Vestibular and optokinetic testing for research and clinic

用于研究和临床的前庭和光动测试

• 批准号: 7194677
• 负责人: Chris R. S. Kaneko
• 金额: $ 27.94万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7194677
• 关键词: Animal Model; Animals; Basic Science; Behavior; Behavioral; Behavioral Paradigm; Cerebellar Ataxia; Clinic; Clinical; Complex; Data; Development; Diagnostic; Exhibits; Eye; Eye Movements; Family; Functional disorder; Future; Genetic; Genetic Techniques; Genotype; Goals; Human; Human Pathology; Inherited; Investigation; Laboratories; Lead; Learning; Mammals; Manufacturer Name; Measurement; Measures; Mechanics; Medical center; Methods; Modeling; Molecular; Molecular Genetics; Motor; Mus; Mutant Strains Mice; NIH Program Announcements; Nervous System Physiology; Neurodegenerative Disorders; Neurons; Numbers; Organism; Pathology; Phenotype; Primates; Process; Public Health; Reflex action; Research; Research Personnel; Scientist; Sensory; Site; Source; System; Techniques; Testing; Universities; Visual; Washington; Work; base; combinatorial; comparative; falls; genetic manipulation; high throughput screening; improved; interest; miniaturize; mouse model; mutant; mutant mouse model; neuromechanism; oculomotor; oculomotor behavior; programs; relating to nervous system; scale up; size; tool; vestibulo-ocular reflex

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.

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，研究分子机制所采用的技术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。因此，有必要在用于研究实验对象的行为和/或选择的技术中妥协。潜在的例外是对小鼠的多种正常和突变菌株的研究，它们使用分子遗传技术进行研究，但仍显示出许多在较高哺乳动物中表现出来的行为。不仅是感觉和运动过程，还包括例如学习和可塑性的基本机制，已经对分子机制进行了许多侵害。最近出现的一个突出的模型是前庭形式反射（VOR）的自适应可塑性。较早的研究主要是关于灵长类动物的，既暗示了简单的3-神经元反射和小脑絮凝物作为重要的地点，以进行更集中的研究。这些研究已经发展到研究了适应过程的基础的亚细胞机制。一个主要的绊脚石是无法轻易地适应灵长类动物中发展的行为范式，以适合于细胞，亚细胞和遗传研究（如小鼠）的动物。这种困难的核心是由于小鼠的眼睛尺寸很小，无法精确测量眼睛运动。在拟议的支持期间，我们计划通过开发适合小鼠的新型巩膜搜索线圈来克服这一障碍，以准确测量其眼睛运动。然后，我们将使用该线圈筛选许多突变小鼠菌株，以记录其动眼缺陷。最后，我们将针对包括小鼠在内的小动物开发更完整的前卫测试设施。这些目的将使我们最终可以常规测试和筛选突变小鼠，不仅对可塑性，而且是正常和病理性起源的基本神经机制进行了各种研究。与公共卫生的相关性将是模型小鼠系统的扩展，以研究人类病理学和治疗，例如，神经退行性疾病，例如小脑共济失调。