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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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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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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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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DOI: https://doi.org/10.1038/nn.3145
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