Development & Connections of Cochlear Spinal Ganglion

描述(由申请人提供)：这项拟议的研究解决了关于耳蜗的发育和螺旋神经节向耳蜗核(CN)投射的地形组织的建立的具体问题。神经元束追踪的细胞化学标记技术(NB和DIL)将与电生理记录和广泛的定量光和电子显微镜分析相结合。我们最近的研究表明，在出生后的早期发育过程中，从螺旋神经节的基底区到CN的每个亚区的投射都经历了显着的细化。对前腹侧亚区(AVCN)的投射，新生儿比成人宽50%以上，这些神经元投射到背侧(DCN)和后腹侧(PVCN)亚区的下行侧支比成人宽30%。拟议实验的目标包括：1)进一步研究妊娠晚期和出生后早期对CN每个细分的投影的时间和序列的细节。2)观察耳蜗尖的投射，以确定其CN投射的成熟是否与Corti器官从基端到顶端的成熟平行。3)完成新生儿耳聋对成年后严重听力剥夺后的CN投射的特异性影响的定量研究。4)确定CN投射是否正常发育，或是否由于发育早期螺旋神经节的局限性病变而发生显著重组。5)确定慢性电刺激所致频率选择性明显丧失的基础是否是CN投射的解剖重构。6)通过检测螺旋神经节自发活动的性质，探讨听神经投射正常发育的机制。7)研究Corti猫器官出生后发育的某些超微结构特征。拟议的实验将增加我们对发育中的听觉系统中信息处理机制的解剖学框架的理解，并将解决关于关键期和可塑性的重要问题。此外，在聋人动物身上进行的研究对儿童人工耳蜗术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.