Functional Implications of Tonic and Phasic Activity Changes in Nucleus Basalis Neurons

Abstract

The basal forebrain cholinergic system (BFCS) has become a focus of research in many laboratories over the past decade. Current interest in this system began in the mid-1970s when a population of neurons in the basal forebrain was discovered to project to cerebral cortex (Divac, 1975; Kievit and Kuypers, 1975). It was later established that the neurotransmitter for the cortically projecting neurons was acetylcholine (ACh) (Mesulam et al., 1983; Rye et al., 1984) and that these neurons provided the major source of cholinergic input to cortex (Lehmann et al., 1980; Wenk et al., 1980; Johnston et al., 1981; Struble et al., 1986). Also in the mid-1970s, ACh became strongly implicated in Alzheimer’s disease (AD) because cholinergic markers were found to be severely reduced in the brains of AD patients (Davies and Maloney, 1976; Perry et al., 1977; Spillane et al., 1977). By the early 1980s, the nucleus basalis, the largest component of the BFCS, was shown to have a substantial loss of neurons in patients with AD (Whitehouse et al., 1982). The depletion of nucleus basalis neurons was hypothesized to account for the decrease in cortical cholinergic markers which could possibly lead to the cognitive deterioration of AD (Bartus et al., 1982; Coyle et al., 1983). These findings stimulated a great deal of interest in the anatomical and physiological properties of the BFCS in an effort to understand its role in normal brain function and dementia.