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Long-term plasticity of inhibitory synapses in the hippocampus and spatial learning depends on matrix metalloproteinase 3.
Cellular and Molecular Life Sciences ( IF 6.2 ) Pub Date : 2020-09-21 , DOI: 10.1007/s00018-020-03640-6
Grzegorz Wiera 1 , Katarzyna Lebida 1 , Anna Maria Lech 1, 2 , Patrycja Brzdąk 1, 2 , Inge Van Hove 3 , Lies De Groef 3, 4 , Lieve Moons 3, 4 , Enrica Maria Petrini 5 , Andrea Barberis 5 , Jerzy W Mozrzymas 1
Affiliation  

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.



中文翻译:


海马抑制性突触和空间学习的长期可塑性取决于基质金属蛋白酶 3。



众所周知,学习和记忆取决于突触可塑性。尽管兴奋性突触可塑性变化的参与已得到充分证实,但抑制性突触的可塑性机制才刚刚开始被发现。已知细胞外蛋白水解是谷氨酸能可塑性的关键因素,但对其在 GABA 能突触中的作用尚不清楚。我们发现,药物抑制 MMP3 活性或基因敲除MMP3基因可以消除突触后 iLTP 的诱导。此外,外源活性MMP3的应用模拟了iLTP的主要表现:mIPSC振幅增加、突触gephyrin簇增大以及突触GABA A受体扩散系数降低,有利于它们在突触内的捕获。最后,我们发现 MMP3 缺陷小鼠在 Morris 水迷宫中表现出更快的空间学习能力,并增强了情境恐惧条件反射。我们得出的结论是,MMP3 在 iLTP 机制和可能部分依赖于 GABA 能可塑性的行为中发挥着关键作用。

更新日期:2020-09-22
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