Regressive phenomena: Refining connections

Progressive events, such as the elaboration of axons and dendrites, create a template for the circuits that govern the many functions of our nervous system. As the nervous system develops, neurons are instructed through the extracellular milieu by guidance cues and form synaptic connections once they have reached their target region. Progressive events result not only in the creation of the proper circuitry, but also the formation of a number of supernumerary connections. In order for the nervous system to function properly, these connections must be removed through regressive events. Regressive events encompass a number of developmental processes, ranging from the removal of entire neurons and their processes, to restraining the development of microstructures at the level of the synapse. These processes often share a number of characteristics with programmed cell death. Furthermore, many of the guidance cues that instructed neurons to their target initially also regulate regressive events later in development. Beyond the removal of supernumerary connections, regressive processes also allow for the creation of a number of complex synaptic structures and the refinement of individual connections. Thus, the formation of a healthy and functional nervous system requires not only progressive events that establish initial neural connectivity, but also regressive events that further refine these neuronal circuits.