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Calbindin controls release probability in ventral tegmental area dopamine neurons

Nature Neuroscience volume 15, pages 813815 (2012) | Download Citation

Abstract

Relatively little is known about the molecular control of midbrain dopamine release. Using high-fidelity imaging of pHluorin-tagged vesicular monoamine transporter 2 in dopamine neurons, we found that exocytosis was more loosely coupled to calcium entry than in fast synapses. In ventral tegmental area neurons, this allows exocytosis to be efficiently controlled by a native fast calcium buffer, calbindin-D28k, maintaining a lower vesicular release probability compared with substantia nigra neurons.

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Acknowledgements

We wish to thank R. Edwards (University of California San Francisco) for generously providing VMAT-pHluorin, A. Lee (University of Iowa) for providing pcDNA3.1–calbindin-D28k, A. Miyawaki (RIKEN) for providing CY3.60 and members of the Ryan laboratory for helpful discussions. This work was supported by funds from the National Institute on Drug Abuse (DA0101540) and the National Institute of Mental Health (MH085783).

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Affiliations

  1. Department of Biochemistry, Weill Cornell Medical College, New York, New York, USA.

    • Ping-Yue Pan
    •  & Timothy A Ryan

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Contributions

P.-Y.P. and T.A.R. designed the experiments. P.-Y.P. performed the experiments. P.-Y.P. and T.A.R. analyzed the data and wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Timothy A Ryan.

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DOI

https://doi.org/10.1038/nn.3099

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