REVIEW How many neurons do you have? Some dogmas of quantitative neuroscience under revision Roberto Lent, 1,2 Frederico A. C. Azevedo, 1, * Carlos H. Andrade-Moraes 1 and Ana V. O. Pinto 1 1 Instituto de Cie ˆ ncias Biome ´ dicas (ICB), Centro de Cie ˆncias da Sau ´ de Bl. F, Universidade Federal do Rio de Janeiro (UFRJ), CEP 21941-902, Rio de Janeiro, Brazil 2 Instituto Nacional de Neurocie ˆ ncia Translacional (INNT), Brazil Keywords: brain development, brain evolution, glial cell number, neuron number Abstract Owing to methodological shortcomings and a certain conservatism that consolidates wrong assumptions in the literature, some dogmas have become established and reproduced in papers and textbooks, derived from quantitative features of the brain. The first dogma states that the cerebral cortex is the pinnacle of brain evolution – based on the observations that its volume is greater in more ‘intelligent’ species, and that cortical surface area grows more than any other brain region, to reach the largest proportion in higher primates and humans. The second dogma claims that the human brain contains 100 billion neurons, plus 10-fold more glial cells. These round numbers have become widely adopted, although data provided by different authors have led to a broad range of 75– 125 billion neurons in the whole brain. The third dogma derives from the second, and states that our brain is structurally special, an outlier as compared with other primates. Being so large and convoluted, it is a special construct of nature, unrelated to evolutionary scaling. Finally, the fourth dogma appeared as a tentative explanation for the considerable growth of the brain throughout development and evolution – being modular in structure, the brain (and particularly the cerebral cortex) grows by tangential addition of modules that are uniform in neuronal composition. In this review, we sought to examine and challenge these four dogmas, and propose other interpretations or simply their replacement with alternative views. Introduction: Four dogmas of quantitative neuroscience Quantitative neuroscience should not, perhaps, be properly defined as a discipline, within the broad field of the neural sciences, as the whole field employs quantitative methods to investigate the morphology, physiology, cell biology and molecular interactions in the nervous system. It should rather be considered as an important, normative collection of quantitative methods and data that can be used by neuroscientists to approach evolutionary and developmental issues, and to ask new questions about these and other aspects of brain structure and function. However, over time, because of methodological limitations (Box 1) and strong adherence to tradition, some beliefs derived from quantitative features of the nervous system have been extensively reproduced in papers and textbooks, becoming undisputed dogmas of neuroscience. For instance, if asked how many neurons the human brain has, the reader will probably answer – 100 billion. However, this figure is not soundly supported by empirical evidence, and its origin in the literature is unknown. In this review, we analyze and question four dogmas of quantitative neuroscience, and propose new interpretations or alternative views. These dogmas were chosen and brought together because they have a common relationship with the evolution and development of the nervous system. They are probably not the only ones, but are perhaps those most commonly quoted in the literature. The first dogma states that the cerebral cortex is the highest achievement of brain evolution, on the basis of the observations that brain volume is greater in more ‘intelligent’ species, and that cortical surface area seems to grow more than any other brain region, to reach the largest proportion in higher primates and humans. According to this view, the traditional concept of evolutionary encephalization could actually be translated as ‘corticalization’, to express the volumetric predominance of the cerebral cortex as the brain has evolved in vertebrates. The second dogma targets the human brain and its computational ‘units’ – our brain would contain 100 billion neurons, plus about 10 times more glial cells. These round, ‘magic’ numbers have become largely adopted in the literature, despite the fact that estimates by different authors vary as much as 10-fold in the cortex and 1.5-fold in the cerebellum, leading to a broad discrepancy range of 75–125 billion neurons in the whole brain (a 50% range around the adopted number). As a sort of corollary, the third dogma states that the human brain is structurally and functionally special, and exquisitely sophisticated as compared with those of other primates. Its large and highly convoluted structure would give it the status of a unique construct of evolution, somehow unrelated to comparative scaling. Such a concept places the human brain apart from mammalian evolutionary rules, in contradiction to most, if not all, empirical evidence. Finally, the fourth dogma connects evolution with Correspondence: R. Lent, as above. E-mail: rlent@icb.ufrj.br *Present address: Max Planck Institute for Biological Cybernetics, Tubingen, Germany. Received 22 May 2011, revised 18 September 2011, accepted 27 September 2011 European Journal of Neuroscience, Vol. 35, pp. 1–9, 2012 doi:10.1111/j.1460-9568.2011.07923.x ª 2011 The Authors. European Journal of Neuroscience ª 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd European Journal of Neuroscience