Mossy fiber synapses onto CA3 pyramidal neurons have many unique features distinct from other excitatory synapses. Regarding synaptic plasticity, the most striking difference is that NMDAR-independent plasticity can be induced upon high frequency presynaptic stimulation. Given that mossy fibers activate substantial NMDAR-mediated currents in CA3 neurons, the role of the NMDARs at this synapse is unclear. Here, we investigate spike-timing dependent plasticity (STDP) at mossy fiber CA3 synapses in acute hippocampal slices of P21 rodents. Our results indicate that spike-timing dependent LTP is induced at this synapse, when a EPSP evoked by presynaptic stimulation in stratum lucidum is closely followed by postsynaptic APs. With a time delay of 10 to 40 milliseconds between EPSP and APs, a 89% increase in synaptic efficacy is observed. This increase is partly dependent on NMDAR activation, since the same STDP protocol results in only a 39% increase in EPSP amplitudes in presence of the NMDAR antagonist D-AP5. Furthermore, paired pulse facilitation, tested with a 50 ms interstimulus interval, is not altered following STDP, excluding an increase in release probability. We are currently investigating, if an STDP protocol in which an AP leads the EPSP on the order of tens of milliseconds, results in long-term depression, as it was reported for a number of other cortical and hippocampal synapses. Supported by DFG 1064/5-2