Acetylcholinesterase-rich neurons of the human cerebral cortex: cytoarchitectonic and ontogenetic patterns of distribution.

Layers 3 and 5 of the adult human cerebral cortex contain a very large number of pyramidal neurons that express intense acetylcholinesterase (AChE) enzymatic activity and AChE-like immunoreactivity. The density of these neurons is high in motor, premotor, and neocortical association areas but quite low in paralimbic cortex. These AChE-rich neurons are located predominantly within layer 3 in the premotor and association cortex, within layer 5 in the non-isocortical components of the paralimbic cortex, and are equally prominent in layers 3 and 5 in the motor cortex. Almost all Betz cells in the motor cortex and up to 80% of layer 3 pyramidal neurons in some parts of the association neocortex yield an AChE-rich staining pattern. The existence of a specific laminar and cytoarchitectonic distribution suggests that the AChE-rich enzymatic pattern of these neurons is selectively regulated. The AChE-rich enzymatic reactivity of the layer 3 and layer 5 neurons is not detectable during early childhood, becomes fully established during adulthood, and does not show signs of decline during advanced senescence in mentally intact individuals. The AChE activity (or enzyme synthesis) in these neurons is therefore held in check for several years during infancy and childhood and begins to be expressed at a time when the more advanced motor and cognitive skills are also being acquired. The absence of immunostaining with an antibody to choline acetyltransferase suggests that these AChE-rich neurons are not cholinergic. The regional distribution of these AChE-rich neurons does not parallel the regional variations of cortical cholinergic innervation. Whereas the AChE-rich pyramidal neurons of layers 3 and 5 almost certainly represent one subgroup of cholinoceptive cortical neurons, their AChE-rich enzymatic pattern is probably also related to a host of non-cholinergic processes that may include maturational changes and plasticity in the adult brain.