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MECHANISM FOR MAMMALIAN OPTOKINETIC NYSTAGMUS

哺乳动物视动眼球震颤的机制

基本信息

批准号：
3256842
负责人：
LAWRENCE H PINTO
金额：
$ 11.04万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-08-01 至 1991-07-31
项目状态：
已结题

项目摘要

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性的机制，眼震（OKN）在哺乳动物。据推测，眼球运动的反射性集合是由三个副视终核和视神经核道，每个核介导OKN，这是由一个刺激，在一个优选的方向移动，优选的方向在核之间分离。的提出的实验将使用OKN测试这一假设- 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）的生理响应特性（i）提供其传入输入的视网膜神经节细胞，以及（ii）将表征核本身的神经元。的核的解剖传出连接也将被测定细胞核的整体代谢活动，对水平和垂直方向运动的刺激的反应将用2-脱氧-D-葡萄糖技术测量。的还将测量正常小鼠的前庭眼反射。还将对突变小鼠进行上述测量，眼睛会向上运动，以响应水平方向- 移动的视觉刺激。将进行类似的实验在视束核上，被认为位于水平OKN通路。前庭眼反射将在第二种类型上测量没有OKN的突变体，产生眼睛的“最后共同途径”异常动作如果发现后一种突变体具有正常的前庭眼反射，其视网膜离体投射到OKN- 将测量相关的原子核。提出用于研究的突变体作为各种先天性人类疾病：Chediak-Higashi病（米色和酪氨酸酶阴性白化病（白化病-2 J和himalyan）和酪氨酸酶阳性白化病（米色、红宝石眼-2和红宝石色）。其中一个被提议用于研究的突变（红宝石眼-2）位于大约7 来自人和小鼠之间同源的基因的cM，和因此，有大约40%的概率位于保守的染色体片段因此，关于突变基因的作用机制可能是适用于人类。