Differential cholinergic innervation within functional subdivisions of the human cerebral cortex: A choline acetyltransferase study

Authors

  • M.-Marsel Mesulam M.D.,

    Corresponding author
    1. Bullard and Denny-Brown Laboratories, Division of Neuroscience and Behavioral Neurology, Harvard Neurology Department and the Dana Research Institute of the Beth Israel Hospital, Boston, Massachusetts
    • Department Neurology, Beth Israel Hospital, 330 Brookline Avenue, Boston, MA 02215
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  • Louis B. Hersh,

    1. University of Texas Health Science Center, Dallas, Texas
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  • Deborah C. Mash,

    1. Department of Neurology, University of Miami, Miami, Florida
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  • Changiz Geula

    1. Bullard and Denny-Brown Laboratories, Division of Neuroscience and Behavioral Neurology, Harvard Neurology Department and the Dana Research Institute of the Beth Israel Hospital, Boston, Massachusetts
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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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