DIFFERENTIAL DISTRIBUTION OF THE PUTATIVE VESICULAR TRANSPORTER FOR ACETYLCHOLINE IN THE RAT CENTRAL-NERVOUS-SYSTEM

The organization and distribution of the mRNA for the putative vesicul ar transporter for acetylcholine (VAChT) was studied in the rat brain by use of digoxigenin-labeled riboprobes and in situ hybridization tec hnology. Signal was observed in all neural regions deduced to contain cholinergic somata on the basis of previous histochemical investigatio ns employing choline acetyltransferase riboprobes and prior immunocyto chemical studies with antibodies against choline acetyltransferase. It was absent in areas believed to contain no cholinergic neurons. Anti- sense riboprobes hybridized to the mRNA for the putative VAChT: (a) th e projection neurons of the various nuclei of the basal nuclear comple x, (b) the local circuit cells of the dorsal and ventral striata, (c) the projection neurons of the mesopontine complex, (d) perikarya in th e ventral 2/3 of the medial habenula, (e) the somatic motor and autono mic cells of cranial nerves 3-7 and 9-12, as well as perikarya in the dorsal and ventral cochlear nuclei presumably giving rise to efferent fibers of cranial nerve 8, and (f) the a-motor and gamma-efferent moto r neurons of the spinal cord. In addition, the mRNA for the VAChT was found in a few somata, probably ectopically located cells of the basal nuclear complex, in the internal capsule, central nucleus of the amyg dala, entopeduncular nucleus, and zona incerta. It was also detected i n some cell bodies in the reticular part of the substantia nigra, prob ably the rostral extension of the mesopontine complex, in the parabige minal nucleus, and around the central canal in the spinal cord but not in cortical, hippocampal, and cerebellar perikarya. It is concluded t hat, like choline acetyltransferase, the mRNA for the putative acetylc holine vesicular transporter is another specific marker for neurons ut ilizing acetylcholine as a neurotransmitter. Further investigations of that transporter could have important implications for various diseas es involving cholinergic systems, such as Alzheimer's disease.