Neural Control of a Complex Oculomotor Plant

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DESCRIPTION (provided by applicant): Significance: Almost 40 years of oculomotor physiology have been based on the powerful simplifying notion that the oculomotor nuclei, their cranial nerves, and the extraocular muscles (EOMs) constitute a simple, homogeneous Final Common Path (FCP), in which supernuclear signals controlling the several types of eye movement combine anonymously. It was, therefore, surprising when studies of vergence eye movement using direct muscle force measurements and magnetic resonance imaging (MRI) failed to confirm predictions that would follow from earlier, well-replicated motoneuron (MN) studies, if the FCP hypothesis were correct. This hypothesis now appears untenable, and the oculomotor plant ripe for exploration of its long-neglected functional richness. Supernuclear disorders are mostly inaccessible to treatment, whereas functions localized to the oculomotor periphery may be readily subject to pharmacologic, surgical and genetic manipulations. An understanding of related motoneuron and muscle fiber specializations would make it possible to effect subtle changes, compared to the gross manipulations of muscle action currently available to treat strabismus and related disorders. Studies: Our first overall aim is to delineate failures of the FCP hypothesis: (1) We will strongly verify the "missing lateral rectus (LR) force paradox" by recording identified abducens MNs and simultaneously measuring LR forces in vergence, continuing (2) to distinguish changes in slopes and Y-intercepts of MN rate-position curves, and to study the variation of LR and medial rectus (MR) convergence forces across the horizontal gaze plane. (3) We will replicate in monkeys, an MRI study in humans that found no globe retraction in convergence, and will extend it using "gold bead fiducials" (GBFs) to visualize orbital contents. (4) Using our muscle force transducers (MFTs) we will determine if LR and MR forces are consistent with globe translation, muscle paths and connective tissue movements observed with GBFs. Our second overall aim is to characterize complex articulations of the oculomotor plant. (5) We will determine if decreases in LR path length offset the convergence-related increase in contractile force predicted by the MN studies. (6) We will microstimulate MNs and use GBFs to visualize globe, pulley and other tissue movements, (7) determine if MN recruitment order varies with vergence state, and (8) if muscle forces vary with fixation accuracy. (9) We will study EOM unit summation in-vivo using multi-electrode stimulation and MFTs.