Ca2+ Dynamics in Growth cones during Target Recognition and their Role in Presynaptic Terminal Differentiation

Determining the mechanisms that establish the wiring of connections between nerve cells in the brain has become an important scientific objective. Understanding these mechanisms is likely to have future medical relevance to therapeutic strategies to correct or ameliorate developmental disorders. This project tests the hypothesis that signaling by calcium ions is a key part of target recognition and formation of connections when growth cones at the tips of outgrowing nerve processes contact target cells. Preliminary work has identified transient elevations of calcium ions that occur during target recognition and prior to formation of connections. The detailed characterization of patterns of calcium elevations involved in signaling between nerve cells and target cells to which they become connected is one of the goals of this project. The project will also define the aspects of molecular differentiation of the growth cone, as it becomes a presynaptic terminal, which are regulated by transient elevation of intracellular calcium. To achieve these goals, imaging calcium elevations of nerve cells by confocal microscopy will be used in combination with electrophysiology and immunocytochemistry, which will detect the molecular changes at these processes.