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Dopamine neurons release transmitter via a flickering fusion pore

Nature Neuroscience volume 7, pages 341–346 (2004)Cite this article

Abstract

A key question in understanding mechanisms of neurotransmitter release is whether the fusion pore of a synaptic vesicle regulates the amount of transmitter released during exocytosis. We measured dopamine release from small synaptic vesicles of rat cultured ventral midbrain neurons using carbon fiber amperometry. Our data indicate that small synaptic vesicle fusion pores flicker either once or multiple times in rapid succession, with each flicker releasing ∼25–30% of vesicular dopamine. The incidence of events with multiple flickers was reciprocally regulated by phorbol esters and staurosporine. Thus, dopamine neurons regulate the amount of neurotransmitter released by small synaptic vesicles by controlling the number of fusion pore flickers per exocytotic event. This mode of exocytosis is a potential mechanism whereby neurons can rapidly reuse vesicles without undergoing the comparatively slow process of recycling.

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Figure 1: Dopamine release from axonal varicosities of rat ventral midbrain dopamine neurons.
Figure 2: Amplitudes of flickers within complex events.
Figure 3: Pharmacological regulation of the incidence of complex events.
Figure 4: Mechanisms that may explain complex events (left column) and predicted averaged amperometric event shape (right column).
Figure 5: Simulated dopamine spillover in the striatum.

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Acknowledgements

We thank Q. Al-Awqati, K. Larsen, M. Nirenberg and Y. Schmitz for critique of the manuscript, and A. Petrenko for α-latrotoxin. Supported by the National Alliance for Research on Schizophrenia and Depression, the Lowenstein Foundation, the Parkinson's Disease Foundation, the National Institute on Drug Abuse and the National Institute of Neurological Disorders and Stroke.

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Authors and Affiliations

  1. Department of Neurology, Black 305, 650 West 168th St, Columbia University, New York, 10032, New York, USA

    Roland G W Staal, Eugene V Mosharov & David Sulzer

  2. Department of Psychiatry, Black 305, 650 West 168th St, Columbia University, New York, 10032, New York, USA

    David Sulzer

  3. Department of Neuroscience, New York State Psychiatric Institute, 722 West 168th Street, New York, 10032, New York, USA

    David Sulzer

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  1. Roland G W Staal
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Correspondence to David Sulzer.

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Supplementary information

Supplementary Fig. 1

To estimate the frequency of stochastically overlapping events, the fraction of interspike intervals within 1 s bins is indicated on the y axis. The best-fit exponential decay and corresponding time constant determined by least squares is shown for each experimental group. (JPG 32 kb)

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Staal, R., Mosharov, E. & Sulzer, D. Dopamine neurons release transmitter via a flickering fusion pore. Nat Neurosci 7, 341–346 (2004). https://doi.org/10.1038/nn1205

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