Receptor function in cortical rat brain regions after lesion of nucleus basalis

The present study was undertaken to study the interaction of cholinergic and glutamatergic mechanisms in cholinoceptive cortical target regions which is assumed to play an important role for realizing cognitive functions. The densities of cortical muscarinic cholinergic receptor subtypes and corresponding receptor genes m1 through m4, as well as NMDA, AMPA and kainate glutamate receptor subtypes were measured in rats one week after unilateral mechanical lesion of the anterior part of the nucleus basalis magnocellularis (NbM) applying quantitative receptor autoradiography and in situ hybridization. The studies revealed that in cortical regions displaying a low amount of acetylcholinesterase activity due to forebrain cholinergic lesion, NMDA receptor binding was markedly reduced in comparison to the unlesioned side, whereas AMPA and kainate binding has been significantly increased in these regions. M1-muscarinic cholinergic receptor binding was not changed in any of the cortical regions studied, whereas M2-receptor densities are slightly reduced in frontal and parietal cortices following lesion. These alterations in cortical M2-muscarinic receptor binding are complemented by corresponding changes in the m2- and m4-mRNA transcripts. The comparison of binding profiles through selected cortical regions of both lesioned and normal brain side revealed that lesion of the NbM affects NMDA receptors in all cortical layers of the lesioned side, whereas AMPA receptors are affected preferentially in the upper and kainate receptors preferentially in the middle and deeper cortical layers. The differential changes in glutamate 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 presynaptic cortical cholinergic deficits might affect glutamatergic functions with different intensity and different directions.