Developmental and target-dependent regulation of vesicular glutamate transporter expression by dopamine neurons.
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.
Department of Pharmacology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada H3C 3J7.
Jose Alfredo
JA
Mendez
Marie-Josée
MJ
Bourque
Gregory
G
Dal Bo
Mathieu L
ML
Bourdeau
Marc
M
Danik
Sylvain
S
Williams
Jean-Claude
JC
Lacaille
Louis-Eric
LE
Trudeau
D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000096:biosynthesis* / Q000235:genetics
D050599:Vesicular Glutamate Transport Protein 2; D004298:Dopamine