Mapping of the basal forebrain cholinergic system of the dog: a choline acetyltransferase immunohistochemical study.

Abstract

In an effort to produce a canine model of basal forebrain ischemia with memory deficits, we have shown that dogs possess a medial striate artery that perfuses basal forebrain territory, homologous to the human recurrent artery of Heubner. In the present study, we set out to delineate the precise topography of the cholinergic neurons in the canine forebrain, a neuronal system implicated in cognitive and memory functions. Floating coronal sections, derived from the head of the caudate nucleus to the rostral border of the hippocampus, were stained for choline acetyltransferase using a monoclonal antibody. Representative sections from one dog brain were drawn. These outlines were used for measurement of cell density, cell size, number of processes, and cell roundness. Choline acetyltransferase-positive neurons constituted four major subdivisions within the basal forebrain. A relatively dense population of cholinergic neurons was present in the medial septal nucleus (Ch1). A continuum of densely packed cells was also delineated within the vertical (Ch2) and horizontal (Ch3) nuclei of the diagonal band of Broca. A fourth group of heterogeneously packed cholinergic neurons represented the nucleus basalis magnocellularis (Ch4). Except for the caudal component of the Ch4 population, the forebrain cholinergic corticopetal system was located within the perfusion territory of the medial striate arteries. The Ch4 cell group in dogs is better defined than that of rodents but is not as sharply demarcated as in human and nonhuman primates. Our findings indicate that the dog may serve as an excellent model for assessing neurological and memory deficits, which, in humans, results from hypoperfusion of the recurrent artery of Heubner.