The role of matrix metalloprotease subtypes in EPSP-to-spike (E-S) plasticity in CA3 associational network

Learning and memory formation are often linked to long-term synaptic plasticity but some components of memory storage are coded by nonsynaptic changes, i.e. neuronal excitability. Matrix metalloproteases (MMPs) play a crucial role in long-term synaptic plasticity, but to what extent they affect other neuronal functions remains poorly understood. Here we studied the impact of MMP-3 and MMP-2/9 specific inhibitors on evoked EPSPs and population spikes (PS) in CA3 hippocampal autoassociative network in rat P30–P60 brain slices. We found that MMPs inhibition reduced long-term E-S coupling and spiking coherence evoked with stimulation of associational/commisural synapses alone (4×100 Hz) or paired in bursts with mossy-fibers. Moreover, broad spectrum MMPs inhibitor did not occlude with E-S plasticity recorded in the presence of GABAARs or L-type calcium channels blockers but significantly reduced LTP of NMDAR-mediated EPSPs. Finally, MMPs inhibition determined the saturation level of E-S coupling depending on synaptic activity pattern. In conclusion, our data provide a novel link between MMPs activity (particularly MMP-3), postsynaptic depolarization and neural excitability. By regulating E-S plasticity and by limiting the number of neurons firing, MMPs could influence information processing in CA3 associational network. Supported by MNiSW grant “Iuventus Plus” IP2010_047870 and partially by 3/Pbmn and N N401541540 grant.