GENETIC ENHANCEMENT OF LEARNING AND MEMORY

DESCRIPTION Psychological and behavioral studies of humans and animals suggest that the juvenile years are marked by a high capacity for learning and memory. It has been long speculated that the decrease in the performance of learning and memory afterwards is a result of the decrease in synaptic plasticity in the adult brain. The long-term goals of this project are to understand the role of dynamic regulation of synaptic plasticity in memory formation, and to provide rational strategy for improving learning and memory in the adult mammalian brain. This application will test a key hypothesis that the restoration of NMDA-mediated plasticity in the adult brain to the juvenile level will lead to an improvement in learning and memory in the adult animals. A recently developed, region-specific genetic technology will be applied to produce a series of transgenic mice to examine this hypothesis. Moreover, the pure C57Bl/6 inbred mouse strain, a preferred strain for behavioral studies, will be used for the production of all transgenic mice in this project so that the potential problems related with genetic backgrounds of different strains can be avoided. The first set of experiments aims to produce transgenic mice in which the NMDA receptor activity and plasticity are enhanced in the mouse forebrain regions specifically. An integrated analysis at cellular, electrophysiological and behavioral levels will be carried out to investigate whether the enhanced NMDAmediated synaptic plasticity will result in better learning and memory in these mice. The second set of experiments is designed to further define whether the heightened NMDA plasticity in hippocampal subregion(s) is sufficient for the enhancement in those memory tasks.