Quantitative Architecture Distinguishes Prefrontal Cortical Systems in the Rhesus Monkey
Abstract
The prefrontal cortex encompasses a large and heterogeneous set of areas, whose borders have been variously mapped in different architectonic studies. Differences in cortical maps present a formidable problem in comparing data across studies and in constructing databanks on the connections and functional attributes of cortical areas. Here we used quantitative approaches to cortical mapping to investigate (i) if architectonic areas of the prefrontal cortex in adult rhesus monkeys have unique profiles and (ii) if groups of architectonic areas belonging to distinct cortical types, ranging from agranular to eulaminate, have similar features. In addition, we used multidimensional analyses to see if, and how, prefrontal areas form clusters when multiple features are considered simultaneously. We used quantitative unbiased sampling procedures to estimate the areal and laminar density of neurons, glia and neurons positive for the calcium binding proteins parvalbumin (PV), calbindin (CB) and calretinin (CR) among 21 prefrontal areas or subdivisions of areas. Neuronal density varied among the prefrontal cortices (range: 38 569 +/- 4078 to 58 708 +/- 2327 neurons/mm(3)); it was lowest in caudal orbitofrontal and medial areas (OPAll, OPro, 13, 24a, 32, M25) and highest in lateral prefrontal areas (subdivisions of areas 46 and 8). Neurons positive for PV were most prevalent in lateral prefrontal areas and least prevalent in caudal orbitofrontal and medial pre-frontal areas, whereas the opposite trend was noted for neurons that expressed CB. Neurons positive for CR did not show regional differences, and the density of glia showed small variations among prefrontal cortices. The differences among areas, along with differences in the thickness of individual areas and layers, were used to establish a quantitative profile for each area. The results showed that differences in the density of neurons, and the preponderance of neurons positive for PV and CB, were related to different architectonic types of areas found within the prefrontal cortex. Conventional as well as multiparameter statistical analyses distinguished at one extreme the agranular and dysgranular (limbic) cortices, which were characterized by prominent deep layers (V-VI), the lowest neuronal density, the highest ratio of glia/neurons, and the lowest density of PV and the highest for CB. At the other extreme, lateral eulaminate cortices were characterized by the highest density of neurons, a prominent granular layer IV, denser supragranular (II-III) than infragranular (V-VI) layers, and a balanced distribution of neurons positive for PV and CB. The results provide insights into potentially different rates of development or maturation of limbic and eulaminate prefrontal areas, and their differential vulnerability in neurological and psychiatric diseases. The quantitative methods used provide an objective approach to construct maps, address differences in nomenclature across studies, establish homologies in different species and provide a baseline to identify changes in pathologic conditions.
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In nonhuman primates and humans, glial cells seem to somewhat outnumber neurons in the PFC, with regional variation likely contributing to formation of secondary and tertiary gyri.
“In nonhuman primates and human, glial cells seem to somewhat outnumber neurons in the PFC, albeit with regional variation which is likely to contribute to the formation of secondary and tertiary gyri [77–81].”
From Development of prefrontal cortex (2022) · cites this paper as [79]
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- Authors
- Dombrowski, S. M.
- Affiliations
- Boston University (US)
- Corresponding author
- Dombrowski, S.M.
- ORCID
- Dombrowski, S.M.
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-10-01
- Volume
- 11
- Issue
- 10
- Pages
- 975-988
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2120223285
- Cited by
- 240
- References
- 105
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 7 · 2023: 14 · 2022: 8 · 2021: 10 · 2020: 12 · 2019: 11 · 2018: 18 · 2017: 12 · 2016: 13 · 2015: 11 · 2014: 14 · 2013: 10 · 2012: 6
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS57414, NS24760)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- prefrontal cortex, rhesus monkeys, neuronal density, glial density, parvalbumin, calbindin, calretinin, calcium-binding proteins, lateral prefrontal cortex, orbitofrontal cortex, medial prefrontal cortex
- MeSH terms
- Animals, Brain Mapping, Cell Count, Macaca mulatta, Neural Pathways, Neuroglia, Neurons, Parvalbumins, Prefrontal Cortex, Calbindins, S100 Calcium Binding Protein G, Calbindin 2
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