The beginning of sapiens

Before turning to an analysis of the mechanisms that explain the changes in cortical size, particularly the significant enlargement of the cortex in sapiens , I'd like to draw a provisional conclusion on the importance, in terms of variations in the relative size of areas, of the expression levels of morphogens and transcription factors, particularly those that define the edges. We should also bear in mind that changes in the periphery, for example in the expression of Hox genes, which lead to changes in peripheral organs, such as changes in hand size, will be reflected at cortical level.

The changes that can be observed between species almost always concern the size of the cortical sheet, in comparison with that of the body. These variations are considerable. After 200 million years of evolution, the size of the brain, especially the cortex, can vary by a factor of 1 to 100,000 among the 4,600 living mammalian species.

In a small number of species, including our own, encephalization has been accompanied by an increase in the number of cortical fields and changes in the connectivity of these cortical fields. But these increases in size, whose origin will always be the result of regulation of cell proliferation or survival, can conceal several phenomena. A comparison between rodents and primates is a convincing example.

In rodents, brain size is a hyperbolic function of neuron number, and the glia/neuron ratio increases with brain size. If we applied the same hyperbolic law to primates, with 100 billion neurons, we'd have a brain weighing 45 kg and a body weighing 109 tonnes. In primates, neuronal density remains constant. Neuron size does not change, and brain growth is isometric. If the brain is 11 times bigger, there are 10 times more neurons and 12 times more glia. Applying the "linear" rule to sapiens , we arrive at 1.4 kg of brain for a height of 1.70 m, still for 100 billion neurons.

The increase in cortex size can be the result of several phenomena. For example, an extension of the time during which symmetrical divisions of neuroepithelial precursors take place, the speed of division, or the rate of cell death. This increase may reflect a lengthening of the brain's growth period. The progenitor division hypothesis is supported by the fact that cortical progenitors divide 11-fold in mice, at least 28-fold in macaques and probably much more in humans.

In the course of our descriptions, we have emphasized the increase in volume of the median ganglionic eminences in sapiens . This leads to an increase in the number of GABA neurons, also explained by the fact that in sapiens , these neurons are also generated from the ventricular cortical zone. As a result, we can say that the growth of the cortex in primates, and in sapiens in particular, corresponds to an increase in the number of glutamatergic and GABAergic neurons in the superficial layers of the cortex (mainly II and III).

Regarding the significant increase in these inhibitory interneurons, Santiago Ramon y Cajal's disillusioned remark is worth noting: "The opinion generally accepted at the time that the differences between the brains of mammals other than man (cats, dogs, monkeys, etc.) and those of man are only quantitative, seemed to me unlikely and even a little offensive to human dignity.... My research has shown that the functional superiority of the human brain is intimately linked to the prodigious abundance and unusual richness of form of the so-called short-axon neurons."