The six-layered neocortex is a hallmark of mammalian evolution. It is profusely interconnected within and between hemispheres, yet only Eutherians evolved a corpus callosum. We recently showed that marsupials and monotremes share a pan-mammalian cortical connectome via the anterior commissure, which is largely driven by conserved but heterochronic developmental principles. However, how cortical areas differentiate from each other has remained poorly understood due to challenges in studying live development at embryonic stages. To overcome this, we studied an Australian marsupial, the fat-tailed dunnart, whose postnatal corticogenesis allows for unique studies of generative mechanisms in vivo. In-pouch electroporation of GCaMP6s followed by widefield imaging across both hemispheres revealed the rostro-caudal maturation of cortical areas, and the establishment of a mirror-like symmetry of spontaneous activity as commissural axons reach the contralateral hemisphere. Independent component analyses followed by hierarchical clustering indicates functional parcellations of cortical areas, which coincide with experimental disruptions of the sensory periphery. We further mapped cortical areas throughout adulthood in dunnarts by combining tracer injections, MRI, and molecular marker expression, which validate developmental parcellations and reveal an enlargement of visual regions consistent with their active hunting behaviours. Moreover, integration of brain MRI with skull CT scans in the same 3D space provides a detailed open-source map in stereotaxic coordinates. Our findings reveal developmental rules of cortical area specification and wiring that likely originated early in mammalian ancestors, at least 80 million years before corpus callosum evolution.

More information:

• https://biomedical-sciences.uq.edu.au/profile/11446/rodrigo-suarez