The proposed research addresses specific questions about the development of the auditory periphery and the establishment of the topographic organization of cochlear spiral ganglion projections to the cochlear nuclei (CN). Cytochemical labeling techniques (NB and DiI) for neuronal tract tracing combined with physiological recording and extensive light and electron microscopic analyses will be employed. Initial studies have revealed that projections from basal sectors of the spiral ganglion to the anteroventral subdivision (AVCN) undergo substantial remodeling during post natal development, but the descending collaterals of these same neurons projecting to the dorsal (DCN) and posteroventral (PVCN) subnuclei form nearly adult-like, refined projections at birth. Objectives of further experiments include: 1) To determine in detail the timing and sequence of topographic refinement during development of the highly ordered projections to each subdivision of the CN; specifically to characterize remodeling of projections to DCN and PVCN by studying earlier ages. 2) To examine projections from the apical cochlea to determine of maturation of CN projections parallels the basal-to-apical maturation of the organ of corti. 3) To determine whether CN projections develop normally or if significant reorganization occurs as a consequence of lesions of the spiral ganglion created during early development. 3) To determine whether anatomical remodeling of CN projections underlies the apparent loss of frequency selectivity induced by electrical stimulation with a cochlear implant. 4) To determine whether development of CN projections is activity dependent by examining the effects of inhibition of nitrous oxide synthesis and of blockade of auditory nerve activity. 5) To characterize specific ultrastructural features of postnatal development of the cat cochlea at specific frequency locations. The proposed experiments will increase our understanding of the anatomical framework for information processing mechanisms in the developing peripheral auditory system and will address important questions regarding critical periods and plasticity. Studies in deafened animals have practical implications regarding efficacy and optimization of cochlear implants in children.
