Behavioural Specificity of Neocortical Grafts of Fetal Basal Forebrain Tissue After Unilateral Lesion of the Nucleus Basalis with α-Amino-3-OH-4-Isoxozole Propionic Acid (AMPA)

Abstract

The previous articles in this series [4, 9] have shown that unilateral AMPA lesions of the nucleus basalis magnocellularis (nbm) produced widepread morphological and functional changes to the forebrain cholinergic projection system that could be reversed by transplants of fetal cholinergic tissue. At earlier postgraft time points, the effects of cholinergic grafts were specific to the neocortical region (frontal or parietal cortex) into which the grafts were targeted. Here we report that nbm lesion-induced spatial learning and memory deficits in the Morris water maze were reversed at 6–8 weeks postsurgery only by cholinergic grafts placed in the frontal cortex or frontal and parietal cortices combined. Similar grafts to parietal cortex only and noncholinergic fetal transplants to any cortical site were ineffective. In contrast, using separate groups of animals, deficits in sensorimotor function could be reversed in only one measure (open field turning) by cholinergic transplants targeted to the parietal (somatosensory) cortex or frontal and parietal cortex combined. These behavioural dissociations demonstrate that the frontal cortical cholinergic innervation from the nbm is necessary for effective spatial cognitive performance.