MECHANISM FOR MAMMALIAN OPTOKINETIC NYSTAGMUS

哺乳动物视动眼球震颤的机制

• 批准号: 3256841
• 负责人: LAWRENCE H PINTO
• 金额: $ 10.87万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-08-01 至 1990-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3256841
• 关键词: afferent nerve; congenital vision disorder; efferent nerve; electrophysiology; eye disorder diagnosis; eye movements; fluorescence microscopy; histology; innervation; laboratory mouse; mutant; neuroanatomy; neurophysiology; nystagmus; optic tract; radioassay; reflex; retinal ganglion; stimulus /response; visual stimulus

The applicant proposes to study the mechanisms for optokinetic nystagmus (OKN) in mammals. It has been postulated that this reflexive set of eye movements is mediated by the activity of the three accessory optic terminal nuclei and the nucleus of the optic tract, that each nucleus mediates OKN which is induced by a stimulus that mvoes in a preferred direction and that the preferred directions are segregated among the nuclei. The proposed experiments will test this hypothesis using the OKN- related nuclei that receive the major retinal innervation in the mouse. For the medial terminal nucleus (thought to lie in the vertical OKN pathway) the physiological response properties of (i) the retinal ganglion cells that provide its afferent input, and (ii) the neurons of the nucleus itself will be characterized. The anatomical efferent connections of the nucleus will also be determined. The overall metabolic activity of the nucleus in response to stimuli that move in horizontal and vertical directions will be measured with the 2-deoxy-D-glucose technique. The vestibulo-ocular reflex will also be measured for normal mice. The above measurements will also be made for mutant mice and that have upward eye movements in response to horizontally- moving visual stimuli. Similar experiments will be performed upon the nucleus of the optic tract, thought to lie in the horizontal OKN pathway. The vestibulo-ocular reflex will be measured upon a second type of mutant with no OKN whatsoever in order to search for abnormalities in the "final common pathway" for producing eye movements. If this latter type of mutant is found to have normal vestibulo-ocular reflex its retinofugal projections to the OKN- related nuclei will be measured. The mutants proposed for study serve as models for various congenital human diseases: Chediak-Higashi disease (beige and beige-J); tyrosinase negative albinism (albino-2J and himalyan) and tyrosinase positive albinism (beige, ruby-eye-2, and ruby). One of the mutations proposed for study (ruby-eye-2) lies about 7 cM from a gene that is homologous between man and mouse, and therefore has a probability of about 40% to lie within a conserved chromosomal segment. Thus, what is learned about the mechanism of action of the mutant genes will probably be applicable to the human.

申请人建议研究视动机制 哺乳动物的眼球震颤（OKN）。 据推测，这 反射性眼球运动是由眼球的活动介导的 三个附属视神经终末核和视神经核 束，每个核介导 OKN，这是由 刺激朝着首选方向移动，并且 优选方向在核之间是分离的。 这 拟议的实验将使用 OKN- 来检验这一假设 接受主要视网膜神经支配的相关核团 老鼠。 对于内侧终核（被认为位于 垂直 OKN 通路）的生理反应特性 (i) 提供传入输入的视网膜神经节细胞，以及（ii） 细胞核本身的神经元将被表征。 这 核的解剖传出连接也将是 决定。 细胞核的总体代谢活动 对水平和垂直方向移动的刺激的反应 将使用 2-脱氧-D-葡萄糖技术进行测量。 这 还将测量正常小鼠的前庭眼反射。 上述测量也适用于突变小鼠和 眼球向上运动以响应水平方向 移动的视觉刺激。 将进行类似的实验 视神经束核上，被认为位于 水平 OKN 通路。 前庭眼反射将根据第二种类型进行测量 没有任何 OKN 的突变体以搜索 产生眼睛的“最终共同途径”异常 动作。如果发现后一种类型的突变体具有正常的 前庭眼反射将其视网膜投射到 OKN- 将测量相关的原子核。 提议研究的突变体可作为各种模型 人类先天性疾病：Chediak-Higashi 病（米色和 米色-J);酪氨酸酶阴性白化病（albino-2J 和喜马拉雅） 酪氨酸酶阳性白化病（米色、ruby-eye-2 和 ruby​​）。 提议研究的突变之一 (ruby-eye-2) 约为 7 来自人和小鼠同源基因的cM，以及 因此，有大约 40% 的概率位于保守区域内 染色体片段。 由此，我们了解到关于 突变基因的作用机制可能是 适用于人类。