Matrix metalloproteinase-9 (MMP-9) mediates cholinergic-induced plasticity of the excitatory input to hippocampal fast spiking interneurons

• Autorzy: Salamian A. , Beroun A. , Kaczmarek L.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: MMP-9 is an extracellular protease involved in modification of synaptic functions. Cholinergic receptors activation in the hippocampus, that is mostly mediated by projections from the medial septum, plays an important role in the hippocampal synaptic plasticity. Additionally, activation of muscarinic cholinergic receptors can be involved in synaptic transmission between parvalbumin positive cells, known as fast spiking inhibitory interneurons, and pyramidal cells. AIM(S): The aim of this study was to evaluate the effect of MMP-9 on the cholinergic-induced synaptic plasticity. METHOD(S): To induce synaptic plasticity, carbachol, a cholinergic agonist, triggering rhythmic activity, which causes a lasting synaptic enhancement, was applied to cultured hippocampal organotypic slices. MMP-9 activity was either genetically or pharmacologically blocked. Using whole-cell patch-clamp technique, AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) were recorded. Enzymatic activity of MMP-9 was assessed by gelatin zymography. RESULTS: One hour of carbachol treatment, followed by an overnight carbachol‑free incubation, produced significant increase in frequency of mEPSCs. Treatment with either MMP-9 inhibitor I or genetic ablation of MMP-9 along with carbachol further enhanced frequency of mEPSCs. Recording mEPSCs from fast spiking GABAergic interneurons located at the stratum radiatum showed enhancement of mEPSCs frequency by carbachol. The increased excitatory inputs to those inhibitory interneurons were impaired while MMP-9 activity was inhibited. Evaluation of gelatinase activity in conditioned cultured medium indicated remarkable increase in the level of MMP-9 compared with control around 24 hours after carbachol treatment. CONCLUSIONS: MMP-9 proteolytic activity can have a marked impact on the cholinergic-induced synaptic plasticity and transmission between pyramidal neurons and inhibitory interneurons. FINANCIAL SUPPORT: ITN training network EU FP7 grant “EXTRABRAIN”.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.95

Twórcy

autor

Salamian A.

• Nencki Institute of Experimental Biology, Department of Molecular and Cellular Neurobiology, Warsaw, Poland

autor

Beroun A.

• Nencki Institute of Experimental Biology, Department of Molecular and Cellular Neurobiology, Warsaw, Poland

autor

Kaczmarek L.

• Nencki Institute of Experimental Biology, Department of Molecular and Cellular Neurobiology, Warsaw, Poland