Dendritic and axonal targeting of the vesicular acetylcholine transporter to membranous cytoplasmic organelles in laterodorsal and pedunculopontine tegmental nuclei

Autoregulation of cholinergic neurons in the laterodorsal tegmental (LDT) a nd pedunculopontine (PPT) nuclei has been implicated in many functions, mos t importantly in drug reinforcement and in the pathophysiology of schizophr enia. This autoregulation is attributed to the release of acetylcholine, bu t neither the storage or release sites are known. To determine these sites, Re used electron microscopy for the immunocytochemical localization of ant ipeptide antiserum raised against the vesicular acetylcholine transporter ( VAchT) that is responsible for the uptake of acetylcholine into storage ves icles. The cellular and subcellular distribution of VAchT was remarkably si milar in the two regions by by using each of two methods, immunogold and im munoperoxidase. In both PPT and LDT nuclei, VAchT labeling was seen mainly on membranous organelles including the trans-Golgi network in many somata. VAchT-immunoreactive tubulovesicles resembling saccules of smooth endoplasm ic reticulum were often seen near the plasma membrane in dendrites. The VAc hT-containing dendrites comprised almost 50% of the labeled profiles (1027/ 2129) in PPT and LDT nuclei. The remaining VAchT-immunoreactive profiles we re primarily small unmyelinated axons and axon terminals. Ln axon terminals , VAchT was densely localized to membranes of small synaptic resides. The V AchT-immunoreactive axon terminals formed either symmetric or asymmetric sy napses. The postsynaptic targets of these axon terminals included dendrites that were with (36/110) or without (74/110) VAchT immunoreactivity. Our re sults suggest that dendrites, as well as axon terminals, have the potential for storage and release of acetylcholine in the LDT and PPT nuclei. The re leased acetylcholine is likely to play a major role in autoregulation of me sopontine cholinergic neurons. J. Comp, Neurol. 419:32-48, 2000, (C) 2000 W iley-Liss, Inc.