CELLULAR ANALYSIS OF THE VESTIBULO-OCULAR REFLEX

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DESCRIPTION: (Adapted From The Applicant's Abstract.) The ability to see clearly during self-motion depends critically on the performance of the vestibuloocular reflex(VOR). The VOR enables stable vision during head movements by producing compensatory eye movements that are opposite in direction and equal in amplitude to head motion. Much is understood about the neural circuitry that mediates the VOR and about the signals carried by the constituent neurons. However, relatively little is known about the cellular and molecular mechanisms that underlie the day-to-day performance and long-term adaptive capabilities of the VOR. The goals of this research are to investigate the cellular and synaptic basis of signal transformations in the VOR and to provide a foundation for understanding the cellular and molecular basis of adaptive plasticity in the VOR. A brainstem slice preparation will be used to examine the cellular mechanisms governing signal transformations in vestibular interneurons in the medial vestibular nucleus (MVN). First, the dynamic properties of spike generation (the transduction from neuronal inputs into time-varying patterns of action potentials) will be studied by making intracellular recordings from MVN neurons and measuring firing responses to intracellular current injection. Second, the roles of intrinsic membrane conductances in sculpting the dynamics of spike generation will be investigated with pharmacological blockers of calcium and potassium channels. Third, the roles of neurotransmitters in modulating spike generation dynamics will be examined with pharmacological agonizes of acetylcholine, histamine, serotonin, noradrenaline, and the NMDA receptor, agents that have been shown to affect either the VOR itself or spontaneous firing in vestibular neurons. Finally, the relationship between physiologically and pharmacologically distinct MVN neurons and the cell classes defined by anatomical and behavioral studies in vivo will be determined with a combination of intracellular dye injection and electrical stimulation of input and output pathways. The results should provide insights into the cellular and synaptic mechanisms that mediate the normal operation and adaptive capabilities of the VOR They may furthermore lead to the development of pharmacological treatments of neuro-ophthalmological disorders of ocular motility, including nystagmus.