CEREBELLAR MODULES AND EYE MOVEMENT CONTROL

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DESCRIPTION (provided by applicant): The broad goal of the research is to better understand cerebellar function by investigating the neuronal signal processing underlying compensatory eye movements. For the most part the experimental method will be manipulation of the extracellularly recorded activity of Purkinje cells and interneurons in the cerebellar flocculus through presentation of natural visual and vestibular stimuli to the awake rabbit. The central theme is that signal processing in the flocculus entails mapping within and between neuronally synthesized reference frames (coordinate systems) that represent the three-dimensional geometry of the semicircular canals and the extraocular muscles, and that these reference frames have an anatomical counterpart in the modular (compartmental) organization of the flocculus. The primary focus is the signal content and synchrony of the climbing fiber input activity, recorded as Purkinje cell complex spikes, in each of the anatomically distinguishable modules. A second focus is the contribution of the Golgi cell class of interneurons to the spatiotemporal filtering of mossy fiber-granule cell activity in relation to the floccular modules. The first specific aim is to investigate the relations between the vestibularly induced modulation of complex spike activity and aspects of eye movement behavior (kinematics, vestibulo-ocular response gain, and vergence) Interaction between the complex spike modulations produced by vestibular and by full-field visual (optokinetic) stimuli will also be studied to determine the rules governing how these two signals are non-linearly combined In the second specific aim the contribution of the brainstem prepositus hypoglossi nuclei to the vestibularly induced complex spike modulation will be assessed using ablative and chemical lesions. Two other specific aims deal with complex spike synchrony and its role in motor behavior. Synchrony occurring during vestibular stimulation will be compared to that occurring without stimulation. In a related specific aim spike-triggered averaging of eye movements will be used to determine if complex spikes have a motoric effect distinguishable from that of simple spikes, and if vestibular stimulation enhances complex spike-triggered eye movements. The fifth specific aim addresses the function of a class of cerebellar interneurons thought to be Golgi cells. These cells will be anatomically identified with intracellular labeling and their modulation will be characterized using multi-axis vestibular and full-field visual stimulation.