3.12 - How to Build a Bigger Brain: Cellular Scaling Rules for Rodent Brains

Abstract

How do cell number and size determine brain size? Stereological measurements of decreasing neuronal densities in the cerebral cortex and cerebellum with increasing brain size suggest that increased neuronal size contributes significantly to larger brain volume, but do not indicate how the contribution of cell size towards final brain volume compares to the contribution of cell numbers. Using a novel method, the isotropic fractionator, we show that the number of neurons in different brain areas scales faster than their average size in the order Rodentia. The addition of neurons is paralleled by the addition of much larger number of non-neuronal cells of relatively stable average size, such that the ratio between total neuronal and non-neuronal mass remains constant across species. Analysis of the cellular composition of the brain with this novel method also shows that, while relative cerebellar volume remains stable and relative cortical volume increases across rodent species of increasing brain size, the number of neurons in the cerebellum increases more rapidly than in cortex, such that the cerebellar fraction of total brain neurons increases with brain size, while the cortical fraction remains constant. We propose that the faster increase in average neuronal size in cerebral cortex than in cerebellum as these structures gain neurons and the fast-increasing glial numbers that generate glial mass to match total neuronal mass are fundamental cellular constraints which lead to the relative expansion of cerebral cortical volume across species. This apparent cortical expansion masks a major expansion of the relative number of neurons in the cerebellum, which suggests that cerebellum, rather than cerebral cortex, is the fastest-growing structure in terms of computational power as brain size increases.