A signaling protein Ras is important for many processes essential for the regulation of neuronal connection such as strengthening of synaptic contacts, formation of new synapses and regulation of cellular activity. Consistent with essential roles of Ras signaling in many neuronal signaling processes, failures of Ras signaling cause diseases associated with learning and cognitive deficits including X linked mental retardation and possibly autism. Therefore, detailed analyses of Ras signaling in neurons are crucial for a better understanding of Ras-related mental diseases. To study Ras signaling in neurons, Dr. Yasuda has developed a novel technique that allows imaging Ras activity at the single synapse level in living neurons deep in brain tissue. Such analysis occurs in real-time and can be performed when neurons are subjected to different physiological conditions. Because this protein is involved in so many cellular mechanisms and processes, the function may be dependent on the location of this protein within the neuron. The Yasuda lab is set up to investigate sub-cellular localization of proteins and evaluate expression of Ras during different physiologic conditions. Significance: By dissecting the roles and mechanisms of Ras signaling using this technique, the proposed research is expected to better demonstrate how Ras signaling controls cellular function under different conditions. Such results will provide significant insights into basic pathophysiological mechanisms that underlie Ras-related diseases, possibly including autism.