The long-range goal of this research is to understand the cellular and molecular mechanisms that mediate the normal performance and adaptive plasticity of the vestibulo-ocular reflex (VOR). The VOR prevents blurred vision during self-motion by producing eye movements that precisely compensate for motion of the head. Neuronal mechanisms of plasticity enable the VOR to perform accurately in the face of development, trauma, and disease. Although the roles of particular classes of neurons to signal transformations and plasticity have been identified, little is understood about how cellular mechanisms contribute to the day-to-day performance and adaptive capabilities of the VOR. The objective of the proposed research is to elucidate how intrinsic membrane properties of neurons in the medial vestibular nucleus (MVN) contribute to signaling and plasticity in the VOR. The central hypothesis is that the adaptive capabilities of the VOR are mediated, in part, by changes in the intrinsic firing properties of MVN neurons. The proposed research will use a brainstem slice preparation to examine the intrinsic firing properties and ionic currents of cerebellar target neurons, which mediate cerebellar influences on signaling and plasticity in the VOR. The influence of neuronal activity on plasticity of intrinsic firing properties will be compared in cerebellar target neurons and other identified MVN neurons. The contributions of plasticity in intrinsic firing properties to VOR plasticity will be examined by assessing intrinsic firing mechanisms of MVN neurons recorded from slices obtained at different stages of adaptive gain changes in the VOR. These studies will provide foundations for targeted investigations of the molecular mechanisms that underlie vestibulo-ocular reflex plasticity as well as for pharmacological treatments of oculomotor disorders that cause nystagmus. ? ?
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