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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS053270-02
Application #
7223530
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Gwinn, Katrina
Project Start
2005-09-01
Project End
2010-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
2
Fiscal Year
2006
Total Cost
$32,245
Indirect Cost
Name
Stanford University
Department
Neurology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Espinosa, J Sebastian; Wheeler, Damian G; Tsien, Richard W et al. (2009) Uncoupling dendrite growth and patterning: single-cell knockout analysis of NMDA receptor 2B. Neuron 62:205-17
Espinosa, J Sebastian; Luo, Liqun (2008) Timing neurogenesis and differentiation: insights from quantitative clonal analyses of cerebellar granule cells. J Neurosci 28:2301-12