A major question in developmental neurobiology is how neuronal cells develop into their mature phenotypes. This proposal investigates the development of the Purkinje neuron in relation to one of its afferents, cerebellar granule cells. These developmental processes are examined in a noel culture system in which purified Purkinje cells undergo full dendritic differentiation when co-cultured with purified granule cells as well as in cerebellar slices. The culture system provides a unique opportunity to study the dynamics of Purkinje cell development nd its interactions with one of its presynaptic cells without the confounding influence of many other cell types that have been present in previous work. In the first set of experiments the dynamics of behavior of developing dendritic spines of the Purkinje cells will be characterize in culture and slices using time lapse microscopy. These experiments will provide a bioassay for testing the role of agents that could be provided by granule cells in the development of dendritic spines. As a first step, the role of BDNF in spine formation will be tested. In the second set of experiments ultrastructural and molecular analysis of Purkinje-granule cell synapse formation will be performed. The process of assembly of molecular components of a functional synapse will be monitored on both the structural (electron microscopy and immunocytochemistry) and functional level (synaptic vesicle recycling. These studies will provide much needed information about the process of development of an important central synapse.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS010370-01A1
Application #
2711309
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Spinella, Giovanna M
Project Start
1998-12-01
Project End
Budget Start
1998-06-18
Budget End
1999-06-15
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Pathology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032