Regulation of Cortical Circuit Formation

The complex functions of the mammalian neocortex depend on the formation of precise networks and subnetworks among its many neuron types during development. These networks are formed in a stereotyped manner that creates a reproducible human cortex and facilitates common human behavior. The accuracy and complexity of cortical circuitry predicts that the developmental mechanisms that direct each of these neurons to connect with its siblings must be precise. In recent years, remarkable advances have been made in our understanding of the several developmental mechanisms that direct cortical connectivity, but we still know only a fraction of the coordinated events and molecular elements involved. An additional difficulty is that the intricate connectivity and physiology of these circuits is far from being definitively untangled. Much of the knowledge comes from relatively simple animal models, such as rodents, ferrets, and cats. Relevant information is also derived from the study of human genetic conditions that affect intellectual capabilities. This chapter briefly describes the connectivity of excitatory neurons of the cerebral cortex, which integrate and transmit information among neocortex regions and to other regions of the brain. We will try to give an extended overview of the mechanisms that shape this connectivity during development, with special emphasis on implications in humans.