Evolution of cellular architecture and function of the hippocampus: insights from the artificial selection experiment

Inter-specifically, mammalian species with larger brains built of numerous neurons have higher cognitive abilities (CA) but at the expense of higher metabolic costs. It is unclear, however, how this pattern emerged since evolutionary mechanisms act intra-specifically, not inter-specifically. Here, we tested the existence of the above pattern at the species level in the hippocampus-the brain structure underlying CA. We used an artificial selection experiment consisting of lines of laboratory mice divergently selected for basal metabolic rate (BMR)-a trait implicated in brain size evolution, its metabolic costs and CA. Selection on BMR did not affect hippocampus size as a correlated response to this selection. However, the high BMR mice had superior CA and manifested increased neuronal density, higher cytochrome c oxidase density (indexing metabolic costs of neuronal activity) and dendritic spine density (indexing connectivity between neurons). Thus, our study calls into question the generality of patterns of the evolution of CA apparent interspecifically. At the species level, increased CA may arise through the rearrangement of the architecture and function of neurons without a conspicuous increase in their size but increase metabolism.