: The proposed research involves the generation of mice lacking all C13 subunits of protein kinase A (PKA). These mice will be utilized in studies examining the role of this PKA subunit in learning and memory. PKA is an essential enzyme in the process of learning and memory, and the Cb subunit is expressed in regions of the brain known to be critical for the establishment of long-term memory. Mice lacking Cb will be tested in spatial and fear learning tasks to determine the significance of Cb in these types of memory. The molecular mechanism of learning and memory will be examined by determining the effect of knocking out Cb on signal transduction and gene expression events thought to be important for learning and memory. Finally, a transgenic approach will be utilized to attempt to rescue the phenotype of the Cb knockout mice. A detailed understanding of the molecular mechanism of learning and memory is necessary if we are to reduce, reverse or even prevent the memory loss associated with old age and neurological disease.