This proposal examines the interaction of intrinsic and extrinsic factors in: neuronal growth, the generation of characteristic neuronal architecture, and the formation and breaking of neuronal connections. The buccal ganglia of Helisoma, with their identifiable neurons previously have been shown to display neuronal plasticity in highly predictable patterns and to provide a tractable model for this study. A series of technical innovations now makes possible high resolution continuous observations of living neurons in a variety of conditions ranging from isolated identified neurons in cell culture to interconnected neurons in situ. The use of video fluorescence microscopy has made possible investigations on the geometry of living neurons and their motile growth cones in the context of their normal ganglionic and nerve trunk environment. Factors regulating growth and the generation of neuronal architecture will provide half of the focus of these studies, while factors regulating connectivity form the second half. We will investigate the degree to which adult neurons are fixed and differentiated as opposed to the degree to which they can exhibit plasticity and participate in newly developed circuitry. It is already clear that these adult neurons are encoded with alternate programs for connectivity which can be expressed under appropriate conditions. Such connections arise by a process of formation of many connections, with subsequent breaking of """"""""inappropriate"""""""" connections upon formation of a """"""""priority"""""""" connection. This leaves a single stable functional connection. This proposal will investigate the mechanisms underlying neuronal growth, the formation of such novel connections and the specific selection of a """"""""priority"""""""" connection by elimination of those of lower priority. The emphasis of this proposal is on the mechanisms regulating changes in neuronal form and function. The system in Helisoma, with the technical innovations of the past 2 years provides an opportunity for a comprehensive understanding of the intrinsic and extrinsic factors regulating growth and connectivity of adult neurons. This proposal addresses questions such as: What factors stabilize neuronal architecture? What factors can initiate growth from adult neurons? Can growing adult neurons modulate, form or break connections in a programmed fashion?
