Matrix metalloproteinase 3 critically affects postsynaptic long-term potentiation at GABAergic synapses in the mouse hippocampal CA1 region

• Autorzy: Brzdak P. , Lebida K. , Mozrzymas J.W.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Matrix metalloproteinases (MMPs) are extracellular proteases that play a crucial role in various forms of neuronal plasticity. We have recently shown that MMP-3 supports NMDAR-mediated long-term potentiation and L-type calcium channel-dependent LTP. An extensive body of evidence revealed that, besides glutamatergic transmission, GABAergic synapses are also plastic; however, the underlying mechanisms remain elusive. AIM(S): Herein we addressed the question if activity of MMP-3 is involved in GABAergic synaptic plasticity in mice acute hippocampal slices. METHOD(S): We performed whole-cell patch-clamp recordings of miniature inhibitory postsynaptic currents (mIPSCs) from hippocampal CA1 pyramidal neurons. To induce iLTP, we applied NMDA in bath solution (3 min, 20µM) in the presence of 20 μM DNQX and 1μM TTX to slices from wild-type (WT) animals and mice lacking the mmp‑3 gene (MMP‑3 KO). To block the activity of MMP‑3, we used inhibitor UK 356618 (2 μM) in different time windows upon iLTP induction. RESULTS: We found that, in contrast to control conditions (WT), iLTP evoked in MMP-3 KO mice was completely abolished (CTR: 122±8%, n=9; MMP‑3 KO: 99±4%, n=13; p<0.05). We next studied the impact of the MMP‑3 inhibitor (UK356618) on iLTP during different time windows. The application of the MMP‑3 inhibitor before induction blocked iLTP (UK 356618: 92±3%; n=7; CTR: 116±3%; p<0.05). In slices that were treated with UK 356618 at various time points after starting the NMDA application, we found that the activity of MMP-3 is required for up to 13 minutes post induction of iLTP (UK 356618: 113±2%; n=6; CTR: 116±3%; n=7; p>0.05). CONCLUSIONS: The present results provide evidence that the activity of MMP-3 plays a crucial role in iLTP in the hippocampal CA1 region within a specific time window. FINANCIAL SUPPORT: Supported by Polish National Science Centre grant SONATA 2017/26/D/NZ4/00450 and PB is supported by Polish National Science Centre scholarship ETIUDA 2018/28/T/NZ4/00344.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.LXIII

Twórcy

autor

Brzdak P.

• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland
• Department of Physiology and Molecular Neurobiology, Wroclaw University, Wroclaw, Poland

autor

Lebida K.

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

autor

Mozrzymas J.W.

• Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland
• Department of Physiology and Molecular Neurobiology, Wroclaw University, Wroclaw, Poland