Cholinergic innervation of the cerebral neocortex arises from the basal forebrain and projects to all cortical regions. Acetylcholinesterase (AChE), the enzyme responsible for deactivating acetylcholine, is found within both cholinergic axons arising from the basal forebrain and a subgroup of pyramidal cells in layers III and V of the cerebral cortex. This pattern of staining varies with cortical location and may contribute uniquely to cortical microcircuitry within functionally distinct regions. To explore this issue further, we examined the pattern of AChE staining within auditory, auditory association, and putative language regions of whole, postmortem human brains.

The density and distribution of acetylcholine-containing axons and pyramidal cells vary systematically as a function of auditory processing level. Within primary auditory regions AChE-containing axons are dense and pyramidal cells are largely absent. Adjacent cortical regions show a decrease in the density of AChE-containing axons and an increase in AChE-containing pyramidal cells. The posterior auditory and language regions contain a relatively high density of AChE-containing pyramidal cells and AChE-containing axons. Although right and left posterior temporal regions are functionally asymmetrical, there is no apparent asymmetry in the general pattern of AChE staining between homologous regions of the two hemispheres. Thus, the pattern of AChE staining covaries with processing level in the hierarchy of auditory cortical regions, but does not vary between the functionally distinct right and left posterior regions.

An asymmetry in the size of layer III AChE-rich pyramidal cells was present within a number of cortical regions. Large AChE-rich pyramidal cells of layer III were consistently greater in size in the left hemisphere as compared to the right. Asymmetry in layer III pyramidal cell size was not restricted to language-associated regions, and could potentially have a variety of etiologies including structural, connectional, and activational differences between the left and right hemisphere.