Building and Repairing the Cerebral Cortex : Physics and Boolean Logic, Rather than Stamp Collecting

The mammalian cerebral cortex processes multiple modalities of sensory information, controls motor output, and mediates higher-level cognitive functions. Its grossly visible organization into six distinct layers belies an extraordinary diversity of thousands of neuronal subtypes, which serve as building blocks for computationally powerful neural circuitry. This sophisticated circuitry and diverse repertoire of neuronal subtypes is generated during development under precise molecular regulation.

In recent years, a set of key controls over generation and refinement of cortical "projection neurons", those that communicate information relatively long distances within and from the cerebral cortex, have been identified. This work provides a foundation for a “nested”, multi-stage Boolean “molecular logic” underlying cortical development, and increasingly supports a model in which individual progenitor-stage and post-mitotic (after terminal cell division, but still during maturation) regulators are embedded within highly interconnected networks that gate sequential developmental decisions. At each stage, molecular programs establish boundaries in an “n-dimensional identity space” between distinct projection neuron subtypes and sub-subtypes with distinct multi-dimensional characteristics (and functions), this “n-dimensional subtype space” varies in distinct cortical areas. I will discuss some of the system background, types of cellular and circuit diversity and developmental decisions, and interacting controls directing progressive development of cortical projection neuron circuitry, system function, and routes to repair.