(Author's abstract): We propose to continue our behavioral and single unit studies of the vestibuloocular reflex (VOR) focusing on processes that alter its gain and symmetry with changes in target distance and eccentricity. While these processes can produce very large changes almost instantaneously in the angular and linear VORs (AVOR and LVOR), very little is known about their dynamic properties or neuronal substrates. This is especially true for the LVOR, which has only begun to be investigated with state-of-the-art techniques. We will therefore give high priority to examining both low frequency tilt-related and high frequency translational LVORs. Four series of experiments are planned. The first will use intra-axonal recording to study the signals carried by specific groups of feline and primate vestibuloocular relay neurons (VORNs) after which these neurons will be stained to reveal their terminations and somato-dendritic morphology. Other experiments in this series will use extracellular recordings in alert animals to specify the VOR-related signals carried by VORNs whose projections and inputs are identified electrophysiologically. The second series will quantify the 3 dimensional spatial and dynamic properties of tilt and translational LVORs and of processes that adjust the AVOR and LVORs to changes fixation distance or direction in behaving primates while the third will quantify the behavior of identified VORNs during the same behaviors. A fourth series of experiments, carried out by Dr. R. McCrea at University of Chicago, will record activity of single neurons in the nucleus prepositius hypoglossi (a site that plays a major role in integrating VOR eye velocity signals to generate an eye position command) during fixation of near, eccentric visual targets to determine how this nucleus generates the asymmetrical eye position commands required when animals fixate such targets. Extensive use will be made of mathematical models of VOR circuits to predict VOR and neural behavior and interpret experimental results. Because the modulatory processes they will study are essential to maintain the accurate fixation needed to maintain good visual acuity, these studies will have important implications for diagnosing and treating patients with vestibular and cerebellar dysfunction. These studies will also contribute to a broader, multilevel analysis of vestibular signal processing by quantifying the signal transformations that take place in the VOR and relating them to specific classes of vestibular and prepositus hypoglossi neurons, which other projects will then study in vitro to determine whether the same classes of neuron have the requisite biophysical properties to carry out such transformations.
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