Response of the monkey cholinergic septohippocampal system to fornix transection: a histochemical and cytochemical analysis

Transection of the fimbria-fornix pathway is a paradigm that has been richly exploited in rats to assess the structural and functional correlates of cognitive behavior, neural grafting, and growth factor administration. Principally, the degeneration of cholinergic neurons within the septal/diagonal band region has received detailed attention following this manipulation. In contrast, no studies have examined the response of the cholinergic septal/diagonal neurons following axotomy in nonhuman primates. This study examined the neuronal and glial responses within the septal region to selective fornix transection (without cingulate gyrus ablation) in four Cebus apella monkeys. One month following unilateral transection of the fornix by means of an open microsurgical approach, a comprehensive loss of acetylcholinesterase AChE]-containing fibers was observed throughout the hippocampal formation and dentate gyrus ipsilateral to the lesion. Decreases in AChE fiber densities were also observed within the entorhinal cortex ipsilateral to the lesion. No such changes in AChE-fiber density were consistently observed within the subicular region. The decrease in hippocampal AChE-positive fibers was paralleled by a 49.5% reduction in cholinergic medial septal neurons as revealed by Nissl stains and immunohistochemical staining for the receptor for nerve growth factor, a marker of cholinergic basal forebrain neurons in primates. In contrast, no significant changes in the number of neurons within the vertical limb of the diagonal band were noted. Following the transection, a relatively intense reactive gliosis was observed within the dorsal half of the septal region ipsilateral to the transection and within the overlying transected corpus callosum. These data provide the foundation in nonhuman primates on which novel therapeutic factors can be evaluated in paradigms relevant to the study of Alzheimer's disease.