Mechanisms regulating the assembly, dynamics and stability of mammalian presynaptic active zones

• Applicant: Christoph Maas, Ph.D.
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2008 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 65287182

Mammalian synapses are asymmetric sites of cell-cell contact designed for rapid and efficient transfer of information between neuronal cells. Whereas the classical view of synapses based on ultrastructural studies suggests that they are extremely stable structures that change little during their lifetime, electrophysiological studies imply that synapses are rather plastic being able to change their strength and composition based on activity dependent experience. Mechanistically, one could reconcile these differences by having a core set of proteins organized to create a stable network of synaptic scaffold proteins with minimal dynamics and a second group that are highly dynamic coordinating the fluid docking, fusing and recycling of synaptic vesicles in an activity dependent manner. A major goal of this project is to understand the relationship between synapse life and the dynamic properties of individual components. Specifically, I propose to test the hypothesis that key proteins of the cytoskeletal matrix assembled at active zones (CAZ) regulate the stability of the presynaptic active zone and thus synapse life. This is a highly significant problem as synapse stability/plasticity is thought to be a major contributor to normal learning and memory. Furthermore, abnormal settings of synapses seem to cause a reduction in cognitive performance both in developmental disorders as well as neurodegeneration.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Craig C. Garner