Multiple output pathways of the basal forebrain: organization, chemical heterogeneity, and roles in vigilance

Studies over the last decade have shown that the basal forebrain (BF) consists of more than its cholinergic neurons. The BF also contains non-cholinergic neurons, including gamma-aminobutyric acid-ergic neurons which co-distribute and co-project with the cholinergic neurons. Both types of neuron project, in variable proportions, to the cerebral cortex, hippocampus, thalamus, amygdala, and olfactory bulb, whereas descending projections to the posterior hypothalamus and brainstem nuclei are predominantly non-cholinergic. Some of the cholinergic and non-cholinergic projection neurons contain neuropeptides such as galanin, nitric oxide synthase, and possibly glutamate. To understand better the function of the BF, the organization of the multiple ascending and descending projections of BF neurons is reviewed along with their neurochemical heterogeneity, and possible functions of individual pathways are discussed. It is proposed that BF neurons belong to multiple systems with distinct cognitive, motivational, emotional, motor, and regulatory functions, and that through these pathways, the BF plays a role in controlling both cognitive and non-cognitive aspects of vigilance.