Quantitative light microscopic autoradiographic localization of cholinergic muscarinic receptors in the human brain: Forebrain

Abstract

The distribution of muscarinic cholinergic receptors in the human forebrain and cerebellum was studied in detail by quantitative autoradiography using N-[ 3H]methylscopolamine as a ligand. Only postmortem tissue from patients free of neurological diseases was used in this study. The highest densities of muscarinic cholinergic receptors were found in the striatum, olfactory tubercle and tuberal nuclei of the hypothalamus. Intermediate to high densities were observed in the amygdala, hippocampal formation and cerebral cortex. In the thalamus muscarinic cholinergic receptors were heterogeneously distributed, with densities ranging from very low to intermediate or high. N-[ 3H]Methylscopolamine binding was low in the hypothalamus, globus pallidus and basal forebrain nuclei and very low in the cerebellum and white matter tracts. The localization of the putative muscarinic cholinergic receptors subtypes M 1 and M 2 was analysed in parallel using carbachol and pirenzepine at a single concentration to partially inhibit N-[ 3H]methylscopolamine binding. Mixed populations of both subtypes were found in all regions. M 1 sites were largely predominant in the basal ganglia, amygdala and hippocampus and constituted the majority of muscarinic cholinergic receptors in the cerebral cortex. M 2 sites were preferentially localized in the diencephalon, basal forebrain and cerebellum. In some areas such as the striatum and substantia innominata there was a tendency to lower densities of muscarinic cholinergic receptors with increasing age. In general, we observed a slight decrease in M 2 sites in elderly cases. Muscarinic cholinergic receptor concentrations seemed to be reduced following longer postmortem periods. The distribution of acetylcholinesterase was also studied using histochemical methods and compared with the localization of muscarinic cholinergic receptors and other cholinergic markers. The correlation between the presence of muscarinic cholinergic receptors and the involvement of cholinergic mechanisms in the function of specific brain areas is discussed. Their implication in neurological diseases is also reviewed.