Protein translation was not thought to occur in axons, but more recent data has provided evidence that many mRNAs are found in axons in the mammalian nervous system. Evidence indicating that local translation in axons may be regulated by electrical activity, neurotrophic factors, and stress has led to the hypothesis that axonal translation is particularly important for plasticity during learning or in response to environmental stressors. In support of this idea, defects in local translation have been linked to fragile X syndrome, which causes cognitive problems and autistic behaviors, but the mechanisms are not understood. To address this problem, these studies will develop a new technique called spaceSTAMP. This technique allows one to tag proteins made in one part of the cell and to follow these components as they move in time and space. The goal of this proposal is develop the spaceSTAMP approach and use it to ask: Is there regulated local translation in axons? Are such locally translated proteins functionally important? Are locally translated proteins restricted to the axonal compartment, or do they facilitate communication between axonal terminals and remote portions of the neuronal cell body? Once spaceSTAMP has been developed, this approach can be used by the scientific community to solve problems such as the functional importance of the fragile X gene product and ways in which activity or neurotrophin regulated translation contribute to neuro-psychiatric disorders.