REGULATION OF NEURITE OUTGROWTH AND CONNECTIVITY

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Electrical activity plays a fundamental role in communication along nerve cells. It has long been thought that electrical activity might play a much broader role in the control of neuronal form and connectivity. The recent demonstration that action potentials inhibit neurite outgrowth now provides the conceptual link whereby these ubiquitous signals can directly influence neuronal structure and the formation of neural circuits. The aims of the proposal are to determine the role of electrical activity in regulating neuronal morphology and connectivity and to show that these effects may be mediated by calcium changes in growth cones. Specific attention is given to how electrical activity regulates the movements of growth cones at the tips of elongating neurites. These experiments utilize a high resolution system of identified neurons from the snail Helisoma which are uniquely characterized in terms of their normal morphology, biophysical properties, and connections with other neurons. Cell bodies of identified neurons will be individually removed from their normal ganglionic environment and placed in cell culture to facilitate quantitative spatial and temporal measurements of neurite outgrowth. Cell bodies will be electrically stimulated directly and the effects on the large growth cones that are characterized of this species will be quantitatively assessed to test how: 1) integrative properties of electrical signals affect outgrowth and the final morphology of neurons, 2) electrical signals in neural circuits may exert both global and local control over neuronal morphology, 3) electrical activity affects synapotogenesis, and 4) changes in growth cone calcium may mediate these effects. These findings will establish a link between neuronal structure and function. They will provide insight into the regulation of neuronal architecture and connectivity which underlie the establishment of adult neuronal circuits.