IBN: 9724064 PI: JELLIES Dr. Jellies will employ a system of stereotyped motor neurons, interneurons and muscles to investigate the roles of cell-cell interactions and retrograde as well as retrospective influences in the generation of a functional neural circuit. The model system he will use is the one that produces the heartbeat rhythm in the leech. In all animals, neural circuits are generated during development and modified throughout life by dynamic processes driven by molecular and cellular mechanisms such as differential adhesion, selective fasciculation, cytoskeletal modifications and trophic support. In many cases the underlying mechanisms used by single cells to generate particular phenotypes appear to be intrinsic to the individual cell. Yet, because a neural circuit used in even a simple behavior requires the coordinated differentiation of many cells to generate particular patterns of connections, it is necessary to understand how these single cells are coordinated. For example, a behavioral defect or variation may reflect a change in the timing or spatial placement of a signaling event between two or more neurons rather than any particular deficiency or genetic change intrinsic to a neuron. The studies by Dr. Jellies will examine the hypothesis that interactions between developing neurons and potential targets are one of the major sets of factors that coordinate circuit formation, and furthermore, that particular interactions are required for instructing the subsequent formation of one pattern of connections rather than an alternative pattern. These studies will also begin to characterize the signals that are generated in one set of cells to influence the subsequent differentiation of another. Results from the project are expected to yield significant insights into the way that cues derived from one set of developing cells exert a long-lasting influence over the functionally important development of others, and perhaps make it possible to predict the development of comp lex neural circuits.
