u=4145118900,2551151607&fm=21&gp=0

约翰霍普金斯大学研究人员近日进行了一项研究,研究结果显示公认的长期记忆形成模式(长期记忆形成取决于大脑中的某种单一酶)并不准确。该研究发现,没有这种酶的小鼠实际上依然能像普通小鼠那样形成长期记忆。

-2013年1月17日《自然》

中文翻译


【题目】PKM-ζ不是海马突触可塑性,学习和记忆所必需的因子

【译文】长时程增强(LTP)是突触可塑性的一种界定较好的形式,被长期认为是学习和记忆的细胞关联。尽管LTP可以持续很长时间,但进行性蛋白翻转和突触活性中间的LTP维持的潜在机制尚不清楚。脑特异性蛋白激酶C (PKC)亚型蛋白激酶M-ζ (PKM-ζ)的持续活化被认为对于LTP维持和长期记忆是必需的。利用基于PKM-ζ假底物序列的突触ζ抑制肽(ZIP)抑制PKM-ζ活性可以逆转体外和体内建立的LTP。更显著的是,注射ZIP消除了不断增加的经历依赖性行为的记忆,包括活化的位置逃避、条件性味觉厌恶、恐惧条件反射以及空间学习。然而,支持PKM-ζ在LTP和记忆中作用的大多数证据过度依赖于ZIP产生的PKM-ζ药理学抑制。为了进一步研究PKM-ζ在LTP和记忆维持中的作用,我们制造了缺乏PKC-ζ和PKM-ζ的转基因小鼠。我们发现常规的和条件性PKC-ζ/PKM-ζ敲除小鼠均表现出谢弗侧枝–CA1突触上的正常突触传导和LTP,并且在一些海马依赖性学习和记忆中没有缺陷。值得注意的是,ZIP仍然可以逆PKC-ζ/PKM-ζ敲除的小鼠中的LTP,表明ZIP的效应不依赖PKM-ζ。

英文原稿


[Title]: PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory

[Authors]:Lenora J. Volk,1, 2 Julia L. Bachman,1, 2 Richard Johnson,1 Yilin Yu1 & Richard L. Huganir1

[Abstract]Long-term potentiation (LTP), a well-characterized form of synaptic plasticity, has long been postulated as a cellular correlate of learning and memory. Although LTP can persist for long periods of time, the mechanisms underlying LTP maintenance, in the midst of ongoing protein turnover and synaptic activity, remain elusive. Sustained activation of the brain-specific protein kinase C (PKC) isoform protein kinase M-ζ (PKM-ζ) has been reported to be necessary for both LTP maintenance and long-term memory. Inhibiting PKM-ζ activity using a synthetic zeta inhibitory peptide (ZIP) based on the PKC-ζ pseudosubstrate sequence reverses established LTP in vitro and in vivo. More notably, infusion of ZIP eliminates memories for a growing list of experience-dependent behaviours, including active place avoidance, conditioned taste aversion, fear conditioning and spatial learning. However, most of the evidence supporting a role for PKM-ζ in LTP and memory relies heavily on pharmacological inhibition of PKM-ζ by ZIP. To further investigate the involvement of PKM-ζ in the maintenance of LTP and memory, we generated transgenic mice lacking PKC-ζ and PKM-ζ. We find that both conventional and conditional PKC-ζ/PKM-ζ knockout mice show normal synaptic transmission and LTP at Schaffer collateral–CA1 synapses, and have no deficits in several hippocampal-dependent learning and memory tasks. Notably, ZIP still reverses LTP in PKC-ζ/PKM-ζ knockout mice, indicating that the effects of ZIP are independent of PKM-ζ.

原文地址

http://www.nature.com/nature/journal/v493/n7432/full/nature11802.html

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