cerebellar Afferent Integration Studied In Vitro

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DESCRIPTION (provided by applicant): The cerebellar cortex (Cb) is a continuous neural layer of gray matter made up of identical repeating processing modules. Although the circuitry of these modules is similar for all vertebrates, the cortical surface is highly foliated in birds and mammals with complex regional specializations. Therefore, an analysis of Cb topography and its function is difficult because only a small fraction of cortical area is observed on the exposed folial surface. We posit that a radial system of inputs onto Purkinje cells from segregated Cb afferents and ascending granule cell axons is the primary processing unit of the Cb module. This primary system is acted on by a secondary, orthogonal system of parallel fibers and inhibitory interneurons. The proposed study will test this hypothesis with a unique in vitro turtle Cb preparation with the brainstem and sensory nerves attached. The primary advantage of the flat turtle Cb is that it is thin enough to permit optical recordings of the entire Cb surface during trans-illumination. Using voltage-sensitive absorbance dyes, Cb topography can be characterized from large responses to individual sensory stimuli. The small cortical size also permits a topographic anatomical analysis of afferent inputs based on a complete reconstruction of serial sections. Optical recording and pathway tracing experiments will be performed to reveal how sensory afferents map onto the Cb and how these different maps overlap. This project will focus on the effects of visual and vestibular afferents by measuring optical responses in vitro to natural stimulation or electrical microstimulation within the brainstem. Additional experiments will examine the basic cerebellar module: mossy fiber inputs, the radial and orthogonal axonal outputs of the granule cell and the convergence of excitatory and inhibitory inputs onto the Purkinje cell. Finally, climbing fiber inputs to Cb will be measured anatomically and physiologically to understand their role in plasticity and modulation of information flow through the basic cerebellar module. This in vitro preparation will thereby provide a unique model system for the study of learning and adaptation of motor behaviors.