Growth cones have been among the most intriguing and elusive neuronal structures studied since their initial description by Cajal and subsequent observation in tissue culture by Harrison. While the importance of growth cones in events such as neurite outgrowth, pathfinding, target recognition and synaptogenesis is well-established, growth cone activity and their physiological control are poorly understood. However, recent technical advancements have made it possible to investigate growth cone motility more readily. The identified neurons of the snail 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. In this proposal we will examine quantitative aspects of growth cone movements of different identified neurons. We will utilize a variety of extrinsic "trophic" factors (growth-promoting, growth-inhibiting, and chemotactic) and interaction with "target" cells (other neurons and neuro-effector tissues) to modulate these movements. Furthermore, we will also examine the biophysical properties of growth cones using voltage clamp techniques and pharmacological methods. This will provide information not only on the ionic currents across the growth cone membrane but also on how these currents may be related to growth cone motility. Thus, this proposal seeks to understand the intrinsic and extrinsic factors which affect growth cone movement and their possible ionic basis.