The human brain is often considered to be the most cognitively capable among mammalian brains and to be much larger than expected for a mammal of our body size. Although the number of neurons is generally assumed to be a determinant of computational power, and despite the widespread quotes that the human brain contains 100 billion neurons and ten times more glial cells, the absolute number of neurons and glial cells in the human brain remains unknown. Here we determine these numbers by using the isotropic fractionator and compare them with the expected values for a human-sized primate. We find that the adult male human brain contains on average 86.1 +/- 8.1 billion NeuN-positive cells ("neurons") and 84.6 +/- 9.8 billion NeuN-negative ("nonneuronal") cells. With only 19% of all neurons located in the cerebral cortex, greater cortical size (representing 82% of total brain mass) in humans compared with other primates does not reflect an increased relative number of cortical neurons. The ratios between glial cells and neurons in the human brain structures are similar to those found in other primates, and their numbers of cells match those expected for a primate of human proportions. These findings challenge the common view that humans stand out from other primates in their brain composition and indicate that, with regard to numbers of neuronal and nonneuronal cells, the human brain is an isometrically scaled-up primate brain.
The human brain has often been viewed as outstanding among mammalian brains: the most cognitively able, the largest-than-expected from body size, endowed with an overdeveloped cerebral cortex that represents over 80% of brain mass, and purportedly containing 100 billion neurons and 10× more glial cells. Such uniqueness was seemingly necessary to justify the superior cognitive abilities of humans over larger-brained mammals such as elephants and whales. However, our recent studies using a novel method to determine the cellular composition of the brain of humans and other primates as well as of rodents and insectivores show that, since different cellular scaling rules apply to the brains within these orders, brain size can no longer be considered a proxy for the number of neurons in the brain. These studies also showed that the human brain is not exceptional in its cellular composition, as it was found to contain as many neuronal and non-neuronal cells as would be expected of a primate brain of its size. Additionally, the so-called overdeveloped human cerebral cortex holds only 19% of all brain neurons, a fraction that is similar to that found in other mammals. In what regards absolute numbers of neurons, however, the human brain does have two advantages compared to other mammalian brains: compared to rodents, and probably to whales and elephants as well, it is built according to the very economical, space-saving scaling rules that apply to other primates; and, among economically built primate brains, it is the largest, hence containing the most neurons. These findings argue in favor of a view of cognitive abilities that is centered on absolute numbers of neurons, rather than on body size or encephalization, and call for a re-examination of several concepts related to the exceptionality of the human brain.
For half a century, the human brain was believed to contain about 100 billion neurons and one trillion glial cells, with a glia:neuron ratio of 10:1. A new counting method, the isotropic fractionator, has challenged the notion that glia outnumber neurons and revived a question that was widely thought to have been resolved. The recently validated isotropic fractionator demonstrates a glia:neuron ratio of less than 1:1 and a total number of less than 100 billion glial cells in the human brain. A survey of original evidence shows that histological data always supported a 1:1 ratio of glia to neurons in the entire human brain, and a range of 40–130 billion glial cells. We review how the claim of one trillion glial cells originated, was perpetuated, and eventually refuted. We compile how numbers of neurons and glial cells in the adult human brain were reported and we examine the reasons for an erroneous consensus about the relative abundance of glial cells in human brains that persisted for half a century. Our review includes a brief history of cell counting in human brains, types of counting methods that were and are employed, ranges of previous estimates, and the current status of knowledge about the number of cells. We also discuss implications and consequences of the new insights into true numbers of glial cells in the human brain, and the promise and potential impact of the newly validated isotropic fractionator for reliable quantification of glia and neurons in neurological and psychiatric diseases.
Stereological techniques that estimate cell numbers must be restricted to well defined structures of isotropic architecture and therefore do not apply to the whole brain or to large neural regions. We developed a novel, fast, and inexpensive method to quantify total numbers of neuronal and non-neuronal cells in the brain or any dissectable regions thereof. It consists of transforming highly anisotropic brain structures into homogeneous, isotropic suspensions of cell nuclei, which can be counted and identified immunocytochemically as neuronal or non-neuronal. Estimates of total cell, neuronal, and non-neuronal numbers can be obtained in 24 h and vary by Ͻ10% among animals. Because the estimates obtained are independent of brain volume, they can be used in comparative studies of brain-volume variation among species and in studies of phylogenesis, development, adult neurogenesis, and pathology. Applying this method to the adult rat brain, we show, for example, that it contains ϳ330 million cells, of which 200 million are neurons, and almost 70% of these are located in the cerebellum alone. Moreover, contrary to what is commonly assumed in the literature, we show that glial cells are not the majority in the rat brain.
How do cell number and size determine brain size? Here, we show that, in the order Rodentia, increased size of the cerebral cortex, cerebellum, and remaining areas across six species is achieved through greater numbers of neurons of larger size, and much greater numbers of nonneuronal cells of roughly invariant size, such that the ratio between total neuronal and nonneuronal mass remains constant across species. Although relative cerebellar size remains stable among rodents, the number of cerebellar neurons increases with brain size more rapidly than in the cortex, such that the cerebellar fraction of total brain neurons increases with brain size. In contrast, although the relative cortical size increases with total brain size, the cortical fraction of total brain neurons remains constant. We propose that the faster increase in average neuronal size in the cerebral cortex than in the cerebellum as these structures gain neurons and the rapidly increasing glial numbers that generate glial mass to match total neuronal mass at a fixed glia͞neuron total mass ratio are fundamental cellular constraints that lead to the relative expansion of cerebral cortical volume across species.allometry ͉ brain size ͉ comparative neuroanatomy ͉ number of glia ͉ number of neurons B rain size varies by a factor of Ϸ100,000 across mammalian species (1, 2), and, although the cellular composition of the brain is one of the major determinants of its computational capacities (3), little is known about how the cellular composition varies with brain size. What are the cellular scaling rules that determine brain allometry? How do numbers of neuronal and nonneuronal cells contribute to structure size? What are the relative contributions of these cells across species of different brain sizes?Glia are said to be the most numerous cell type in the brain (4, 5) and to be 10-50 times more numerous than neurons in humans (6). Evidence for this assertion, however, is scant. The ratio between the total number of glial and neuronal cells (glia͞neuron ratio) in the cerebral cortex has been shown to increase with brain size (1, 7). However, the numeric expansion of glial cells relative to neurons seems to contradict the observation that the neuronal need for metabolic support remains similar across species (8). Data on how neuronal and glial cell sizes scale with brain size might help solve this discrepancy, but such data are lacking in the literature.Not much is known, either, about the total numbers of neuronal and nonneuronal cells in the brains of different species, because methodological limitations have largely restricted comparative studies of brain anatomy to analyses of volumetric data published by a small number of laboratories. Strikingly, analyses of the same data yield conflicting conclusions. For instance, although the neocortical fraction of brain volume increases from 14% in basal insectivores to 80% in humans (9), the cerebellar fraction varies little across individuals of different mammalian orders (10), a discrepancy that the latter au...
Some birds achieve primate-like levels of cognition, even though their brains tend to be much smaller in absolute size. This poses a fundamental problem in comparative and computational neuroscience, because small brains are expected to have a lower information-processing capacity. Using the isotropic fractionator to determine numbers of neurons in specific brain regions, here we show that the brains of parrots and songbirds contain on average twice as many neurons as primate brains of the same mass, indicating that avian brains have higher neuron packing densities than mammalian brains. Additionally, corvids and parrots have much higher proportions of brain neurons located in the pallial telencephalon compared with primates or other mammals and birds. Thus, large-brained parrots and corvids have forebrain neuron counts equal to or greater than primates with much larger brains. We suggest that the large numbers of neurons concentrated in high densities in the telencephalon substantially contribute to the neural basis of avian intelligence.intelligence | evolution | brain size | number of neurons | birds
Neuroscientists have become used to a number of “facts” about the human brain: It has 100 billion neurons and 10- to 50-fold more glial cells; it is the largest-than-expected for its body among primates and mammals in general, and therefore the most cognitively able; it consumes an outstanding 20% of the total body energy budget despite representing only 2% of body mass because of an increased metabolic need of its neurons; and it is endowed with an overdeveloped cerebral cortex, the largest compared with brain size. These facts led to the widespread notion that the human brain is literally extraordinary: an outlier among mammalian brains, defying evolutionary rules that apply to other species, with a uniqueness seemingly necessary to justify the superior cognitive abilities of humans over mammals with even larger brains. These facts, with deep implications for neurophysiology and evolutionary biology, are not grounded on solid evidence or sound assumptions, however. Our recent development of a method that allows rapid and reliable quantification of the numbers of cells that compose the whole brain has provided a means to verify these facts. Here, I review this recent evidence and argue that, with 86 billion neurons and just as many nonneuronal cells, the human brain is a scaled-up primate brain in its cellular composition and metabolic cost, with a relatively enlarged cerebral cortex that does not have a relatively larger number of brain neurons yet is remarkable in its cognitive abilities and metabolism simply because of its extremely large number of neurons.
Primates are usually found to have richer behavioral repertoires and better cognitive abilities than rodents of similar brain size. This finding raises the possibility that primate brains differ from rodent brains in their cellular composition. Here we examine the cellular scaling rules for primate brains and show that brain size increases approximately isometrically as a function of cell numbers, such that an 11؋ larger brain is built with 10؋ more neurons and Ϸ12؋ more nonneuronal cells of relatively constant average size. This isometric function is in contrast to rodent brains, which increase faster in size than in numbers of neurons. As a consequence of the linear cellular scaling rules, primate brains have a larger number of neurons than rodent brains of similar size, presumably endowing them with greater computational power and cognitive abilities.allometry ͉ brain size ͉ evolution ͉ number of neurons ͉ number of glia B rain size varies by as much as 100,000ϫ across mammalian species (1, 2), and a large number of comparative studies have concentrated on finding the shared regularities behind brain morphology and cellular composition across species of different brain sizes (1,3,4). Although any such regularities may reveal general principles underlying the development and evolution of the brain, one must keep in mind that major differences across orders may also exist. Because cellular composition of the brain is one of the major determinants of its computational capacities (5), species belonging to different orders, having different cognitive abilities, and possessing brains of similar sizes would be expected to differ in cellular composition.We recently described the cellular scaling rules that apply to rodent brains from the mouse to the capybara (6). In that work, we showed that the rodent brain scales hypermetrically as a function of its numbers of neurons, and that the average neuronal size is larger in larger brains, whereas the average nonneuronal cell size remains comparatively stable. As in previous reports (1-3, 7-13), neuronal density decreases and the glia/neuron ratio increases with increasing brain size. We also showed that the ratio of total neuronal mass/total nonneuronal mass remains constant across rodent species, and we offered an explanation for how this ratio could be achieved during development (6).These results prompted us to investigate whether the same scaling rules apply to other mammalian orders. Our aim was to establish what rules are shared among mammalian brains, and thus might reflect characteristics inherited from a common ancestor, and what rules differ across orders of mammals, and thus might account for phylogenetic variance across groups. We were particularly interested in cellular scaling differences that might have arisen in primates. If the same rules relating numbers of neurons to brain size in rodents (6) also applied to primates, a brain comparable to ours, with Ϸ100 billion neurons, would weigh Ͼ45 kg and belong to a body of 109 tons, about the mass of the heavies...
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