Neurobiology of Learning and Memory最新文献_第2页

Sex differences and the influence of sex hormones on fear extinction and exposure therapy across the lifespan: A systematic review of studies in rodents and humans 性别差异和性激素对恐惧消退和暴露治疗的影响：对啮齿动物和人类研究的系统回顾。

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2026-01-01 Epub Date: 2025-11-24 DOI: 10.1016/j.nlm.2025.108116

Jodie E. Pestana, Fionn Dunphy-Doherty, Madison Brooke, Bronwyn M. Graham

Fear extinction is a laboratory model that informs the mechanisms of exposure therapy for anxiety disorders. Although knowledge on fear extinction is primarily based on males, converging research shows that fear extinction and exposure therapy are influenced by sex-specific variables, including sex hormones. This systematic review aimed to synthesise the research on sex differences in fear extinction, and the influences of sex hormones on fear extinction, across the lifespan in rodents and humans, as well as the impact of these variables on exposure therapy in clinical populations. Pubmed and Scopus were searched through to May 2024 for articles that compared fear extinction or exposure therapy outcomes (behavioural and neurobiological measures) between sexes or examined the influence of sex hormones (or related factors, e.g., hormonal contraception) on these outcomes. One hundred and fifty-seven articles met inclusion criteria. Across species and ages, sex differences in fear extinction were commonly reported although the nature and direction of these differences were inconsistent. When accounting for female hormonal status, studies showed strong evidence that oestradiol enhances fear extinction and exposure therapy; conversely, hormonal contraceptives may disrupt extinction and exposure therapy. Sex and sex hormones frequently moderated the effects of other variables (e.g., drugs, stress) on fear extinction. This evidence synthesis strongly suggests future work on fear extinction and exposure therapy should routinely include both sexes, conduct sex-disaggregated analyses, and consider hormonal status. Given the heightened prevalence of anxiety disorders in women, such practices will facilitate more valid, useful, and equitable scientific models of anxiety treatments.

恐惧消退是一个实验室模型，它告知了焦虑障碍暴露疗法的机制。虽然关于恐惧消退的知识主要基于男性，但趋同的研究表明，恐惧消退和暴露疗法受到性别特定变量的影响，包括性激素。本系统综述旨在综合研究啮齿动物和人类一生中恐惧消退的性别差异，性激素对恐惧消退的影响，以及这些变量对临床人群暴露治疗的影响。Pubmed和Scopus检索了截至2024年5月的文章，这些文章比较了性别之间的恐惧消除或暴露治疗结果（行为和神经生物学测量），或检查了性激素（或相关因素，例如激素避孕）对这些结果的影响。157篇文章符合纳入标准。尽管这些差异的性质和方向并不一致，但在不同的物种和年龄中，恐惧消退的性别差异被普遍报道。当考虑到女性荷尔蒙状态时，研究表明雌二醇可以增强恐惧消除和暴露疗法；相反，激素避孕药可能会破坏灭绝和暴露疗法。性和性激素经常缓和其他变量（如药物、压力）对恐惧消退的影响。这一证据综合强烈表明，未来关于恐惧消除和暴露治疗的工作应该常规地包括两性，进行性别分类分析，并考虑荷尔蒙状况。考虑到女性焦虑症的高患病率，这种做法将促进更有效、有用和公平的焦虑治疗科学模型。

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引用次数: 0

Ensembles and engrams in mouse cortical and sub-thalamic brain regions supporting context and memory recall 支持上下文和记忆回忆的小鼠皮层和丘脑下脑区域的集合和印记。

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2026-01-01 Epub Date: 2025-12-22 DOI: 10.1016/j.nlm.2025.108128

William W. Taylor , Vienna Gao , Laura Korobkova , Brian G. Dias

Associative learning supports learning about outcomes associated with contexts and cues. During learning, cellular ensembles that become active can be incorporated into memory engrams and later reactivated to support recall. Studies exploring engram formation and reactivation have primarily used contextual conditioning in mice and made little distinction between ensembles supporting contextual information versus cue-associated learning and recall. Furthermore, often missing in such analyses is exploration of sex differences in ensemble dynamics. Using auditory fear conditioning and activity-dependent tagging in mice, we set out to disaggregate context-associated ensembles from those associated with cue-related learning and recall while also profiling potential sex differences. Specifically, we quantified cellular activity during context exposure, fear recall, extinction training, and extinction recall in cortical and subthalamic brain regions supporting learning and memory. We found that male mice had denser ensembles of cells active in the infralimbic prefrontal cortex (IL-PFC) during context exposure, while female mice had a significantly greater proportion of newly active cells in the IL-PFC during fear recall. We also found a sexually dimorphic pattern of correlation between activity in the IL-PFC and in the zona incerta (ZI). Across sexes, we found denser overlapping cells and greater reactivation of extinction ensembles in the IL-PFC. These results emphasize that there is a distinction to be made between ensembles supporting contextual information from those encoding cue-associated memory and highlight important sex differences in ensemble dynamics.

联想学习支持学习与上下文和线索相关的结果。在学习过程中，活跃的细胞集合可以被整合到记忆印痕中，然后重新激活以支持回忆。探索印迹形成和再激活的研究主要是在小鼠中使用上下文条件反射，并且在支持上下文信息的集合与线索相关学习和回忆之间几乎没有区别。此外，在这种分析中经常缺少对系综动力学中的性别差异的探索。在小鼠中使用听觉恐惧条件反射和活动依赖标记，我们开始从与线索相关的学习和回忆相关的集合中分离情境相关的集合，同时也分析了潜在的性别差异。具体来说，我们量化了支持学习和记忆的皮层和丘脑下脑区在情境暴露、恐惧回忆、消退训练和消退回忆期间的细胞活动。我们发现，在情境暴露期间，雄性小鼠在边缘下前额叶皮层（IL-PFC）中有更密集的活跃细胞群，而雌性小鼠在恐惧回忆期间，IL-PFC中有更大比例的新活跃细胞。我们还发现在IL-PFC和incerta （ZI）的活性之间存在一种性别二态的相关模式。在不同性别中，我们发现IL-PFC中有更密集的重叠细胞和更大的灭绝集合的再激活。这些结果强调，从编码线索相关记忆的集合中支持上下文信息的集合之间存在区别，并强调了集合动力学中重要的性别差异。

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引用次数: 0

Implicit and explicit reversal of trained oculomotor movements 训练后的动眼肌运动的内隐和外显逆转

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2026-01-01 Epub Date: 2025-11-28 DOI: 10.1016/j.nlm.2025.108114

Mario Michiels , David Luque , Ignacio Obeso

Habitual behavior is thought to emerge with extended training and reduced sensitivity to outcome devaluation. However, little is known about how habit-like oculomotor responses adapt when devaluation is implicit or embedded within a previously learned context. We examined this in a novel oculomotor learning task involving visual shape-reward associations with both standard and overtrained stimuli. Twenty-six participants completed a shape-color learning task while their eye movements were recorded using an eye-tracker system (1000 Hz). The task involved 11 blocks, including training, intra-block reversal (implicit stimulus-reward changes), and classical devaluation phases (explicitly instructed reward changes). Statistical analyses were performed using linear mixed-effects models on accuracy and response time (RT) measures. As expected, higher accuracy and faster responses for overtrained versus standard-trained stimuli were observed during training, confirming stronger learning. In the classical devaluation phase, overtrained stimuli elicited significantly more errors compared to standard-trained stimuli, relative to the performance in the training phase. This indicates stronger resistance to goal-directed updating. The effect was more pronounced during intra-block reversal of associations, where reward contingencies changed without warning. While RTs were not affected by classical devaluation, intra-block reversal significantly increased RTs for overtrained stimuli, relative to RTs in the training phase. This suggests a higher cognitive cost for overriding well-learned habitual responses when changes are unpredictable. These findings provide new evidence for the behavioral rigidity associated with overtraining of oculomotor behavior and suggest that unexpected outcome changes impose an additional switch cost on habitual oculomotor behavior.

习惯性行为被认为是随着长期的训练和对结果贬值的敏感度降低而出现的。然而，当贬值是隐含的或嵌入在先前学习的背景中时，关于习惯样动眼肌反应是如何适应的，我们知之甚少。我们在一个新的动眼肌学习任务中检验了这一点，该任务涉及视觉形状奖励与标准和过度训练刺激的关联。26名参与者完成了形状-颜色学习任务，同时他们的眼球运动被用眼动追踪系统（1000赫兹）记录下来。这项任务涉及11个区块，包括训练、区块内逆转（隐性刺激-奖励变化）和经典贬值阶段（明确指示奖励变化）。使用准确度和反应时间（RT）测量的线性混合效应模型进行统计分析。正如预期的那样，在训练过程中，与标准训练刺激相比，过度训练刺激的准确性更高，反应更快，证实了更强的学习能力。在经典贬值阶段，相对于训练阶段的表现，过度训练刺激引起的错误明显多于标准训练刺激。这表明对目标导向更新的抵抗力更强。这种效应在区域内逆转联想中更为明显，在这种情况下，奖励偶然性会毫无征兆地发生变化。虽然经典贬值对即时反应没有影响，但相对于训练阶段的即时反应，过度训练刺激的即时反应显著增加。这表明，当变化不可预测时，推翻已经习得的习惯反应需要更高的认知成本。这些发现为过度训练动眼肌行为与行为僵化相关提供了新的证据，并表明意外的结果变化对习惯性动眼肌行为施加了额外的转换成本。

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引用次数: 0

Sleep promotes illusory word compositions, a distinct form of false memory 睡眠促进了虚幻的单词组合，这是一种不同形式的错误记忆。

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2026-01-01 Epub Date: 2025-12-22 DOI: 10.1016/j.nlm.2025.108129

Itamar Lerner, Sarah C. Hamm

Extensive evidence supports the beneficial effects of sleep on memory and learning, including the consolidation and reorganization of memories and the extraction of regularities from encoded experiences. Nevertheless, some studies suggest that sleep may also increase false memories, potentially as a byproduct of regularities extraction. Physiologically, time-compressed memory replay in the hippocampus during non-rapid-eye-movement (nREM) sleep is believed to contribute to the consolidation process, although the functional significance of time compression remains elusive. Recently, we proposed that compressed replay might allow associating events that happened at disparate times, thus supporting the extraction of regularities with a temporal nature. This model predicted that sleep might also facilitate a distinct kind of false memories, in which two separate events occurring consecutively are encoded as a single composite event. Here, we tested this prediction by exposing male and female adults to separate word pairs (e.g., car, pet) that could form a new composite word if combined (carpet). We then tested their memory for composite words following a period of sleep or wake. Confirming our main prediction, we found that sleep actively facilitated false composite memories. Furthermore, EEG recordings indicated the involvement of nREM sleep in the process, albeit in a nuanced manner: While some slow-wave or spindle-related parameters predicted increase in false memories, others were associated with fewer false memories and a decline in veridical memories. The latter result resembles previous findings from non-composite false memory studies and could suggest a competitive mechanism between semantic and episodic consolidation during sleep.

大量证据支持睡眠对记忆和学习的有益影响，包括记忆的巩固和重组以及从编码经验中提取规律。然而，一些研究表明，睡眠也可能增加错误记忆，这可能是规律提取的副产品。生理上，尽管时间压缩的功能意义尚不明确，但在非快速眼动（nREM）睡眠期间，海马体中的时间压缩记忆重放被认为有助于巩固过程。最近，我们提出压缩重播可能允许将发生在不同时间的事件关联起来，从而支持提取具有时间性质的规律。该模型预测，睡眠也可能促进一种独特的错误记忆，在这种错误记忆中，连续发生的两个独立事件被编码为一个单一的合成事件。在这里，我们通过让成年男性和成年女性接触单独的单词对（例如，汽车，宠物）来测试这一预测，这些单词对如果组合起来可以形成一个新的合成词（地毯）。然后，我们在一段时间的睡眠或清醒后测试了他们对复合单词的记忆。证实了我们的主要预测，我们发现睡眠积极地促进了虚假的合成记忆。此外，脑电图记录表明非快速眼动睡眠参与了这一过程，尽管是以一种微妙的方式：虽然一些慢波或纺锤波相关的参数预测了错误记忆的增加，但其他参数与错误记忆的减少和真实记忆的下降有关。后一个结果与之前非复合错误记忆研究的结果相似，可能表明睡眠期间语义巩固和情景巩固之间存在竞争机制。

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引用次数: 0

Reconceptualizing human fear memory through the defense cascade 通过防御级联重新定义人类恐惧记忆。

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2026-01-01 Epub Date: 2025-12-12 DOI: 10.1016/j.nlm.2025.108126

Maria Alemany-González, Ai Koizumi

Human fear memory and its associated pathologies are predominantly studied within fear conditioning frameworks. While this reductionist approach has provided valuable insights into the neural and behavioral mechanisms of fear memory, it inadequately captures the diverse dysfunctions in defense responses observed in post-traumatic disorders. These dysfunctions include maladaptive immobility and aberrant fight-or-flight reactions, contributing to substantial individual variability. Traditional paradigms in human studies typically present conditioned stimuli without accounting for the imminence or spatio-temporal proximity of the threat and rely on univariate physiological measures like skin conductance to quantify magnitudes of conditioned responses. Such methods fail to encompass the full range of qualitatively distinct defense behaviors. In contrast, models on defense mechanisms highlight the cascade of defense responses across the threat imminence continuum. This review explores emerging theoretical and methodological innovations that integrate these models to extend the fear memory framework in humans. Key advancements include the dynamic manipulation of threat imminence and the integration of whole-body movements to elicit and evaluate a wider spectrum of defense modes. These innovations offer a promising path for understanding how traumatic experiences disrupt the defense system and contribute to the development of heterogeneous pathological outcomes.

人类恐惧记忆及其相关病理主要是在恐惧制约框架内研究的。虽然这种还原论的方法为恐惧记忆的神经和行为机制提供了有价值的见解，但它没有充分捕捉到在创伤后障碍中观察到的防御反应的各种功能障碍。这些功能障碍包括不适应的不动和异常的战斗或逃跑反应，导致了大量的个体差异。人类研究中的传统范式通常呈现条件刺激，而不考虑威胁的迫切性或时空接近性，并依赖于单变量生理测量，如皮肤电导，来量化条件反应的大小。这种方法不能涵盖所有性质不同的防御行为。相比之下，防御机制模型强调了跨越威胁迫近连续体的防御反应级联。这篇综述探讨了新兴的理论和方法创新，这些创新整合了这些模型，以扩展人类的恐惧记忆框架。关键的进步包括威胁迫切性的动态操纵和全身运动的整合，以引出和评估更广泛的防御模式。这些创新为理解创伤经历如何破坏防御系统和促进异质病理结果的发展提供了一条有希望的途径。

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引用次数: 0

Reductions in protein degradation in the retrosplenial cortex regulate contextual fear memory formation in a sex-independent manner 脾后皮层蛋白质降解的减少以一种与性别无关的方式调节情境恐惧记忆的形成。

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2026-01-01 Epub Date: 2025-12-13 DOI: 10.1016/j.nlm.2025.108127

Meagan Turner , Olivia Ball , W.Keith Ray , Richard F. Helm , Timothy J. Jarome

The retrosplenial cortex (RSC), which serves as a hub to connect the hippocampus and amygdala with other cortical regions, has been shown to play a role in the formation of contextual fear memories. However, the molecular mechanisms by which the RSC forms memories and whether sex differences exist within these mechanisms remain largely unknown. Increases in ubiquitin–proteasome-mediated protein degradation have been shown to be sex-dependently involved in the formation of contextual fear memories in multiple brain regions, including the hippocampus and amygdala. To date, whether increases in protein degradation are needed in the RSC for memory formation in either sex has yet to be examined. Here, we found that proteasome function in the RSC decreases after contextual fear conditioning in both male and female rats. Consistent with this, increasing proteasome activity in the RSC via CRISPR-dCas9-mediated upregulation of Psmd14 impaired contextual fear memory in a mixed sex cohort. Interestingly, proteomic analysis of degradation-specific lysine-48 (K48) polyubiquitination in the RSC of fear-conditioned rats showed largely distinct protein degradation targets and impacted pathways across the sexes. This suggests that despite the shared need for reductions in protein degradation, males and females are using this mechanism in different ways to form the same memory. Together, these data demonstrate that reductions in protein degradation in the RSC are critical for contextual fear memory formation in both males and females and indicate that the molecular changes in the RSC during memory formation may be distinct from those of other more commonly studied brain regions.

脾后皮层（RSC）作为连接海马体和杏仁核与其他皮质区域的枢纽，已被证明在情境恐惧记忆的形成中发挥作用。然而，RSC形成记忆的分子机制以及在这些机制中是否存在性别差异在很大程度上仍然未知。泛素蛋白酶体介导的蛋白质降解的增加已被证明是性别依赖的，涉及到包括海马体和杏仁核在内的多个大脑区域的情境恐惧记忆的形成。迄今为止，对于记忆形成是否需要RSC中蛋白质降解的增加，两性都还有待研究。在这里，我们发现在雄性和雌性大鼠的情境恐惧条件反射后，RSC中的蛋白酶体功能下降。与此一致的是，通过crispr - dcas9介导的Psmd14上调，RSC中蛋白酶体活性的增加损害了混合性队列中的情境恐惧记忆。有趣的是，对恐惧条件大鼠RSC中降解特异性赖氨酸-48 （K48）多泛素化的蛋白质组学分析显示，不同性别的蛋白质降解靶点和影响途径存在很大差异。这表明，尽管男性和女性都需要减少蛋白质的降解，但它们利用这一机制形成相同记忆的方式不同。总之，这些数据表明，在男性和女性中，RSC中蛋白质降解的减少对情境恐惧记忆的形成至关重要，并表明记忆形成过程中RSC的分子变化可能与其他更常研究的大脑区域不同。

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引用次数: 0

Threat Acquisition and Extinction Differences Between Patients With Panic Disorder or Specific Phobia and Non-Clinical Controls: A Systematic Review 惊恐障碍或特定恐惧症患者与非临床对照的威胁获得和消失差异：系统回顾。

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2026-01-01 Epub Date: 2025-12-16 DOI: 10.1016/j.nlm.2025.108125

Kane Steggles, Matthew Garner, Jayne Morriss

The study of threat conditioning and extinction processes in anxiety disorders (AD) may further our understanding of the genesis, maintenance, and treatment of these conditions. As it stands, there have been multiple systematic reviews carried out in this area. Patient-control differences in threat acquisition and extinction have been investigated in relation to ADs, obsessive–compulsive disorder (OCD), and social anxiety disorder (SAD). However, this remains to be investigated in either panic disorder (PD) or specific phobia (SP). In this paper, a narrative systematic review was carried out to collate and critically assess the literature investigating patient-control differences in threat acquisition, extinction, and extinction retention processes in relation to PD and SP separately. Specifically, across fMRI, EEG, EMG, SCR, and self-report. This resulted in the inclusion of 14 PD studies and 7 SP studies. Across PD studies, the review identified reliable evidence for lowered discrimination between conditioned threat and safety cues, and mixed evidence for increased responding to the threat cue, during acquisition in PD patients vs. non-anxious controls. Across SP studies, the review identified strong evidence for heightened discrimination between conditioned threat and safety cues during acquisition, and strong evidence for heightened responding to the threat cue during extinction, in SP patients vs. non-anxious controls. In both PD and SP studies, patient-control differences were identified more frequently in relation to subjective, as opposed to physiological, measures. The findings of this review are then critiqued and compared to the wider literature. Finally, implications, limitations, and directions for future research are discussed.

对焦虑障碍（AD）中威胁条件反射和消退过程的研究可能会进一步加深我们对这些疾病的发生、维持和治疗的理解。目前，在这一领域进行了多次系统审查。威胁获得和消失的患者-控制差异与ad、强迫症（OCD）和社交焦虑症（SAD）有关。然而，这在惊恐障碍（PD）或特殊恐惧症（SP）中仍有待研究。在本文中，我们进行了一项叙述性的系统回顾，以整理和批判性地评估分别研究PD和SP相关的威胁获取、消失和消失保留过程的患者-对照差异的文献。具体来说，通过fMRI， EEG， EMG， SCR和自我报告。结果纳入了14项PD研究和7项SP研究。在PD研究中，回顾发现了可靠的证据，证明在PD患者获得过程中，条件威胁和安全线索之间的区别降低了，并且混合证据表明PD患者对威胁线索的反应比非焦虑对照组增加了。在所有的SP研究中，回顾发现了强有力的证据，表明在习得过程中条件威胁和安全线索之间的区别增强了，在SP患者与非焦虑对照组中，在灭绝过程中对威胁线索的反应增强了。在PD和SP研究中，与生理测量相反，在主观测量中更频繁地发现患者-对照差异。这篇综述的发现随后被批评并与更广泛的文献进行比较。最后，讨论了未来研究的意义、局限性和方向。

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引用次数: 0

Intrinsic excitability changes in amygdala neurons following observational fear conditioning in mice 小鼠观察性恐惧条件反射后杏仁核神经元内在兴奋性的变化。

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2026-01-01 Epub Date: 2025-11-24 DOI: 10.1016/j.nlm.2025.108115

Eun-Hwa Hong , Yang In Kim , Young-Beom Kim , June-Seek Choi

Observational fear conditioning (OFC) is used to study the social transmission of aversive information within a social context. In a typical experiment, observers exhibit defensive responses after witnessing a demonstrator’s reaction to repeated footshocks. Despite its relevance to socially acquired fear, the underlying cellular plasticity remain poorly understood. In this study, we investigated changes in the intrinsic excitability of amygdala neurons following OFC. In Experiment 1, we classified amygdala neurons into burst, regular and late-firing types, and found that burst-firing neurons in the basolateral amygdala (BLA) and late-firing neurons in the central amygdala (CeA) of the observer mice showed increased intrinsic neuronal excitability. In Experiment 2, we found that intrinsic excitability changes in both BLA and CeA neurons were selectively enhanced when observers witnessed the demonstrator’s high-frequency jumping behavior, but not freezing. In Experiment 3, an opaque wall and a distractor were used to investigate the role of visual transmission during OFC. Although both the opaque wall and the distractor blocked observer’s fear response, burst-firing BLA neurons in the distractor group nonetheless exhibited enhanced excitability, whereas late-firing CeA neurons did not. These findings suggest that amygdala subpopulations play dissociable roles in OFC: burst-firing BLA neurons appear to be involved in processing emotionally salient sensory cues, while late-firing CeA neurons appear to mediate the expression of socially acquired fear.

观察性恐惧条件反射（OFC）用于研究厌恶信息在社会情境中的社会传递。在一个典型的实验中，观察者在看到一个示威者对重复的脚震的反应后表现出防御反应。尽管它与社会获得性恐惧有关，但潜在的细胞可塑性仍然知之甚少。在这项研究中，我们研究了OFC后杏仁核神经元内在兴奋性的变化。在实验1中，我们将杏仁核神经元分为爆发型、规则型和迟发型，发现观察小鼠基底外侧杏仁核（BLA）的爆发型神经元和中央杏仁核（CeA）的迟发型神经元表现出神经元的内在兴奋性增加。在实验2中，我们发现当观察者看到演示者的高频跳跃行为时，BLA和CeA神经元的内在兴奋性变化都有选择性地增强，而不是冻结。实验3采用不透明墙和干扰物研究OFC过程中视觉传递的作用。尽管不透明壁和分心物都阻断了观察者的恐惧反应，但分心物组的猝发BLA神经元仍然表现出增强的兴奋性，而迟发CeA神经元则没有。这些发现表明，杏仁核亚群在OFC中扮演着可分离的角色：突发放电的BLA神经元似乎参与处理情感上显著的感觉线索，而晚发放电的CeA神经元似乎介导社交获得性恐惧的表达。

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引用次数: 0

The mechanisms of memory traces storage and interaction in snails: Role of DNA methylation and protein synthesis 蜗牛记忆痕迹储存和相互作用的机制：DNA甲基化和蛋白质合成的作用。

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2025-12-01 Epub Date: 2025-10-10 DOI: 10.1016/j.nlm.2025.108105

Vladimir P. Nikitin , Svetlana V. Solntseva , Pavel V. Nikitin

Understanding the molecular mechanisms underlying the storage and interaction of different memory traces remains an important, yet underexplored, topic in neurobiology. We addressed this using grape snails trained to reject two food-conditioned stimuli (CS). Our results indicate that memory storage mechanisms for distinct CS are independent, as selective impairment of memory reconsolidation with an NMDA receptor antagonist affected only one CS. When both CS reconsolidations were simultaneously disrupted, the snails developed amnesia, which manifested as anterograde amnesia on late amnesia stage, where repeated training failed to induce long-term memory formation. Intriguingly, shortened retraining in the presence of a DNA methyltransferase (DNMT) inhibitor facilitated memory recovery for one CS while preserving amnesia for the other, suggesting that latent memory traces are maintained via DNA methylation. Moreover, training to new food type aversion under a DNMT inhibitor induced spontaneous memory recovery for an old CS memory, which was tested the next day after training. This recovery did not occur during new training in the absence of the DNMT inhibitor. It was also found that a protein synthesis inhibitor administered before new training suppressed the restoration of old memory, whereas an inhibitor administered after new training, but not before it, prevented the formation of new memory. These findings demonstrate that independent molecular and epigenetic mechanisms preserve memory traces within the same neuronal ensemble and that new information can reactivate latent memories through specific protein synthesis and DNA methylation processes, offering fresh insights into memory storage and reconsolidation.

了解不同记忆痕迹的存储和相互作用的分子机制仍然是神经生物学中一个重要但尚未充分探索的话题。我们通过训练葡萄蜗牛来拒绝两种食物条件刺激（CS）来解决这个问题。我们的研究结果表明，不同CS的记忆存储机制是独立的，因为NMDA受体拮抗剂对记忆再巩固的选择性损伤仅影响一种CS。当两种CS再巩固同时被破坏时，蜗牛出现健忘症，表现为健忘症晚期的顺行性健忘症，反复训练无法诱导长期记忆的形成。有趣的是，在DNA甲基化酶（DNMT）抑制剂的存在下，缩短再训练有助于一个CS的记忆恢复，同时保持另一个CS的健健性，这表明潜在的记忆痕迹是通过DNA甲基化维持的。此外，在DNMT抑制剂下对新食物类型厌恶的训练诱导了对旧CS记忆的自发记忆恢复，这在训练后的第二天进行了测试。在缺乏DNMT抑制剂的新训练中，这种恢复没有发生。研究还发现，在新训练之前使用的蛋白质合成抑制剂抑制了旧记忆的恢复，而在新训练之后使用的抑制剂则阻止了新记忆的形成。这些发现表明，独立的分子和表观遗传机制在相同的神经元集合中保留了记忆痕迹，新的信息可以通过特定的蛋白质合成和DNA甲基化过程重新激活潜在的记忆，为记忆存储和再巩固提供了新的见解。

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引用次数: 0

How environmental enrichment influences conditioned taste aversion: A case of behavioral tagging 环境富集如何影响条件味觉厌恶：一个行为标签的案例。

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2025-12-01 Epub Date: 2025-09-09 DOI: 10.1016/j.nlm.2025.108100

Beatriz Gutiérrez-Vera, Gerardo R. Perera-Murcia, Martha L. Escobar

Exposure to environmental enrichment (EE) has demonstrated a remarkable ability to modulate cognitive processes. These effects have been associated with brain-derived neurotrophic factor (BDNF), a protein recognized for regulating synaptic plasticity in the adult brain. Previous research from our group revealed that exposure to EE prior to the acquisition of a strong form of conditioned taste aversion (CTA) weakens the aversive response by restoring BDNF levels in the insular cortex (IC), a region in the temporal lobe involved in multimodal sensory integration and learning and memory processes. The behavioral tagging model offers a framework to explain how salient or novel events can strengthen weak memory traces encoded within critical time windows before or after the novel experience. However, to date, the effect of brief exposure to an enriched environment at the critical timeframe between the acquisition phase and the aversion test has not been fully clarified. The present study aimed to evaluate the effects of environmental enrichment on the strength of CTA memory, when the EE is presented during the period spanning from acquisition to aversion test. To do so, Wistar rats were exposed to environmental enrichment for seven days between the acquisition session and the CTA aversion test. Our results show for the first time that a brief exposure to an enriched environment can strengthen the aversive response of a weak CTA. Our results also show that the response strengthening is accompanied by a reduction in BDNF levels in the IC. These findings present evidence that an aversive memory response can be modified through innovative and complex behavioral manipulation, highlighting enriched environments as potential modulators of aversive memory within critical periods of memory processing.

暴露于环境富集（EE）已经证明了一个显着的能力调节认知过程。这些作用与脑源性神经营养因子（BDNF）有关，BDNF是一种在成人大脑中调节突触可塑性的蛋白质。我们小组之前的研究表明，在获得强烈的条件性味觉厌恶（CTA）之前，暴露于情感表达会通过恢复岛叶皮层（IC）中的BDNF水平来减弱厌恶反应，岛叶皮层是颞叶中参与多模态感觉整合和学习记忆过程的区域。行为标记模型提供了一个框架来解释突出或新奇的事件如何加强在新奇经历之前或之后的关键时间窗内编码的弱记忆痕迹。然而，迄今为止，在收购阶段和厌恶测试之间的关键时间框架内，短暂暴露于丰富环境的影响尚未得到充分澄清。本研究旨在评价环境富集对情感表达在习得到厌恶阶段记忆强度的影响。为了做到这一点，Wistar大鼠在习得阶段和CTA厌恶测试之间暴露在环境富集环境中7天。我们的研究结果首次表明，短暂暴露于丰富的环境中可以增强弱CTA的厌恶反应。我们的研究结果还表明，反应增强伴随着IC中BDNF水平的降低。这些发现表明，厌恶记忆反应可以通过创新和复杂的行为操纵来改变，强调了在记忆加工的关键时期，丰富的环境是厌恶记忆的潜在调节剂。

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引用次数: 0