9604622 PI: VanBerkum After neurons are born, they must extend axons over great distances to innervate their target cells. The tip of the extending axon, called the growth cone, detects a variety of molecular cues along its path which guide the neuron to its target. These cues are converted inside the neuron into signals regulating axon outgrowth, steering and ultimately the formation of a functional connection (a synapse) with a target cell. Calcium ions are critical to this conversion process inside a neuron. In his previous work, Dr. VanBerkum established that the inhibition of calcium signaling in selected outgrowing axons causes these axons to stall or follow abnormal trajectories. The goal of the present experiments is to elucidate which proteins are used inside the axon to correctly convert calcium-dependent guidance information into proper pathway formation. A combination of cell and genetic experiments are being conducted to specifically inhibit individual components of the calcium signaling pathway inside these neurons. The inhibition of a protein component is expected to elicit similar developmental defects as previously observed. Thus the results of these experiments will elucidate the molecular mechanism by which calcium regulates the development of functional connections in the nervous system. Moreover, since calcium is also used in the adult to modulate synaptic activity, these experiments will shed light on how calcium is used during learning and memory.
