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Calbindin controls release probability in ventral tegmental area dopamine neurons

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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Figure 1: Synaptic vesicles are loosely coupled to calcium entry in DA neurons.
Figure 2: Endogenous calbindin-D28k regulates Pv in DA neurons.
Figure 3: Calbindin-D28k knockdown in VTA DA neurons enhanced Pv and synaptic depression during action potential bursts.

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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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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.

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Correspondence to Timothy A Ryan.

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The authors declare no competing financial interests.

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Pan, PY., Ryan, T. Calbindin controls release probability in ventral tegmental area dopamine neurons. Nat Neurosci 15, 813–815 (2012). https://doi.org/10.1038/nn.3099

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