Role of metalloproteinases in synoptic plasticity in hippocampal mossy fiber-CA3 pathway

• Autorzy: Mozrzymas J.W. , Wojtowicz T. , Wiera G. , Gendosz D. , Chmielewska M. , Wawrzyniak M.
• Języki publikacji: EN

Abstrakty

EN

Matrix metalloproteinases (MMPs) are widely recognized as endopeptidases involved in remodeling of extracellular matrix. Last decade studies revealed these enzymes as important regulators of synaptic plasticity and cognitive processes. In particular, MMPs inhibition led to impairment of hippocampus-dependent learning and to down regulation of long-term potentiation (LTP) maintenance in the Schaffer collateral– CA1 (SC-CA1) pathway. However, the impact of MMPs on plasticity in other hippocampal paths was not known. In our recent studies, we have we addressed the impact of MMPs on plasticity in mossy fiber-CA3 (mf-CA3) projection in which, in contrast to SC-CA1, LTP expression in presynaptic. We found that pharmacological blockade of MMPs nearly abolished the late phase of LTP. Induction of LTP resulted in increased immunoreactivity for MMP-9 and enhanced gelatinase activity (in situ zymography) and these effects were associated with up regulation of de novo expression of active and latent MMP-9 forms (gel zymography). Interestingly, the late phase of LTP in the mf-CA3 pathway was reduced both in the MMP-9 KO mice and in rats overexpressing MMP-9. This finding indicates that maintenance of synaptic plasticity requires an optimal, finely tuned MMP-9 activity level. Pyramidal neurons in the CA3 region form a dense autoassociative network due to associational/commissural (AC) projections and plasticity mechanisms in AC and mf-CA3 synapses are different. Recently, we found that the late LTP phase in the AC synapses is also impaired by MMPs inhibition. Moreover, EPSC-spike potentiation in the CA3 region is strongly down regulated by MMPs blockade. In conclusion, MMPs appear to play a universal role in consolidation of synaptic plasticity in various hippocampal pathways characterized by different mechanisms of synaptic plasticity. Supported by Ministry for Science and Higher Education grants PN/030/2006 and N N401 541540.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: S
• Opis fizyczny: p.15

Twórcy

autor

Mozrzymas J.W.

• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Wojtowicz T.

• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Wiera G.

• Department of Molecular Animal Physiology, Wroclaw University, Wroclaw, Poland

autor

Gendosz D.

• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Chmielewska M.

• Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland

autor

Wawrzyniak M.

• Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland

Uwagi

Rekord w opracowaniu