We have used the hippocampal formation as a model system to study the process of synapse formation in the mature nervous system. It is now well known that new synapses form rapidly and in highly specific patterns in reaction to lesions of extrinsic hippocampal afferents or certain other perturbations. In the next grant period we shall continue our studies on reactive synaptogenesis. We will study the reorganization of hippocampal circuitry after kainic acid-produced lesions. These lesions selectively destroy intrinsic hippocampal neurons and create a type of damage which is similar in many respects to hippocampal damage in man. We shall examine the reactive growth of various afferents and we shall study, as well, the possible plasticity of receptors for the transmitters in certain of these hippocampal fibers. These experiments will provide information on the nature of reinnervation following intrinsic cell loss and certain possible mechanisms guiding growth. Some studies on the mechanism of kainic acid will also be undertaken. We shall attempt to characterize the nature of the receptor for kainic acid.