Developmental forebrain cholinergic lesion and environmental enrichment: behaviour, CA1 cytoarchitecture and neurogenesis.

Intraventricular injections of 192 IgG saporin in 7-day-old rat severely reduced hippocampal cholinergic innervation as reflected by both decreased acetylcholinesterase staining and immunoreactivity for the p75 neurotrophin receptor. It was determined if this altered the effects of environmental enrichment on spatial learning, hippocampal CA1 cell cytoarchitecture as reflected by the Golgi stain, and neurogenesis in the dentate gyrus as indicated by doublecortin immunoreactivity. At weaning, lesioned and control rats were either group housed in large, environmentally enriched cages or housed two per standard cage for 42 days. When subsequently assessed with a working-memory spatial navigation task, both lesioned and control rats showed enhanced learning as a result of enrichment. Quantitative analysis of Golgi stained sections indicated that enrichment did not affect CA1 dendritic branching, total dendritic length or dendritic spine density. However, the lesion reduced the number of apical branches, spine density on intermediate to distal apical dendrites, and the length of basal branches. It also reduced the number of doublecortin immunoreactive neurons in the dentate gyrus and appeared to prevent their increase due to environmental enrichment. It is concluded that developmental cholinergic lesioning does not attenuate neurobehavioral plasticity, at least as reflected by the behavioral consequences of enrichment. It does, however, attenuate neurogenesis in the dentate gyrus, like adult-inflicted cholinergic lesions. As previously found for cortical neurons, it also reduces CA1 pyramidal cell dendritic complexity and spine density in adulthood. The results have implications for the loss of synapses that occurs in both developmental and aging-related brain disorders involving cholinergic dysfunction.