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The Journal of Neuroscience, June 18, 2008, 28(25):6309-6318; doi:10.1523/JNEUROSCI.1331-08.2008

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Cellular/Molecular
Developmental and Target-Dependent Regulation of Vesicular Glutamate Transporter Expression by Dopamine Neurons

Jose Alfredo Mendez,^1,3 Marie-Josée Bourque,^1,3 Gregory Dal Bo,^1,3 Mathieu L. Bourdeau,^2,3 Marc Danik,⁴ Sylvain Williams,⁴ Jean-Claude Lacaille,^2,3 and Louis-Eric Trudeau^1,2,3

¹Department of Pharmacology, ²Department of Physiology, and ³CNS Research Group, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada H3C 3J7, and ⁴Department of Psychiatry, Douglas Hospital Research Center, McGill University, Montreal, Quebec, Canada H4H 1R3

Correspondence should be addressed to Dr. Louis-Eric Trudeau, Department of Pharmacology, Faculty of Medicine, University of Montreal, C.P. 6128, Succursale Centre-Ville, Montreal, Quebec, Canada H3C 3J7. Email: louis-eric.trudeau{at}umontreal.ca

Mesencephalic dopamine (DA) neurons have been suggested to use glutamate as a cotransmitter. Here, we suggest a mechanism for this form of cotransmission by showing that a subset of DA neurons both in vitro and in vivo expresses vesicular glutamate transporter 2 (VGluT2). Expression of VGluT2 decreases with age. Moreover, when DA neurons are grown in isolation using a microculture system, there is a marked upregulation of VGluT2 expression. We provide evidence that expression of this transporter is normally repressed through a contact-dependent interaction with GABA and other DA neurons, thus providing a partial explanation for the highly restricted expression of VGluT2 in DA neurons in vivo. Our results demonstrate that the neurotransmitter phenotype of DA neurons is both developmentally and dynamically regulated. These findings may have implications for a better understanding of the fast synaptic action of DA neurons as well as basal ganglia circuitry.

Key words: VGluT2; VTA; substantia nigra; cotransmission; dopamine; glutamate

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Received March 27, 2008; revised April 29, 2008; accepted May 5, 2008.

Correspondence should be addressed to Dr. Louis-Eric Trudeau, Department of Pharmacology, Faculty of Medicine, University of Montreal, C.P. 6128, Succursale Centre-Ville, Montreal, Quebec, Canada H3C 3J7. Email: louis-eric.trudeau{at}umontreal.ca

This article has been cited by other articles:

				Y. Schmitz, J. Luccarelli, M. Kim, M. Wang, and D. Sulzer Glutamate Controls Growth Rate and Branching of Dopaminergic Axons J. Neurosci., September 23, 2009; 29(38): 11973 - 11981. [Abstract] [Full Text] [PDF]

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