Multiplicative computation in the vestibulo-ocular reflex (VOR)

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DESCRIPTION (provided by applicant): The long-term objective of the application is to understand the neural mechanisms of sensorimotor transformation in the vestibular system. Over the past several decades, the investigation of the VOR has established that the VOR response to a given head movement is not fixed, but is under the modulation of behavioral contexts (i.e., viewing distance). Deficits in the context-dependent VOR gain modulation resulting from disease or environmental changes can severely impair vision. The neural mechanisms underlying this important VOR function, however, remain to be explored. Our recent studies demonstrate that the interaction of vestibular and eye position signals in the direct VOR pathways is multiplicative, rather than additive as presently assumed. Our modeling analysis further suggests a novel neural mechanism that implements the VOR gain modulation by viewing distance. The specific aims of the application are to employ single unit recording and computational modeling approaches to further study the interaction of vestibular and eye position signals in the key components of the direct VOR circuits. A unique strength of the proposal is that we take advantage of the acoustic activation of vestibular system and employ click to evoke impulse responses of the VOR to a unilateral vestibular stimulation. This paradigm permits us examine the neural substrate and signal processing underlying VOR gain modulation. The first aim is to use single unit recording techniques to quantitatively analyze the interaction of vestibular and eye position signals in identified motoneurons that innervate the medial or lateral rectus muscles. These experiments will identify whether the multiplicative computation is performed in the motoneuron pools of the VOR pathway. The second aim is to use single unit recording techniques to quantitatively analyze the interaction of vestibular and eye position signals in three groups of VOR premotor neurons. These experiments will identify whether these VOR interneurons are the sites for multiplicative computation. Computational model simulation will examine the cellular mechanisms underlying the multiplicative interaction in both premotor and motoneurons. This application will provide important knowledge for understanding the fundamental vestibular and oculomotor neurophysiology and improving the diagnosis and treatment of vestibular disorders in humans.