This research program is concerned with specific aspects of the related problems of normal synaptic development in the brain, and how development is modified by brain damage. These anatomical studies utilize the interpeduncular nucleus in rats, a system where specific questions can be answered in detail because of the favorable features known from previous studies. These including separation of specific types of synapses into separate subnuclei, the pairing of one left and one right habenular afferent at 90% of crest synapses, and the location of 95% of S synapses in the ipsilateral half of the central subnucleus in spite of the fact that the axons making these synapses traverse both halves repeatedly. Electron microscopic degeneration will be used to determine the initial distribution of these synapses during development, and whtehter there is subsequent modification of this distribution. These experiments will also determine the developmental process which leads to the left and right synaptic relationships. Horseradish peroxidase will be used to fill and demonstrate the distribution of the synapses formed by individual afferent axons relative to subnuclear boundaries. Also the relation of synapses to the multiple segments of these axons as they recross the interpeduncular nucleus will be determined in normal adult rats, and in neonatally lesioned animals when they have matured. Horseradish peroxidase will also be used to directly determine the relationship of synapse location to subnuclear location of neurons on whose dendrites they occur. The results of these experiments will provide a basis for hypotheses concerning the mechanisms which determine the observed phenomena and concerning possible treatments which would modify these processes. The long term goal is to develop such treatments, and a system on which they can be tested in detail. The use of such treatments would improve the recovery of neurological function in patients suffering from a wide variety of neurological injuries and diseases, ranging from lifelong genetic and acquired diseases to stroke, trauma and the degenerative diseases of the brain and spinal cord at all ages.