For the brain to operate correctly, the connections among nerve cells must be appropriate. During embryological development, some of these "synaptic" connections may be made because the cells are genetically pre-programmed to make them. In other cases, however, the synaptic inputs to a nerve cell may influence which other cells it, in turn, contacts. A knowledge of how peripheral targets can influence synaptic connections in the brain is basic to an understanding of how nerve cells originally make and then refine and maintain their proper connections. Synaptic connections in the spinal cord between sensory and motor nerve cells innervating muscles, the simple knee-jerk reflex, provide an excellent experimental system for studying this problem at the level of single nerve cells. In the spinal cord, these connections initially form with a high degree of specificity. However, if a group of sensory cells is forced to innervate a different target during development, the synaptic connections formed within the spinal cord are appropriate for this new target. The experiments in this grant are designed to explore, using anatomical and microelectrode recording techniques, the following questions: When, during development, is a nerve cell specified to have a particular function? To what extent is this function determined by the previous history of the cell (its lineage) versus its present molecular environment? These studies should provide useful information concerning how synapses are made during normal development and even how they might be repaired after spinal injury.
