Dopamine neurons in culture express VGLUT2 explaining their capacity to release glutamate at synapses in addition to dopamine

Abstract

Dopamine,neurons,have,been,suggested,to use glutamate,as a cotransmitter. To identify the basis of such a phenotype, we have,examined,the expression,of the three recently,identified vesicular,glutamate,transporters,(VGLUT1-3) in postnatal,rat dopamine,neurons,in culture. We,found,that the majority,of isolated dopamine neurons express VGLUT2, but not VGLUT1 or 3. In comparison, serotonin neurons express only VGLUT3. Single-cell RT-PCR experiments,confirmed,the presence,of VGLUT2 mRNA in dopamine,neurons.,Arguing for phenotypic heterogeneity among axon terminals, we find that only a proportion,of terminals,established,by dopamine neurons are VGLUT2-positive. Taken together, our results provide,a basis for the ability of dopamine,neurons,to release glutamate,as a cotransmitter. A detailed,analysis,of the con- ditions under,which,DA neurons,gain or loose a glutamatergic phenotype,may,provide,novel,insight into pathophysiological processes that underlie diseases such as schizophrenia, Parkinson’s disease,and drug,dependence. Keywords: culture, dopamine, glutamate, mesencephalon, vesicular,glutamate,transporters. J. Neurochem. (2004) 88, 1398‐1405. Although,neurons,have,long,been,known,to have,the capacity,to release,neuropeptides,in addition,to small- molecule neurotransmitters such as acetylcholine, glutamate and GABA, the co-release of two different small neurotrans- mitters by neurons,has been,less extensively,investigated. However, data has been provided in support of the co-release