SENSORY PROCESSING IN THE VESTIBULAR ORGANS

这项工作的长期目标是了解前庭器官， 脑的位置和运动、功能和发育。好 健康取决于这些器官的正常功能。损伤可能导致 使人虚弱的眩晕、晕眩和无法保持稳定的凝视。 前庭器官的初级传入神经元的敏感性不同 和对头部运动刺激的反应的时间过程。一些 变化与感觉器官内的区域相关。在埃里奥特斯，a 变异的另一个来源可能是两个类之间的差异 感觉毛细胞I型和II型。本申请建议采取 哺乳动物前庭器官处理刺激的三种方法， 以啮齿动物的椭圆囊为模型。第一个目标是测试是否有 是区域和细胞类型特异性差异的性质， 毛细胞的机械敏感传感器电导， 运动刺激转化为受体电位。 第二，毛细胞 电压门控钾电导，它塑造受体电位， 将在分子水平上通过应用针对 候选蛋白质和信使RNA。这些电导不同 基本上介于I型和II型毛细胞之间。第三个目标是 从高峰期开始表征毛细胞的正常发育 终末有丝分裂（产前）至动物出生。 出生时，小鼠 椭圆囊毛细胞表达一些电压门控电导， 超微结构分析表明，虽然胞果不成熟， 在许多方面，一些细胞可以被识别为I型或II型。产前时间 获取电压门控电导的过程将由 全细胞记录电压门控性钾通道的表达 蛋白质将被分子探针及时跟踪。产前 将表征胞果的形态分化。这些 实验应该提供深入了解毛细胞的早期分化 和支持细胞，以及确定钾通道的效用 蛋白质作为毛细胞分化的标志物。

The long-term goal of this work is to understand how vestibular organs, which transduce head position and movement, function and develop. Good health depends on the normal function of these organs. Damage can lead to debilitating vertigo, dizziness and an inability to maintain steady gaze. The primary afferent neurons to vestibular organs vary in the sensitivity and time course of their responses to head movement stimuli. Some of the variation correlates with region within the sensory organ. In amniotes, a further source of variation is likely to be differences between two classes of sensory hair cell, type I and II. This application proposes to take three approaches to stimulus processing by mammalian vestibular organs, using the rodent utricle as a model. The first aim is to test whether there are regional and cell-type-specific differences in the properties of the hair cell's mechanosensitive transducer conductance, which converts head movement stimuli into the receptor potential. Second, the hair cells' voltage-gated potassium conductances, which shape the receptor potential, will be characterized at the molecular level by applying probes directed at candidate proteins and messenger RNA. These conductances differ substantially between type I and II hair cells. The third aim is to characterize the normal development of hair cells from the period of peak terminal mitoses (prenatal) to birth of the animal. At birth, mouse utricular hair cells express some voltage-gated conductances and ultrastructural analysis shows that although the utricle is immature in many ways, some cells can be recognized as type I or II. The prenatal time course of acquisition of voltage-gated conductances will be determined with whole-cell recording. The expression of voltage-gated potassium channel proteins will be followed in time with molecular probes. Prenatal morphological differentiation of the utricle will be characterized. These experiments should provide insight into early differentiation of hair cells and supporting cells, as well as determine the utility of potassium channel proteins as markers of hair cell differentiation.