SENSORY PROCESSING IN THE VESTIBULAR ORGANS

这项工作的长期目标是了解前庭器官是如何， 它传递头部的位置和运动，功能和发展。好的 健康取决于这些器官的正常功能。损坏可能会导致 使人虚弱的眩晕、眩晕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。 以及它们对头部运动刺激的反应的时间进程。其中一些 变异与感觉器官内的区域相关。在羊膜中，一种 进一步的差异来源可能是两个类别之间的差异 感觉毛细胞，I型和II型。这个应用程序建议采用 哺乳动物前庭器官处理刺激的三种方法， 以啮齿动物的椭圆形为模型。第一个目标是测试是否有 是区域和特定于单元格类型的 毛细胞的机械敏感换能器电导，它将头部 运动刺激进入感受器电位。第二，毛细胞 电压门控的钾电导，它塑造了受体的电势， 将通过应用定向的探针在分子水平上进行表征 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 动物出生前的终末有丝分裂。在出生的时候，老鼠 椭圆形毛细胞表达一些电压门控电导和 超微结构分析表明，虽然胞果还未成熟，但 在许多方面，一些细胞可以被识别为I型或II型。产前时间 电压门控电导的获取过程将通过以下方式确定 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 将对椭圆体的形态分化进行表征。这些 实验应该为毛细胞的早期分化提供洞察力 和支持细胞，以及确定钾通道的用途 蛋白质作为毛细胞分化的标记物。

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.