Differential cholinergic innervation within functional subdivisions of the human cerebral cortex: A choline acetyltransferase study
Abstract
The distribution of cholinergic fibers in the human brain was investigated with choline acetyltransferase immunocytochemistry in 35 cytoarchitectonic subdivisions of the cerebral cortex. All cortical areas and all cell layers contained cholinergic axons. These fibers displayed numerous varicosities and, on occasion, complex preterminal profiles arranged in the form of dense clusters. The density of cholinergic axons tended to be higher in the more superficial layers of the cerebral cortex. Several distinct patterns of lamination were identified. There were also major differences in the overall density of cholinergic axons from one cytoarchitectonic area to another. The cholinergic innervation of primary sensory, unimodal, and heteromodal association areas was lighter than that of paralimbic and limbic areas. Within unimodal association areas, the density of cholinergic axons and varicosities was significantly lower in the upstream (parasensory) sectors than in the downstream sectors. Within paralimbic regions, the non‐isocortical sectors had a higher density of cholinergic innervation than the isocortical sectors. The highest density of cholinergic axons was encountered in core limbic structures such as the hippocampus and amygdala. These observations show that the cholinergic innervation of the human cerebral cortex displays regional variations that closely follow the organization of information processing systems.
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Within the PFC, the cholinergic innervation initially terminates in layers III and IV, slowly losing laminar preference over time.
“Within the PFC, the cholinergic innervation initially terminates in layers III and IV slowly losing laminar preference over time [221–223].”
From Development of prefrontal cortex (2022) · cites this paper as [221]
The entire cortex and hippocampus are innervated by cholinergic projections that originate from several regions in the basal forebrain.
“The entire cortex and hippocampus are innervated by cholinergic projections that originate from several regions in the basal forebrain (Rye et al, 1984; Lysakowski et al, 1989; Mesulam et al, 1992; Kitt et al, 1994).”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Mesulam et al, 1992
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- Authors
- Mesulam, M. ‐., Hersh, L. B., Mash, D. C., & Geula, C.
- Affiliations
- Harvard University (US)
- University of Texas Health Science Center at Dallas (US)
- University of Miami (US)
- Corresponding author
- Mesulam, M.‐Marsel
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 1992-04-15
- Volume
- 318
- Issue
- 3
- Pages
- 316-328
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W2076151759
- Cited by
- 188
- References
- 42
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 8 · 2017: 8 · 2016: 8 · 2015: 3 · 2014: 10 · 2013: 9 · 2012: 7
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29ns025785-05, 5r01ns020285-15)
- National Institute on Aging (P50AG005134, AG 05134)
- National Institute of Neurological Disorders and Stroke (NS 25785, NS 20285)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- cholinergic innervation, cerebral cortex, choline acetyltransferase, cholinergic axons, varicosities, cortical lamination, cytoarchitectonic areas, association cortex, limbic system, hippocampus, amygdala
- MeSH terms
- Adult, Axons, Cerebral Cortex, Choline O-Acetyltransferase, Cholinergic Fibers, Humans, Immunohistochemistry, Male, Middle Aged, Neutral Red, Oxazines, Parasympathetic Nervous System, Staining and Labeling, Benzoxazines
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