The overall goal of research in our laboratory is to investigate the post-natal development of the ocular motor system in normal monkeys and monkeys reared under conditions to induce developmental problems such as ocular misalignment (strabismus). Strabismus of sensory origin is a significant public health problem since it affects 2-5% of the infant population. Previously we have shown, in an animal model for strabismus, that a slow vergence eye movement pathway involving projections from the midline cerebellar nuclei to the supraoculomotor area and thereafter the medial rectus motoneurons in the oculomotor nucleus partially drives the steady state misalignment. In the present investigation of strabismus mechanisms, we propose to investigate the neural basis for three strabismus properties - 1) eye misalignment, 2) fixation instability and 3) fixation-switch. Each o these strabismus properties implicates an important oculomotor control structure, the Superior Colliculus (SC), and our plan is to couple behavioral studies with neurophysiological investigation of SC contributions. The experiments are organized into three specific aims.
In specific aim 1, we propose single unit recording studies and muscimol inactivation studies in the rostral SC with the goal of determining contribution of the rostral SC in defining state of eye misalignment. The motivation for these studies is that human clinical and animal neural recording and lesion studies suggest that the rostral SC is important in control of slow vergence movements including alignment of the eyes.
In aim 2, we propose single-unit recording studies and muscimol inactivation studies of the rostral SC to determine its role in fixation instability, problem frequently associated with strabismus and amblyopia. The motivation for these experiments is that studies in normal monkeys have proposed a framework where balanced activity across the two rostral colliculi promotes fixation.
In aim 3, we propose single unit recording studies of neurons in the caudal SC to determine their role in fixation-switch (alternating saccade) behavior frequently observed in humans and monkeys with strabismus. We propose to test a framework wherein fixation-switch behavior is driven via the same neural mechanisms that drive target selection in normal monkeys. Studies will be performed in juvenile rhesus monkeys previously induced with a sensory form of strabismus by rearing them under special viewing conditions (optical prism rearing) for the first four months of their life. In summary, each of the specific aims in this project is likely to significantly advance our understanding of strabismus mechanisms and neural circuitry and has the potential to eventually help guide the development of rationally based therapies.
Ocular misalignment (strabismus) is a developmental disorder that affects a significant number of children born every year in the United States and around the world. A better understanding of neural mechanisms that are affected in the different forms of strabismus will help develop rationally based therapy. This particular project will combine various physiological methods and behavior investigation in an animal model to investigate neural correlates to oculomotor disruptions in strabismus including eye misalignment, fixation instability and fixation-switch behavior.
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