Much of our present understanding of the oculomotor system has evolved from morphological, physiological, and clinicopathological studies of the neurons, nuclei, and pathways that are related to various types of eye movement. Certain fundamental principles regarding motoneuronal organization in the oculomotor system have been elucidated to the extent that the soma-dendritic profiles, synaptic organization, and afferent and efferent connections of motoneurons in the extraocular motor nuclei are now well defined and differ according to brainstem location and their role in horizontal or vertical eye movements. Over the past decade, considerable knowledge also has accumulated regarding the putative neurotransmitters that are utilized by excitatory and inhibitory premotor neurons in the oculomotor system. However, a critical gap exists in the knowledge of the neurotransmitter receptors that are associated with the synaptic connections in the brainstem oculomotor system, particularly those of second-order vestibular inputs to motoneurons in the extraocular motor nuclei. The major emphasis of the proposed studies is directed toward continued studies of neurotransmitter utilization in the brainstem oculomotor system, specifically in regard to the neurotransmitters and their receptors that are associated with the vestibular inputs to motoneurons in the oculomotor, trochlear, and abducens nuclei, as well as in the cervical spinal cord, as they relate to the control of horizontal and vertical gaze. The overall purpose of these studies is to determine if neurotransmitter differences exist between different populations of second-order vestibular neurons (e.g., vestibulo-ocular, vestibulo-collic, vestibulo-oculo-collic) that might be related to known differences in their physiological activity in relation to the control of eye movement versus head movement and/or gaze. Another major goal of the proposed studies is to determine the extent to which the neurotransmitters and receptors of second-order vestibulo-ocular and vestibulospinal neurons are regulated during development in the kreisler mouse, a genetic mutant strain in which specific rhombomeres in the embryonic hindbrain are absent.
The specific aims of this research are consistent with the long-term goal of understanding the neuronal and synaptic organization of the oculomotor system underlying the control of gaze and the sequelae, both central and peripheral, of neurological disorders that are characterized by deficits in ocular motility.
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