Humans, as foveate creatures, continuously examine their environment through a series of gaze changes involving saccadic eye movements and, in many cases, quick accompanying head movements. Normal visual perception requires that these movements be accurate and precisely coordinated. Consequently, neurological disorders that interfere with gaze are quite debilitating, often producing symptoms that result in the initial clinical visit. Our long-term goal is to analyze the circuitry underlying gaze. The central mesencephalic reticular formation (cMRF) represents the major midbrain target of the superior colliculus (SCol), and is believed to provide input to brainstem visual motor structures, and the spinal cord, in addition to feeding back upon the SCoI. cMRF stimulation elicits gaze changes, and this region contains several different physiological cell types that fire before saccadic eye movements. However, our knowledge of cMRF connectivity is limited. In this study, a series of dual tracer experiments will be undertaken in macaque monkeys to define cMRF connections with reticulospinal neurons in the medulla, motoneurons in the spinal cord, SCol neurons projecting in the predorsal bundle, and with the paramedian pontine reticular formation (PPRF). These projections will be tested utilizing post-embedding immunohistochemistry to determine whether they are GABAergic (inhibitory). Multiple fluorescent tracer injections will be utilized to determine whether separate neuronal populations provide inputs to the SCol, PPRF, and head movement centers in the medulary reticular formation and cervical cord. In addition, these cMRF neurons will be characterized with respect to their collicular input. Light and electron microscopic analysis of the dual tracer experiments will allow input/output relationships in the cMRF and its targets to be specified at the neuronal level. The results from these experiments will test the hypothesis that the cMRF provides the SCol with separate channels to modulate the eye and head components of gaze. In addition, they will provide an understanding of the cMRF and SCol circuitry at the neuronal level that can help delineate the feasibility of current and future models of gaze generation. Thus, this study will provide a scientific basis for better understanding gaze mechanisms and pathology. ? ?
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