Matrix metalloproteinases (MMPs) are a large family of extracellularly-acting endopeptidases. MMPs were shown to play an important role in hippocampal plasticity phenomena such as LTP, learning and memory. In particular, in Shaffer collateral/ CA1 (Sch/CA1) synapses, MMPs are crucial for maintenance of long term plasticity requiring NMDA receptor (NMDAR) activation. However, it is not known whether MMPs affect plastic changes in mossy-fi ber/CA3 (mf/CA3) synapses, where LTP is basically presynaptic and NMDAR-independent. Field potential (fEPSPs) recordings in CA3 region (mf stimulation) revealed no effect of FN439 (panmetalloprotease inhibitor) on the short-term plasticity but the late phase of LTP was abolished by this agent similar to Sch/CA1 pathway. Since maintenance of LTP in Sch/CA1 was specifi cally dependent on MMP-9 activity, we have performed immunostaining for MMP-9 in mf/CA3 pathway. Semi-quantitative analysis revealed that induction of LTP resulted in several fold increase in MMP-9 immunoreactivity within hilar and CA3 region relative to control slices. We conclude that MMPs are crucial for long- but not short-term plasticity in mf/CA3 synapses and that LTP induction in this pathway is accompanied by a robust increase in MMP-9 immunoreactivity. It seems thus that consolidation phase of LTP is critically dependent on MMP activity in the two major hippocampal pathways (Sch/CA1 and mf/CA3) where LTP induction mechanisms show profound differences. Support: Grant No. P-N/030/2006.
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