Visual Working Memory Requires Permissive and Instructive NO/cGMP Signaling at Presynapses in the Drosophila Central Brain
Visual Working Memory Requires Permissive and Instructive NO/cGMP Signaling at Presynapses in the Drosophila Central Brain
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DOI：
10.1016/j.cub.2016.12.056
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发表时间：
2017-03-06
期刊：
影响因子：
9.2
通讯作者：
Strauss, Roland
中科院分区：
文献类型：
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作者：
Kuntz, Sara;Poeck, Burkhard;Strauss, Roland
气态第二信使一氧化氮（NO）已被证明通过激活从突触后到突触前的逆行信号级联来调节记忆形成，所述级联涉及环鸟苷一磷酸（cGMP）产生以诱导突触可塑性和转录变化。在这项研究中，我们分析了NO在形成视觉工作记忆中的作用，这种记忆只持续几秒钟。这种记忆被编码在果蝇大脑中形成椭圆体的环状神经元的子集中。使用遗传和药理学操作，我们表明，NO信号是cGMP介导的CREB激活所必需的，导致表达的能力因子，如突触homer蛋白。有趣的是，这种细胞自主功能也可以由硫化氢（H2S）通过会聚途径实现，首次揭示了内源性产生的H2S在记忆过程中的作用。值得注意的是，NO合酶严格定位于环状神经元的轴突输出分支，并且这种定位似乎是NO信号传导的第二阶段作用所必需的。我们提供了一个模型的证据，NO调节cGMP调节的阳离子通道的开放编码的短期记忆痕迹。局部生产的NO/cGMP的环状神经元的限制性分支似乎代表了对象的印迹，并比较单个环状神经元之间的信号水平被用来定位苍蝇在搜索行为。由于其半衰期短，NO似乎是一个独特的合适的第二信使，编码的工作记忆，必须限制在其持续时间。
The gaseous second messenger nitric oxide (NO) has been shown to regulate memory formation by activating retrograde signaling cascades from post-to presynapse that involve cyclic guanosine mono phosphate (cGMP) production to induce synaptic plasticity and transcriptional changes. In this study, we analyzed the role of NO in the formation of a visual working memory that lasts only a few seconds. This memory is encoded in a subset of ring neurons that form the ellipsoid body in the Drosophila brain. Using genetic and pharmacological manipulations, we show that NO signaling is required for cGMP-mediated CREB activation, leading to the expression of competence factors like the synaptic homer protein. Interestingly, this cell-autonomous function can also be fulfilled by hydrogen sulfide (H2S) through a converging pathway, revealing for the first time that endogenously produced H2S has a role in memory processes. Notably, the NO synthase is strictly localized to the axonal output branches of the ring neurons, and this localization seems to be necessary for a second, phasic role of NO signaling. We provide evidence for a model where NO modulates the opening of cGMP-regulated cation channels to encode a short-term memory trace. Local production of NO/cGMP in restricted branches of ring neurons seems to represent the engram for objects, and comparing signal levels between individual ring neurons is used to orient the fly during search behavior. Due to its short half-life, NO seems to be a uniquely suited second messenger, to encode working memories that have to be restricted in their duration.