REGENERATIVE PHENOMENA IN THE DEVELOPING ORGAN OF CORTI

描述：这项研究涉及形态和生化事件 引导和伴随着科尔蒂器官的再生/修复 从新生小鼠身上取出培养物，用激光损伤。 具体地说，建议研究：1)细胞间的相互作用 受损的毛细胞及其支持细胞。超微结构证据 提示支持细胞参与毛细胞的存活和 恢复。这项研究将试图阐明支持的萌芽 细胞和损伤毛细胞上的包裹取决于毛细胞的程度 损伤(通过不同强度的激光)或损伤位置，有针对性 毛细胞或选择性支持细胞；2)毛细胞 激光消融其传入神经元后的变性。两根头发 在消除螺旋的过程中观察到细胞死亡和损伤 神经元。这项研究旨在了解这些变化是否由 激光照射导致膜电压升高的过程 放射状纤维的电位或突然失神经所致。这个 激光在烧蚀和机械消融过程中的衰减 螺旋神经元的数量应该有助于区分导致 二次破坏毛细胞；3)选择性破坏毛细胞 通过激光消融螺旋神经元。这项研究提出了具有挑衅性的 通过突触将损伤从神经细胞转移到 它的目标细胞。通过改变被消融神经元的位置，我们将尝试 诱导内、外毛细胞选择性变性；4) 毛细胞侧枝神经元萌发的再神经支配。它是 预计一些螺旋神经元的消除将导致侧枝循环 从幸存的神经节细胞发芽。这些实验是经过精心设计的 研究新的突触接触的获得；5)毛发的重组 损伤后细胞顶端特化。毛发的广度和恒定性 细胞修复将被检查：a)立体纤毛束的再生 将通过高分辨率扫描电子显微镜进行研究；b) 毛细胞角质板的生化重建将 细胞骨架蛋白的超微结构免疫细胞化学检测 (与N.B.斯莱佩基合作) 该项目的一个长期目标是开发和定义体外模型 对毛细胞的可复制损伤，以了解机制(S)和 导致受体细胞存活和恢复的因素。这个 这项研究的意义在于揭示了材料的可塑性 哺乳动物的听力器官和识别促进 维护其完整性。

DESCRIPTION: The research concerns the morphological and biochemical events that lead o and accompany the regeneration/repair of the organ of Corti in cultures explanted from the neonatal mouse and injured by laser beam. Specifically, it is proposed to study: 1) Cellular interactions between injured hair cells and their supporting cells. Ultrastructural evidence indicate that supporting cells participate in hair cell survival and recovery. The study will attempt to elucidate if sprouting of supporting cells and wrapping on injured hair cells depends on a degree of hair cell damage (by varying intensity of laser beam) or the site of injury, targeted either at hair cell or selectivity at supporting cells; 2) Hair cell degeneration following laser ablation of their afferent neurons. Both hair cell death and damage have been observed upon the elimination of spiral neurons. The study aims to understand if these changes are caused by the process of laser irradiation that led tot he increase in voltage of membrane potential of the radial fibers or by the sudden denervation. The attenuation of the laser beam during the ablation and mechanical elimination of spiral neurons should help in distinguishing the factor that led to the secondary destruction of hair cells; 3) Selective destruction of hair cells by laser ablation of spiral neurons. The study raises provocative possibility of the trans-synaptic transfer of damage from the nerve cell to its target cell. By varying the site of ablated neurons we will try to induce the selective degeneration of inner versus outer hair cells; 4) Reinnervation of hair cells by collateral neuronal sprouting. It is expected that elimination of some spiral neurons will induce the collateral sprouting from the surviving ganglion cells. These experiments are designed to study the acquisition of new synaptic contacts; 5) Reformation of hair cell apical specializations after injury. The extent and constancy of hair cell repair will be examined: a) the regrowth of the stereociliary bundle will be studied by high resolution scanning electron microscope; b) the biochemical reconstruction of the hair cell cuticular plates will be examined by ultrastructural immunocytochemistry of the cytoskeletal proteins (in collaboration with N.B. Slepecky). A long-term goal of the project is to develop and in vitro model of defined reproducible injury to the hair cell in order to understand mechanism(s) and factors that lead to survival and recovery of the receptor cells. The significance of the research lies in bringing to light the plasticity of the mammalian hearing organs and identifying cellular processes that facilitate the preservation of its integrity.