GABAergic hippocampal plasticity critically depends on matrix metalloproteinase 3

• Autorzy: Mozrzymas J.W. , Brzdak P. , Lebida K. , Lech A. , Wiera G.
• Języki publikacji: EN

Abstrakty

EN

Matrix metalloproteinases (MMPs) are known to play a crucialrole in neuronal plasticity. In particular, MMP‑3 has been reported to be involved in glutamatergic plasticity and related cognitive processes. Recently, a growing body of evidence indicates that GABAergic synapses are also plastic, but the underlying mechanisms remain elusive. Herein we addressed the question if the activity of MMP-3 is involved in GABAergic synaptic plasticity in mice acute hippocampal slices or in neuronal cultures. The presentation at symposium aims to offer an overview of experimental evidence obtained by our research group while more details will be presented at the posters. We performed whole‑cell patch‑clamp recordings of miniature inhibitory postsynaptic currents (mIPSCs) from hippocampal CA1 pyramidal neurons. To induce inhibitory LTP (iLTP), we applied NMDA in bath solution (3 min, 20µM) in the presence of 20 μM DNQX and 1μM TTX to slices or neuronal cultures from wild‑type (WT) animals and mice lacking mmp‑3 gene (MMP‑3 KO). To block the activity of MMP-3 we used inhibitor UK 356618 (2 μM). Besides functional manifestations, iLTP induction was associated with a significant increase in synaptic gephyrin cluster area. We found that, in both slices and neuronal cultures, iLTP evoked in MMP-3 KO mice was completely abolished in contrast to WT. An analogous effect was observed when using UK356618. Interestingly, administration of active MMP-3 to neuronal cultures resulted in iLTP and an increase in average size of synaptic gephyrin cluster. In addition, analysis of membrane mobility of synaptic GABAARs showed a decrease in their diffusion coefficient after MMP-3 treatment indicating a strengthening of inhibitory synapses through receptor trapping. We show that the activity of MMP-3 plays a crucial role in iLTP in the hippocampal CA1 region. 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.XXXIII-XXXIV

Twórcy

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

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

Lech A.

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

autor

Wiera G.

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