MMP-3 and MMP-9 divergently regulate LTP in hippocampal mosy fiber-CA3 and CA3-CA1 projections
Matrix metalloproteinases (MMPs) comprise a family of proteolytic enzymes that modify membrane and extracellular matrix proteins. Broad-spectrum MMP inhibitors were shown to impair LTP consolidation in two hippocampal projections: mossy fiber (MF)-CA3 and CA3-CA1 which deeply differ in LTP induction as well as in expression sites and induction mechanisms. The aim of this study was to address the specific roles of MMP-3 and gelatinases in LTP in these projections. Using field potentials recording in acute mice brain slices we have shown that specific MMP-3 inhibitor (NNGH) disrupts LTP late phase in CA3-CA1 pathway (NNGH: 119 ± 10% of baseline two hours after induction, n=9; CTR: 177 ± 29%, n=8; P=0.01) but does not affect LTP in MF-CA3 (NNGH: 186 ± 27%, n=7; CTR: 172 ± 11%; n=7, P=0.34). Another MMP-3 inhibitor UK356618 gave similar results. Interestingly, knock-out mice without functional MMP-9 show impaired long term plasticity in MF-CA3 pathway (KO: 115 ± 17%, n=8; CTR 181 ± 13%, n=13; P<0.01) and a weak if any change in LTP in CA3-CA1 projection (KO: 139 ± 8%, n=7; CTR: 159 ± 13%, n=8; P=0.22). These results suggest that the role of particular MMPs in LTP expression is not universal in considered projections. Moreover, we provide the first evidence that MMP-3 and MMP-9 proteases differentially modify LTP consolidation in the MF-CA3 and CA3-CA1 pathways. Support: NCN grant N N401541540.