title: Maintenance of long-term potentiation in hippocampal mossy fiber-CA3 pathway requires fine-tuned MMP-9 proteolytic activity.
abstract: Mechanisms of synaptic plasticity involve proteolytic activity mediated by a complex system of proteases, including members of metalloproteinase (MMP) family. In particular, MMP-9 is critical in LTP maintenance in the Schaffer collateral-CA1 pathway and in the acquisition of hippocampus-dependent memory. Recent studies from this laboratory revealed that in the mossy fiber-CA3 (MF-CA3) projection, where LTP induction and expression are largely presynaptic, MMPs blockade disrupts LTP maintenance and that LTP induction is associated with increased MMP-9 expression. Here we used acute brain slices from MMP-9 knock-out mice and transgenic rats overexpressing MMP-9 to determine how manipulations in endogenous MMP-9 affect LTP in the MF-CA3 projection. Both types of transgenic models showed a normal basal synaptic transmission and short-term plasticity. Interestingly, the maintenance of LTP induced in slices from knock-out mice and overexpressing rats was nearly abolished. However, in the presence of active MMP-9, a gradual fEPSP autopotentiation was observed and tetanization evoked a marked LTP in knock-out mice. Additionally, in MMP-9-treated slices from wild-type mice, fEPSP autopotentiation also occurred and partially occluded LTP. This indicates that exogenous protease can restore LTP in null mice whereas in the wild-type, MMP-9 excess impairs LTP. We expected that LTP maintenance in transgenic rats could be re-established by a partial MMP blockade but non-saturating concentrations of MMP inhibitor were ineffective. In conclusion, we demonstrate that LTP maintenance in MF-CA3 pathway requires fine-tuned MMP-9 activity and raises the possibility that altered MMP-9 level might be detrimental for cognitive processes as observed in some neuropathologies.
authors: Department of Biophysics, Laboratory of Neuroscience, Wroclaw Medical University, Wroclaw, Poland. gwiera@biol.uni.wroc.pl
authors: Grzegorz
authors: G
authors: Wiera
authors: Grazyna
authors: G
authors: Wozniak
authors: Malgorzata
authors: M
authors: Bajor
authors: Leszek
authors: L
authors: Kaczmarek
authors: Jerzy W
authors: JW
authors: Mozrzymas
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000201:enzymology*; D009434:Neural Pathways / Q000502:physiology; D009924:Organ Culture Techniques; D059748:Proteolysis; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar
chemical_list: D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse