MECHANISM FOR MAMMALIAN OPTOKINETIC NYSTAGMUS

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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.