EFFECTS OF NUCLEUS BASALIS LESION ON MUSCARINIC RECEPTOR SUBTYPES

The cholinergic system in the central nervous system is an important c omponent of the neural circuitry of learning, memory and cognition. A decline of cholinergic innervation in the human brain is a characteris tic feature of dementia of Alzheimer's type. In this study, changes in cholinergic markers were studied after a unilateral lesion of the nuc leus basalis magnocellularis (nbM). Acetylcholinesterase (AChE) histoc hemistry showed a loss of cortical AChE-containing neurons, and cholin e acetyltransferase (ChAT) immunohistochemistry demonstrated a loss of cholinergic cells in nbM. The localizations of muscarinic M1 and M2 r eceptors using [H-3]pirenzepine ([H-3]PZ) and [H-3]AF-DX384, respectiv ely, were studied by quantitative autoradiography 1, 2, 4 and 6 weeks following unilateral ibotenic acid lesion of nbM. A significant decrea se in [H-3]PZ binding sites was observed at postlesion week 1 in the p arietal and temporal cortices. The decrease in [H-3]AF-DX 384 binding sites on the lesioned side was observed throughout frontal, parietal a nd temporal cortices after postlesion week 1, with a significant incre ase after 6 weeks, possibly as result of loss of presynaptic receptors and upregulation of postsynaptic ones. Moreover, laminar distribution after nbM lesion shows that M1 and M2 receptor binding sites are more affected in superficial layers (I,II,III) than in the deep layers (IV ,V,VI), depending on ligand, postlesion period and cortical region. Fu rthermore, nbM lesion causes a higher deficit of M2 receptors than of M1 receptors. These data suggest the existence of a presynaptic popula tion as well as a postsynaptic population of M1 and M2 receptors which are differently affected after unilateral nbM lesion.