Receptor Architecture of Human Cingulate Cortex: Evaluation of the Four-Region Neurobiological Model

• Type of Material: Article
• Authors: Nicola Palomero-Gallagher, Research Centre Jülich; Brent A. Vogt, Cingulum Neurosciences Institute; Axel Schleicher, University of Dusseldorf; Helen Mayberg, Emory University; Karl Zilles, Research Centre Jülich
• Language: English
• Date: 2009-08-01
• Publisher: Wiley
• Publication Version: Final Published Version
• Copyright Statement: © 2008 Wiley-Liss, Inc.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/hbm.20667
• Title of Journal or Parent Work: Human Brain Mapping
• Volume: 30
• Issue: 8
• Start Page: 2336
• End Page: 2355
• Grant/Funding Information: None declared
• Keywords: Neurosciences; Deep brain stimulation; Neuroimaging; Prefrontal cortex; Science & Technology; mapping; Functional neuroanatomy; ligand binding; Retrospenial cortex; hierarchical clustering analysis; Monkey; limbic system; Major neurotransmitter receptors; Motor; Cytology; Radiology, Nuclear Medicine & Medical Imaging; autoradiography; Posterior cingulate; Neurosciences & Neurology; Transmitter receptors; Life Sciences & Biomedicine
• Research Categories: Biophysics, Medical; Biology, Physiology; Biology, Neuroscience; Health Sciences, Radiology

Abstract

The structural and functional organization of the human cingulate cortex is an ongoing focus; however, human imaging studies continue to use the century-old Brodmann concept of a two region cingulate cortex. Recently, a four-region neurobiological model was proposed based on structural, circuitry, and functional imaging observations. It encompasses the anterior cingulate, midcingulate, posterior cingulate, and retrosplenial cortices (ACC, MCC, PCC, and RSC, respectively). For the first time, this study performs multireceptor autoradiography of 15 neurotransmitter receptor ligands and multivariate statistics on human whole brain postmortem samples covering the entire cingulate cortex. We evaluated the validity of Brodmann's duality concept and of the four-region model using a hierarchical clustering analysis of receptor binding according to the degree of similarity of each area's receptor architecture. We could not find support for Brodmann's dual cingulate concept, because the anterior part of his area 24 has significantly higher AMPA, kainate, GABA B, benzodiazepine, and M3 but lower NMDA and GABA A binding site densities than the posterior part. The hierarchical clustering analysis distinguished ACC, MCC, PCC, and RSC as independent regions. The ACC has highest AMPA, kainate, α2, 5-HT1A, and D1 but lowest GABAA densities. The MCC has lowest AMPA, kainate, α2, and D1 densities. Area 25 in ACC is similar in receptor-architecture to MCC, particularly the NMDA, GABA A, GABAB, and M2 receptors. The PCC and RSC differ in the higher M1 and α1 but lower M 3 densities of PCC. Thus, multireceptor autoradiography supports the four-region neurobiological model of the cingulate cortex.