Ras, part of the mitogen-activated protein kinase (MAPK) pathway, is a protein expressed ubiquitously in eukaryotic cells which plays a critical role in transmitting extracellular signals. It has been shown that expression of the active RasG12V mutation in glutamatergic forebrain neurons of mice results in enhanced hippocampal-dependent learning and LTP at Schaffer collateral synapses. In addition, short-term synaptic depression was attenuated and paired-pulse facilitation was increased. We have also demonstrated that RasG12V mice have enhanced MAPK-dependent phosphorylation of synapsin I (SFN 2002 abstract # 779.9). Collectively, this implicates a potential function for Ras in presynaptic vesicle distribution. This possibility was addressed through serial electron microscopy of excitatory axospinuous synapses in CA1. Reconstructions of complete terminals and spines revealed a significant increase in the number of docked vesicles in RasG12V mice without any change in the size of the vesicular pool or termi...