9511869 Day Some estimates state that as much as one third of the mammalian genome, some 30,000 genes, are expressed in the brain, but only a very small number have been assigned clearly defined roles in neural development or function. Increasing our knowledge of the genes involved in synapse formation and stability is fundamental to our understanding of neural development, learning, and memory. The major goal of this research is to identify genes with roles in the compensatory synaptic reorganization that occurs after surgical alteration of the adult brain. The studies to be performed will identify changes in neuronal messenger RNAs induced by cutting neural connections to the hippocampus, a region involved in learning and memory. Molecular cloning will then be used to identify genes with increased activity during the brain's attempt to compensate for the loss of these hippocampal connections. The cloning strategy involves subtraction hybridization of complementary DNA libraries constructed from brains having two different types of hippocampal alterations. The complementary nature of these cloning strategies will remove gene products associated with the non-specific effects, and enrich the resulting cDNA library with synapse-specific neuronal clones. Careful screening of these candidate clones will determine their roles in synapse formation and stability. This research will identify specific genes that are involved in neural development and regeneration and, ultimately, define the role of these genes in these fundamental neural processes.