CENTRAL CHOLINERGIC PATHWAYS IN THE RAT : AN OVERVIEW BASED ON AN ALTERNATIVE NOMENCLATURE ( Chl-Ch 6 )

Monoclonal antibodies to choline acetyltransferase and a histochemical method for the concurrent demonstration of acetylcholinesterase and horseradish peroxidase were used to investigate the organization of ascending cholinergic pathways in the central nervous system of the rat. The cortical mantle, the amygdaloid complex. the hippocampal formation, the olfactory bulb and the thalamic nuclei receive their cholinergic innervation principally, from cholinergic projection neurons of the basal forebrain and upper brainstem. On the basis of connectivity patterns, we subdivided these cholinergic neurons into six major sectors. The Chl and Ch2 sectors are contained within the medial septal nucleus and the vertical limb nucleus of the diagonal band, respectively. They provide the major cholinergic projections of the hippocampus. The Ch3 sector is contained mostly within the lateral portion of the horizontal limb nucleus of the diagonal band and provides the major cholinergic innervation to the olfactory bulb. The Ch4 sector includes cholinergi~ neurons in the nucleus basalis, and also within parts of the diagonal band nuclei. Neurons of the Ch4 sector provide the major cholinergic innervation of the cortical mantle and the amygdala. The Ch5-Ch6 sectors are contained mostly within the pedunculopontine nucleus of the pontomesencephalic reticular formation (Ch.5) and within the laterodorsal tegmental gray of the periventricular area (Ch6). These sectors provide the major cholinergic innervation of the thalamus. The Ch5-Ch6 neurons also provide a minor component of the corticopetal cholinergic innervation. These central cholinergic pathways have been implicated in a variety of behaviors and especially in memory function. It appears that the age-related changes of memory function as well as some of the behavioral disturbances seen in the dementia of Alzheimer’s Disease may be related to pathological alterations along central cholinergic pathways. Neurons in the basal forebrain provide the major source of cholinergic innervation for the entire neocortex, the hippocampus, the amygdala and the olfac5 20.21,30.35.37,40.41.42.50.52.54.57.58.59,66,6~.73,76 tory bulb:. Based on observations in the macaque brain, we subdivided these cholinergic projection neurons of the basal forebrain into four major sectors which we designated ChlLCh4.‘? In our initial report, the Ch designation referred to the entire nucleus that contained cholinergic projection neurons. We have since modified our position so that we reserve the Ch designation only for the subset of cholinergic neurons within the relevant nuclei. In the macaque, the Chl and Ch2 sectors are contained within the medial septal nucleus and the vertical limb nucleus of the diagonal band, respectively. They collectively provide the major source of cholinergic projections to the hippocampus. The Ch3 sector is contained, at least in part, within the horizontal limb nucleus of the diagonal band and provides the major source of Chl-Ch4 projections to the olfactory bulb. The Ch4 sector Ahhreviufions: AChE. acetylcholinesterase: ChAT, choline acetyltransferase; HRP, horseradish peroxidase; WGA. wheat germ agglutinin. most closely corresponds to the nucleus basalis of Megnert but also includes cholinergic neurons within the nucleus of the ansa lenticularis, the nucleus of the ansa peduncularis, the medullary laminae of the globus pallidus, and the substantia innominata. The Ch4 neurons provide the principal cholinergic innervation for the amygdala and neocortical areas. This extensive and continuous system of Chl-Ch4 neurons gives rise to topographically organized cholinergic projections which innervate the entire neocortical mantle as well as many limbic and olfactory structures. In addition to these telencephalic structures, thalamic nuclei also appear to receive substantial cholinergic innervation.t7,24.69.*3 Several lines of investigation strongly suggest that this innervation originates in the region of the pontomesencephalic reticular formation.‘5.32.33.5’.76 The experiments that we report here served two purposes. First, we wanted to see if an analagous Chl-Ch4 nomenclature, based on the same set of cytochemical and anatomical considerations which we used in the macaque brain, could be proposed for the choline@ neurons of the rat forebrain. A second purpose was to identify the individual neurons which give rise to the cholinergic innervation of the thal-