The effects of neonatal basal forebrain lesions oncognition : towards understanding the developmental roleof the cholinergic basal forebrain

Abstract

Abnormal development of the cholinergic basal forebrain has been implicated innumerous developmental disabilities such as Rett Syndrome and Down Syndrome. This reviewsummarizes recent data using two rodent animal models that involve interrupting cholinergic basalforebrain projections on postnatal day 1 and postnatal day 7 when basal forebrain fibers arebeginning to innervate their neocortical and hippocampal targets, respectively. In one model,electrolytic lesions in mice aimed at the basal forebrain on postnatal day 1 transiently reducecholinergic markers in neocortex which induce permanent alterations in neocortical anatomy thatcorrelate with impairments on cognitive tasks. Furthermore, the lesion effects are sex dependent.In another model, 192 IgG saporin lesions in rats on postnatal day 7 permanently reducecholinergic markers in neocortex and hippocampus, and result in mild impairments in spatialprocessing, acquisition and exploratory activities. These data suggest that during the firstpostnatal week of development the cholinergic basal forebrain system is critical for normalneocortical differentiation and, possibly synaptogenesis in neural circuits that will be important forspatial memory and acquisition of spatial data. During the second postnatal week of development,the cholinergic basal forebrain system appears to take on a role largely similar to its adult role inselective attention and processing of new information. These studies also suggest strongly thatinterrupting cholinergic basal forebrain innervation of neocortex and hippocampus leads toanatomical and neurochemical abnormalities that may serve as neural substrates for some of thecognitive deficits seen in disorders such as Rett Syndrome and Down Syndrome.