Abstract
Von Economo neurons (VENs) are specialized projection neurons with a characteristic spindle-shaped soma and thick basal and apical dendrites. VENs have been described in restricted cortical regions, with their most frequent appearance in layers III and V of the anterior cingulate cortex, anterior insula, and frontopolar cortex of humans, great apes, macaque monkeys, elephants, and some cetaceans. Recently, a ubiquitous distribution of VENs was reported in various cortical areas in the pygmy hippopotamus, one of the closest living relatives of cetaceans. That finding suggested that VENs might not be unique to only a few species that possess enlarged brains. In the present analysis, we assessed the phylogenetic distribution of VENs within species representative of the superordinal clade that includes cetartiodactyls and perissodactyls, as well as afrotherians. In addition, the distribution of fork cells that are often found in close proximity to VENs was also assessed. Nissl-stained sections from the frontal pole, anterior cingulate cortex, anterior insula, and occipital pole of bowhead whale, cow, sheep, deer, horse, pig, rock hyrax, and human were examined using stereologic methods to quantify VENs and fork cells within layer V of all four cortical regions. VENs and fork cells were found in each of the species examined here with species-specific differences in distributions and densities. The present results demonstrated that VENs and fork cells were not restricted to highly encephalized or socially complex species, and their repeated emergence among distantly related species seems to represent convergent evolution of specialized pyramidal neurons. The widespread phylogenetic presence of VENs and fork cells indicates that these neuron morphologies readily emerged in response to selective forces,whose variety and nature are yet to be identified.
Similar content being viewed by others
References
Allman J, Watson K, Tetreault N, Hakeem A (2005) Intuition and autism: a possible role for von Economo neurons. Trends Cogn Sci 9:367–373
Allman JM, Tetreault NA, Hakeem AY, Manaye KF, Semendeferi K, Erwin JM, Park S, Goubert V, Hof PR (2010) The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. Brain Struct Funct 214:495–517
Bauernfeind AL, de Sousa AA, Avasthi T, Dobson SD, Raghanti MA, Lewandowski AH, Zilles K, Semendeferi K, Allman JM, Craig AD, Hof PR, Sherwood CC (2013) A volumetric comparison of the insular cortex and its subregions in primates. J Hum Evol 64:263–279
Betz W (1881) Über die feinere Struktur der Gehirnrinde des Menschen. Centralbl Med Wiss 19(193–195):209–234
Brüne M, Schobel A, JKarau R, Benali A, Faustmann PM, Juckel G, Petrasch-Parwez E (2010) Von Economo neuron density in the anterior cingulate cortex is reduced in early onset schizophrenia. Acta Neuropathol 119:771–778
Brüne M, Schobel A, Karau R, Faustmann PM, Dermietzel R, Juckel G, Petrasch-Parwez E (2011) Neuroanatomical correlates of suicide in psychosis: the possible role of von Economo neurons. PLoS One 6:e20936
Butti C, Hof PR (2010) The insular cortex: a comparative perspective. Brain Struct Funct 214:477–493
Butti C, Sherwood CC, Hakeem AY, Allman JM, Hof PR (2009) The number and volume of von Economo neurons in the cerebral cortex of cetaceans. J Comp Neurol 515:243–259
Butti C, Raghanti MA, Sherwood CC, Hof PR (2011) The neocortex of cetaceans: cytoarchitecture and comparison with other aquatic and terrestrial species. Ann NY Acad Sci 1225:47–58
Butti C, Santos M, Uppal N, Hof PR (2013) Von Economo neurons: clinical and evolutionary perspectives. Cortex 49:312–326
Butti C, Fordyce RE, Raghanti MA, Gu X, Bonar CJ, Wicinski B, Wong EW, Roman J, Brake A, Eaves E, Tang CY, Jacobs B, Sherwood CC, Hof PR (2014) The cerebral cortex of the pygmy hippopotamus, Hexaprotodon liberiensis (Cetartiodactyla, Hippopotamidae). Anat Rec 297:670–700
Chow KL, Blum JS, Blum K (1950) Cell ratios in the thalamocortical visual system of Macaca mulatta. J Comp Neurol 92:227–239
Cobos I, Seeley WW (2013) Human von Economo neurons express transcription factors associated with layer V subcerebral projection neurons. Cereb Cortex. doi:10.1093/cercor/bht219
Craig AD (2009) How do you feel now? The anterior insula and human awareness. Nat Rev Neurosci 10:59–70
Evrard HC, Forro T, Logothetis NK (2012) Von Economo neurons in the anterior insula of the macaque monkey. Neuron 74:482–489
Gatesy J, O’Leary MA (2001) Deciphering whale origins with molecules and fossils. Trends Ecol Evol 16:562–570
Hakeem AY, Sherwood CC, Bonar CJ, Butti C, Hof PR, Allman JM (2009) Von Economo neurons in the elephant brain. Anat Rec 292:242–248
Hans Thewissen JGM, Cooper LN, Clementz MT, Bajpai S, Tiwari BN (2007) Whales originated from aquatic artiodactyls in the Eocene epoch of India. Nature 450:1190–1195
Hans Thewissen JGM, George J, Rosa C, Kishida T (2011) Olfaction and brain size in the bowhead whale (Balaena mysticetus). Mar Mammal Sci 27:282–294
Hayashi M, Ito M, Shimizu K (2001) The spindle neurons are present in the cingulate cortex of chimpanzee fetus. Neurosci Lett 309:97–100
Hof PR, Van der Gucht E (2007) Structure of the cerebral cortex of the humpback whale, Megaptera novaeangliae (Cetacea, Mysticeti, Balaenopteridae). Anat Rec 290:1–31
Kaufman JA, Paul LK, Manaye KF, Granstedt AE, Hof PR, Hakeem AY, Allman JM (2008) Selective reduction of von Economo neuron number in agenesis of the corpus callosum. Acta Neuropathol 116:479–489
Kennedy DP, Semendeferi K, Courchesne E (2007) No reduction of spindle neuron number in frontoinsular cortex in autism. Brain Cogn 64:124–129
Kim EJ, Sidhu M, Macedo MN, Huang EJ, Hof PR, Miller BJ, DeArmond SJ, Seeley WW (2012) Frontoinsular von Economo neuron and fork cell loss in early behavioral variant frontotemporal dementia. Cereb Cortex 22:251–259
Manger PR (2006) An examination of cetacean brain structure with a novel hypothesis correlating thermogenesis to the evolution of a big brain. Biol Rev 81:293–338
Manger PR, Prowse M, Haagensen M, Hemingway J (2012) Quantitative analysis of neocortical gyrencephaly in African elephants (Loxodonta africana) and six species of cetaceans: comparisons with other mammals. J Comp Neurol 520:2430–2439
Marx FG (2011) The more the merrier? A large cladistic analysis of mysticetes, and comments on the transition from teeth to baleen. J Mammal Evol 18:77–100
Ngowyang G (1932) Beschreibung einer Art von Spezialzellen in der Inselrinde - zugleich Bemerkungen über die v. Economoschen Spezialzellen. J Psychol Neurol 44:671–674
Ngowyang G (1936) Neuere Befunde über die Gabelzellen. Cell Tissue Research 25:236–239
Nikaido M, Hamilton H, Makino H, Sasaki T, Takahashi K, Goto M, HKanda N, Pastene LA, Okada N (2006) Baleen whale phylogeny and a past extensive radiation event revealed by SINE insertion analysis. Mol Biol Evol 23:866–873
Nimchinsky EA, Vogt BA, Morrison JH, Hof PR (1995) Spindle neurons of the human anterior cingulate cortex. J Comp Neurol 355:27–37
Nimchinsky EA, Gilissen E, Allman JM, Perl DP, Erwin JM, Hof PR (1999) A neuronal morphologic type unique to humans and great apes. Proc Natl Acad Sci USA 96(9):5268–5273
Pillay P, Manger PR (2007) Order-specific quantitative patterns of cortical gyrification. Eur J Neurosci 25:2705–2712
Price SA, Bininda-Emonds ORP, Gittleman JL (2005) A complete phylogeny of the whales, dolphins and even-toed hoofed mammals (Cetartiodactyla). Biol Rev 80:445–473
Raghanti MA, Spurlock LB, Uppal N, Sherwood CC, Butti C, Hof PR (2014) Von Economo neurons. In: Zilles K, Amunts K (eds) Brain Mapping: An Encyclopedic Reference. Elsevier, Amsterdam (in press)
Reep RL, O’Shea TJ (1990) Regional brain morphometry and lissencephaly in the Sirenia. Brain Behav Evol 35:185–194
Ridgway SH, Brownson RH (1984) Relative brain sizes and cortical surface areas in odontocetes. Acta Zool Fenn 172:149–152
Rogalski EJ, Gefen T, Shi J, Samimi M, Bigio E, Weintraub S, Geula C, Mesulam M-M (2013) Youthful memory capacity in old brains: anatomic and genetic clues from the Northwestern SuperAging Project. J Cogn Neurosci 25:29–36
Rubes J, Musilova P, Kopecna O, Kubickova S, Cernohorska H, Kulemsina AI (2012) Comparative molecular cytogenetics in Cetartiodactyla. Cytogenet Genome Res 137:194–207
Santos M, Uppal N, Butti C, Wicinski B, Schmeidler J, Giannakopoulos P, Heinsen H, Schmitz C, Hof PR (2011) von Economo neurons in autism: a stereologic study of the frontoinsular cortex in children. Brain Res 1380:206–217
Sasaki T, Nikaido M, Hamilton H, Goto M, Kato H, Kanda N, Pastene LA, Okada N (2005) Mitochondrial phylogenetics and evolution of mysticete whales. Syst Biol 54:77–90
Seeley WW (2008) Selective functional, regional, and neuronal vulnerability in frontotemporal dementia. Curr Opin Neurol 21:701–707
Seeley WW, Carlin DA, Allman J, Macedo MN, Bush C, Miller BL, DeArmond SJ (2006) Early frontotemporal dementia targets neurons unique to apes and humans. Ann Neurol 60:660–667
Seeley WW, Allman J, Carlin DA, Crawford RK, Macedo MN, Greicius MD, DeArmond SJ, Miller BL (2007) Divergent social functioning in behavioral variant frontotemporal dementia and Alzheimer disease: reciprocal connections and neuronal evolution. Alzheimer Dis Assoc Disord 21:S50–S57
Seeley WW, Merkle FT, Gaus SE, Craig AD, Allman JM, Hof PR (2012) Distinctive neurons of the anterior cingulate and frontoinsular cortex: a historical perspective. Cereb Cortex 22:245–250
Simms ML, Kemper TL, Timbie CM, Bauman ML, Blatt GJ (2009) The anterior cingulate cortex in autism: heterogeneity of qualitative and quantitative cytoarchitectonic features suggests possible subgroups. Acta Neuropathol 118:673–684
Song S, Liu L, Edwards SV, Wu S (2012) Resolving conflict in eutherian mammal phylogeny using phylogenomics and the multispecies coalescent model. Proc Natl Acad Sci USA 109:14942–14947
Spaulding M, O’Leary MA, Gatesy J (2009) Relationships of Cetacea (Artiodactyla) among mammals: increased taxon sampling alters interpretations of key fossils and character evolution. PLoS One 4:e7062
Stimpson CD, Tetreault NA, Allman JM, Jacobs B, Butti C, Hof PR, Sherwood CC (2011) Biochemical specificity of von Economo neurons in hominoids. Am J Hum Biol 23:22–28
Van Essen DC (1997) A tension-based theory of morphogenesis and compact wiring in the central nervous system. Nature 385:313–318
von Economo C (1926) Eine neue Art Spezialzellen des Lobus cinguli und Lobus insulae. Z Ges Neurol Psychiat 100:706–712
von Economo C, Koskinas GN (1925) Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen. J. Springer, Wien und Berlin
Welker W (1990) Why does cerebral cortex fissure and fold? A review of determinants of gyri and sulci. In: Jones EG, Peters A (eds) Comparative structure and evolution of cerebral cortex, Part II. Cerebral cortex, vol 8B. Plenum, New York, pp 3–136
Acknowledgments
This work was supported by the National Science Foundation (BCS-0921079 and BCS-1316829) and the James S. McDonnell Foundation (grant 22002078). Brain materials used in this study were obtained through the Northwestern University Alzheimer’s Disease Center Brain Bank (supported by an Alzheimer’s Disease Core Center grant, P30 AG013854, from the National Institute on Aging to Northwestern University, Chicago, Illinois), Ward’s Scientific (horse, pig, and calf), and Jessica Sudduth (white-tailed deer, permit # 6739695382), and the Department of Wildlife Management, North Slope Borough, Barrow, AK (bowhead whale). We thank the J. Craig George, Barrow captains and crew members, the Barrow Whaling Commission, and the Alaska Eskimo Whaling Commission for allowing collection of bowhead whale brain samples. Through this and other projects, the Inupiat Eskimos have made significant contributions to the general scientific knowledge of cetaceans. The samples were collected under the authority of NOAA-NMFS permit No. 814-1899 to the North Slope Borough. We thank Paul Nader for extracting the bowhead whale brains nearly two decades ago. We also thank Jessica Sudduth, Nathan Heinrichs, Melissa Edler, and Alexa Stephenson for their expert technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Raghanti, M.A., Spurlock, L.B., Robert Treichler, F. et al. An analysis of von Economo neurons in the cerebral cortex of cetaceans, artiodactyls, and perissodactyls. Brain Struct Funct 220, 2303–2314 (2015). https://doi.org/10.1007/s00429-014-0792-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00429-014-0792-y