Responses of basal forebrain cholinergic neurons to damage in the adult brain

The basal forebrain cholinergic system, which projects to all cortical areas, is a good model for the study of the responses of central nervous system (CNS) neurons to injury. Much is known about the specific neurotrophic factors of basal forebrain cholinergic neurons, and there are many techniques available to chart the progress of degeneration and recovery of cholinergic neurons after damage. There is also a clinical version of damage to cholinergic neurons which is part of the selective pathology of Alzheimer's disease. In general, CNS neurons do not regenerate well after brain damage. The first part of the review describes how the CNS promotes only limited neuronal regeneration, and that this is because of the presence of inhibitory factors and the lack of growth factors. Despite this, some CNS areas may provide a better environment for CNS regeneration than others. In the second part of the review, the degeneration and regeneration of basal forebrain cholinergic pathways in the adult rat are discussed. It is shown how the collateral sprouting of cholinergic axons occur more readily in the hippocampal formation than in neocortical areas, and that this could be linked with the more neuroplastic properties of the hippocampus. The third part of the review describes how the degeneration of cholinergic pathways in Alzheimer's disease is likely to be secondary to the pathology or degeneration of certain cortical areas. The hypothesis is put forward that the severity of the pathology in highly plastic limbic cortical areas could be linked with their susceptibility to risk factors of Alzheimer's disease such as ageing, and genetic and environmental factors.