Genetically directed synapse formation and synapse analysis in brain

• Applicant: Dr. Stephan Maxeiner
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2007 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 43762092

Synapse formation is a highly regulated process characterized by subsequent steps starting with initial contacts between future axon and dendrites, recruitment of pre- /postsynaptic proteins and stabilization of synaptic contacts. Among other neuronal cell adhesion molecules, the interactions of neurexins with neuroligins are a key step initiating and promoting processes underlying synapse formation. Mutations in neuroligin genes, for instance, have shown to be involved in neurological disorders such as autism. The herein described projects have the goal to establish a system that allows visualizing the early steps in synapse formation upon the proper reconstitution of two none-fluorescent subunits of GFP attached to neurexin/neuroligins in vitro and to trace it in transgenic mice in vivo. The second project aims to induce synapse formation artificially using modified neurexin/neuroligin proteins in vitro basing on the interaction of FKBP with FRAP upon the application of rapamycin. In a mouse model the forced synapse formation may help to generate or shift inhibitory or excitatory synaptic inputs locally in distinct brain regions and temporally due to the application of a dimerizing agent, which could help to understand the genesis of neurological diseases.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Thomas Christian Südhof