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Roles of feedback and feed-forward networks of dopamine subsystems: insights from Drosophila studies. 多巴胺子系统反馈和前馈网络的作用:果蝇研究的启示。
IF 1.8 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-06-11 Print Date: 2024-05-01 DOI: 10.1101/lm.053807.123
Andrew M Davidson, Toshihide Hige

Across animal species, dopamine-operated memory systems comprise anatomically segregated, functionally diverse subsystems. Although individual subsystems could operate independently to support distinct types of memory, the logical interplay between subsystems is expected to enable more complex memory processing by allowing existing memory to influence future learning. Recent comprehensive ultrastructural analysis of the Drosophila mushroom body revealed intricate networks interconnecting the dopamine subsystems-the mushroom body compartments. Here, we review the functions of some of these connections that are beginning to be understood. Memory consolidation is mediated by two different forms of network: A recurrent feedback loop within a compartment maintains sustained dopamine activity required for consolidation, whereas feed-forward connections across compartments allow short-term memory formation in one compartment to open the gate for long-term memory formation in another compartment. Extinction and reversal of aversive memory rely on a similar feed-forward circuit motif that signals omission of punishment as a reward, which triggers plasticity that counteracts the original aversive memory trace. Finally, indirect feed-forward connections from a long-term memory compartment to short-term memory compartments mediate higher-order conditioning. Collectively, these emerging studies indicate that feedback control and hierarchical connectivity allow the dopamine subsystems to work cooperatively to support diverse and complex forms of learning.

在不同的动物物种中,多巴胺操作的记忆系统由解剖学上分离的、功能多样的子系统组成。虽然单个子系统可以独立运行以支持不同类型的记忆,但子系统之间的逻辑相互作用有望使现有记忆影响未来学习,从而实现更复杂的记忆处理。最近对果蝇蘑菇体进行的全面超微结构分析揭示了多巴胺子系统--蘑菇体腔室之间错综复杂的相互联系网络。在此,我们回顾了其中一些连接的功能,这些功能已开始为人们所了解。记忆巩固由两种不同形式的网络介导:一个区室中的循环反馈回路可维持巩固记忆所需的持续多巴胺活动,而跨区室的前馈连接可使一个区室中的短期记忆形成为另一个区室中的长期记忆形成打开大门。厌恶记忆的消退和逆转也依赖于类似的前馈回路模式,这种模式将省略惩罚作为一种奖励信号,从而触发可塑性,抵消原有的厌恶记忆痕迹。最后,从长期记忆区到短期记忆区的间接前馈连接介导了高阶条件反射。总之,这些新出现的研究表明,反馈控制和分级连接使多巴胺子系统能够协同工作,支持多种复杂的学习形式。
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引用次数: 0
The Phylogeny of the Hymenopteran Brain. 膜翅目动物大脑的系统发育。
IF 1.8 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-06-11 Print Date: 2024-05-01 DOI: 10.1101/lm.053894.123
Hans V Alten
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引用次数: 0
How emotional contexts modulate item memory in individuals with high and low negative affect and worry. 情绪情境如何调节高负面情绪和低负面情绪及担忧情绪个体的项目记忆。
IF 2 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-05-13 Print Date: 2024-04-01 DOI: 10.1101/lm.053891.123
Nina Becker, Simone Kühn, Andreas Olsson

Emotional stimuli are usually remembered with high confidence. Yet, it remains unknown whether-in addition to memory for the emotional stimulus itself-memory for a neutral stimulus encountered just after an emotional one can be enhanced. Further, little is known about the interplay between emotion elicited by a stimulus and emotion relating to affective dispositions. To address these questions, we examined (1) how emotional valence and arousal of a context image preceding a neutral item image affect memory of the item, and (2) how such memory modulation is affected by two hallmark features of emotional disorders: trait negative affect and tendency to worry. In two experiments, participants encoded a series of trials in which an emotional (negative, neutral, or positive) context image was followed by a neutral item image. In experiment 1 (n = 42), items presented seconds after negative context images were remembered better and with greater confidence compared to those presented after neutral and positive ones. Arousal ratings of negative context images were higher compared to neutral and positive ones and the likelihood of correctly recognizing an item image was related to higher arousal of the context image. In experiment 2 (n = 59), better item memory was related to lower trait negative affect. Participants with lower trait negative affect or tendency to worry displayed higher confidence compared to those with high negative affect or tendency to worry. Our findings describe an emotional "carry-over" effect elicited by a context image that enhances subsequent item memory on a trial-by-trial basis, however, not in individuals with high trait negative affect who seem to have a general memory disadvantage.

对情绪刺激的记忆通常具有很高的可信度。然而,除了对情绪刺激本身的记忆之外,对情绪刺激之后遇到的中性刺激的记忆是否会增强,目前仍是未知数。此外,人们对由刺激引起的情绪和与情感倾向有关的情绪之间的相互作用知之甚少。为了解决这些问题,我们研究了:(1) 中性项目图像之前的情境图像的情绪价值和唤醒如何影响项目记忆;(2) 这种记忆调节如何受到情绪障碍的两个标志性特征的影响:特质消极情绪和担忧倾向。在两个实验中,参与者对一系列试验进行编码,在这些试验中,情绪(消极、中性或积极)背景图像之后是中性项目图像。在实验 1(n = 42)中,与在中性和正面情境图像后出现的项目相比,在负面情境图像后几秒钟出现的项目记忆效果更好,信心也更强。与中性和正面图像相比,负面背景图像的唤醒度更高,正确识别项目图像的可能性与背景图像的唤醒度有关。在实验 2(n = 59)中,较好的项目记忆与较低的特质负面情绪有关。特质负面情绪或担忧倾向较低的参与者与负面情绪或担忧倾向较高的参与者相比,表现出更高的自信。我们的研究结果描述了一种由情境图像引起的情绪 "带入 "效应,这种效应在逐次试验的基础上增强了随后的项目记忆,然而,对于特质消极情绪较高的个体却没有这种效应,因为他们似乎在记忆方面普遍处于劣势。
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引用次数: 0
The impact of extinction timing on pre-extinction arousal and subsequent return of fear 灭绝时间对灭绝前唤醒和随后恐惧恢复的影响
IF 2 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-04-01 DOI: 10.1101/lm.053902.123
Miriam Kampa, Rudolf Stark, Tim Klucken
Exposure-based therapy is effective in treating anxiety, but a return of fear in the form of relapse is common. Exposure is based on the extinction of Pavlovian fear conditioning. Both animal and human studies point to increased arousal during immediate compared to delayed extinction (>+24 h), which presumably impairs extinction learning and increases the subsequent return of fear. Impaired extinction learning under arousal might interfere with psychotherapeutic interventions. The aim of the present study was to investigate whether arousal before extinction differs between extinction groups and whether arousal before extinction predicts the return of fear in a later (retention) test. As a highlight, both the time between fear acquisition and extinction (immediate vs. delayed) and the time between extinction and test (early vs. late test) were systematically varied. We performed follow-up analyses on data from 103 young, healthy participants to test the above hypotheses. Subjective arousal ratings and physiological arousal measures of sympathetic and hypothalamic pituitary adrenal axis activation (tonic skin conductance and salivary cortisol) were collected. Increased pre-extinction arousal in the immediate extinction group was only confirmed for subjective arousal. In linear regression analyses, none of the arousal measures predicted a significant return of fear in the different experimental groups. Only when we aggregated across the two test groups, tonic skin conductance at the onset of extinction predicted the return of fear in skin conductance responses. The overall results provide little evidence that pre-extinction arousal affects subsequent extinction learning and memory. In terms of clinical relevance, there is no clear evidence that exposure could be improved by reducing subjective or physiological arousal.
暴露疗法能有效治疗焦虑症,但以复发形式出现的恐惧卷土重来也很常见。暴露疗法的基础是巴甫洛夫恐惧条件反射的消退。动物和人体研究都表明,与延迟消退(24 小时以上)相比,立即消退时的唤醒程度更高,这可能会损害消退学习并增加随后的恐惧复发。唤醒状态下的消退学习受损可能会干扰心理治疗干预。本研究的目的是调查不同的消退组在消退前的唤醒程度是否存在差异,以及消退前的唤醒程度是否能预测在之后的(保持)测试中恐惧感的恢复。为了突出研究的重点,我们系统地改变了恐惧获得与消退之间的时间(即时消退与延迟消退)以及消退与测试之间的时间(早期测试与晚期测试)。我们对 103 名年轻健康参与者的数据进行了后续分析,以验证上述假设。我们收集了主观唤醒评分以及交感神经和下丘脑垂体肾上腺轴激活的生理唤醒测量(强直性皮肤电导和唾液皮质醇)。只有在主观唤醒方面证实了立即灭绝组在灭绝前唤醒程度的增加。在线性回归分析中,没有一个唤醒测量指标能预测不同实验组中恐惧的显著恢复。只有当我们将两个试验组的情况汇总时,开始消退时的强直性皮肤电导才能预测皮肤电导反应中恐惧的恢复。总体结果几乎没有证据表明,消退前的唤醒会影响随后的消退学习和记忆。就临床相关性而言,没有明确的证据表明可以通过降低主观或生理唤醒来改善暴露。
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引用次数: 0
Remembering what we imagine: the role of event schemas in shaping how imagined autobiographical events are recalled 记住我们的想象:事件图式在塑造如何回忆想象的自传体事件中的作用
IF 2 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-04-01 DOI: 10.1101/lm.053993.124
Can Fenerci, Bianca Adjei, Signy Sheldon
Much like recalling autobiographical memories, constructing imagined autobiographical events depends on episodic memory processes. The ability to imagine events contributes to several future-oriented behaviors (e.g., decision-making, problem solving), which relies, in part, on the ability to remember the imagined events. A factor affecting the memorability of such events is their adherence to event schemas—conceptualizations of how events generally unfold. In the current study, we examined how two aspects of event schemas—event expectancy and familiarity—affect the ability to recall imagined events. Participants first imagined and described in detail autobiographical events that either aligned with or deviated from an event, expected to occur in a context (e.g., a kitchen) that was either familiar or unfamiliar. This resulted in imaginations ranging from maximally schema-congruent (expected events in a familiar context) to maximally novel (unexpected events in an unfamiliar context). Twenty-four hours later, participants recalled these imagined events. Recollections were scored for the number of reinstated details from the imaginations and the number of newly added details. We found greater reinstatement of details for both the maximally congruent and maximally novel events, while maximally novel events were recalled more precisely than other events (i.e., fewer added details). Our results indicate a complementary benefit to remembering schematic and novel imagined events, which may guide equally important but distinct future-oriented behaviors.
与回忆自传体记忆一样,构建想象的自传体事件也依赖于外显记忆过程。想象事件的能力有助于若干面向未来的行为(如决策、解决问题),而这些行为部分依赖于记忆想象事件的能力。影响这些事件可记性的一个因素是它们是否符合事件图式--对事件一般如何发展的概念化。在本研究中,我们考察了事件图式的两个方面--事件预期和熟悉程度--如何影响回忆想象事件的能力。被试首先想象并详细描述了自传体事件,这些事件或与事件一致,或与事件相背离,预计将发生在熟悉或不熟悉的环境中(如厨房)。这导致了从最大限度的图式一致(熟悉环境中的预期事件)到最大限度的新颖(陌生环境中的意外事件)的想象。24 小时后,参与者回忆这些想象事件。对回忆中恢复的想象细节数量和新添加的细节数量进行评分。我们发现,最大程度一致的事件和最大程度新颖的事件都能恢复更多的细节,而最大程度新颖的事件比其他事件的回忆更精确(即增加的细节更少)。我们的研究结果表明,记忆图式事件和新颖的想象事件有互补的好处,这可能会引导同样重要但又不同的面向未来的行为。
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引用次数: 0
Adolescents flexibly adapt action selection based on controllability inferences. 青少年根据可控性推断灵活调整行动选择。
IF 1.8 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-03-25 Print Date: 2024-03-01 DOI: 10.1101/lm.053901.123
Hillary A Raab, Noam Goldway, Careen Foord, Catherine A Hartley

From early in life, we encounter both controllable environments, in which our actions can causally influence the reward outcomes we experience, and uncontrollable environments, in which they cannot. Environmental controllability is theoretically proposed to organize our behavior. In controllable contexts, we can learn to proactively select instrumental actions that bring about desired outcomes. In uncontrollable environments, Pavlovian learning enables hard-wired, reflexive reactions to anticipated, motivationally salient events, providing "default" behavioral responses. Previous studies characterizing the balance between Pavlovian and instrumental learning systems across development have yielded divergent findings, with some studies observing heightened expression of Pavlovian learning during adolescence and others observing a reduced influence of Pavlovian learning during this developmental stage. In this study, we aimed to investigate whether a theoretical model of controllability-dependent arbitration between learning systems might explain these seemingly divergent findings in the developmental literature, with the specific hypothesis that adolescents' action selection might be particularly sensitive to environmental controllability. To test this hypothesis, 90 participants, aged 8-27, performed a probabilistic-learning task that enables estimation of Pavlovian influence on instrumental learning, across both controllable and uncontrollable conditions. We fit participants' data with a reinforcement-learning model in which controllability inferences adaptively modulate the dominance of Pavlovian versus instrumental control. Relative to children and adults, adolescents exhibited greater flexibility in calibrating the expression of Pavlovian bias to the degree of environmental controllability. These findings suggest that sensitivity to environmental reward statistics that organize motivated behavior may be heightened during adolescence.

从生命的早期开始,我们就会遇到可控环境和不可控环境,在可控环境中,我们的行为可以对我们所经历的奖励结果产生因果影响,而在不可控环境中,我们的行为则无法对奖励结果产生因果影响。理论上认为,环境的可控性可以组织我们的行为。在可控的环境中,我们可以学会主动选择工具性行动,从而获得理想的结果。而在不可控的环境中,巴甫洛夫式学习能使我们对预期的、动机突出的事件做出硬性的、条件反射式的反应,提供 "默认 "的行为反应。以往关于巴甫洛夫学习系统和工具性学习系统在不同发育阶段的平衡特点的研究得出了不同的结论,一些研究观察到巴甫洛夫学习在青春期的表达有所增强,而另一些研究则观察到巴甫洛夫学习在这一发育阶段的影响有所减弱。在本研究中,我们旨在探讨学习系统之间依赖于可控性的仲裁理论模型是否可以解释发育文献中这些看似不同的研究结果,并提出一个具体的假设,即青少年的行动选择可能对环境可控性特别敏感。为了验证这一假设,90 名年龄在 8 至 27 岁之间的参与者完成了一项概率学习任务,该任务能够在可控和不可控条件下估计巴甫洛夫对工具学习的影响。我们将参与者的数据与强化学习模型进行了拟合,在该模型中,可控性推断会适应性地调节巴甫洛夫控制与工具控制的优势。与儿童和成人相比,青少年在根据环境的可控性程度调整巴甫洛夫偏向的表达方面表现出更大的灵活性。这些研究结果表明,在青少年时期,对组织动机行为的环境奖励统计的敏感性可能会提高。
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引用次数: 0
Semantic associations restore neural encoding mechanisms 语义关联恢复神经编码机制
IF 2 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-03-01 DOI: 10.1101/lm.053996.124
Isabelle L. Moore, Nicole M. Long
Lapses in attention can negatively impact later memory of an experience. Attention and encoding resources are thought to decline as more experiences are encountered in succession, accounting for the primacy effect in which memory is better for items encountered early compared to late in a study list. However, accessing prior knowledge during study can facilitate subsequent memory, suggesting a potential avenue to counteract this decline. Here, we investigated the extent to which semantic associations—shared meaning between experiences—can counteract declines in encoding resources. Our hypothesis is that semantic associations restore neural encoding mechanisms, which in turn improves memory. We recorded scalp electroencephalography (EEG) while male and female human participants performed a delayed free recall task. Half of the items from late in each study list were semantically associated with an item presented earlier in the list. We find that semantic associations improve memory specifically for late list items and selectively modulate the neural signals engaged during the study of late list items. Relative to other recalled items, late list items that are subsequently semantically clustered—recalled consecutively with their semantic associate—elicit increased high-frequency activity and decreased low-frequency activity, a hallmark of successful encoding. Our findings demonstrate that semantic associations restore neural encoding mechanisms and improve later memory. More broadly, these findings suggest that prior knowledge modulates the orientation of attention to influence encoding mechanisms.
注意力的缺失会对后来的经验记忆产生负面影响。注意力和编码资源被认为会随着连续遇到更多的经历而下降,这也是 "优先效应 "的原因,即在学习列表中,早期遇到的项目比晚期遇到的项目记忆效果更好。然而,在学习过程中获取先前的知识可以促进后续记忆,这就为抵消这种下降提供了潜在的途径。在这里,我们研究了语义联想--经验之间的共享意义--能在多大程度上抵消编码资源的下降。我们的假设是,语义联想能恢复神经编码机制,进而改善记忆。我们在男女人类参与者进行延迟自由回忆任务时记录了他们的头皮脑电图(EEG)。每个研究列表中后期出现的项目有一半与列表早期出现的项目存在语义关联。我们发现,语义关联可以改善对晚期列表项目的记忆,并在研究晚期列表项目时选择性地调节神经信号。相对于其他被回忆的项目,随后被语义聚类--与其语义关联连续被回忆--的晚期列表项目会引起高频活动增加和低频活动减少,这是成功编码的标志。我们的研究结果表明,语义关联能恢复神经编码机制,改善后期记忆。更广泛地说,这些研究结果表明,先验知识会调节注意力的方向,从而影响编码机制。
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引用次数: 0
Monoubiquitination of histone H2B is a crucial regulator of the transcriptome during memory formation 组蛋白 H2B 的单泛素化是记忆形成过程中转录组的关键调节因子
IF 2 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-03-01 DOI: 10.1101/lm.053912.123
Shaghayegh Navabpour, Kayla Farrell, Shannon E. Kincaid, Nour Omar, Madeline Musaus, Yu Lin, Hehuang Xie, Timothy J. Jarome
Posttranslational modification of histone proteins is critical for memory formation. Recently, we showed that monoubiquitination of histone H2B at lysine 120 (H2Bub) is critical for memory formation in the hippocampus. However, the transcriptome controlled by H2Bub remains unknown. Here, we found that fear conditioning in male rats increased or decreased the expression of 86 genes in the hippocampus but, surprisingly, siRNA-mediated knockdown of the H2Bub ligase, Rnf20, abolished changes in all but one of these genes. These findings suggest that monoubiquitination of histone H2B is a crucial regulator of the transcriptome during memory formation.
组蛋白的翻译后修饰对记忆的形成至关重要。最近,我们发现组蛋白 H2B 在赖氨酸 120 处的单泛素化(H2Bub)对海马的记忆形成至关重要。然而,由 H2Bub 控制的转录组仍然未知。在这里,我们发现雄性大鼠的恐惧条件反射会增加或减少海马中 86 个基因的表达,但令人惊讶的是,siRNA 介导的 H2Bub 连接酶 Rnf20 的敲除会消除所有这些基因的变化,只有一个基因除外。这些发现表明,组蛋白 H2B 的单泛素化是记忆形成过程中转录组的一个关键调节因子。
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引用次数: 0
Prelimbic cortex ensembles promote appetitive learning-associated behavior. 前边缘皮层集合促进与食欲学习相关的行为
IF 2 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-02-26 Print Date: 2024-01-01 DOI: 10.1101/lm.053892.123
Michelle Surets, Albit Caban-Murillo, Steve Ramirez

Memories of prior rewards bias our actions and future decisions. To determine the neural correlates of an appetitive associative learning task, we trained male mice to discriminate a reward-predicting cue over the course of 7 d. Encoding, recent recall, and remote recall were investigated to determine the areas of the brain recruited at each stage of learning. Using cFos as a proxy for neuronal activity, we found unique brain-wide patterns of activity across days that seem to correlate with distinct stages of learning. In particular, the prelimbic (PL) cortex was significantly recruited during the encoding of a novel association presentation, but its activity decreases as learning continues. To causally dissect the role of the PL in a reward memory across days, we chemogenetically inhibited first the PL entirely and then only tagged memory-bearing cells that were active during encoding in two stages of learning: early and late. Both nonspecific and specific PL inhibition experiments indicate that the PL drives behavior during late stages of learning to facilitate appropriate cue-driven behavior. Overall, our work underscores memory's role in discriminative reward seeking, and points to the PL as a target for modulating disorders in which impaired reward processing is a core component.

对先前奖励的记忆会影响我们的行动和未来决策。为了确定食欲性联想学习任务的神经相关性,我们对雄性小鼠进行了为期7天的训练,以辨别奖励预测线索。我们对编码、近期回忆和远期回忆进行了调查,以确定在学习的每个阶段所调用的大脑区域。使用 cFos 作为神经元活动的替代物,我们发现了跨天的独特全脑活动模式,这似乎与不同的学习阶段相关。特别是,前边缘(PL)皮层在新联想的编码过程中被显著招募,但其活动随着学习的继续而减少。为了从因果关系上剖析前边缘皮层在跨天奖励记忆中的作用,我们首先用化学方法完全抑制了前边缘皮层,然后只标记了在学习早期和晚期两个阶段编码过程中活跃的记忆细胞。非特异性和特异性 PL 抑制实验都表明,PL 在学习后期会驱动行为,以促进适当的线索驱动行为。总之,我们的研究强调了记忆在辨别奖赏寻求中的作用,并指出 PL 是调节以奖赏处理受损为核心成分的失调症的目标。
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引用次数: 0
Evidence for novelty reward cross-cueing in the odor span task in rats: implications for odor-based reward-motivated tasks. 大鼠气味跨度任务中新奇奖赏交叉提示的证据:对基于气味的奖赏动机任务的影响。
IF 2 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-01-29 Print Date: 2024-01-01 DOI: 10.1101/lm.053871.123
Timothy J Onofrychuk, Aiden E Glass, Quentin Greba, John G Howland

The odor span task (OST) infers working memory capacity (WMC) by requiring rodents to discriminate between previously presented and session-novel odors to obtain a hidden food reward. Here, rats' responses to session-novel odors and food rewards were assessed to determine whether rats use mitigating strategies in the OST. Rats accurately responded to session-novel odors but also reliably responded to the food reward alone and performed at chance when both a session-novel odor and food reward were presented in separate locations. The inclusion of unscented sand in the cups holding the food reward significantly reduced the rats' responses to the food reward alone. Collectively, these results demonstrate the need for rigorous tests of potential mitigating strategies and hold wide implications for rodent odor discrimination-based behavioral tasks.

气味跨度任务(OST)通过要求啮齿类动物分辨先前呈现的气味和会话中的新气味来获得隐藏的食物奖励,从而推断工作记忆能力(WMC)。在此,我们评估了大鼠对会话新气味和食物奖励的反应,以确定大鼠是否在 OST 中使用了缓解策略。实验结果表明,大鼠不仅对新奇气味做出了准确的反应,而且还对食物奖励做出了可靠的反应。在盛放食物奖赏的杯子中加入无味沙子会显著降低大鼠对单独食物奖赏的反应。总之,这些结果表明有必要对潜在的缓解策略进行严格的测试,并对基于气味辨别的啮齿动物行为任务产生了广泛的影响。
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引用次数: 0
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