Phylogenetic variation in cortical layer II immature neuron reservoir of mammals

Abstract

The adult mammalian brain is mainly composed of mature neurons. A limited amount of stem cell-driven neurogenesis persists in postnatal life and is reduced in large-brained species. Another source of immature neurons in adult brains is cortical layer II. These cortical immature neurons (cINs) retain developmentally undifferentiated states in adulthood, though they are generated before birth. Here, the occurrence, distribution and cellular features of cINs were systematically studied in 12 diverse mammalian species spanning from small-lissencephalic to large-gyrencephalic brains. In spite of well-preserved morphological and molecular features, the distribution of cINs was highly heterogeneous, particularly in neocortex. While virtually absent in rodents, they are present in the entire neocortex of many other species and their linear density in cortical layer II generally increased with brain size. These findings suggest an evolutionary developmental mechanism for plasticity that varies among mammalian species, granting a reservoir of young cells for the cerebral cortex.

eLife digest

To acquire new skills or recover after injuries, the mammalian brain relies on plasticity, the ability for the brain to change its architecture and its connections during the lifetime of an animal.

Creating new nerve cells is one way to achieve plasticity, but this process is rarer in humans than it is in mammals with smaller brains. In particular, it is absent in the human cortex: this region is enlarged in species with large brains, where it carries out complex tasks such as learning and memory. Producing new cells in the cortex would threaten the stability of the structures that retain long-term memories.

Another route to plasticity is to reshape the connections between existing, mature nerve cells. This process takes place in the human brain during childhood and adolescence, as some connections are strengthened and others pruned away.

An alternative mechanism relies on keeping some nerve cells in an immature, ‘adolescent’ state. When needed, these nerve cells emerge from their state of arrested development and ‘grow up’, connecting with the appropriate brain circuits. This mechanism does not involve producing new nerve cells, and so it would be suitable to maintain plasticity in the cortex. Consistent with this idea, in mice some dormant nerve cells are present in a small, primitive part of the cortex.

La Rosa et al. therefore wanted to determine if the location and number of immature cells in the cortex differed between mammals, and if so, whether these differences depended on brain size. The study spanned 12 mammal species, from small-brained species like mice to larger-brained animals including sheep and non-human primates.

Microscopy imaging was used to identify immature nerve cells in brain samples, which revealed that the cortex in larger-brained species contained more adolescent cells than its mouse counterpart. The difference was greatest in a region called the neocortex, which has evolved most recently. This area is most pronounced in primates – especially humans – where it carries out high-level cognitive tasks.

These results identify immature nerve cells as a potential mechanism for plasticity in the cortex. La Rosa et al. hope that the work will inspire searches for similar reservoirs of young cells in humans, which could perhaps lead to new treatments for brain disorders like dementia.