The Vesicular and Plasmalemmal Dopamine Transporters: Ultrastructural Localization in Nigrostriatal Dopaminergic Neurons

Abstract

Dopaminergic neurotransmission is regulated by two distinct membrane-bound transporters: the vesicular monoamine transporter-2 (VMAT2), and the plasmalemmal dopamine transporter (DAT). These transporters play important roles in the initiation and termination of dopaminergic neurotransmission, respectively. In the present report, we review our recent electron microscopic studies showing the immunocytochemical localization of VMAT2 and DAT in rat brain. We have focused on the nigrostriatal dopaminergic neurons, which are known to release dopamine both from their somata and/or dendrites in the substantia nigra (SN) and from their axonal processes in the dorsal striatum. Our studies show that VMAT2 is selectively localized to small synaptic vesicles (SSVs) and large dense core vesicles (DCVs) in dopaminergic axons and terminals in the striatum, and to tubulovesicular organelles and rare SSVs or DCVs within dopaminergic somata, dendrites, and dendritic spines in the SN. These findings support the proposal that the axonal storage and release of dopamine are primarily vesicle-mediated, but suggest that somatodendritic dopamine storage and release may also involve vesicle-independent mechanisms. The subcellular localization of DAT was strikingly different from that of VMAT2, with extensive labeling of extrasynaptic portions of the plasma membranes of dopaminergic axons and terminals in the striatum, and of dopaminergic dendrites and dendritic spines in the SN. Dopaminergic perikarya in the SN, however, almost never contained detectable plasmalemmal labeling for DAT, suggesting that extrasynaptic portions of the distal dendritic and axonal processes are the primary functional sites for DAT-mediated dopamine reuptake. Together, these studies have provided important new information regarding the potential sites for release and reuptake of dopamine within nigrostriatal dopaminergic neurons.