Monoaminergic–cholinergic interactions in the primate basal forebrain

• Published in: Neuroscience Vol. 93; no. 3; pp. 817 - 829
• Main Authors: Smiley, J.F., Subramanian, M., Mesulam, M.-M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.1999; Elsevier
• Subjects: acetylcholine; Alzheimer's disease; Animals; Axons - metabolism; Axons - ultrastructure; Biological and medical sciences; Brain Stem - cytology; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Choline O-Acetyltransferase - metabolism; Cholinergic Fibers - metabolism; Cholinergic Fibers - ultrastructure; dopamine; Dopamine - metabolism; Dopamine beta-Hydroxylase - metabolism; Fundamental and applied biological sciences. Psychology; Immunoenzyme Techniques; Macaca fascicularis; Macaca nemestrina; Microscopy, Electron; monoamines; Nerve Tissue Proteins - metabolism; Neurons - metabolism; Neurons - ultrastructure; norepinephrine; Norepinephrine - metabolism; nucleus basalis; Prosencephalon - metabolism; serotonin; Serotonin - metabolism; Tyrosine 3-Monooxygenase - metabolism; Vertebrates: nervous system and sense organs; norepinephrine; Ch4, cholinergic cells of the nucleus basalis of Meynert; DAB, diaminobenzidine; nucleus basalis; ChAT, choline acetyltransferase; NGFr, nerve growth factor receptor; serotonin; AD, Alzheimer's disease; TH, tyrosine hydroxylase; DBH, dopamine-β-hydroxylase; Trp-OH, tryptophan hydroxylase; acetylcholine; Ch1, cholinergic cells in the medial septal nucleus; Ch2, cholinergic cells of the vertical limb of the diagonal band; dopamine; Alzheimer's disease; Human; Dopamine; Serotonin; Alzheimer disease; Central nervous system; Monkey; Projection; Catecholamine; Anatomy; Prosencephalon; Vertebrata; Nucleus basalis; Mammalia; Neurotransmitter; Primates; Acetylcholine; Norepinephrine
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(99)00116-5

Anatomical studies in the rat have shown that the cholinergic cells of the nucleus basalis receive synapses from monoamine axons, but similar evidence is lacking in primates. We used single- and double-labeling immunocytochemistry to visualize monoamine axons and their relationship with the cholinergic cells of the basal forebrain of the monkey. Norepinephrine axons, labeled with dopamine-β-hydroxylase antibodies, formed a bed of fine varicose axons that co-distributed with the cholinergic cells. Tyrosine hydroxylase-immunoreactive axons, presumed to be mainly dopaminergic, were 10–20 times more abundant than dopamine-β-hydroxylase axons throughout the basal forebrain, except in the medial septal area, where their density was lower. Serotonin-immunoreactive axons formed a dense axon plexus throughout the basal forebrain. Double-labeling light microscopy demonstrated that each of the three types of monoamine axons formed frequent direct contacts with the cholinergic cells. Electron microscopy showed that the noradrenergic and the putative dopaminergic axons synapsed on the cholinergic cells. In the human brain, immunolabeling with antibodies to dopamine-β-hydroxylase, tyrosine hydroxylase and tryptophan hydroxylase (for serotonin axons) showed axon densities in the nucleus basalis comparable to those of the monkey brain. The data demonstrate that all three of these monoamine systems innervate the cholinergic and possibly also the non-cholinergic cells of the nucleus basalis, and therefore affect the release of acetylcholine in the cerebral cortex.