The research proposed in this grant is directed at the question of when during development does CNS target tissue provide trophic (survival) support and tropic (guidance) cues that enable afferent neurons of different neurotransmitter phenotypes to form specific patterns of target innervation. Our approach is to denervate the target structure in vivo at different developmental stages, then transplant into the region of the denervated target embryonic cells that would normally provide the innervation. Survival of transmitter-specific neuron types within the transplant can then be evaluated, along with the specificity of host target reinnervation by the different types of cells in the transplant. We will also examine the ability of the target structure denervated at different ages to continue to provide trophic support and tropic cues in the protracted absence of its normal innervation by placing the transplants into the host after a long post-lesion delay. In all animals the functional relevance of transplant cell survival and host target innervation will also be assayed using a behavioral test. Our ultimate goal is to identify biologically active molecules produced by the target that support specific neuron survival and target innervation appropriate for specific behavioral functions.
