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组蛋白乙酰化对陆生蜗牛中5-羟色胺介导的长期突触可塑性的作用。

Contribution of histone acetylation to the serotonin-mediated long-term synaptic plasticity in terrestrial snails.

作者信息

Zuzina Alena B, Balaban Pavel M

机构信息

Cellular Neurobiology of Learning Lab, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.

出版信息

J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2022 Nov;208(5-6):521-535. doi: 10.1007/s00359-022-01562-1. Epub 2022 Aug 9.

Abstract

Serotonin plays a decisive role in long-term synaptic plasticity and long-term memory in mollusks. Previously, we demonstrated that histone acetylation is a regulatory mechanism of long-term memory in terrestrial snail. At the behavioral level, many studies were done in Helix to elucidate the role of histone acetylation and serotonin. However, the impact of histone acetylation on long-term potentiation of synaptic efficiency in electrophysiological studies in Helix has been studied only in one paper. Here we investigated effects of serotonin, histone deacetylases inhibitors sodium butyrate and trichostatin A, and a serotonergic receptor inhibitor methiothepin on long-term potentiation of synaptic responses in vitro. We demonstrated that methiothepin drastically declined the EPSPs amplitudes when long-term potentiation was induced, while co-application either of histone deacetylase inhibitors sodium butyrate or trichostatin A with methiothepin prevented the weakening of potentiation. We showed that single serotonin application in combination with histone deacetylase blockade could mimic the effect of repeated serotonin applications and be enough for sustained long-lasting synaptic changes. The data obtained demonstrated that histone deacetylases blockade ameliorated deficits in synaptic plasticity induced by different paradigms (methiothepin treatment, the weak training protocol with single application of serotonin), suggesting that histone acetylation contributes to the serotonin-mediated synaptic plasticity.

摘要

血清素在软体动物的长期突触可塑性和长期记忆中起决定性作用。此前,我们证明组蛋白乙酰化是陆生蜗牛长期记忆的一种调节机制。在行为层面,已经在盖罩大蜗牛中开展了许多研究以阐明组蛋白乙酰化和血清素的作用。然而,在盖罩大蜗牛的电生理研究中,组蛋白乙酰化对突触效率长期增强的影响仅在一篇论文中有所研究。在此,我们研究了血清素、组蛋白去乙酰化酶抑制剂丁酸钠和曲古抑菌素A以及一种血清素能受体抑制剂甲硫噻平对体外突触反应长期增强的影响。我们证明,当诱导长期增强时,甲硫噻平会大幅降低兴奋性突触后电位(EPSPs)的幅度,而将组蛋白去乙酰化酶抑制剂丁酸钠或曲古抑菌素A与甲硫噻平共同应用可防止增强作用减弱。我们表明,单独应用血清素并联合组蛋白去乙酰化酶阻断可模拟重复应用血清素的效果,并且足以引发持续的长期突触变化。所获得的数据表明,组蛋白去乙酰化酶阻断改善了由不同范式(甲硫噻平处理、单次应用血清素的弱训练方案)诱导的突触可塑性缺陷,这表明组蛋白乙酰化有助于血清素介导的突触可塑性。

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Histone deacetylase inhibitors rescue the impaired memory in terrestrial snails.组蛋白去乙酰化酶抑制剂可挽救陆地蜗牛受损的记忆。
J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2020 Jul;206(4):639-649. doi: 10.1007/s00359-020-01422-w. Epub 2020 May 14.
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Histone acetylation: molecular mnemonics on the chromatin.组蛋白乙酰化:染色质上的分子记忆符。
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