Nucleus basalis (Ch4) and cortical cholinergic innervation in the human brain: Observations based on the distribution of acetylcholinesterase and choline acetyltransferase

Abstract

The nucleus basalis (NB) of the human brain is a large, complex, and highly differentiated structure. Many of its neurons are magnocellular, hyperchromic, isodendritic, acetylcholinesterase-rich, and choline-acetyltransferase-positive. Concurrent histochemical and immunological staining demonstrated that all choline-acetyltransferase-positive NB neurons in the human brain also contain acetylcholinesterase enzyme activity. Only a small minority of acetylcholinesterase-rich magnocellular cell bodies in the NB failed to show choline acetyltransferase immunoreactivity. Sections that were counterstained for Nissl substance showed that 80-90% of all magnocellular neurons in the NB were choline-acetyltransferase-positive and therefore cholinergic. These characteristics, which are very similar to those of the NB in the monkey brain, justified the designation of these cholinergic neurons in the human brain as the Ch4 (or NB-Ch4) complex. On morphological grounds, the compact parts of the human NB-Ch4 complex were divided into distinct sectors which appeared to show a greater level of differentiation than in the monkey brain. In addition to the compact sectors, interstitial elements of NB Ch4 were embedded within adjacent fiber bundles. The putative cortical projections from NB-Ch4 were identified in the form of acetylcholinesterase-rich fibers. These fibers formed a dense plexus in all cortical regions but also displayed laminar and regional variations. Limbic and paralimbic areas had higher concentrations of these fibers than the immediately adjacent neocortical association areas. Alzheimer's disease was associated with a marked depletion of cortical acetylcholinesterase. Two cases of Alzheimer's disease with relatively selective NB-Ch4 cell loss supported the hypothesis that the corticopetal cholinergic pathways in the human brain may have a topographical organization similar to that in the monkey brain.

Stereotaxic probabilistic maps of the magnocellular cell groups in human basal forebrain

“…The topographical organization of corticopetal cholinergic projection in humans has been confirmed in cases of Alzheimer's disease that had relatively selective cell loss in various sectors of the basal forebrain. From these cases one can conclude that medial frontal and cingulate cortices are innervated from more medial cell groups, whereas the lateral neocortex, including the prefrontal, temporal, parietal and occipital cortices receive their projections from more lateral subdivisions of the magnocellular system (Arendt et al, 1985;Mesulam and Geula, 1988). Mesulam et al (1983) proposed a Ch nomenclature to differentiate cholinergic neurons according to their cortical target areas.…”

“…Large neurons in this area are continuous with similar cells in the medial septum and in the nuclei of the diagonal band and with scattered large cells in association with various fiber bundles, including the internal capsule and anterior commissure. A substantial proportion of the magnocellular neurons in primates represent cholinergic corticopetal projection neurons (Mesulam, 1983;Saper and Chelimsky, 1984;Mesulam and Geula, 1988) that have received particular attention due to their loss in Alzheimer's and related disorders (Perry et al, 1984;Price et al, 1986). Cholinergic neurons in rodents are intermingled with GABAergic, and glutamatergic corticopetal neurons and various peptidergic interneurons (reviewed in Zaborszky and Duque, 2003;Hur and Zaborszky, 2005).…”

Cholinergic Stimulation Enhances Neural Activity Associated with Encoding but Reduces Neural Activity Associated with Retrieval in Humans

“…Central hubs for episodic memory encoding and retrieval, i.e., the hippocampal formation (Schacter and Wagner, 1999;Burgess et al, 2002) and the amygdala (Canli et al, 2000;McGaugh et al, 2002;McIntyre et al, 2003;Rutishauser et al, 2008), are major recipients of cholinergic fibers which originate in the subnuclei of the basal forebrain (Mesulam et al, 1983;Mesulam and Geula, 1988;Mufson et al, 2003;McGaugh, 2004). A premature degeneration of these cholinergic neurons is observed in Alzheimer's dementia (AD), which is characterized by a rapid decline in the ability to encode new information (Mesulam, 2004).…”

History of falls in Parkinson disease is associated with reduced cholinergic activity

“…The nucleus basalis of Meynert (NBM) provides the principal cholinergic input of the entire cortical mantle and degenerates in PD. 5 The pedunculopontine nucleus (PPN), a brainstem locomotor center, provides cholinergic inputs to the basal ganglia, thalamus, cerebellum, several brainstem nuclei, and the spinal cord, 6 and also degenerates in PD. 7 [ 11 C]PMP PET imaging assesses cholinergic terminal integrity with cortical activity reflecting NBM integrity and thalamic uptake reflecting PPN integrity.…”