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Cited by 395Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchParkinson's Disease Mechanisms and Treatments

Catecholamine innervation of the human cerebral cortex as revealed by comparative immunohistochemistry of tyrosine hydroxylase and dopamine-beta-hydroxylase

Gaspar, Patricia, Berger, Brigitte, Febvret, Aude, Vigny, Annette, Henry, Jean Pierre·1989·Journal of Comparative Neurology
DOI 10.1002/cne.902790208
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Abstract

The organization of the cortical monoamine systems, dopamine (DA), and noradrenaline (NA), which have been studied extensively in the rat and more recently in the monkey, had not yet been investigated directly in the human brain. We report here the first systematic account of the regional and laminar distributions of the catecholamine fibers in the human cerebral cortex, using immunohistochemistry of the catecholamine biosynthetic enzymes, tyrosine hydroxylase (TH), and dopamine‐β‐hydroxylase (DBH) in 13 cytoarchitectonic areas (4, 6, 9, 3b, 5, 40, 17, 18, 23, 24, 29, insula, and hippocampus) sampled postmortem. The noradrenergic (NA) innervation, mapped with DBH‐immunoreactivity (DBH‐IR), displayed a characteristic density gradient in the neocortex (highest in the primary sensorimotor areas, decreasing rostrally and caudally) that contrasted with the more uniform density in the limbic cortices (24, 23, 29, insula, hippocampus). NA axons were present in all cortical layers and were least numerous in layer I. The DBH‐IR fibers were only partly TH‐immunostained (10–50%, on double‐labeled sections), suggesting a heterogeneity of the cortical NA axons. The putative dopaminergic (DA) fibers were identified by comparing alternate or double‐immunolabeled (DBH‐TH) sections, as the TH‐IR fibers which contain no DBH‐IR. A DA‐like innervation was present in all cortical areas, with major regional differences in density and laminar distribution, which closely paralleled cytoarchitectural buildups: (1) the DA‐like innervation was densest in the agranular areas, primary and secondary motor areas, anterior cingulate, and insula; it distributed throughout layers I–VI; (2) density was lower in the granular cortices, areas 9 (prefrontal cortex), 23, 3b, 5, 40, and 18, displaying a bilaminar pattern in layers I and V–VI. In all areas, DA‐like fibers were most abundant in the molecular layer, with a predominant distribution in its deepest part. Convoluted and coily fibers represented a unique morphologic aspect of the CA innervation in the human cortex. These findings are in agreement with findings in nonhuman primates and demonstrate major evolutionary changes in the organization of the cortical aminergic input as compared with rodents. The most striking features are the expansion of the DA innervation to the whole cortex and the peak of highest density in the motor areas. The regional differentiation of NA innervation is also accentuated. Slight differences were found in the laminar distributions of the amines in humans and primates. These data seem quite promising and open new research fields in neurologic and psychiatric diseases.

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  • Many if not all regions of the interoceptive circuit are characterized by a high density of dopaminergic receptors and terminals across all cortical layers, particularly visceromotor regions like AIC, ACC, or OFC.

    “Notably, many if not all regions of the interoceptive circuit in Figure 7, are characterized by a high density of dopaminergic receptors and terminals across all cortical layers; this is particularly well-established for visceromotor regions like AIC, ACC, or OFC (Gaspar et al., 1989; Hurd et al., 2001; Lewis et al., 2001).”

    From Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression (2016) · cites this paper as Gaspar et al., 1989

  • The anterior insula receives dopaminergic innervations.

    “It is well established that the aIns receives dopaminergic innervations (Gaspar et al., 1989) and processes dopamine-associated RPEs.”

    From Cognitive flexibility in adolescence: Neural and behavioral mechanisms of reward prediction error processing in adaptive decision making during development (2015) · cites this paper as Gaspar et al., 1989

  • The entire granular subregion has notably high dopamine utilization, with the aIC having high density D1-subtype receptors surrounding dopaminergic terminals from the VTA and substantia nigra.

    “The entire granular subregion has notably high dopamine utilization (Gaspar et al., 1989) with the aIC having high density D1-subtype receptors surrounding dopaminergic terminals from the VTA and substantia nigra.”

    From The Insula: A Brain Stimulation Target for the Treatment of Addiction (2019) · cites this paper as Gaspar et al., 1989

  • The insula has a high level of endogenous opioids, high density of μ-subtype opioid receptors, high density of hypocretin subtype-1 receptors, and a high level of nicotinic acetylcholine receptors containing the β2 subunit, the major subtype of nAChR implicated in nicotine reward.

    “Furthermore, the insula has a high level of endogenous opioids (Gaspar et al., 1989), high density of µ-subtype opioid receptors (Baumgartner et al., 2006), high density of hypocretin subtype-1 receptors (Hollander et al., 2008), and a high level of nicotinic acetylcholine receptors (nAChRs) containing the β2 subunit”

    From The Insula: A Brain Stimulation Target for the Treatment of Addiction (2019) · cites this paper as Gaspar et al., 1989

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Authors
Gaspar, P., Berger, B., Febvret, A., Vigny, A., & Henry, J. P.
Affiliations
  • Inserm (FR)
  • Institut de Biologie Physico-Chimique (FR)
Venue
Journal of Comparative Neurology
Publisher
Wiley
Published
1989-01-08
Volume
279
Issue
2
Pages
249-271
ISSN
  • 0021-9967 (ISSN-L)
  • 1096-9861
DOI
10.1002/cne.902790208
OpenAlex
W2069412440
Cited by
395
References
79
Citations by year
2026: 4 · 2025: 11 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 14 · 2020: 13 · 2019: 9 · 2018: 9 · 2017: 11 · 2016: 8 · 2015: 11 · 2014: 11 · 2013: 12 · 2012: 9
FWCI
5.64
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 5753 d)
Locations
  • The Journal of Comparative Neurology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
catecholamine innervation, human cerebral cortex, noradrenergic innervation, dopaminergic innervation, tyrosine hydroxylase, dopamine beta-hydroxylase, cortical laminar distribution, cytoarchitectonic areas, molecular layer, neocortex, limbic cortex, norepinephrine, postmortem brain
MeSH terms
Adult, Aged, Aged, 80 and over, Catecholamines, Cerebral Cortex, Dopamine beta-Hydroxylase, Female, Humans, Immunohistochemistry, Male, Middle Aged, Nerve Fibers, Tyrosine 3-Monooxygenase

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