PEPTIDERGIC INNERVATION AND THE NICOTINIC ACETYLCHOLINE-RECEPTOR IN THE PRIMATE BASAL NUCLEUS

Peptidergic innervation and localization of the neuronal nicotinic ace tylcholine receptor (nAChR) was studied in the basal forebrain of Maca ca fascicularis in order to provide microstructural proofs for the the ory (Changeux et al., 1992) that calcitonin gene-related peptide (CGRP ) is responsible for the maintenance of the acetylcholine receptor. Di stribution and localization of five neuropeptides, namely substance P (SP), CGRP, neuropeptide Y (NPY), vasoactive intestinal polypeptide (V IP) neurotensin (NT), and the neuropeptides parvalbumin (PV) and the a lpha-bungarotoxin- (alpha-BTX-) binding protein was studied by means o f light-and electron microscopic pre-embedding immunocytochemistry. Im munohistochemical double staining revealed that large cholinergic prin cipal nerve cells in the basal forebrain, corresponding to cell group Ch4 constituting Meynert's basal nucleus (BNM), and exerting intense c holine acetyltransferase (ChAT) immunoreactivity, are synaptically inn ervated by axons displaying CGRP immunoreactivity. While SP, NPY, PV a nd CGRP establish dense networks in BNM, innervation by NT and VIP is sparse. Biotinylated alpha-BTX visualizes beaded axons that surround d endrites and perikarya of cholinergic principal cells. Electron micros copic organization of the neuropil in BNM is characterized by a glomer ular (or rather cartridge-like) arrangement of axons surrounding dendr ites of non-cholinergic principal nerve cells. At least one of the axo ns establishing the glomerulus (cartridge) exerts CGRP immunopositivit y while alpha-BTX-immunnopostive axons, presynaptic to dendrites of pr incipal cells, are attached to the glomeruli (cartridges) from outside , As alpha-BTX-binding indicates localization of the alpha 7 subunit o f the neuronal nAChR, the microtopographical arrangement supports the idea that, in a manner similar to that in the neuromuscular junction, CGRP might contribute to the maintenance of nAChR also in BNM. Our res ults suggest that presynaptic nAChR-s are involved in the regulation o f acetylcholine release from a feed-forward amplification mechanism of cholinergic principal cells of BNM.