The Patterning of Neuronal Connections1

SYNOPSIS. The final level of development in the vertebrate nervous system concerns the patterning, or modelling, of the connections of the postmitotic neurons at target tissues. The growth of target tissue and the sprouting of newly-arrived axons is followed by a regulated distribution of the sprouts, and often the development of specific contacts (synapses). Usually there are more sprouts than can be accommodated; the result is competition for target sites and regression of unsuccessful endings, leading to the characteristic pattern of connections. Studies particularly of the reinnervation of denervated skin in salamanders and rats have revealed a number of conditions and processes that influence competition. Spatial and temporal constraints restrict the sprouting of certain nerves but not others. Substances conveyed to nerve terminals by fast axoplasmic transport can “neutralize” sprouting influences believed to derive from target tissues, and can “mask” target features that nerves recognize; other substances are needed for sprouting to occur at all. Increased impulse activity in certain nerves accelerates their sprouting. Intriguingly, regenerating nerves will recapture targets from sprouted endings. Most of the identified conditions and processes occur in the adult animal; they could therefore provide a basis for remodelling of neuronal connections. Remodelling occurs when the characteristic early hyperinnervation of target tissues converts after birth to the adult pattern; in cutaneous “touch domes” targets are eliminated in addition to endings. Perhaps remodelling plays a role in the development of behaviour even in mature animals.