Dementia: animal models of the cognitive impairments following damage to the basal forebrain cholinergic system

The finding that patients with Alzheimer's disease (AD) have significant degeneration of neurons in the basal forebrain cholinergic system (BFCS) stimulated a great deal of research to determine the cognitive impairments resulting from selective damage to this area. The experiments reviewed here indicate that lesions of the nucleus basalis magnocellularis (NBM) and of the medial septal area (MSA) reproduce the behavioral symptoms following lesions of their respective target sites, the frontal cortex (FC) and the hippocampus (HIP). Impairments of recent memory are one of the most striking symptoms in AD patients at the beginning of their disease, and lesions of the BFCS induce similar impairments. Comparisons of the effects of the lesions produced by different neurotoxins, ibotenic (IBO) acid and quisqualic (QUIS) acid, have raised questions about the role of cholinergic and noncholinergic neurotransmitter systems in the basal forebrain. The implications of these data for the cholinergic hypothesis of mnemonic functions are discussed.