UP inhibits LTD in the hippocampus via regulation of GSK3β
UP inhibits LTD in the hippocampus via regulation of GSK3β
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DOI：
10.1016/j.neuron.2007.01.029
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发表时间：
2007-03-01
期刊：
影响因子：
16.2
通讯作者：
Collingridge, Graham L.
中科院分区：
文献类型：
--
作者：
Peineau, Stephane;Taghibiglou, Changiz;Collingridge, Graham L.
糖原合成酶激酶-3（GSK 3）与主要的神经系统疾病有关，但其在正常神经功能中的作用在很大程度上是未知的。在这里，我们表明，GSK 3 β介导的两种主要形式的突触可塑性之间的相互作用，在大脑中，N-甲基-D-天冬氨酸（NMDA）受体依赖的长时程增强（LTP）和NMDA受体依赖的长时程抑制（LTD）。在大鼠海马脑片中，GSK 3 β抑制剂阻断LTD的诱导。此外，在LTD过程中，GSK 3 β的活性通过PP 1的激活而增强。相反，在诱导LTP之后，存在对GSK 3 β活性的抑制。这种调节的GSK 3 β在LTP涉及激活NMDA受体和PI 3 K-Akt通路和破坏突触的能力进行LTD长达1 hr. We的结论是，GSK 3 β活性的调节提供了一个强大的机制，以保护信息编码在LTP从擦除随后的LTD，也许从而允许初步巩固的学习信息。
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 GSK3 beta 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, GSK3 beta inhibitors block the induction of LTD. Furthermore, the activity of GSK3 beta is enhanced during LTD via activation of PP1. Conversely, following the induction of LTP, there is inhibition of GSK3 beta activity. This regulation of GSK3 beta 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 GSK3 beta 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.