The cholinergic nuclei of the basal forebrain of the rat: normal structure, development and experimentally induced degeneration

Abstract The normal morphology and distribution of the cholinergic neurones of the basal forebrain of the rat have been studied qualitatively and quantitatively after staining immunohistochemically with a monoclonal antibody to choline acetyl transferase (ChAT). This was done in order to provide an adequate control for the changes found in these cells on both sides of the brain in the experimental investigation of the reaction of the cells to damage of their axons. The cholinergic cells form a more or less continuous anteroposterior band, but they can be subdivided into distinct nuclear groups on the basis of the size and form of the cell bodies and dendrites, their position and arrangement. These nuclei conform closely to previous descriptions of Nissl-stained material: the medial septal nucleus, the vertical and horizontal nuclei of the diagonal band and the basal nucleus. Quantitative measurements of the cross-sectional areas of the cells in the different nuclei confirmed the conclusions drawn from the qualitative examination. measurements of the ChAT cells at different ages showed that in all nuclei they are significantly larger in size in infancy than in the adult, and they shrink to the mature zize by 46 days. The cells in the various cholinergic nuclei show distinctly different reactions to damage of their terminal axonal fields. After removal of a large part of the neocortex by removal of the overlying pia-arachnoid mater of the cells in the basal nucleus in the operated hemisphere underwent retrograde cellular degeneration, being swollen and paler-staining up to 14 days, and thereafter shrinking by 20–30% (as compared with those in the brains of age- and sex-matched littermate controls). The degree of shrinkage was appreciably greater when the animals were operated upon at the neonate stage. No cell loss was found, qualitatively or quantitatively, in the basal nucleus. After removal of the hippocampus there is marked loss of cholinergic neurones in the medial septal nucleus and in the vertical nucleus of the diagonal band, and with severe shrinkage of the remaining cells. Removal of the olfactory bulb results in only slight shrinkage of the cells, and no cell loss, in the horizontal nucleus of the diagonal band. Application of excitotoxic drugs, kainic acid, ibotenic acid or N-methyl- d -aspartic acid to the neocortex caused marked cell loss and atrophy of the cortex, and resulted in shrinkage of the cholinergic cells in the basal nucleus comparable to that after mechanical lesions of the cortex. Application of these excitotoxic drugs to the hippocampus also caused cellular shirnkage in the medial septal nucleus and in the vertical nucleus of the diagonal band but there was no cell loss. The occurrence of a similar degree of degeneration in the basal nucleus, cell shrinkage without cell loss, after the placement of the excitatory amino acid on the dura as after devascularization of the cortex suggests that the cellular change is due to loss of the postsynaptic sites of the cholinergic fibres rather than to direct damage of the fibres. It would appear, therefore, that the degeneration of the cholinergic neurones is transneuronal in nature .