Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, GABA, iLTP, Mmps, Metalloproteinases, Synaptic plasticity, Synaptic inhibition, BRAIN EXTRACELLULAR-MATRIX, NMDA RECEPTOR, SYNAPTIC-TRANSMISSION, MEMORY, MATRIX-METALLOPROTEINASE-9, POTENTIATION, MICE, MECHANISMS, EXOCYTOSIS, EXCITATION, Animals, Female, Hippocampus, Humans, Long-Term Potentiation, Male, Matrix Metalloproteinase 3, Maze Learning, Mice, Inbred C57BL, Mice, Knockout, N-Methylaspartate, Neural Inhibition, Neuronal Plasticity, Receptors, GABA-A, Spatial Learning, Synapses, Mice, 0601 Biochemistry and Cell Biology, 0606 Physiology, 1103 Clinical Sciences, 3101 Biochemistry and cell biology, 3205 Medical biochemistry and metabolomics, 3211 Oncology and carcinogenesis

Abstract:

Learning and memory are known to depend on synaptic plasticity. Whereas the involvement of plastic changes at excitatory synapses is well established, plasticity mechanisms at inhibitory synapses only start to be discovered. Extracellular proteolysis is known to be a key factor in glutamatergic plasticity but nothing is known about its role at GABAergic synapses. We reveal that pharmacological inhibition of MMP3 activity or genetic knockout of the Mmp3 gene abolishes induction of postsynaptic iLTP. Moreover, the application of exogenous active MMP3 mimics major iLTP manifestations: increased mIPSCs amplitude, enlargement of synaptic gephyrin clusters, and a decrease in the diffusion coefficient of synaptic GABAA receptors that favors their entrapment within the synapse. Finally, we found that MMP3 deficient mice show faster spatial learning in Morris water maze and enhanced contextual fear conditioning. We conclude that MMP3 plays a key role in iLTP mechanisms and in the behaviors that presumably in part depend on GABAergic plasticity.