This project will investigate the inputs and physiology of premotor neurons controlling the near triad actions of vergence, lens accommodation and pupillary constriction; critical actions in the etiology of strabismus and amblyopia. It will: 1. provide the first detailed anatomical demonstration of the circuits underlying vergence functions; 2. characterize the function and connections of a novel set of near triad premotor neurons, and 3. test competing current models of eye movement control. The results will confer a better understanding of the mechanisms for obtaining stereoscopic vision. Two opposing models of eye movement control in 3-D space provide the context. One traces its lineage to Hering, who believed that conjugate and vergence eye movement signals were added together at the level of the motoneuron. The other traces its heritage to Helmhotz, who believed that the movement of each eye is independently controlled, and that conjugate and vergence movements represent learned patterns of volitional coordination. We will characterize the physiological responses and determine the inputs to two populations of neurons: perioculomotor vergence cells believed to lie in the supraoculomotor area (SOA) and a newly discovered set of premotor neurons located in the central mesencephalic reticular formation (cMRF). These two populations contact the preganglionic motoneurons in the Edinger-Westphal nucleus (EWpg) that control the lens and pupil, and medial rectus motoneurons active in vergence, indicating a function in near triad control. The study will determine whether the perioculomotor vergence cells and/or premotor cMRF neurons are targeted by the caudal, saccade-related component of the colliculus, the rostral colliculus, which contains cells active during fixation and vergence, or the frontal eye fields (FEF) vergence zone. The 5 inter-related aims carried out in macaque monkeys utilize physiological recording in awake behaving animals, conventional neuronal tracers and transneuronal transport of conventional and recombinant viruses.
Aim 1 will compare the precise anatomical location of perioculomotor vergence cells and premotor cMRF neurons.
Aim 2 will test the Hering and Helmhotz models by using transneuronal tracing to determine whether these two populations or premotor neurons in the pons are anatomically eye- specific.
Aim 3 recordings will test the hypothesis that only the premotor cMRF neurons control the near triad during disjunctive saccades.
Aim 4 will examine whether the pattern of tectal projections to these two populations supports such a functional division.
Aim 5 will combine physiological and anatomical approaches to ask the same question about FEF inputs. The dramatically augmented understanding of eye movement control circuits and cell function afforded by this project will provide a critical basis for improved concepts of eye movement control and coordination in health and disease.
Work towards cures for strabismus and amblyopia are among the prime goals of the NEI, but one of the great difficulties we have in addressing these clinical problems is a lack of understanding of their underlying mechanisms, and specifically a poor understanding of the neuronal circuits that control lens focus or that adjust and maintain proper eye alignment under normal conditions. The aims of this grant are directed at determining the location, activity and connections of neuronal circuits that control the changes in eye position, lens shape and pupil size that occur when we direct and focus our eyes at nearby objects; for example, when working with our hands. The proposed experiments will directly test parts of the cortex and brainstem believed to take part in these functions in order to determine the signals carried and the cells involved, and so provide a better understanding of how the two eyes are controlled and focused.
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