CELLULAR PHYSIOLOGY OF VESTIBULAR REFLEXES

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This project examines the cellular basis of signal transformations that occur in vestibular reflexes. Studies of the vestibuloocular reflex have revealed short and long-term multiplicative changes in reflex gain. Functional considerations suggest similar changes should occur in the vestibulocollic reflex. The principal aim of this project is to understand and quantitate the fundamental cellular mechanisms involved in such reflex modulations using an in vitro mouse brain slice preparation. We will study the electrophysiological and pharmacological properties of vestibular afferent input to medial vestibular nucleus (MVN) neurons in these slices. focusing on the kinetic behavior of the ionotrophic glutamate receptors (NMDA and AMPA) which underlie the synaptic currents elicited by repetitive (physiologic) activation of vestibular afferents. These studies will employ both whole-cell recordings of the synaptic currents, and excised patch recordings of single and macroscopic glutamate receptor-mediated currents. We will then study the modulation of this glutamatergic afferent input to vestibular nucleus neurons by cerebellar projections, examining the cellular mechanisms by which GABAergic cerebellar afferents sculpt the response of vestibular reflex interneurons to vestibular afferent inputs. Neuroanatomical labeling techniques will be used to reveal the projections of neurons that are studied so that we can relate our data to afferent activation and cerebellar modulation of speciflt- vestibuloocular and vestibulospinal reflexes. Data obtained from experimental portions of this study will then be used to generate models of vestibular signal processing in the MVN. which will provide key. insights into the neuronal substrates of signal transformations in these vestibular reflexes. Understanding of these reflexes is important since they are essential to maintain the clear vision and stable posture required to carry out many activities of daily living.