The experiments proposed in this application address specific questions relating to the postnatal maturation of the auditory periphery in the cat. These studies will provide fundamental new information about the morphology of the developing organ of Corti and about anatomical details of the development of cochlear spiral ganglion cell projections to the cochlear nuclei (CN) in normal and deafened animals. Cytochemical labeling (BRP) techniques for neuronal tract tracing and single fiber labeling combined with physiological recording and extensive light and electron microscopic analyses will be employed in these studies. Among the objectives are the following: 1) To map the postnatal development of spiral ganglion projections to the CN utilizing HRP microinjections into the spiral ganglion, and to determine if refined isofrequency laminae are present at birth and/or prior to the development of adult auditory thresholds. 2) To determine if cochlear nucleus projection patterns remain static, or undergo topographic remodeling following profound sensory deprivation from ototoxic drug-induced deafness. 3) To examine the consequences of chronic electrical stimulation upon the organization of CN projections, and thus to determine if anatomical remodeling of projections underlies the striking loss of frequency selectivity in the auditory midbrain produced by electrical stimulation in neonatally deafened cats. 4) To determine the nature of spontaneous activity in the auditory nerve of neonatally deafened cats, and thus to assess how it might contribute to the establishment of the normal tonotopic organization of the CN. 5) To explore mechanisms underlying the striking disparity between patterns of ganglion cell and organ of Corti degeneration observed following neonatal deafening by ototoxic drugs. 6) To characterize specific ultrastructural features of postnatal development of the cat cochlea at locations defined by the adult frequency map of the basilar membrane. 7) To correlate the functional development of individual, physiologically-characterized auditory nerve fibers with the morphologic features of organ of Corti development at cochlear locations innervated by individual labeled neurons. This proposed work will increase our understanding of the anatomical framework for information processing mechanisms in the developing peripheral auditory system and should be of critical interest to many investigators. Studies in deafened animals address important questions regarding sensitive periods and plasticity in the auditory system, and have practical implications regarding the efficacy and optimization of cochlear implants in children.
