Cortical cholinergic deafferentation following the intracortical infusion of 192 IgG-saporin: a quantitative histochemical study

Abstract

The immunotoxin 192 IgG-saporin has been hypothesized to selectively lesion cholinergic neurons that bear the low-affinity p75 nerve growth factor (NGF) receptor. To evaluate the usefulness of this toxin in studies intended to determine the functions of cholinergic afferents of cortical areas, relatively small concentrations and volumes of the immunotoxin (0.01–0.05 μg/0.5–1.0 μl) were infused into cortical areas of one hemisphere of rats, while the vehicle was infused into homologous areas of the contralateral hemisphere. The effects of these infusions on the density of cortical acetylcholinesterase (AChE)-positive fibers and of normal fibers (as revealed by a reduced silver stain) were quantified. The infusion of the immunotoxin did not produce local gliosis in excess of the gliosis resulting from the infusion of vehicle. When compared with the frontoparietal cortex of the intact hemisphere, the number of cortical AChE-positive fibers was reduced by 36–39% and the density of the silver-stained fibers was decreased by 20–25%. While the loss of AChE-positive fibers and silver-stained fibers correlated significantly in layers V/VI, a linear regression analysis suggested that the magnitude of the loss of AChE-positive fibers was greater than would be predicted on the basis of the residual density of normal fibers. Thus, the data suggest that infusions of 192 IgG-saporin into the cortex did not result in the loss of non-cholinergic afferents. Intracortical infusions of relatively small concentrations and volumes of 192 IgG-saporin appear to provide a useful approach for the examination of the functions of cholinergic inputs to specific cortical regions.