The Role of BK Channels in Oculomotor Plasticity

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DESCRIPTION (provided by applicant): The long-range goal of this research is to understand the cellular and molecular mechanisms that mediate the normal performance and adaptive plasticity in eye movements. The vestibulo-ocular and optokinetic reflexes (VOR and OKR, respectively) prevent blurred vision during self-motion by producing eye movements that precisely compensate for motion of the head. Neuronal mechanisms of plasticity enable these reflexes 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 oculomotor system. The objective of this proposal is to elucidate the role of a particular type of ion channel, the BK-type calcium activated potassium channel, in the induction and maintenance of oculomotor plasticity. The central hypothesis is that regulation of BK currents plays a critical role in adaptive changes in the VOR and OKR induced both by peripheral dysfunction and by prolonged visual-vestibular mismatch experience. The proposed research will use a combination of behavioral and electrophysiological analyses in transgenic mice to investigate the forms of oculomotor plasticity that require BK channels and the critical locations of BK channels within the oculomotor circuit. Extracellular recordings from the cerebellar flocculus will complement behavioral analyses of mice in which BK channels are deleted either globally or specifically in Purkinje cells. These studies will provide foundations for targeted investigations of the molecular mechanisms that underlie cerebellar-dependent plasticity as well as for pharmacological treatments of oculomotor disorders that cause nystagmus.