title: Peptidergic innervation and the nicotinic acetylcholine receptor in the primate basal nucleus.
abstract: Peptidergic innervation and localization of the neuronal nicotinic acetylcholine receptor (nAChR) was studied in the basal forebrain of Macaca fascicularis in order to provide microstructural proofs for the theory (Changeux et al., 1992) that calcitonin gene-related peptide (CGRP) is responsible for the maintenance of the acetylcholine receptor. Distribution and localization of five neuropeptides, namely substance P (SP), CGRP, neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) neurotensin (NT), and the neuropeptides parvalbumin (PV) and the alpha-bungarotoxin- (alpha-BTX-) binding protein was studied by means of light- and electron microscopic pre-embedding immunocytochemistry. Immunohistochemical double staining revealed that large cholinergic principal nerve cells in the basal forebrain, corresponding to cell group Ch4 constituting Meynert's basal nucleus (BNM), and exerting intense choline acetyltransferase (ChAT) immunoreactivity, are synaptically innervated by axons displaying CGRP immunoreactivity. While SP, NPY, PV and CGRP establish dense networks in BNM, innervation by NT and VIP is sparse. Biotinylated alpha-BTX visualizes beaded axons that surround dendrites and perikarya of cholinergic principal cells. Electron microscopic organization of the neuropil in BNM is characterized by a glomerular (or rather cartridge-like) arrangement of axons surrounding dendrites of non-cholinergic principal nerve cells. At least one of the axons establishing the glomerulus (cartridge) exerts CGRP immunopositivity while alpha-BTX-immunopositive axons, presynaptic to dendrites of principal cells, are attached to the glomeruli (cartridges) from outside. As alpha-BTX-binding indicates localization of the alpha7 subunit of 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 results suggest that presynaptic nAChR-s are involved in the regulation of acetylcholine release from a feed-forward amplification mechanism of cholinergic principal cells of BNM.
authors.affiliation: Section of Neurobiology, Yale University Medical School, New Haven, CT, USA. bert@bay.u-szeged.hu
authors.forename: B
authors.initials: B
authors.lastname: Csillik
authors.forename: P
authors.initials: P
authors.lastname: Rakic
authors.forename: E
authors.initials: E
authors.lastname: Knyihár-Csillik
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis; D005260:Female; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008297:Male; D009479:Neuropeptides / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology*
chemical_list: D009479:Neuropeptides; D011978:Receptors, Nicotinic; D015740:Calcitonin Gene-Related Peptide