Vestibular and optokinetic testing for research and clinic

研究神经系统功能的一个基本目标是了解复合体的分子基础。 行为系统。不幸的是，用于研究分子机制的技术并非如此。 很容易应用于通常表现出最有趣和最复杂行为的复杂生物体。 因此，有必要在用于研究行为的技术和/或 实验对象的选择。一个潜在的例外是对各种正常和突变菌株的研究 利用分子基因技术进行研究的小鼠，但仍然表现出许多 这些行为在高等哺乳动物中表现出来，并最初被描述为特征。已经取得了一些进展 不仅是感觉和运动过程的分子机制，而且还有基本的机制 例如，学习和可塑性。 最近出现的一个突出模式是前庭-眼反射的适应性可塑性。 (VOR)。早期的研究，主要是针对灵长类动物的研究表明，简单的3神经元VOR反射和 小脑小叶作为重点研究的重要部位。这些研究已经发展到 重点是研究作为适应过程基础的亚细胞机制。一个重大的绊倒 障碍是无法轻易地将灵长类动物中形成的行为范式更多地适应于动物 适合于细胞、亚细胞和遗传学研究，如小鼠。这一困难的核心是无法 由于鼠标的眼睛很小，因此可以精确测量眼睛的运动。 在拟议的支持期内，我们计划通过开发一种新型的 适合老鼠使用的巩膜搜索线圈，可以准确测量它们的眼球运动。然后我们将使用它 线圈筛选一些突变的小鼠品系，以记录它们的眼球运动缺陷。最后，我们会 为包括老鼠在内的小动物开发更完善的前庭视动测试设备。这些目标 将使我们最终能够对突变小鼠进行常规测试和筛选，以进行广泛的基础研究 神经机制不仅是VOR可塑性，而且是正常和病理起源的。 与公共健康相关的将是扩展用于人类研究的模型小鼠系统 例如，小脑性共济失调等神经退行性疾病的病理和治疗。

A basic goal in studying nervous system function is to understand the molecular basis of complex behavioral systems. Unfortunately, the techniques employed to investigate molecular mechanisms are not easily applied to complex organisms that normally exhibit the most interesting and sophisticated behaviors. Thus, it has been necessary to compromise either in the techniques used to study the behavior and/or the choice of experimental subjects. A potential exception is the study of a variety of normal and mutant strains of mice which lend themselves to investigation using molecular genetic techniques but still display many of the behaviors exhibited and initially characterizedin higher mammals. A number of inroads have been made into the molecular mechanisms underlying not only sensory and motor processes but also basic mechanisms of, for example, learning and plasticity. One prominent model that has emerged recently is the adaptive plasticity of the vestibulo-ocular reflex (vor). Earlier studies, mostly on primates, have implicated both the simple, 3-neuron vor reflex and the cerebellar flocculus as important sites for more focused investigation. These studies have advanced to the point of investigating the sub-cellular mechanisms that underlie the adaptive process. A major stumbling block has been the inability to readily adapt the behavioral paradigms developed in primates to animals more suited for cellular, sub-cellular, and genetic investigation, like mice. Central to this difficulty is the inability to precisely measure eye movements due to the small size of the eye of the mouse. During the proposed support period, we plan to overcome this obstacle by developing a new type of scleral search coil suitable for mice that will accurately measure their eye movements. We will then use that coil to screen a number of mutant mice strains in order to document their oculomotor deficits. Finally, we will develop a more complete vestibulo-optokinetic testing facility for small animals including mice. These aims will allow us to eventually routinely test and screen mutant mice for a wide variety of investigations into basic neural mechanisms not only of vor plasticity but of normal and pathological origin. The relevance to public health will be the expansion of model mouse systems for the study of human pathology and treatment in, for example, neurodegenerativediseases like cerebellar ataxia.