A protein phosphatase 2A deficit in the hippocampal CA1 area impairs memory extinction

A protein phosphatase 2A deficit in the hippocampal CA1 area impairs memory extinction
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海马 CA1 区蛋白磷酸酶 2A 缺陷会损害记忆消退

DOI:
10.1186/s13041-019-0469-9
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发表时间:
2019
期刊:
影响因子:
3.6
通讯作者:
Gao Xiang
Gao Xiang
中科院分区:
医学3区
文献类型:
--
作者:
Wang Jing;Xie Ran;Kou Xiaolin;Liu Yu;Qi Cui;Liu Rui;You Weiyan;Gao Jun;Gao Xiang

文献摘要

相似文献

蛋白质磷酸化在学习和记忆中起着重要作用。蛋白磷酸酶2A(PP 2A)是一种丝氨酸/苏氨酸磷酸酶,参与神经突触可塑性的调节。在此,为了确定PP 2A是否是成功的学习和记忆所必需的,我们利用aTg(Camk 2a-cre)T29- 2St 1小鼠特异性敲低小鼠中海马PP 2A的表达。通过行为分析,我们观察到海马CA 1区PP 2A的缺失不影响记忆的形成,但损害了情境恐惧记忆的消退。我们利用电生理记录来寻找突触机制。结果表明,PP 2A条件性基因敲除(CKO)小鼠的基础突触传递和突触可塑性受损。此外,PP 2A CKO小鼠表现出饱和的长时程增强诱导强theta爆发刺激,但没有去增强后,低频刺激。综上所述,我们的研究结果提供了证据,PP 2A参与突触传递和海马依赖的记忆消退。
Protein phosphorylation plays an important role in learning and memory. Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase involved in the regulation of neural synaptic plasticity. Here, to determine if PP2A is necessary for successful learning and memory, we have utilized aTg (Camk2a-cre) T29–2Stlmice to specific knock down the expression of hippocampal PP2A in mice. By analysing behavioural, we observed that loss of PP2A in the hippocampal CA1 area did not affect the formation of memory but impaired contextual fear memory extinction. We use the electrophysiological recording to find the synaptic mechanisms. The results showed that the basic synapse transmission and synaptic plasticity of PP2A conditional knockout (CKO) mice were impaired. Moreover, PP2A CKO mice exhibited a saturating long-term potentiation inducted by strong theta burst stimulation but no depotentiation after low-frequency stimulation. Taken together, our results provide the evidence that PP2A is involved in synaptic transmission and hippocampus-dependent memory extinction.