When larger brains do not have more neurons: increased numbers of cells are compensated by decreased average cell size across mouse individuals

Abstract

There is a strong trend toward increased brain size in mammalian evolution, with larger brains composed of more and larger neurons than smaller brains across species within each mammalian order. Does the evolution of increased numbers of brain neurons, and thus larger brain size, occur simply through the selection of individuals with more and larger neurons, and thus larger brains, within a population? That is, do individuals with larger brains also have more, and larger, neurons than individuals with smaller brains, such that allometric relationships across species are simply an extension of intraspecific scaling? Here we show that this is not the case across adult male mice of a similar age. Rather, increased numbers of neurons across individuals are accompanied by increased numbers of other cells and smaller average cell size of both types, in a trade-off that explains how increased brain mass does not necessarily ensue. Fundamental regulatory mechanisms thus must exist that tie numbers of neurons to numbers of other cells and to average cell size within individual brains. Finally, our results indicate that changes in brain size in evolution are not an extension of individual variation in numbers of neurons, but rather occur through step changes that must simultaneously increase numbers of neurons and cause cell size to increase, rather than decrease.

Cellular Scaling Rules for the Brains of Marsupials: Not as “Primitive” as Expected

“…Since only one hemisphere of each brain was used for this analysis, values reported here are multiplied by 2 to give estimates for the whole brain that can be compared with our previously published data on eutherians. While this practice ignores possible asymmetries between the hemispheres, and also does not address variation across individuals, such asymmetries and intraspecific variations would have only a negligible influence on the results reported here given that, whereas any asymmetries would be of the order of a few percentage points between the hemispheres and the coefficient of variation in number of brain neurons across mouse individuals is below 15% [Herculano-Houzel et al, 2015c], the present comparison across species spans several orders of magnitude.…”

You Do Not Mess with the Glia

“…Importantly, this cell quantification technique has been found by three independent groups to yield results that are comparable to those obtained with unbiased stereology, but are much faster to obtain and far less prone to user error and undersampling [66][67][68]. The consistency of the approach and technique across studies allowed us to collect data that could be compared systematically across structures in individual brains; across individuals of the same species; across species within a clade; across mammalian clades ( Figure 4); and even across mammals, birds, and non-avian reptiles [53][54][55][56][57][58][59][60][61][62][63][64][69][70][71]. While published results have so far been limited to numbers of neuronal and non-neuronal cells, one advantage of the isotropic fractionator is that, because all tissue heterogeneities in cell distribution are literally dissolved, only very small samples are required for counting, which allows for storage of the remaining suspension at −20 • C for later studies employing new markers or morphological criteria [65].…”

“…Within a single species (Swiss mouse), neuronal and non-neuronal densities vary together (as assumed in our model that estimates average cell volume from density [69]), such that those individuals with higher neuronal densities in a given brain structure also have higher non-neuronal cell densities in the structure, although always within a much-restricted range, than across species ( Figure 6B, shades of orange/magenta; [69]). Neuronal and non-neuronal cell densities are positively correlated across individuals within each of the main brain structures (cerebral cortex, cerebellum, and the rest of brain), despite the much higher neuronal densities in the cerebellum [69]. Consistently, neuronal and non-neuronal densities were also positively correlated across different cortical areas identified by cytoarchitectural features in four C57B/6J mouse individuals ( Figure 6B, shades of blue and green; [76]) and in one human cerebral cortex ( Figure 7; [77]).…”

“…(B) Neuronal and other cell densities across brain structures and regions in the mouse and elephant brains, and in individual mice. Each point in black represents neuronal and other cell density in different structures, cortical regions, or subsections of the cerebellum in one African elephant brain hemisphere [61]; each point in shades of orange to magenta represents neuronal and other cell density in the cerebral cortex (circles), cerebellum (squares), or rest of brain (triangles) of one hemisphere of each of 19 individual male mice of similar age [69]. Each point in one of four shades of blue or green represents neuronal and other cell density in one of 19 cortical areas in the brain in one of four mouse individuals [76].…”

Effects of Habitat and Social Complexity on Brain Size, Brain Asymmetry and Dentate Gyrus Morphology in Two Octodontid Rodents

“…Mammalian brain evolution has often been studied with the implicit assumption of common scaling rules. However, the relationship between brain size and the number of neurons varies between individuals, among species and among neuroanatomical structures [Herculano-Houzel et al, 2015]. Subsequent studies are needed to determine how this absolute differences associate with brain structures other than DG.…”