899 (2009).

    Article  CAS  Google Scholar 

  5. Bromberg-Martin, E.S. & Hikosaka, O. Nat. Neurosci. 14, 1209–1216 (2011).

    Article  CAS  Google Scholar 

  6. Jhou, T.C., Fields, H.L., Baxter, M.G., Saper, C.B. & Holland, P.C. Neuron 61, 786–800 (2009).

    Article  CAS  Google Scholar 

  7. Perrotti, L.I. et al. Eur. J. Neurosci. 21, 2817–2824 (2005).

    Article  Google Scholar 

  8. Matsui, A. & Williams, J.T. J. Neurosci. 31, 17729–17735 (2011).

    Article  CAS  Google Scholar 

  9. Ji, H. & Shepard, P.D. J. Neurosci. 27, 6923–6930 (2007).

    Article  CAS  Google Scholar 

  10. van Zessen, R., Phillips, J.L., Budygin, E.A. & Stuber, G.D. Neuron 73, 1184–1194 (2012).

    Article  CAS  Google Scholar 

  11. Matsumoto, M. & Hikosaka, O. Nat. Neurosci. 12, 77–84 (2009).

    Article  CAS  Google Scholar 

  12. Tan, K.R. et al. Neuron 73, 1173–1183 (2012).

    Article  CAS  Google Scholar 

  13. Li, B. et al. Nature 470, 535–539 (2011).

    Article  CAS  Google Scholar 

  14. Shabel, S.J., Proulx, C.D., Trias, A., Murphy, R.T. & Malinow, R. Neuron 74, 475–481 (2012).

    Article  CAS  Google Scholar 

  15. Stephenson-Jones, M., Floros, O., Robertson, B. & Grillner, S. Proc. Natl. Acad. Sci. USA 109, E164–E173 (2012).

    Article  CAS  Google Scholar 

  16. Stuber, G.D. et al. Nature 475, 377–380 (2011).

    Article  CAS  Google Scholar 

  17. Stuber, G.D., Hnasko, T.S., Britt, J.P., Edwards, R.H. & Bonci, A. J. Neurosci. 30, 8229–8233 (2010).

    Article  CAS  Google Scholar 

  18. Stuber, G.D. et al. Alcohol. Clin. Exp. Res. 32, 1714–1720 (2008).

    Article  CAS  Google Scholar 

  19. Sparta, D.R. et al. Nat. Protoc. 7, 12–23 (2012).

    Article  CAS  Google Scholar 

  20. Cunningham, C.L., Gremel, C.M. & Groblewski, P.A. Nat. Protoc. 1, 1662–1670 (2006).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank R. Ung, V. Gukassyan and the UNC Neuroscience Center Microscopy Facility, and the members of the Stuber laboratory for discussion. We thank K. Deisseroth (Stanford University) for opsin constructs and the UNC Vector Core for viral packaging. We thank C. Good for sagittal slice preparation advice. This study was supported by the Brain and Behavior Research Foundation, the Foundation for Alcohol Research, the Whitehall Foundation, the Foundation of Hope and the National Institute on Drug Abuse (DA029325 and DA032750; G.D.S.). A.M.S. was supported by the UNC Neurobiology Curriculum training grant (T32 NS007431).

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Authors and Affiliations

  1. University of North Carolina (UNC) Neurobiology Curriculum, UNC Neuroscience Center, UNC at Chapel Hill, Chapel Hill, North Carolina, USA

    Alice M Stamatakis & Garret D Stuber

  2. Departments of Psychiatry & Cellular and Molecular Physiology, UNC Neuroscience Center, UNC at Chapel Hill, Chapel Hill, North Carolina, USA

    Garret D Stuber

Authors
  1. Alice M Stamatakis
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  2. Garret D Stuber
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Contributions

A.M.S. collected all of the data. A.M.S. and G.D.S. designed the experiments, analyzed the data and wrote the manuscript.

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Correspondence to Garret D Stuber.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7 (PDF 14257 kb)

Supplementary Video 1

LHb-to-RMTg activation during real-time place preference. Video of ChR2-EYFP and EYFP-expressing mice during real-time place preference (AVI 19884 kb)

Supplementary Video 2

LHb-to-RMTg activation during positive reinforcement. Video of ChR2-EYFP and EYFP-expressing mice during positive reinforcement where each nose-poke is paired with a 60-Hz optical stimulation. (AVI 34093 kb)

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Stamatakis, A., Stuber, G. Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance. Nat Neurosci 15, 1105–1107 (2012). https://doi.org/10.1038/nn.3145

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