Seminar: "The evolution of adaptive circuitry in mammalian neocortex"

Professor Joshua Trachtenberg is a ​2024/2025 Lowy Distinguished Guest Professor of The Institute of Advanced Studies.

Abstract:

The emergence of mammals in the Late Triassic, some 225 million years ago, brought with it new features, including endothermy, viviparity, lactation, a four chambered heart, a diaphragm, and three middle ear bones. Perhaps most profound was the emergence of the six layered neocortex. The neocortex has expanded considerably thereafter from marsupials, where it occupies less than 20% of the brain to primates, where the cortex is 80% of brain mass. The shift in cortical organization from glires (rodents and lagamorphs) to primates has been extensively studied. Much less is known of the transition in cortical organization as true placental mammals split from metatherians (marsupials).

To determine whether the metatherian/eutherian split brought with it fundamental shifts in the organization of the cortical column – the fundamental unit of cortical processing – we used single-nucleus RNA sequencing and spatial transcriptomics to compare the primary visual cortex of opossums and mice. We find that while many features of neocortical organization are conserved, intratelencephalic glutamatergic neurons differ markedly in their transcriptomic and spatial structure. Viewed through the lens of division-of-labor theory, the opossum cortex appears to follow a more generalist architecture, with broad functional overlap among cell types, whereas the mouse cortex exhibits greater specialization—consistent with evolution along Pareto fronts that favor modularity and task-specific optimization.

Additional differences in inhibitory neuron composition, perineuronal net localization, and oligodendrocyte abundance support the idea that the metatherian–eutherian split was accompanied by a fundamental shift toward a more plastic and dynamically tunable cortical architecture, capable of supporting greater behavioral flexibility and adaptive capacity.