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1 Acta Neurobiologiae Experimentalis

1 2013

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Impact of metaloproteases on synaptic and E+S plasticity in the hippocampal mosy fiber–CA3 and AC path ways

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Morrzymas J. W. , Wiera G. , Wojtowicz T.

nr Suppl.1

Learning and synaptic plasticity is known to involve activity of metalloproteinases (MMPs). Recently, we investigated impact of MMPs on mossy fiber-CA3 (mf-CA3) projection, where LTP is NMDAR-independent and presynaptic, and showed that MMP blockade disrupted LTP maintenance. Using in situ zymography we showed that LTP induction enhances gelatinases activity. Moreover, by means of gelatin zymography, immunohistochemistry and immunofluorescent staining we have shown that this was due to de novo synthesis and activation of MMP-9 (but not MMP-2). Next we found that manipulations in endogenous MMP-9 affected LTP in the mf-CA3 projection. Intriguingly, in slices from both MMP-9 KO and overexperssing rodents, LTP maintenance was nearly abolished. In KO group, LTP could be rescued by administration of active MMP-9. This suggests that LTP maintenance in mf-CA3 pathway requires fine-tuned MMP-9 activity. Neuronal plasticity may involve also changes in excitability and we addressed this issue in associational/commissural synapses formed between CA3 pyramidal neurons. We found that MMPs (MMP-3 and gelatinases) inhibition significantly reduced EPSP-to-spike (E-S) and spike coherence upon LTP indution. Altogether, we show that MMPs play a crucial role in controlling various facets of neuronal plasticity in the mf-CA3 hippocampal projection. Support: NCN grant NN401541540.