Fragile X syndrome is the most common genetic cause of autism and mental retardation. It is caused by a mutation in the gene for the Fragile X mental retardation protein (FMRP), which is required for regulating protein synthesis at synapses. This proposal will apply new molecular tools to reveal the molecular basis of the learning and emotional symptoms in fragile X syndrome. These tools will allow the real-time tracking and control of new protein synthesis and the visualization of kinase pathways involved in activity-induced protein synthesis. The specificity of protein synthesis responses in synaptic strengthening versus weakening, the proteins required for long-lasting synaptic plasticity, and how FMRP loss might alter these processes will be studied. This knowledge will be useful in identifying possible targets for the development of drugs to treat fragile X syndrome and potentially other autism spectrum disorders.