CELLULAR ANALYSIS OF THE VESTIBULO-OCULAR REFLEX

产品说明： （摘自申请人摘要） 的能力 在自我运动中看得清楚，关键取决于 前庭眼反射（vestibulocular reflex，VOR）VOR使 通过产生补偿眼在头部运动期间稳定视力 运动方向相反，幅度相等， 头部运动。我们对神经回路有很多了解， 介导VOR和关于由成分携带的信号 神经元然而，相对而言，对细胞和 分子机制 是日常业绩的基础， VOR的长期适应能力。这项研究的目的是 是研究信号的细胞和突触基础 在VOR中的转换，并提供基础， 理解适应性可塑性的细胞和分子基础 在VOR。 脑干切片准备将用于检查细胞 前庭神经元信号转换机制 前庭内侧核（MVN）的中间神经元。 一是 锋电位产生的动力学特性（ 神经元输入到动作电位的时变模式）将 通过从MVN神经元进行细胞内记录来研究， 测量对细胞内电流注入的放电反应。 第二，内在膜电导在塑造细胞膜中的作用。 穗产生的动力学将研究与 钙和钾通道的药理学阻断剂。 第三、 神经递质在调节锋电位产生中的作用 动力学将用药理学激动剂进行检查， 乙酰胆碱、组胺、5-羟色胺、去甲肾上腺素和NMDA 受体，已被证明影响VOR或 或前庭神经元的自发放电。最后 生理学和生物学特性之间的关系 MVN神经元和由解剖学定义的细胞类别， 体内的行为研究将用以下组合来确定 细胞内染料注射和输入的电刺激， 输出路径。 这些结果将为我们了解细胞和突触 调节正常运行和适应能力的机制 他们可能进一步导致的发展， 神经眼科疾病的药物治疗 眼球运动，包括眼球震颤。

DESCRIPTION: (Adapted From The Applicant's Abstract.) The ability to see clearly during self-motion depends critically on the performance of the vestibuloocular reflex(VOR). The VOR enables stable vision during head movements by producing compensatory eye movements that are opposite in direction and equal in amplitude to head motion. Much is understood about the neural circuitry that mediates the VOR and about the signals carried by the constituent neurons. However, relatively little is known about the cellular and molecular mechanisms that underlie the day-to-day performance and long-term adaptive capabilities of the VOR. The goals of this research are to investigate the cellular and synaptic basis of signal transformations in the VOR and to provide a foundation for understanding the cellular and molecular basis of adaptive plasticity in the VOR. A brainstem slice preparation will be used to examine the cellular mechanisms governing signal transformations in vestibular interneurons in the medial vestibular nucleus (MVN). First, the dynamic properties of spike generation (the transduction from neuronal inputs into time-varying patterns of action potentials) will be studied by making intracellular recordings from MVN neurons and measuring firing responses to intracellular current injection. Second, the roles of intrinsic membrane conductances in sculpting the dynamics of spike generation will be investigated with pharmacological blockers of calcium and potassium channels. Third, the roles of neurotransmitters in modulating spike generation dynamics will be examined with pharmacological agonizes of acetylcholine, histamine, serotonin, noradrenaline, and the NMDA receptor, agents that have been shown to affect either the VOR itself or spontaneous firing in vestibular neurons. Finally, the relationship between physiologically and pharmacologically distinct MVN neurons and the cell classes defined by anatomical and behavioral studies in vivo will be determined with a combination of intracellular dye injection and electrical stimulation of input and output pathways. The results should provide insights into the cellular and synaptic mechanisms that mediate the normal operation and adaptive capabilities of the VOR They may furthermore lead to the development of pharmacological treatments of neuro-ophthalmological disorders of ocular motility, including nystagmus.