CELLULAR ANALYSIS OF THE VESTIBULO-OCULAR REFLEX

描述：(改编自申请人的摘要。)一种能力 在自动运动过程中要看清楚，关键取决于 前庭眼球反射(VOR)的表现。VOR使 在头部运动过程中通过产生代偿眼来稳定视力 方向相反且幅度相等的运动 头部运动。对神经回路的了解很多， 调解VOR和关于成分携带的信号 神经元。然而，相对较少的人对细胞和 日常表现的分子机制和 VOR的长期适应能力。这项研究的目标是 是为了研究信号的细胞和突触基础 VOR中的转换，并为 理解适应性可塑性的细胞和分子基础 在沃尔。 脑干切片准备将被用来检查细胞 前庭中控制信号转换的机制 前庭内侧核(MVN)的中间神经元。首先， 棘波发生的动态特性(来自 神经输入到时变的动作电位模式)将 通过对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，内在膜电导在雕刻过程中的作用 将用来研究穗的产生的动力学 钙和钾通道的药理阻滞剂。第三, 神经递质在调节棘波产生中的作用 动力学将用药理上的痛苦来检查 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的药物 或前庭神经元的自发放电。最后， 生理和药理上不同的关系 MVN神经元和由解剖学和 体内的行为研究将通过组合确定 细胞内染料注射和电刺激输入和 输出路径。 这一结果应该会提供对细胞和突触的洞察 调节正常运行和适应能力的机制 他们可能会进一步导致 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.