MECHANISM FOR MAMMALIAN OPTOKINETIC NYSTAGMUS

申请人建议研究视动的机制。 哺乳动物的眼震(OKN)。据推测，这一点 眼球运动的反射性集合是由 三个副视神经终核和视神经核团 束，即每个核介导OKN，这是由一种 刺激向一个首选的方向移动，并且 择优方向在原子核之间分离。这个 拟议的实验将使用OKN来验证这一假设- 接受视网膜主要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途径)生理反应特性(I) 提供其传入输入的视网膜神经节细胞，以及(Ii) 我们将对细胞核本身的神经元进行描述。这个 核团的解剖传出联系也将是 下定决心。细胞核的整体代谢活性 对沿水平和垂直方向移动的刺激的反应 将用2-脱氧-D-葡萄糖技术测定。这个 还将测量正常小鼠的前庭-眼睛反射。 上述测量也将对突变小鼠和 会有向上的眼球运动来回应水平方向- 移动的视觉刺激。类似的实验将会进行。 在视束的核上，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，以便搜索 产生眼睛的“最终共同途径”中的异常 动静。如果后一种类型的突变被发现是正常的 前庭-眼睛反射其视网膜分离性投射到OKN- 相关的原子核将被测量。 被提议进行研究的突变体可以作为各种 人类先天性疾病：切迪亚克-东氏病(米色和 米色)；酪氨酸酶阴性白化病(白化-2J和喜马拉雅) 酪氨酸酶阳性白化病(米色、红宝石眼2和红宝石)。 建议研究的突变之一(ruby-ye-2)约为7 Cm来自人类和老鼠之间同源的基因，以及 因此有大约40%的概率处于保守的 染色体片段。因此，我们了解到的关于 突变基因的作用机制可能是 适用于人类。

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.