Neocortical arealization: evolution, mechanisms, and open questions

The mammalian neocortex is a structure with no equals in the vertebrates and is the seat of the highest cerebral functions, such as thoughts and consciousness. It is radially organized into six layers and tangentially subdivided into functional areas deputed to the elaboration of sensory information, association between different stimuli, and selection and triggering of voluntary movements. The process subdividing the neocortical field into several functional areas is called "arealization". Each area has its own cytoarchitecture, connectivity, and peculiar functions. In the last century, several neuroscientists have investigated areal structure and the mechanisms that have led during evolution to the rising of the neocortex and its organization. The extreme conservation in the positioning and wiring of neocortical areas among different mammalian families suggests a conserved genetic program orchestrating neocortical patterning. However, the impressive plasticity of the neocortex, which is able to rewire and reorganize areal structures and connectivity after impairments of sensory pathways, argues for a more complex scenario. Indeed, even if genetics and molecular biology helped in identifying several genes involved in the arealization process, the logic underlying the neocortical bauplan is still beyond our comprehension. In this review, we will introduce the present knowledge and hypotheses on the ontogenesis and evolution of neocortical areas. Then, we will focus our attention on some open issues, which are still unresolved, and discuss some recent studies that might open new directions to be explored in the next few years.