gamma-Aminobutyric acid-containing basal forebrain neurons innervate inhibitory interneurons in the neocortex

The basal forebrain-neocortex pathway--involved in higher cognitive processing, selective attention, and arousal--is considered one of the functionally most important ascending subcortical projections. The mechanism by which this relatively sparse subcortical pathway can control neuronal activity patterns in the entire cortical mantle is still unknown. The present study in the cat provides evidence that gamma-aminobutyric acid-containing basal forebrain neurons participate in the neocortical projection and establish multiple synaptic connections with gamma-aminobutyric acid-releasing interneurons containing somatostatin or parvalbumin. We propose that a mechanism by which the numerically small ascending pathways can exert a powerful global effect in the neocortex is by the selective innervation of gamma-aminobutyric acid-releasing interneurons, which, in turn, control the activity of large populations of pyramidal cells through their extensive axon arborizations. Finally, these results demonstrate a direct anatomical link between two cell populations implicated in Alzheimer disease pathology: basal forebrain neurons and cortical somatostatin cells.