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血清反应因子介导的果蝇视觉工作记忆中的基因调控。

Serum response factor-mediated gene regulation in a Drosophila visual working memory.

机构信息

Institut für Zoologie III (Neurobiologie), Universität Mainz, Colonel-Kleinmann-Weg 2, 55099 Mainz, Germany.

出版信息

Curr Biol. 2013 Sep 23;23(18):1756-63. doi: 10.1016/j.cub.2013.07.034. Epub 2013 Sep 5.

Abstract

BACKGROUND

Navigation through the environment requires a working memory for the chosen target and path integration facilitating an approach when the target becomes temporarily hidden. We have previously shown that this visual orientation memory resides in the ellipsoid body, which is part of the central complex in the Drosophila brain. Former analysis of foraging and ignorant mutants have revealed that a hierarchical PKG and RSKII kinase signaling cascade in a subset of the ellipsoid-body ring neurons is required for this type of working memory in flies.

RESULTS

Here we show that mutants in the ellipsoid body open (ebo) gene, which encodes the actin-binding protein Exportin 6, exhibit excessive nuclear accumulation of actin during development and in the adult brain. ebo mutants lack the orientation memory independent of the structural defect in the ellipsoid-body neuropil, and EBO activity in any type of adult ring neurons is sufficient for orientation-memory function. Moreover, genetic interaction studies revealed that nuclear actin accumulation in ebo mutants inhibits the Drosophila coactivator myocardin-related transcription factor A (dMRTF) and therefore the transcriptional activator serum response factor (dSRF). dSRF also functions in different ring neurons, suggesting that it regulates abundance of a diffusible factor that enables a working memory in ellipsoid-body ring neurons.

CONCLUSIONS

To date, SRF has only been implicated in longer forms of memory formation like synaptic long-term potentiation and depression. This study provides the first evidence that SRF-mediated gene regulation is also required for a working memory that lasts only for a few seconds.

摘要

背景

在环境中导航需要一个工作记忆来记住目标和路径整合,以便在目标暂时隐藏时进行接近。我们之前已经表明,这种视觉定向记忆存在于椭圆体中,椭圆体是果蝇大脑中央复合体的一部分。对觅食和无知突变体的先前分析表明,在椭圆体环神经元的亚集中,PKG 和 RSKII 激酶信号级联的分层结构对于这种类型的果蝇工作记忆是必需的。

结果

在这里,我们表明,编码肌动蛋白结合蛋白 Exportin 6 的椭圆体开口(ebo)基因突变体在发育过程中和成年大脑中表现出肌动蛋白的过度核积累。ebo 突变体缺乏定向记忆,与椭圆体神经丛的结构缺陷无关,任何类型的成年环神经元中的 EBO 活性对于定向记忆功能都是足够的。此外,遗传相互作用研究表明,ebo 突变体中的核肌动蛋白积累抑制了果蝇辅激活因子肌球蛋白相关转录因子 A(dMRTF),因此也抑制了转录激活因子血清反应因子(dSRF)。dSRF 也在不同的环神经元中发挥作用,这表明它调节一种扩散因子的丰度,这种因子使椭圆体环神经元能够发挥工作记忆。

结论

迄今为止,SRF 仅被牵连到像突触长时程增强和抑制这样的更长形式的记忆形成中。本研究首次提供证据表明,SRF 介导的基因调控对于持续仅几秒钟的工作记忆也是必需的。

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