Target-selection and the elaboration of terminal arbors are two of the most critical tasks undertaken by growing axons. Yet a significant hiatus remains in our understanding of how cells in the vertebrate nervous system perform these operations. The proposed experiments are designed to advance our knowledge of the structural basis for the formation of precise connections, an to use this knowledge to analyse the nature of axonal growth in mature brains, growth obtained by challenging the adult brain with an environment which is novel, yet permissive for growth. The barrel field cortex of the rat provides a compelling model for addressing these issues. The homeomorphic relationships between the barrel field neurons, thalamic afferent arbors, and the array of mystical vibrissae on the snout will be exploited to examine morphogenetic events underlying afferent-target interactions which lead to the normal development and plasticity of sensory maps in the neocortex. Anatomical and immunohistochemical techniques along with compute-aided microscopy will reveal strategies employed by axons in reaching and arborizing within normal and novel targets. Progressive changes in axon arbor morphologies will be correlated with expression of major growth-activity, and with the clustering of synaptic terminals . Similar studies will be conducted in animals with i) early alterations of the sensory periphery, thus changing the pattern of input to thalamocortical projection cells and ii) alterations in the target tissue itself, to probe target-derived influences on projection patterns. This combination of experiments will elucidate ways in which the growth state of young axons can be recapitulated in mature brains, an issue of critical importance for repair of damage in the human nervous system.
