THE VESICULAR MONOAMINE TRANSPORTER-2 IS PRESENT IN SMALL SYNAPTIC VESICLES AND PREFERENTIALLY LOCALIZES TO LARGE DENSE CORE VESICLES IN RAT SOLITARY TRACT NUCLEI

In central neurons, monoamine neurotransmitters are taken up and store d within two distinct classes of regulated secretory vesicles: small s ynaptic vesicles and large dense core vesicles (DCVs). Biochemical and pharmacological evidence has shown that this uptake is mediated by sp ecific vesicular monoamine transporters (VMATs). Recent molecular clon ing techniques have identified the vesicular monoamine transporter (VM AT2) that is expressed in brain. This transporter determines the sites of intracellular storage of monoamines and has been implicated in bot h the modulation of normal monoaminergic neurotransmission and the pat hogenesis of related neuropsychiatric disease. We used an antiserum ag ainst VMAT2 to examine its ultrastructural distribution in rat solitar y tract nuclei, a region that contains a dense and heterogeneous popul ation of monoaminergic neurons. We find that both immunoperoxidase and immunogold labeling for VMAT2 localize to DCVs and small synaptic ves icles in axon terminals, the trans-Golgi network of neuronal perikarya , tubulovesicles of smooth endoplasmic reticulum, and potential sites of vesicular membrane recycling. In axon terminals, immunogold labelin g for VMAT2 was preferentially associated with DCVs at sites distant f rom typical synaptic junctions. The results provide direct evidence th at a single VMAT is expressed in two morphologically distinct types of regulated secretory vesicles in central monoaminergic neurons.