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Science 324 (5933): 1441-1444

Copyright © 2009 by the American Association for the Advancement of Science

Fluorescent False Neurotransmitters Visualize Dopamine Release from Individual Presynaptic Terminals

Niko G. Gubernator,1,*,{dagger} Hui Zhang,2,3,* Roland G. W. Staal,2 Eugene V. Mosharov,2 Daniela B. Pereira,2 Minerva Yue,2 Vojtech Balsanek,1 Paul A. Vadola,1 Bipasha Mukherjee,4 Robert H. Edwards,4 David Sulzer,2,3,5,{ddagger} Dalibor Sames1,{ddagger}

Abstract: The nervous system transmits signals between neurons via neurotransmitter release during synaptic vesicle fusion. In order to observe neurotransmitter uptake and release from individual presynaptic terminals directly, we designed fluorescent false neurotransmitters as substrates for the synaptic vesicle monoamine transporter. Using these probes to image dopamine release in the striatum, we made several observations pertinent to synaptic plasticity. We found that the fraction of synaptic vesicles releasing neurotransmitter per stimulus was dependent on the stimulus frequency. A kinetically distinct "reserve" synaptic vesicle population was not observed under these experimental conditions. A frequency-dependent heterogeneity of presynaptic terminals was revealed that was dependent in part on D2 dopamine receptors, indicating a mechanism for frequency-dependent coding of presynaptic selection.

1 Department of Chemistry, Columbia University, New York, NY 10027, USA.
2 Departments of Neurology, Psychiatry, and Pharmacology, Columbia University, New York, NY 10032, USA.
3 Departments of Psychiatry and Pharmacology, Columbia University, New York, NY 10032, USA.
4 Departments of Neurology and Physiology, University of California School of Medicine, San Francisco, San Francisco, CA 94143, USA.
5 Division of Molecular Therapeutics, New York Psychiatric Institute, New York, NY 10032, USA.

* These authors contributed equally to this work.

{dagger} Present address: eMolecules, San Diego, CA 92014, USA.

{ddagger} To whom correspondence should be addressed. E-mail: ds43{at}columbia.edu (D. Sulzer); sames{at}chem.columbia.edu (D. Sames)

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