Vestibular and optokinetic testing for research and clinic

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A basic goal in studying nervous system function is to understand the molecular basis of complex behavioral systems. Unfortunately, the techniques employed to investigate molecular mechanisms are not easily applied to complex organisms that normally exhibit the most interesting and sophisticated behaviors. Thus, it has been necessary to compromise either in the techniques used to study the behavior and/or the choice of experimental subjects. A potential exception is the study of a variety of normal and mutant strains of mice which lend themselves to investigation using molecular genetic techniques but still display many of the behaviors exhibited and initially characterizedin higher mammals. A number of inroads have been made into the molecular mechanisms underlying not only sensory and motor processes but also basic mechanisms of, for example, learning and plasticity. One prominent model that has emerged recently is the adaptive plasticity of the vestibulo-ocular reflex (vor). Earlier studies, mostly on primates, have implicated both the simple, 3-neuron vor reflex and the cerebellar flocculus as important sites for more focused investigation. These studies have advanced to the point of investigating the sub-cellular mechanisms that underlie the adaptive process. A major stumbling block has been the inability to readily adapt the behavioral paradigms developed in primates to animals more suited for cellular, sub-cellular, and genetic investigation, like mice. Central to this difficulty is the inability to precisely measure eye movements due to the small size of the eye of the mouse. During the proposed support period, we plan to overcome this obstacle by developing a new type of scleral search coil suitable for mice that will accurately measure their eye movements. We will then use that coil to screen a number of mutant mice strains in order to document their oculomotor deficits. Finally, we will develop a more complete vestibulo-optokinetic testing facility for small animals including mice. These aims will allow us to eventually routinely test and screen mutant mice for a wide variety of investigations into basic neural mechanisms not only of vor plasticity but of normal and pathological origin. The relevance to public health will be the expansion of model mouse systems for the study of human pathology and treatment in, for example, neurodegenerativediseases like cerebellar ataxia.