Project Summary / Abstract We look between targets located in the 3D visual environment by making disjunctive saccades that bring the target image onto both foveae. Each gaze shift is followed by a fixation period for visual analysis during which the new vergence level must be maintained. Most studies have focused on the circuitry controlling conjugate saccades, whereas the neural control of disjunctive saccades and vergence eye movements has received less study. Several models suggest that abducens motoneurons send a monocular command carrying information to each eye to control disjunctive saccades. Other models have proposed the existence of saccade-vergence burst neurons (SVBNs) that project to medial rectus motoneurons and are active only during disjunctive saccades. We have identified this novel cell type, which only discharge during disjunctive saccades, in the central mesencephalic reticular formation (cMRF) lateral to the oculomotor nucleus (OMN). Electrical microstimulation in this region of the cMRF elicits disjunctive saccades, whereas inactivation impairs vergence gaze holding. Recent anatomical findings have demonstrated that premotor neurons related to the near response are located in the cMRF, and that they project to the supraoculomotor area (SOA) and to the OMN. We hypothesize that the cMRF, and the SVBNs in particular, play a critical role in the generation of disjunctive saccades. We further hypothesize that projections between the cMRF and SOA form part of a previously undescribed neural circuit that produces vergence integration, allowing vergence angle to be maintained during fixation. Other anatomical and electrophysiological findings demonstrate that the cerebellum, specifically, the caudal fastigial nucleus and the posterior interposed nucleus, play a role in controlling vergence eye movements in both normal and strabismic individuals. We therefore hypothesize that the cerebellar input to the cMRF/SOA complex helps encode or modulate disjunctive saccades. Guided by these overarching hypotheses, we propose Specific Aims to characterize this neural circuitry. 1. To determine the role of SVBNs and the cMRF in the production of disjunctive saccades; 2. To test the hypothesis that the cMRF/SOA complex is the vergence integrator responsible for maintaining the level of convergence; 3. To determine how the cerebellar projections to the cMRF/SOA circuitry are involved in the generation of disjunctive saccades and vergence eye movements. To test our specific hypotheses, we will use established neurophysiological techniques (electrophysiological recordings, antidromic activation, electrical microstimulation and reversible pharmacological modulation). The overall goal of our project is to substantially increase our understanding of the neural circuitry controlling 3D eye movements in primates, and to broadly impact the oculomotor field, leading to new neurophysiological and modeling approaches. These findings will also provide a cr...