Effects of Matrix Metalloproteinase Inhibition on Long-Term Plasticity at Perforant Pathway/ Dentate Gyrus Synapses: in vivo Study

Purpose: The aim of the study was to explore whether matrix metalloproteinases (MMPs) is a requisite for efficient hippocampal-dependent learning in the perforant pathway/dentate gyrus synapses. With this aim, we infused FN-439 which is a MMPs inhibitor into the dentate gyrus. Material and Methods: The experiments were carried out on 18 male Wistar rats. Rats were anesthetized with urethane, and the head was fixed in stereotaxic head-holder. A bipolar stimulating electrode was placed on the medial perforant path. One of the barrels of double- barreled glass micropipette was filled with aCSF or FN-439 and applied to dentate gyrus before the EPSP recordings. Other barrel was filled with 3 M NaCl and field excitatory postsynaptic potentials (fEPSPs) were recorded from this barrel. The high frequency stimulation (HFS) protocol was applied. Results: Infusion of FN-439 resulted in a clear inhibition of the fEPSP slope and population spike amplitude in the early and maintenance phase. The HFS protocol caused significantly less potentiation of dentate synapses subjected to FN-439 when compared to infusion of aCSF. Conclusion: Acute application of FN-439 significantly inhibited long-term plasticity in the perforant patway/dentate gyrus neurons of anaesthetized rats. Thus, we showed that MMPs are necessary for long term potentials which are important model for learning.