Cerebellar Granule Cell Lineage and Projection Patterns

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DESCRIPTION (provided by applicant): Various methods have characterized cerebellar development in order to understand how connections necessary for normal motor function may be deficient in movement disorders, such as cerebellar ataxia. Using a novel genetic mosaic system that we have developed in our laboratory (termed MADM for Mosaic Analysis with Double Markers), I found that lineage plays a role in specifying the axonal projection pattern of cerebellar granule cells. Granule cells can innervate different parts of the Purkinje cell dendrite, differentially control local inhibitory circuits, and affect cerebellar long-term depression critical for many forms of synaptic plasticity. Thus, where granule cells project their axons is of functional importance. I propose three aims to investigate how granule cell axonal projection patterns are specified by lineage and to elucidate the functional implication of this lineage specificity: (1) Systematic analysis of MADM clones to further characterize the relationship between granule cell lineage and axonal projection patterns. (2) Determine how clonally related granule cells project axons to the same lamina in the molecular layer. (3) Determine whether granule cells with different axonal projection patterns receive input from distinct classes of mossy fibers.