The goal of the proposed research is to study the development of binaural anatomical interrelationships. In mammals this can best be studied in species that have well-developed auditory systems but they are immature enough at birth to be manipulated experimentally at very early stages of development. The ferret is such an animal model. Before experimental manipulations of the system can be interpreted fully, however, it is necessary to understand the mature organization and normal development of the model system. For information from the two ears to be integrated appropriately, developing neurons must establish the appropriate 1) synaptic interactions, 2) laterality of connections, and 3) dendritic morphology. The proposed experiments will address these three issues. First, the synaptic organization of the lateral superior olivary nucleus and its development will be studied using immunocytochemistry, tracing methods and electron microscopy to identify anti-glycine or anti-GABA immunoreactive ending, their origin, and their relationship to specific cell populations in LSO. Second, the development of laterality of ascending auditory projections and of the decussation of trapezoid body fibers will be studied. Development of projections from the cochlear nucleus and to the inferior colliculus will be studied with tracing methods. The relation of decussating trapezoid body fibers to glia will be investigated with immunocytochemistry and electron microscopy. In addition, lectin binding will be used to study developmental changes in the extracellular matrix. Third, the study of dendritic development will now be extended to other nuclei in the binaural pathway. An understanding of the developmental interrelationships of these events in binaural pathways important for hearing, attention, and speech perception, will lead to further experiments that can determine mechanisms involved in development and how drugs infections, or perinatal experience may have deleterious effects on the developing auditory system.
