Cellular Mechanisms of the Vestibular System

前庭系统的细胞机制

• 批准号: 8721908
• 负责人: JAY M GOLDBERG
• 金额: $ 31.51万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8721908
• 关键词: AMPA Receptors; Action Potentials; Aminoglycosides; Architecture; Auditory; Birds; Cell physiology; Clinical; Complex; Crista ampullaris; Electrophysiology (science); Excision; Extracellular Space; Face; Fiber; Frequencies; Gated Ion Channel; Generations; Geometry; Glutamate Receptor; Glutamates; Hair; Hair Cells; Homeostasis; Housekeeping; Human; Immunohistochemistry; In Situ Hybridization; Ion Channel; Ions; Knowledge; Location; Mammals; Molecular; Monkeys; Morphology; N-Methyl-D-Aspartate Receptors; Nervous system structure; Neurotransmitter Receptor; Neurotransmitters; Organ; Physiological; Physiology; Play; Preparation; Problem Solving; Process; Proteins; Rattus; Recording of previous events; Regulation; Relative (related person); Reptiles; Reverse Transcriptase Polymerase Chain Reaction; Rodent; Role; Shapes; Structure; Supporting Cell; Synapses; Synaptic Cleft; Synaptic Transmission; System; Testing; Turtles; Type I Hair Cell; Type II Hair Cell; Vestibular Hair Cells; Vestibular Labyrinth; Whole-Cell Recordings; Work; age related; aminoglycoside-induced ototoxicity; desensitization; electric impedance; information processing; interest; neuroepithelium; neurotransmitter release; postsynaptic; presynaptic; prevent; public health relevance; receptor; response; symporter; transmission process; voltage

DESCRIPTION (provided by applicant): This is a continuing study of synaptic transmission in vestibular organs with emphasis on the type I hair cell and its calyx ending, phylogenetically recent acquisitions only found in reptiles, birds and mammals. These structures are restricted to central/striolar zones in reptiles and birds. Their increasing importance in mammals is suggested by their distribution throughout the neuroepithelium of all organs. In addition, while type I and type II hair cells occur in approximately equal numbers in rodent cristae, type I hair cells predominate in the cristae of monkeys and possibly of humans. The peculiar structure and distinctive physiology of these structures raise problems as to how synaptic transmission is accomplished. 1) Type I hair cells have a distinctive basolateral current that may compromise synaptic transmission; 2) Housekeeping functions cannot be done by supporting cells; and 3) The geometry and electrophysiology of the calyx ending place unusual demands on the flow of synaptic currents to the spike encoder. We have only fragmentary knowledge as to how these problems are solved. Yet, because these structures become of increasing importance in mammals (including humans), such knowledge is crucial to our understanding as to how vestibular organs process information. Of clinical interest, the type I hair cell and/or its calyx ending are especially sensitive to aminoglycoside ototoxicity and age-related degeneration. Physiological studies will be done in the turtle posterior crista and will be integrated with morphological studies to be done in rats and turtles. There are three specific aims. 1) Hair cells: We will characterize synaptic transmission from type I hair cells by making whole- cell recordings from the calyx ending. The hypothesis is that neurotransmitter release from type I hair in low- frequency vestibular hair cells may differ from high-frequency auditory and vibratory organs. 2) Homeostasis: Both K+ ions and glutamate neurotransmitter are released from hair cells during transduction. In the case of type II hair cells, supporting cells serve to clear these substances. The presence of the calyx ending precludes supporting cells from acting in the same way for type I hair cells. We hypothesize that the type I hair cell and/or its ending subsume these housekeeping functions. 3) Postsynaptic mechanisms: We will explore how various ion channels and neurotransmitter receptors shape synaptic and spiking activity. The hypothesis to be tested is that the molecular organization of the calyx creates separate microdomains with discrete functions: synaptic transmission, spike initiation, and discharge regularity.

描述（由申请人提供）：这是对前庭器官突触传播的持续研究，重点是I型毛细胞及其花萼结束，从爬行动物，鸟类和哺乳动物中发现的系统发育近期收购。这些结构仅限于爬行动物和鸟类中的中央/斯特里罗区。它们在哺乳动物中的重要性越来越重要，这是由于它们在所有器官的整个神经上皮中的分布所表明的。另外，虽然I型和II型毛细胞在啮齿动物的cristae中大致相等，但I型毛细胞占猴子和可能的人类的cristae。这些结构的特殊结构和独特的生理学提出了有关如何完成突触传播的问题。 1）I型毛细胞具有独特的基底外侧电流，可能会损害突触传播； 2）不能通过支持细胞来完成管家功能； 3）花萼结束位置的几何形状和电生理学对突触电流流向尖峰编码器的流动不寻常。我们只有关于如何解决这些问题的零碎知识。但是，由于这些结构在哺乳动物（包括人类）中变得越来越重要，因此这种知识对于我们对前庭器官如何处理信息的理解至关重要。具有临床感兴趣的是，I型毛细胞和/或其花萼末端对氨基糖苷耳毒性和与年龄相关的变性特别敏感。生理研究将在乌龟后Crista进行，并将与在大鼠和海龟中进行的形态学研究结合。有三个特定的目标。 1）毛细胞：我们将通过从花萼末端制作全细胞记录来表征I型毛细胞的突触传播。假设是，在低频前庭毛细胞中，神经递质从I型头发释放可能与高频听觉和振动器官不同。 2）体内平衡：转导期间，K+离子和谷氨酸神经递质都从毛细胞中释放出来。在II型毛细胞的情况下，支持细胞可以清除这些物质。花萼结束的存在阻止了支撑细胞以相同的方式对I型毛细胞作用。我们假设I型毛细单元和/或它的结尾包含这些管家功能。 3）突触后机制：我们将探讨各种离子通道和神经递质受体如何塑造突触和尖峰活性。要测试的假设是，花萼的分子组织具有离散功能的单独的微区域：突触传递，尖峰启动和排放规律性。

项目成果

Efferent-mediated binaural interactions between the vestibular end-organs in the chinchilla.

龙猫前庭终末器官之间传出介导的双耳相互作用。

• DOI: 10.1111/j.1749-6632.2001.tb03774.x
• 发表时间: 2001
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Plotnik,M;Marlinski,V;Goldberg,JM
• 通讯作者: Goldberg,JM

Discharge regularity in the turtle posterior crista: comparisons between experiment and theory.

龟后嵴的放电规律：实验与理论的比较。

• DOI: 10.1152/jn.00195.2013
• 发表时间: 2013
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Goldberg,JayM;Holt,JosephC
• 通讯作者: Holt,JosephC

Ultrastructural analysis of the cristae ampullares in the squirrel monkey (Saimiri sciureus).

• DOI: 10.1002/cne.21827
• 发表时间: 2008-11-01
• 期刊: JOURNAL OF COMPARATIVE NEUROLOGY
• 影响因子: 2.5
• 作者: Lysakowski, Anna;Goldberg, Jay M.
• 通讯作者: Goldberg, Jay M.

Vestibular control of the head: possible functions of the vestibulocollic reflex.

• DOI: 10.1007/s00221-011-2611-5
• 发表时间: 2011-05
• 期刊: EXPERIMENTAL BRAIN RESEARCH
• 影响因子: 2
• 作者: Goldberg, Jay M.;Cullen, Kathleen E.
• 通讯作者: Cullen, Kathleen E.

Glutamate transporters EAAT4 and EAAT5 are expressed in vestibular hair cells and calyx endings.

• DOI: 10.1371/journal.pone.0046261
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Dalet A;Bonsacquet J;Gaboyard-Niay S;Calin-Jageman I;Chidavaenzi RL;Venteo S;Desmadryl G;Goldberg JM;Lysakowski A;Chabbert C
• 通讯作者: Chabbert C