Our present understanding of the neuronal and synaptic organizataion of the vertebrate oculomotor system has derived largely from the study of mammalian eye movements. Past efforts have centered around a detailed morphological and physiological analysis of the individual neuronal elements within the oculomotor system in order to better interpret neuronal form in view of cellular function. This overall goal will be continued with major reliance on the use of intracellular recording and HRP staining of identified neurons in the alert animal paradigm. This approach is to be substantially strengthened by including a carefully planned phylogenetic analysis of particular neurons and circuits in the coulomotor system. Assuming that a conservative neuronal plan extends throughout vertebrate oculomotor phylogeny, it is argued that knowledge of vertical and horizontal eye movement in antecedent vertebrates can contribute to a better understanding of basic principles and concepts underlying descendent CNS organization. The research plan encompasses 5 specific areas each of which employ similar experimental approaches, but utilize quite different species. (1) Phylogeny of the abducens nucleus with specific emphasis on internuclear neuron organization will be studied extensively from its first appearance in vertebrates up to, and including, mammals. (2) Synaptic and ionic mechanisms underlying horizontal and vertical saccadic organization will be examined largely in fish. (3) Inhibitory and excitatory second-order vestibulo-ocular neurons will be explored initially in fish, but also in descendent species with focus on their relationship to the phylogenetic origin, history and role of the trochlear motor nucleus in eye movement. (4) Mammalian oculomotor internuclear neurons will be studied and their origin will be sought in antecedent species. (5) Neuronal and synaptic effects of axotomy and regeneration will be evaluated centrally and in respect to neurogenic and myogenic influences on extraocular muscle fiber differentiation. Overall, the plan is to study homologous neurons and circuitry throughout the evolutionary scale in order to provide a solid basis for clarifying their role in mammals. All work envisioned is consistent with the goal of elucidating important relationships in the oculomotor system underlying gaze control and, concommmitantly, a better understanding of oculomotility disorders.
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