The Cytoskeleton of the Frog Motor Nerve Terminal

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For proper functioning of the nervous system, each nerve cell must assemble the molecular machinery required for the release of its signal, the neurotransmitter, at the precise location on its target cell where the signal can be received and a response produced. This precise structural alignment between the release machinery of nerve terminals and the reception molecules of their targets presents a challenge not only for its construction and growth but also for its upkeep and maintenance. The precision of this organization between nerve cells and targets is beautifully illustrated at the frog neuromuscular junction where a linear array of release sites in nerve terminals are separated by distinct nonrelease domains. Using the frog motor nerve terminal, Dr. Connor laboratory recently discovered that cytoskeletal filaments including F-actin, are concentrated in nonrelease domains. The goal is to determine the role of the cytoskeleton and F-actin in fundamental processes of nerve terminals that may occur in nonrelease domains: the recycling of the neurotransmitter release machinery and the stabilization of nerve terminals at their targets. Dr. Connor's group and collaborators at Stanford University, will use electron microscope tomography to construct a high-resolution three-dimension map of the cytoskeleton in nonrelease domains of motor nerve terminals. Such a map will be a valued resource for all researchers, and will allow the structural interpretation of a range of experiments that address nerve terminal function. The investigators will also test whether cytoskeletal elements in nonrelease domains participate in the recapture of the release machinery after stimulation of nerve terminals. Finally, the experiments will also be conducted to determine the role of the terminal Schwann cell in organizing the F-actin in nerve terminals, and how the F-actin distribution in nerve terminals changes in the process of developing, regrowing, and breaking connections. This project will also determine the importance of the cytoskeleton in stabilizing nerve terminals at their targets. These experiments will provide information critical for our understanding of the functioning and maintenance of contacts between nerve cells and their targets. In a broader scope, this project will provide both academic year and summer opportunities for undergraduates to participate in research. Further, graduate students will be trained during this project and they will have the opportunity to mentor undergraduates and present their results at national meetings.