Basal forebrain afferent projections modulating cortical acetylcholine, attention, and implications for neuropsychiatric disorders

Cortical acetylcholine (ACh) mediates the detection, selection, and processing of stimuli and associations, and the allocation of processing resources for these attentional functions, For example, loss of cortical cholinergic inputs impairs the performance of rats In tasks designed to assess sustained or divided attention, Intrabasalis infusions of benzodiazepine receptor (BZR) agonists block increases in cortical ACh efflux and impair attentional abilities, Studies on the regulation of cortical ACh efflux by nucleus accumbens (NAC) dopamine (DA) demonstrate that increases in cortical ACh efflux are attenuated by intra-accumbens administration of D1 and, more potently, D2 receptor antagonists, These and other data support the hypothesis that NAC DA, via GABAergic projections to the basal forebrain, controls the excitability of basal forebrain cholinergic neurons, As increases in NAC DA have been hypothesized to represent a major neuronal mediator of schizophrenia and the compulsive use of addictive drugs, the data predict that the abnormal regulation of cortical ACh release represents a crucial neuronal mechanism mediating the cognitive components of these psychopathological disorders.