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Cocaine inverts rules for synaptic plasticity of glutamate transmission in the ventral tegmental area

Nature Neuroscience volume 14, pages 414–416 (2011)Cite this article

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Abstract

The manner in which drug-evoked synaptic plasticity affects reward circuits remains largely elusive. We found that cocaine reduced NMDA receptor excitatory postsynaptic currents and inserted GluA2–lacking AMPA receptors in dopamine neurons of mice. Consequently, a stimulation protocol pairing glutamate release with hyperpolarizing current injections further strengthened synapses after cocaine treatment. Our data suggest that early cocaine-evoked plasticity in the ventral tegmental area inverts the rules for activity-dependent plasticity, eventually leading to addictive behavior.

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Figure 1: Cocaine alters NMDA and AMPA transmission at single synapses onto dopamine neurons of the VTA.
Figure 2: Cocaine treatment inverts the rules of LTP induction at excitatory inputs onto dopamine neurons of the VTA.

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Acknowledgements

We thank the members of the Lüscher laboratory as well as M. Frerking and A. Holtmaat for comments on the manuscript and B. Cerutti for help with the statistical analysis. This work is supported by the Swiss National Science Foundation (C.L.), the Systems X initiative of the Swiss Confederation (NeuroChoice, C.L.).

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Authors and Affiliations

  1. Department of Basic Neurosciences, Medical Faculty, University of Geneva, Geneva, Switzerland

    Manuel Mameli, Camilla Bellone, Matthew T C Brown & Christian Lüscher

  2. Institut du Fer à Moulin, UMR-S 839 INSERM/UPMC, Paris, France

    Manuel Mameli

  3. Department of Clinical Neurosciences, Clinic of Neurology, Geneva University Hospital, Geneva, Switzerland

    Christian Lüscher

Authors
  1. Manuel Mameli
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  2. Camilla Bellone
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  3. Matthew T C Brown
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  4. Christian Lüscher
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Contributions

M.M. carried out all experiments with two–photon laser glutamate uncaging. M.M., M.T.C.B. and C.B. contributed to the long-term plasticity experiments. C.L. designed the study together with M.T.C.B., C.B. and M.M. and wrote the manuscript with the help of all of the authors.

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Correspondence to Christian Lüscher.

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The authors declare no competing financial interests.

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Mameli, M., Bellone, C., Brown, M. et al. Cocaine inverts rules for synaptic plasticity of glutamate transmission in the ventral tegmental area. Nat Neurosci 14, 414–416 (2011). https://doi.org/10.1038/nn.2763

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