IBOTENIC ACID LESION OF NUCLEUS BASALIS MAGNOCELLULARIS DIFFERENTIALLY AFFECTS CHOLINERGIC, GLUTAMATERGIC AND GABAERGIC MARKERS IN CORTICALRAT-BRAIN REGIONS

The present study was undertaken to study the effect of reduced cortic al cholinergic activity on gamma-aminobutyric acid (GABA)ergic and glu tamatergic mechanisms in cholinoceptive cortical target regions which are assumed to play an important role for realizing cognitive function s. The densities of cortical muscarinic cholinergic receptor subtypes and corresponding receptor genes m(1) through m(4), N-methyl-D-asparta te (NMDA), pha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AM PA) and kainate glutamate receptor subtypes as well as GABA(A) and ben zodiazepine receptors were measured in rats 1 week after unilateral ib otenic acid lesion of the nucleus basalis magnocellularis (Nbm) applyi ng quantitative receptor autoradiography and in situ hybridization, Ib otenic acid lesion resulted in a striking loss of acetylcholinesterase (AChE) staining in the lesioned Nbm which is associated with a 60% de crease in AChE staining and a 30% reduction in [H-3]hemicholinium-3 bi nding in frontal and parietal cortical regions as well fore- and hindl imb areas ipsilateral to the lesion, being more prominent in the more rostral cortical regions. M(1)-muscarinic cholinergic receptor binding was not changed in any of the cortical regions studied 1 week after l esion. M(2)-muscarinic receptor binding levels are slightly increased in the parietal cortex only. The lesion-induced increase in parietal c ortical M(2)-muscarinic receptor binding is complemented by an increas e in the hybridization signal for the corresponding m(4)-mRNA transcri pt. In cortical regions displaying a reduced activity of AChE and decr eased levels of high-affinity choline uptake sites due to forebrain ch olinergic lesion, NMDA receptor binding was markedly reduced in compar ison to the unlesioned brain side whereas AMPA and kainate binding has been significantly increased in these regions. Muscimol binding to GA BA, receptors was increased in the rostral portions of frontal and par ietal cortices as compared with the unlesioned brain side. Binding lev els of benzodiazepine receptors were not affected by the lesion in any of the cortical regions studied. The differential changes in glutamat e and GABA receptor subtypes following lesion might be regarded as the consequence of a cortical reorganization compensating for the reduced cholinergic presynaptic input. The data further suggest that presynap tic cortical cholinergic deficits might affect both glutamatergic and GABAergic functions with different intensity and different directions.