膜相关鸟苷酸激酶动力学揭示了突触稳定性的区域和发育特异性

Jonathan M. Levy, R. Nicoll
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引用次数: 9

摘要

膜相关鸟苷酸激酶(MAGUK)突触支架蛋白家族在中枢神经系统突触上锚定谷氨酸受体。在未成熟的动物中,通过RNAi介导的CA1海马区敲除MAGUK导致谷氨酸能传递的快速和持久的减少。在成熟的动物中,同样的操作几乎没有急性效果。海马齿状回是一个正在进行的成人神经发生的区域,在成熟动物中对MAGUK的丢失很敏感,表现得像一个未成熟的CA1。在很长一段时间内,去除CA1中的MAGUKs会导致谷氨酸能传递减少,这表明成熟动物的突触需要MAGUKs来锚定谷氨酸受体,但更稳定。这些结果证明了突触稳定性的区域和发育控制,并表明在青春期前啮齿类动物的CA1中存在一个海马可塑性增强的敏感期,在整个成年期齿状回中也存在。
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Membrane‐associated guanylate kinase dynamics reveal regional and developmental specificity of synapse stability
The membrane‐associated guanylate kinase (MAGUK) family of synaptic scaffolding proteins anchor glutamate receptors at CNS synapses. MAGUK removal via RNAi‐mediated knockdown in the CA1 hippocampal region in immature animals causes rapid and lasting reductions in glutamatergic transmission. In mature animals, the same manipulation has little acute effect. The hippocampal dentate gyrus, a region with ongoing adult neurogenesis, is sensitive to MAGUK loss in mature animals, behaving like an immature CA1. Over long time courses, removal of MAGUKs in CA1 causes reductions in glutamatergic transmission, indicating that synapses in mature animals require MAGUKs for anchoring glutamate receptors, but are much more stable. These results demonstrate regional and developmental control of synapse stability and suggest the existence of a sensitive period of heightened hippocampal plasticity in CA1 of pre‐adolescent rodents, and in dentate gyrus throughout maturity.
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