The long-term objectives of this proposal are to use grafting procedures to study events and problems of development and age- related developmental plasticity following deafferentation.
The specific aims are to recreate a model sensory system with transplanted neural tissue and to examine conditions associated with reestablishment of potentially functional connections. The olfactory system of rat will be used as the model and deafferentation of olfactory cortex (OC) will be accomplished by olfactory bulb (OB) removal. The system is well-studied, much of it in our laboratory, little used in grafting experiments, and unique in structural organization as to allow new and unusual conditions for studying question of developmental repair, reinnervation, and reafferentation. Specifically fetal rat and fetal mouse OBs will be transplanted at the sites from which the host rat OB had been ablated earlier. Rats of different ages from newborn to adult will be used as hosts, and the survival time after OB removal will be varied form 1 to several days. Conventional light (LM) and electron microscopy (EM) will be supplemented by LM and EM immunocytochemical localization of specific neurotransmitters and quantitative autoradiography of selected receptor binding procedures to study not only the target area (OC) but the graft (new OB) and its input (olfactory mucosa sensory cells). Special attention will be given to studies including distribution of afferents and efferents, possible age-related competition of new and resident afferents, patterns of neurotransmitter immunoreactivity and receptor binding, ultrastructural features of synaptic connectivity and their immunolabeling and the morphological details associated, especially at the synaptic and neurotransmitter level, with a second deafferentation of OC by ablation of the new OB graft. Each of these factors will be related to the age of the subject at the first OB lesion and the initial post-deafferentation survival time. Plans are also considered for behavioral and functional testing. The results should provide new information about events directly affecting the potential for developmental plasticity during recreation of a sensory system following severe damage to it.
