What can comparative neuroscience teach us about the development and plasticity of the mammalian neocortex?

Dr Laura Fenlon
School of Biomedical Sciences
University of Queensland


What can comparative neuroscience teach us about the development and plasticity of the mammalian neocortex?

Abstract: The neocortex is a uniquely mammalian brain structure that underlies many of the complex functions synonymous with this group, including sensorimotor integration higher order cognition. Differences in neocortical size and structure covary with a diversity of function across mammals, including humans who have a relatively large and complex neocortex. This diversification in adult form and function is determined by changes in the developmental formation of the neocortex, however the relationship between developmental events and diversification, as well as the plasticity of these processes among mammals, remain unclear. Here, we compare two distantly related mammalian species in distinct lineages to better understand the diversity and consequences of neocortical developmental mechanisms: the eutherian (placental) mouse and the marsupial fat-tailed dunnart. While in all eutherian mammals, the two neocortical hemispheres are interconnected by corpus callosum, this structure is an evolutionary novelty and is not present in marsupial mammals, whose neocortical connections instead route through the anterior commissure. We employed comparative gene manipulation and fluorescent labelling via in utero and in pouch electroporation to show that the temporal scaling of developmental processes differs between these two species. We further manipulated this timing to recapitulate that of the other group, and found that elements of neocortical structure were phenocopied from one species to the other. Specifically, by speeding up neocortical development in a mouse, we were able to reroute more neocortical axons through the anterior commissure, while slowing down neocortical development in a dunnart produced “pseudocallosum”-like connections, ectopically crossing through the dorsal midline near to where a corpus callosum would be in a mouse. These results indicate that the relative timing of developmental events may have been an evolutionary mechanism that produced diversification of neocortical structure among mammals, and also highlights the importance of developmental timing in the context of neocortical formation and plasticity in mammalian health and disease.