Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain

Abstract

All sectors of the human cerebral cortex receive dense cholinergic input. The origin of this projection is located in the Ch4 cell group of the nucleus basalis of Meynert. However, very little is known about the location of the pathways which link the cholinergic neurons of the nucleus basalis to the human cerebral cortex. This question was addressed in whole-hemisphere sections processed for the visualization of multiple cholinergic markers. Two highly organized and discrete bundles of cholinergic fibres extended from the nucleus basalis to the cerebral cortex and amygdala and were designated as the medial and lateral cholinergic pathways. These bundles contained acetylcholinesterase, choline acetyltransferase and nerve growth factor receptors, confirming their cholinergic nature and origin within the basal forebrain. The medial pathway joined the white matter of the gyrus rectus, curved around the rostrum of the corpus callosum to enter the cingulum and merged with fibres of the lateral pathway within the occipital lobe. It supplied the parolfactory, cingulate, pericingulate and retrosplenial cortices. The lateral pathway was subdivided into a capsular division travelling in the white matter of the external capsule and uncinate fasciculus and a perisylvian division travelling within the claustrum. Branches of the perisylvian division supplied the frontoparietal operculum, insula and superior temporal gyrus. Branches of the capsular division innervated the remaining parts of the frontal, parietal and temporal neocortex. Representation of these cholinergic pathways within a 3D MRI volume helped to identify white matter lesion sites that could interfere with the corticopetal flow of cholinergic pathways.

Nicotinic Acetylcholine Receptor Distribution in Alzheimer's Disease, Dementia with Lewy Bodies, Parkinson's Disease, and Vascular Dementia: In Vitro Binding Study Using 5-[125I]-A-85380

“…Binding of 5-[ 125 I]-A-85380 in white matter in the temporal, occipital, and cingulate cortices appears to course with cholinergic pathway previously observed using acetylcholinesterase histochemistry (Selden et al, 1998). Binding of 5-[ 125 I]-A-85380 shown in the temporal cortex follows the course of the capsular division of the lateral cholinergic pathway.…”

“…Binding of 5-[ 125 I]-A-85380 shown in the temporal cortex follows the course of the capsular division of the lateral cholinergic pathway. Fibers of this pathway run adjacent to the putamen in the medial aspect of the external capsule into the nucleus basalis of Meynert which then project down into the temporal cortex (Selden et al, 1998). Binding of 5-[ 125 I]-A-85380 to fibers in the external capsule was not clearly seen due to moderate binding seen in the putamen and claustrum; however, binding to fibers running from the nucleus basalis of Meynert into the temporal cortex was clearly highlighted.…”

“…Binding of 5-[ 125 I]-A-85380 to fibers in the external capsule was not clearly seen due to moderate binding seen in the putamen and claustrum; however, binding to fibers running from the nucleus basalis of Meynert into the temporal cortex was clearly highlighted. The binding of 5-[ 125 I]-A-85380 in the occipital lobe white matter correlates with lateral and medial cholinergic pathways merging posteriorly in the occipital lobe (Selden et al, 1998). 5-[ 125 I]-A-85380 binding at the tip of the cingulate gyrus correlates with the medial cholinergic pathway supplying the cingulate gyrus (Selden et al, 1998).…”

“…The binding of 5-[ 125 I]-A-85380 in the occipital lobe white matter correlates with lateral and medial cholinergic pathways merging posteriorly in the occipital lobe (Selden et al, 1998). 5-[ 125 I]-A-85380 binding at the tip of the cingulate gyrus correlates with the medial cholinergic pathway supplying the cingulate gyrus (Selden et al, 1998). Streaks of intense [ 3 H]nicotine white matter binding previously seen in foetal cerebellum and temporal lobe may also reflect the presence of nAChRs along The known smoker has been eliminated from these data and ex-smokers are included.…”

Time related effects on functional brain connectivity after serotonergic and cholinergic neuromodulation

“…Combining fMRI data of all time points, we found an increase in connectivity with the visual network which was mostly associated with effects on T  = 6 h. The medial and lateral cholinergic pathways, originating from Meynert's basal nucleus, supply a large portion of the brain and merge in the posterior occipital lobe [Selden et al, 1998]. In dementia and schizophrenia, it is hypothesized that cholinergic dysregulation is responsible for psychotic manifestations and AChEIs have been successfully used for treatment of visual hallucinations [Bentley et al, 2008; Sarter and Bruno, 1998].…”