Peineau Stéphane, Taghibiglou Changiz, Bradley Clarrisa, Wong Tak Pan, Liu Lidong, Lu Jie, Lo Edmond, Wu Dongchuan, Saule Emilia, Bouschet Tristan, Matthews Paul, Isaac John T R, Bortolotto Zuner A, Wang Yu Tian, Collingridge Graham L
MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University Walk, Bristol, BS8 1TD, United Kingdom.
Neuron. 2007 Mar 1;53(5):703-17. doi: 10.1016/j.neuron.2007.01.029.
Glycogen synthase kinase-3 (GSK3) has been implicated in major neurological disorders, but its role in normal neuronal function is largely unknown. Here we show that GSK3beta mediates an interaction between two major forms of synaptic plasticity in the brain, N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) and NMDA receptor-dependent long-term depression (LTD). In rat hippocampal slices, GSK3beta inhibitors block the induction of LTD. Furthermore, the activity of GSK3beta is enhanced during LTD via activation of PP1. Conversely, following the induction of LTP, there is inhibition of GSK3beta activity. This regulation of GSK3beta during LTP involves activation of NMDA receptors and the PI3K-Akt pathway and disrupts the ability of synapses to undergo LTD for up to 1 hr. We conclude that the regulation of GSK3beta activity provides a powerful mechanism to preserve information encoded during LTP from erasure by subsequent LTD, perhaps thereby permitting the initial consolidation of learnt information.
糖原合酶激酶-3（GSK3）与多种主要神经疾病有关，但其在正常神经元功能中的作用仍不清楚。在此我们表明，GSK3β介导大脑中两种主要形式的突触可塑性之间的相互作用，即N-甲基-D-天冬氨酸（NMDA）受体依赖性长时程增强（LTP）和NMDA受体依赖性长时程抑制（LTD）。在大鼠海马切片中，GSK3β抑制剂可阻断LTD的诱导。此外，在LTD期间，通过PP1的激活，GSK3β的活性增强。相反，在LTP诱导后，GSK3β的活性受到抑制。LTP期间对GSK3β的这种调节涉及NMDA受体和PI3K-Akt途径的激活，并在长达1小时内破坏突触发生LTD的能力。我们得出结论，GSK3β活性的调节提供了一种强大的机制，以保护LTP期间编码的信息不被随后的LTD消除，这可能从而允许学习信息的初始巩固。
