Vestibular and optokinetic testing for research and clinic

描述（由申请人提供）：研究神经系统功能的基本目标是了解复杂行为系统的分子基础。不幸的是，用于研究分子机制的技术并不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/或实验对象的选择上做出妥协。一个潜在的例外是对各种正常和突变小鼠的研究，这些小鼠可以使用分子遗传技术进行研究，但仍然表现出许多在高等哺乳动物中表现出来的行为和最初的特征。许多进展已经取得了分子机制的基础上，不仅感觉和运动过程，而且基本机制，例如，学习和可塑性。最近出现的一个突出的模型是前庭眼反射（vor）的适应性可塑性。早期的研究，主要是在灵长类动物身上，暗示了简单的3神经元vor反射和小脑小叶是更集中研究的重要部位。这些研究已经发展到研究亚细胞机制，这是适应过程的基础。一个主要的障碍是无法将灵长类动物的行为模式适应于更适合细胞、亚细胞和基因研究的动物，比如老鼠。这个困难的核心是由于鼠标的眼睛很小，无法精确测量眼球运动。在建议的支持期内，我们计划通过开发一种适合小鼠的新型巩膜搜索线圈来克服这一障碍，该线圈将准确测量小鼠的眼球运动。然后，我们将使用该线圈筛选一些突变小鼠品系，以记录它们的动眼肌缺陷。最后，我们将开发一个更完整的小动物前庭光动力学测试设备，包括小鼠。这些目标将使我们最终能够常规测试和筛选突变小鼠，以进行各种各样的基本神经机制研究，不仅是vor可塑性，而且是正常和病理起源。与公共卫生相关的是模型小鼠系统的扩展，用于研究人类病理和治疗，例如，像小脑性共济失调这样的神经退行性疾病。

DESCRIPTION (provided by applicant): 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 characterized in 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, neurodegenerative diseases like cerebellar ataxia.