The proposed research project is designed to determine the course of normal anatomical development in the cochlear nucleus and other brainstem auditory nuclei and to assess the role that function plays in development. The hamster is a particularly useful subject for studying development of the auditory system because of its relative immaturity at birth. Changes in cell morphology and organization continue to occur after the auditory system becomes functional. The normal time course of synapse formation between the cochlear nerve fibers and their target neurons in the cochlear nucleus will be studied with particular attention to the temporal-spatial pattern of initial synapse formation. In addition, synapse formation which proceeds after the onset of function will be described. One goal of the present research is to alter the normal input throughout development to test whether normal auditory input is necessary for continuing synapse formation. In addition, a study of neuronal orientation in the brainstem auditory nuclei is proposed. The normal development of cells, known to be oriented with respect to their inputs, will be described and the effect of altered auditory input on this orientation will be evaluated. Auditory input will be perturbed through a variety of methods, including cochlear ablation, ossicular removal and ear plugs. The effectiveness of these techniques will be tested for experimental subject with audiometry and behavioral methods. Results will be analyzed on both the light and electron microscopic levels. In particular, changes in the distribution of synaptic terminals will be assessed as well as changes in cell morphology. Golgi-impregnated material and electron microscopy will be used for assessing the role of function in normal development. The use of horseradish peroxidase and ablation/degeneration techniques will be used to verify the obseved effects of altered input on normal development. Alterations in normal functional input during early development are known to affect the organization of the nervous system. The experiments outlined in this proposal are designed to test specific hypotheses regarding the nature of these changes. These hypotheses are being tested in a system (the mammalian auditory system) in which much is known about how anatomical relationships account for the functional attributes of populations of neurons. It anatomical abnormalities are caused by altered early functioning this would suggest that the normal organization in the brainstem auditory nuclei, which is thought to be a substrate for normal hearing capabilities, is dependent on normal auditory input during development.
