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The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans

Allman, John M. and Tetreault, Nicole A. and Hakeem, Atiya Y. and Manaye, Kebreten F. and Semendeferi, Katerina and Erwin, Joseph M. and Park, Soyoung and Goubert, Virginie and Hof, Patrick R. (2010) The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. Brain Structure and Function, 214 (5-6). pp. 495-517. ISSN 1863-2661. doi:10.1007/s00429-010-0254-0.

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The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decision-making, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal pole as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB and GRP signal satiety. The genes for NMB and GRP are expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation of appetite. The loss of these cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. The VENs and fork cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals. We found that the protein encoded by the gene DISC1 (disrupted in schizophrenia) is preferentially expressed by the VENs. DISC1 has undergone rapid evolutionary change in the line leading to humans, and since it suppresses dendritic branching it may be involved in the distinctive VEN morphology.

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Additional Information:© The Author(s) 2010. This article is published with open access at Received: 1 December 2009. Accepted: 21 April 2010. Published online: 29 May 2010. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. The authors would like to thank Dr. Barbara Wold, Dr. Chet Sherwood, Dr. Bill Seeley, Dr. James Rilling, and Dr. A. D. Craig for their invaluable comments and discussion. We thank Dr. Micheal Tyszka and Dr. Jason Kaufman for the MRI imaging of the ape brains. We thank Dr. Kristen Tillisch and Dr. Emeran Mayer for the MR images of the young adult human subject. We are grateful to Dr. John Morris for his suggestion that the expression of neuromedin B and gastrin releasing peptide in the mouse insular cortex might be related to the VENs. We thank Dr. Heidi Griffith for her help in collecting some of the human stereological data. We thank Archibald Fobbs, curator of the Yakovlev and Welker Brain Collections and Dr. Adrianne Noe, Director, National Museum of Health and Medicine for their crucial role in preserving these collections and making them available to us and to the broader scientific community. In the Hof lab, technical help was provided by B. Wicinski and S. Harry. Several of the great ape brains involved in this study were on loan to the ‘‘Great Ape Aging Project’’ from zoological gardens that are accredited by the Association of Zoos and Aquariums (AZA) and that participate in the Ape Taxon Advisory Group (Ape-TAG). We especially appreciate the contribution of zoo veterinarians and staff in collecting and providing specimens. Additional human tissue was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders. Some comparative specimens were collected under the ‘‘Comparative Neurobiology of Aging Resource,’’ NIH/NIA grant AG14308, J. Erwin, PI. This research was supported by the James S. McDonnell Foundation, the David and Lucille Packard Foundation, and the Simons Foundation.
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James S. McDonnell FoundationUNSPECIFIED
David and Lucile Packard FoundationUNSPECIFIED
Simons FoundationUNSPECIFIED
Subject Keywords:von Economo neurons; Fork cells; Anterior cingulate cortex; Frontoinsular cortex; Hominoid brain; Disc1; Neuromedin B
Issue or Number:5-6
Record Number:CaltechAUTHORS:20100623-153838338
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Official Citation:Allman, J., N. Tetreault, et al. (2010). "The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans." Brain Structure and Function 214(5): 495-517.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:18781
Deposited By: Tony Diaz
Deposited On:15 Jul 2010 21:03
Last Modified:08 Nov 2021 23:46

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