Organization of the basal forebrain cholinergic system in the human brain

The mammalian nervous system contains several cholinergic cell groups. The most extensive of these are the cholinergic neurons of the basal forebrain (BFCN). The human BFCN are organized into four cell groups (Ch): Ch1, centered around the medial septum (Ch1-ms), Ch2 in the vertical limb of the diagonal band of Broca (Ch2-dbv), Ch3 around the horizontal limb of the diagonal band of Broca (Ch3-dbh), and Ch4 in the nucleus basalis of Meynert (Ch4-nbM). The Ch4-nbM is the largest of these neuronal groups and is parcellated into sectors based on grouping of cells and anatomic landmarks. Consistent with their cholinergic phenotype, BFCN cell groups are rich in synthetic enzyme choline acetyltransferase (ChAT) and hydrolytic enzyme acetylcholinesterase (AChE). They also have high content of nerve growth factor receptors and calcium-binding protein calbindin-D_28K. In the monkey brain, each BFCN cell group has its preferred cortical targets. Ch1-ms and Ch2-dbv neurons project to the hippocampus, Ch3-dbh neurons to the olfactory bulb, and Ch4-nbM neurons to the entire cortical mantle and the amygdala. Despite extensive projections to all cortical areas, only limbic cortical components project back to the BFCN. Staining for AChE activity and ChAT immunoreactivity visualizes a plexus of cortical cholinergic axons. The highest density of cholinergic axons is found in limbic and paralimbic cortical regions, intermediate density in association cortical areas, and lowest density in primary sensory and motor regions. Acetylcholine interacts with cortical muscarinic and nicotinic receptors, each with varied regional distribution, to produce its effects. Functionally, the BFCN cell groups are implicated in several behaviors including sleep and arousal, mood and affect, and particularly attention and memory. In summary, the BFCN form a highly complex neuronal system with extensive cortical projections that influence cortical activity and cognitive function.