Neuronal growth cones are usually regarded as the unique organelle associated with neuroembryogenesis and neuronal plasticity and are implicated in neurite outgrowth, pathfinding, target recognition, and synaptogenesis. Until recently these structures have been experimentally unapproachable. Recent technical advances now allow direct tests of hypotheses concerning the regulation of neuronal growth cones and their distinctive roles in developing and remodelling nervous systems. Neurons of the pulmonate mollusc, Helisoma, provide a highly tractable experimental system for examining the morphological and biophysical basis of growth cone motility. These identified neurons provide an opportunity to study those growth cone properties which are unique to particular neurons as well as those which are common to all neurons. This proposal will examine quantitative aspects of growth cone movements of different identified neurons. In addition, we now have a large battery of extrinsic factors to serve as candidate cues for altering growth cone behavior. These include growth promoting, growth inhibiting, and potential chemotactic agents as well as normal targets both from the CNS and periphery. Given a knowlege of how individual growth cones can react both in vitro and in situ, we can perform biophysical experiments on the potential ionic controls of this organelle. This is now possible by the application of a variety of patch clamp methods to these rather delicate structures. These experiments will provide information on what ionic currents are found in growth cones and how these currents are related to the control of motility. Given the results of the preceding funding period, it now seems highly probable that the transition of a neuron from growing to stable state is related to and possibly causally derived from changes in ion channel activity. With the comprehensive view proposed here, it will be possible to relate how both neuron-specific, intrinsic features of nerve cells and region specific, extrinic features of the environment interact to produce the distinctive neuronal morphologies characteristic of central neurons. Furthermore, such information will bear on how such architectures are maintained and appropriately or inappropriately allowed to change in adult nervous systems.
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