Matrix matalloproteases regulate the extent of synaptic plasticity and spike potentiation in hippocampal CA3 association network

Matrix metalloproteinases (MMPs) activity support spatial and associative learning in vivo however the underlying mechanisms are poorly understood. It has been shown that MMPs inhibition impairs the maintenance of long-term potentiation (LTP) in hippocampal Sch-CA1 synapses and in mfCA3 pathways. However, it is not known whether MMPs activity influences the scaling of postsynaptic neuronal responses (population spikes, PS) typically associated with synaptic LTP. Therefore, we investigated the plasticity of evoked synaptic transmission (input) and resulting PS (output) in CA3 associative network by simultaneous double electrode extracellular field potentials recording. We found that highfrequency-induced (4 × 100 Hz) LTP of EPSPs and PS was significantly impaired in the presence of broad spectrum MMPs inhibitor FN439 while the EPSP-to-Spike (E-S) curves were right-shifted indicating that less neurons were recruited to fire for a given input. Additionally, these effects could be mimicked by application of MMP-3 inhibitor (NNGH). MMPs inhibitors did not affect input–output function of the CA3 neurons or various forms of short term-plasticity. In conclusion, MMPs and particularly MMP-3 may play an important role in the maintenance of E-S potentiation in the CA3 network and thereby may regulate formation of memory traces in this hippocampal region. Supported by IP2010_047870 grant.

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