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The Journal of Neuroscience, October 1, 2000, 20(19):7297-7306

Synaptic Vesicle Transporter Expression Regulates Vesicle Phenotype and Quantal Size

Emmanuel N. Pothos¹, Kristin E. Larsen¹, David E. Krantz³, Yong-jian Liu⁴, John W. Haycock⁶, Wanda Setlik⁵, Michael D. Gershon⁵, Robert H. Edwards³, and David Sulzer^{1, 2}

¹ Departments of Neurology and Psychiatry, Columbia University, New York, New York 10032, ² Department of Neuroscience, New York State Psychiatric Institute, New York, New York 10032, ³ Departments of Neurology and Physiology, University of California San Francisco School of Medicine, San Francisco, California 94143, ⁴ Departments of Neurology and Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, ⁵ Department of Anatomy and Cell Biology, Columbia University, New York, New York 10032, and ⁶ Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans, Louisiana 70119

While the transporters that accumulate classical neurotransmitters in synaptic vesicles have been identified, little is known about how their expression regulates synaptic transmission. We have used adenoviral-mediated transfection to increase expression of the brain vesicular monoamine transporter VMAT2 and presynaptic amperometric recordings to characterize the effects on quantal release. In presynaptic axonal varicosities of ventral midbrain neurons in postnatal culture, VMAT2 overexpression in small synaptic vesicles increased both quantal size and frequency, consistent with the recruitment of synaptic vesicles that do not normally release dopamine. This was confirmed using noncatecholaminergic AtT-20 cells, in which VMAT2 expression induced the quantal release of dopamine. The ability to increase quantal size in vesicles that were already competent for dopamine release was shown in PC12 cells, in which VMAT2 expression increased the quantal size but not the number of release events. These results demonstrate that vesicle transporters limit the rate of transmitter accumulation and can alter synaptic strength through two distinct mechanisms.

Key words: VMAT2; monoamines; dopamine; quantal size; amperometry; vesicular transporter

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20197297-10$05.00/0

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