Impact of matrix metalloprotease inhibitor NNGH on long-term plasticity of NMDARs-mediated EPSPs in mouse CA1 hippocampal region

The matrix metalloproteinases (MMPs) play a key role in synaptic plasticity, learning and memory. However, the underlying mechanisms remain poorly understood. Here we studied the role of MMPs inhibitor NNGH (10 µM) in shaping NMDAR-mediated component of synaptic plasticity by recording field potentials in Sch-CA1 hippocampal synapses in mice (P30-P45) brain slices. NMDAR-mediated EPSPs were isolated with AMPA/kainate receptors antagonist DNQX (20 µM) in Mg2+-free solutions. We found that NNGH completely abolished NMDAR-mediated LTP (178.7±12% vs. 75.8±2.9% of baseline at 1 hour post 4×100 Hz stimulation, n=6, P<0.05). The role of specific MMPs in this process is currently investigated. In conclusion, MMPs regulate NMDAR-mediated LTP and most likely postsynaptic calcium influx during long-term neuronal plasticity. Support: Ministry of Science and Higher Education grant NN401541540.