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

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 : 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

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 : 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

Mechanisms for punishment learning and decision-making: A special issue 惩罚学习和决策机制：专题。

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2025-12-01 DOI: 10.1016/j.nlm.2025.108108

Philip Jean-Richard-dit-Bressel

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 : 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

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 : 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

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 : 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

Double dissociation between the involvement of Gadd45α and Gadd45β/γ in the perirhinal cortex and hippocampus of male rats for object memory Gadd45α和Gadd45β/γ参与雄性大鼠嗅周皮层和海马客体记忆的双重解离

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2025-11-02 DOI: 10.1016/j.nlm.2025.108113

Krista A. Mitchnick , Samantha D. Creighton , Karanveer S. Johal , Sanya Anoop , Bettina E. Kalisch , Gilda Stefanelli , Boyer D. Winters

The GADD45 family of proteins (GADD45α, GADD45β, GADD45γ) has been implicated in DNA demethylation and long-term memory formation. Recently, conflicting findings have emerged surrounding the involvement of Gadd45α in various object recognition tasks. These discrepancies could be due to differences in Gadd45α KO mouse models and/or task parameters. Further, the use of brain-wide KO models precludes our understanding of Gadd45α in specific brain regions such as the hippocampus (HPC), which processes the spatial location of objects, or the perirhinal cortex (PRh), which has a larger role in object identity memory. Here, using a single object recognition task reliant on both the PRh and HPC – the object-in-place (OiP) task – we show that siRNA knockdown of Gadd45β or Gadd45γ, but not Gadd45α, within the dorsal HPC (dHPC) impaired long-term, but not short-term, OiP memory. Further, OiP learning induced an upregulation of Gadd45β mRNA in the dentate gyrus subregion of the dHPC. Within the PRh, siRNA knockdown of Gadd45α, but not Gadd45β or Gadd45γ, impaired long-term, but not short-term, OiP memory, with a concomitant increase in learning induced PRh Gadd45α mRNA. These results clarify previous discrepancies in the literature by demonstrating a clear necessity for Gadd45α in the PRh, but not the dHPC, for the consolidation of long-term object memories.

GADD45蛋白家族（GADD45α, GADD45β, GADD45γ）与DNA去甲基化和长期记忆形成有关。最近，关于Gadd45α参与各种目标识别任务的研究结果相互矛盾。这些差异可能是由于Gadd45α KO小鼠模型和/或任务参数的差异。此外，全脑KO模型的使用使我们无法理解Gadd45α在特定大脑区域中的作用，如处理物体空间位置的海马（HPC）或在物体身份记忆中发挥更大作用的周围皮层（PRh）。在这里，使用依赖于PRh和HPC的单一物体识别任务-原位物体（OiP）任务-我们发现，在背侧HPC （dHPC）中，Gadd45β或Gadd45γ的siRNA敲低，而不是Gadd45α，会损害长期而不是短期的OiP记忆。此外，OiP学习诱导dHPC齿状回亚区Gadd45β mRNA表达上调。在PRh内，Gadd45α（而非Gadd45β或Gadd45γ）的siRNA敲低会损害长期（而非短期）OiP记忆，并伴随学习诱导的PRh Gadd45α mRNA的增加。这些结果通过证明Gadd45α在PRh（而非dHPC）中对于长期目标记忆巩固的明确必要性，澄清了之前文献中的差异。

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引用次数: 0

Long-lasting avoidance induced by repeated stimulation of the rostromedial tegmental nucleus 反复刺激前额内侧被盖核引起的长时间回避。

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2025-10-28 DOI: 10.1016/j.nlm.2025.108111

J.R. Watson, M.D. Lopez de Leon, E.L. Carlson, P.J. Vento

Adaptive decision-making requires the ability to weigh the relative costs versus the benefits of our actions and to flexibly respond to changing environmental contingencies. While midbrain dopamine (DA) has been a major focus of study for its role in associative learning, motivation, and reward seeking, far less is known regarding the contribution of inhibitory dopamine inputs in promoting behavioral inhibition and avoidance learning. The rostromedial tegmental nucleus (RMTg) sends dense GABAergic projections to DA neurons in the ventral tegmental area (VTA) and mounting evidence suggests the RMTg–VTA circuit is required to suppress reward seeking under punishment, but it remains unclear whether stimulation of this pathway is sufficient to drive learning and promote shifts in cost-benefit decisions. To test this, we developed two separate tasks of passive and active avoidance in rats where lever pressing for food reward was associated with repeated stimulation of the RMTg–VTA circuit. In a one-lever fixed ratio 5 food-seeking task, we found that pairing contingent RMTg–VTA stimulation immediately after responding for reward delivery caused a robust, yet transient suppression of reward seeking that quickly returned to baseline after stimulation ceased. When given an alternative reward choice, however, RMTg–VTA stimulation caused a rapid and enduring shift in subjective choice leading to persistent and selective avoidance of the stimulation-paired reward. These findings support a multifaceted role for the RMTg–VTA pathway in learning and decision-making and provide key insights into the neural mechanisms underlying behavioral avoidance and cost-benefit decisions.

适应性决策要求有能力权衡我们行动的相对成本和收益，并灵活应对不断变化的环境突发事件。虽然中脑多巴胺（DA）在联想学习、动机和寻求奖励中的作用一直是研究的主要焦点，但对抑制性多巴胺输入在促进行为抑制和回避学习中的作用知之甚少。前额内侧被盖核（RMTg）向腹侧被盖区（VTA）的DA神经元发送密集的gaba能投射，越来越多的证据表明，RMTg-VTA回路是抑制惩罚下的奖励寻求所必需的，但目前尚不清楚刺激该通路是否足以驱动学习并促进成本-收益决策的转变。为了验证这一点，我们在大鼠身上开发了两个独立的被动和主动回避任务，其中按压食物奖励的杠杆与RMTg-VTA回路的重复刺激有关。在一个单杠杆固定比例5的寻食任务中，我们发现，在对奖励做出反应后立即配对偶然的RMTg-VTA刺激，会导致对寻求奖励的强烈而短暂的抑制，并在刺激停止后迅速恢复到基线。然而，当给予另一种奖励选择时，RMTg-VTA刺激引起了主观选择的快速和持久的转变，导致持续和选择性地回避刺激配对的奖励。这些发现支持了RMTg-VTA通路在学习和决策中的多方面作用，并为行为回避和成本效益决策背后的神经机制提供了重要见解。

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引用次数: 0

Accelerated maturation of fear regulation systems in infant rats following early life inflammation 幼鼠早期炎症后恐惧调节系统的加速成熟。

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2025-10-27 DOI: 10.1016/j.nlm.2025.108109

Tayla B. McCutcheon, Sara M. Simenson-Braun, Rick Richardson

Early life stress is a well-established risk factor for neuropsychiatric and neurodevelopmental disorders, yet the mechanisms underlying this lifelong vulnerability remain unclear. One possibility is that early stress exposure disrupts the developmental trajectory of neural systems involved in emotion regulation, creating long-term susceptibility to psychopathology. Therefore, here we explored the impact of two forms of early-life adversity on maturation of emotional regulation in infant rats. Two forms of adversity were examined: maternal separation (MS) and to early-life inflammation (ELI) via post-natal injections of the bacterial endotoxin lipopolysaccharide. In Experiment 1, we examined the effects of these two types of early life stress in infant male rats. Based on the results of the first experiment, in Experiment 2 we replicated the procedures from Experiment 1 in females but only examined ELI as an early stressor. In both experiments, ELI infants displayed a precocious emergence of context-mediated relapse of extinguished fear, whereas standard-rearing (SR) and MS male infants did not. These findings suggest that ELI accelerates the development of infant emotion regulation, consistent with studies using other stressors (e.g., psychosocial), and point to shared mechanisms underlying the long-term adverse effects of early-life stress.

早期生活压力是神经精神和神经发育障碍的一个公认的危险因素，但这种终身脆弱性的机制尚不清楚。一种可能性是，早期的压力暴露破坏了参与情绪调节的神经系统的发育轨迹，导致长期对精神病理的易感性。因此，我们在这里探讨了两种形式的早期生活逆境对幼鼠情绪调节成熟的影响。两种形式的逆境进行了检查：产妇分离（MS）和早期生活炎症（ELI）通过产后注射细菌内毒素脂多糖。在实验1中，我们研究了这两种类型的早期生活压力对雄性幼鼠的影响。基于实验2中第一个实验的结果，我们在女性中重复了实验1的过程，但只检查了ELI作为早期应激源。在这两个实验中，ELI婴儿表现出情境介导的消失恐惧复发的早熟，而标准养育（SR）和MS男性婴儿则没有。这些发现表明ELI加速了婴儿情绪调节的发展，这与使用其他压力源（如社会心理）的研究一致，并指出了早期生活压力长期不利影响的共同机制。

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引用次数: 0

Towards a multi-dimensional understanding of brain states 对大脑状态的多维理解

IF 1.8 4区心理学 Q3 BEHAVIORAL SCIENCES

Neurobiology of Learning and Memory

Pub Date : 2025-10-25 DOI: 10.1016/j.nlm.2025.108110

Tomomi Karigo , Adam S. Charles

Animals continuously adapt their behaviors to navigate diverse and dynamic environments effectively. Such behavioral flexibility emerges from internal states that modulate responses to environmental stimuli. Traditionally, these states have been studied individually and treated as discrete, categorical variables. However, recent advances in neural recording and behavioral analyses now enable quantitative extraction of states directly from data, and emerging evidence indicates that animals simultaneously experience multiple, often interacting, internal states that dynamically modulate neural activity and behavior. In this review, we propose a multi-dimensional framework for understanding brain states as modulators that influence the relationship between the environment, neural activity, and behavior. We highlight recent neurobiological studies demonstrating how interacting physiological and emotional states, such as hunger and aggression, can reconfigure behavior through circuit-level integration. Additionally, we discuss evidence from large-scale neural recordings showing distributed and graded representations of internal states across the brain. Computational models, particularly those utilizing unsupervised clustering and dynamical systems, further enable the investigation of these flexible, context-dependent state interactions. Finally, we propose further integration of high-resolution brain-wide recording and computational modeling approaches to understand how multiple internal states integrate to shape neural coding and behavior. Such integrative approaches are critical for uncovering the neural mechanisms underlying flexible and adaptive behaviors in naturalistic settings.

动物不断地调整它们的行为，以有效地在多样化和动态的环境中导航。这种行为的灵活性来自调节对环境刺激反应的内部状态。传统上，这些状态被单独研究，并被视为离散的分类变量。然而，神经记录和行为分析的最新进展现在可以直接从数据中定量提取状态，并且新出现的证据表明，动物同时经历多种，经常相互作用的内部状态，动态调节神经活动和行为。在这篇综述中，我们提出了一个多维框架来理解大脑状态作为影响环境、神经活动和行为之间关系的调节剂。我们重点介绍了最近的神经生物学研究，这些研究表明，生理和情绪状态（如饥饿和攻击）如何相互作用，可以通过电路水平的整合来重新配置行为。此外，我们还讨论了来自大规模神经记录的证据，这些记录显示了大脑内部状态的分布和分级表征。计算模型，特别是那些利用无监督聚类和动态系统的模型，可以进一步研究这些灵活的、依赖于上下文的状态相互作用。最后，我们建议进一步整合高分辨率全脑记录和计算建模方法，以了解多种内部状态如何整合以形成神经编码和行为。这种综合方法对于揭示自然环境中灵活和适应性行为背后的神经机制至关重要。

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引用次数: 0