Activity of MMP-3 protease affects exicitatory and inhibitory synaptic transmission in hippocampus

• Autorzy: Wiera G. , Petrini E. , Barberis A. , Mozrzymas J.W.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Several neuronal processes are regulated by matrix metalloproteinases (MMPs), a family of zincdependent proteases. It is well established that long-term synaptic plasticity, learning and memory involve extracellular activity of MMPs but the role of some of them is not fully identified. The aim of this study was to address the functions of MMP-3 in synaptic plasticity of excitatory and inhibitory synaptic transmission. METHODS: Field potentials recordings in acute mice hippocampal slices and single molecule-tracking of GABAA receptors in neuronal cultures. RESULTS: We have shown that in MMP-3 knock-out mice lateLTP is impaired in CA3-CA1 projection (WT: 180±10% of baseline 2 h after induction, n=15; KO: 134±12%, n=16; P<0.01). Treatment of wild-type slices with SB3CT (a specific MMP-9 inhibitor) also blocked late-LTP, without affecting early phase of LTP These observations suggest that both MMP-9 and MMP-3 together may regulate the maintenance of LTP. We next determined whether impaired late-LTP in MMP-3 KO slices is further weakened by MMP-9 inhibition with SB3CT. Knockout of MMP-3 together with MMP-9 blockade (SB-3CT) caused a strong reduction in  both early and late LTP phases [WT: 170±8% of baseline 20 min after induction, n=16; MMP-3 KO: 157±8%, n=17; MMP-3 KO+SB-3- CT: 138±6%, n=8; P(WT vs. MMP-3 KO)=0.26, P(WT vs. MMP-3 KO+SB-3CT)=0.01]. Additionally, we studied the role of MMP-3 in inhibitory transmission using single molecule tracking of GABAA receptors (α1 subunit). We have found that 10 or 45 min treatment with active MMP-3 protein decreased the diffusion coefficient of both synaptic and extrasynaptic GABAA receptors (P<0.01). CONCLUSIONS: Our observations indicate that activity of MMP-3 is necessary for LTPmaintenance and suggest that MMP-3 regulates membrane mobility of GABA receptors. Future work is needed to elucidate the impact of MMP-3 on plasticity of inhibitory synapses. Support: NCN grants NN401541540, 2013/08/T/NZ3/00999.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S63

Twórcy

autor

Wiera G.

• Wrocław University; Wroclaw Medical University, Wrocław, Poland
• Wrocław University, Wrocław, Poland

autor

Petrini E.

• Italian Istitute of Technology, Genoa, Italy

autor

Barberis A.

• Italian Istitute of Technology, Genoa, Italy

autor

Mozrzymas J.W.

• Wrocław University; Wrocław, Poland
• Wroclaw Medical University, Wrocław, Poland