Development & Connections of Cochlear Spiral Ganglion

描述（由申请人提供）：这项拟议的研究解决了有关耳蜗发育和建立螺旋神经节向耳蜗核（CN）投射的地形组织的具体问题。神经元束追踪的细胞化学标记技术（NB和Dil）结合电生理记录和广泛的定量光和电镜分析将被采用。我们最近的研究表明，从螺旋神经节基底区到CN各细分的投影在出生后早期发育过程中经历了显著的改进。新生儿的前腹侧细分（AVCN）的投影比成人宽50%以上，这些神经元的下行侧枝投射到背侧（DCN）和后腹侧（PVCN）细分比成人宽30%。拟进行的实验目标包括：1)进一步研究在妊娠晚期和出生后早期对CN各细分区的投影进行地形细化的时间和顺序。2)检查耳蜗顶端的突起，以确定其CN突起的成熟是否与Corti器官的基底到根尖的成熟平行。3)完成新生儿耳聋对终身重度听觉剥夺后成年期CN突起特异性影响的定量研究。4)确定CN突起是否正常发育，或者是否由于早期形成的螺旋神经节受限病变而发生重大重组。5)确定慢性耳蜗内电刺激引起的CN突起的解剖重构是否导致频率选择性的明显丧失。6)通过观察螺旋神经节自发活动（如果有的话）的性质，探讨听神经投射正常发育的机制。7)对特定频率部位的猫器官出生后发育的超微结构特征进行表征。提出的实验将增加我们对发育中的听觉系统信息处理机制的解剖框架的理解，并将解决有关关键时期和可塑性的重要问题。此外，在失聪动物中进行的研究对儿童人工耳蜗的应用具有实际意义。

DESCRIPTION (provided by applicant): This proposed research addresses specific questions regarding the development of the cochlea and the establishment of the topographic organization of spiral ganglion projections to the cochlear nuclei (CN). Cytochemical labeling techniques (NB and Dil) for neuronal tract tracing combined with electrophysiological recording and extensive quantitative light and electron microscopic analyses will be employed. Our recent studies have shown that projections from basal sectors of the spiral ganglion to each subdivision of the CN undergo significant refinement during early postnatal development. Projections to the anteroventral subdivision (AVCN) are more than 50% broader in neonates than in adults when normalized for CN size, and the descending collaterals of these same neurons projecting to the dorsal (DCN) and posteroventral (PVCN) subdivisions are 30% broader than their adult counterparts. Goals of proposed experiments include: 1) To further investigate the details of timing and sequence of topographic refinement during late gestation and early postnatal development of the projections to each subdivision of the CN. 2) To examine projections from the apical cochlea to determine if maturation of its CN projections parallels the basal-to-apical maturation of the organ of Corti. 3) To complete quantitative studies of the effects of neonatal deafening upon the specificity of CN projections examined in adulthood after a lifetime of severe auditory deprivation. 4) To determine whether CN projections develop normally or if significant reorganization occurs as a consequence of restricted lesions of the spiral ganglion created during early development. 5) To determine whether anatomical remodeling of CN projections underlies the apparent loss of frequency selectivity induced by chronic intracochlear electrical stimulation. 6) To explore the mechanisms which underlie normal development of the auditory nerve projections by examining the nature of spontaneous activity (if any) in spiral ganglion. 7) To characterize selected ultrastructural features of postnatal development of the cat organ of Corti at specific frequency locations. The proposed experiments will increase our understanding of the anatomical framework for information processing mechanisms in the developing auditory system and will address important questions regarding critical periods and plasticity. In addition, studies to be conducted in deafened animals have practical implications regarding application of cochlear implants in children.