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Astrocyte focal adhesion kinase reduces passive stress coping by inhibiting ciliary neurotrophic factor only in female mice 星形胶质细胞局灶粘附激酶仅通过抑制睫状神经营养因子降低雌性小鼠的被动压力应对能力
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-11 DOI: 10.1016/j.ynstr.2024.100621
Cuihong Jia, W. Drew Gill, Chiharu Lovins, Russell W. Brown , Theo Hagg

Astrocytes have been implicated in stress responses and produce ciliary neurotrophic factor (CNTF), which we have shown in the mouse medial amygdala (MeA) to promote passive stress coping response only in females. Pharmacological inhibition of focal adhesion kinase (FAK) upregulates CNTF expression. Here, we found that inducible knockout of FAK in astrocytes or systemic treatment with an FAK inhibitor increased passive coping behavior, i.e., immobility, in an acute forced swim stress test in female, but not male, mice. Strikingly, four weeks of chronic unpredictable stress (CUS) did not further increase passive coping in female astrocytic FAK knockout mice, whereas it exacerbated it in female wildtype mice and male mice of both genotypes. These data suggest that astrocyte FAK inhibition is required for chronic stress-induced passive coping in females. Indeed, CUS reduced phospho-FAK and increased CNTF in the female MeA. Progesterone treatment after ovariectomy activated amygdala FAK and alleviated ovariectomy-induced passive coping in wildtype, but not astrocytic FAK knockout females. This suggests that progesterone-mediated activation of FAK in astrocytes reduces female stress responses. Finally, astrocytic FAK knockout or FAK inhibitor treatment increased CNTF expression in the MeA of both sexes, although not in the hippocampus. As mentioned, MeA CNTF promotes stress responses only in females, which may explain the female-specific role of astrocytic FAK inhibition. Together, this study reveals a novel female-specific progesterone-astrocytic FAK pathway that counteracts CNTF-mediated stress responses and points to opportunities for developing treatments for stress-related disorders in women.

星形胶质细胞与应激反应有关,并能产生睫状神经营养因子(CNTF)。我们在小鼠内侧杏仁核(MeA)中发现,只有雌性星形胶质细胞能促进被动应激反应。药物抑制局灶粘附激酶(FAK)可上调CNTF的表达。在这里,我们发现诱导性敲除星形胶质细胞中的FAK或用FAK抑制剂进行全身治疗可增加雌性小鼠在急性强迫游泳应激试验中的被动应对行为,即不动。令人吃惊的是,四周的慢性不可预测应激(CUS)并没有进一步增加雌性星形胶质细胞FAK基因敲除小鼠的被动应对行为,但却加剧了雌性野生型小鼠和雄性两种基因型小鼠的被动应对行为。这些数据表明,雌性小鼠慢性应激诱导的被动应对需要星形胶质细胞 FAK 抑制。事实上,CUS能减少雌性MeA的磷酸-FAK并增加CNTF。卵巢切除术后的黄体酮治疗激活了杏仁核FAK,缓解了野生型女性卵巢切除术诱导的被动应对,但没有缓解星形胶质细胞FAK基因敲除女性的被动应对。这表明,黄体酮介导的星形胶质细胞 FAK 激活可减轻女性的应激反应。最后,星形胶质细胞FAK敲除或FAK抑制剂处理增加了CNTF在两性MeA中的表达,尽管不是在海马中。如前所述,MeA CNTF只促进女性的应激反应,这可能解释了星形胶质细胞FAK抑制剂的女性特异性作用。总之,这项研究揭示了一种新的女性特异性黄体酮-星形胶质细胞FAK通路,它能抵消CNTF介导的应激反应,并为开发治疗女性应激相关疾病的方法提供了机会。
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引用次数: 0
Environmental enrichment attenuates depressive-like behavior in maternal rats by inhibiting neuroinflammation and apoptosis and promoting neuroplasticity 环境富集通过抑制神经炎症和细胞凋亡以及促进神经可塑性来减轻母鼠的抑郁样行为
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-11 DOI: 10.1016/j.ynstr.2024.100624
Guopeng Chen , Yuhui Zhang , Ruiling Li , Liuyin Jin , Keke Hao , Jingtong Rong , Hao Duan , Yiwei Du , Lihua Yao , Dan Xiang , Zhongchun Liu

Gestational stress can exacerbate postpartum depression (PPD), for which treatment options remain limited. Environmental enrichment (EE) may be a therapeutic intervention for neuropsychiatric disorders, including depression, but the specific mechanisms by which EE might impact PPD remain unknown. Here we examined the behavioral, molecular, and cellular impact of EE in a stable PPD model in rats developed through maternal separation (MS). Maternal rats subjected to MS developed depression-like behavior and cognitive dysfunction together with evidence of significant neuroinflammation including microglia activation, neuronal apoptosis, and impaired synaptic plasticity. Expanding the duration of EE to throughout pregnancy and lactation, we observed an EE-associated reversal of MS-induced depressive phenotypes, inhibition of neuroinflammation and neuronal apoptosis, and improvement in synaptic plasticity in maternal rats. Thus, EE effectively alleviates neuroinflammation, neuronal apoptosis, damage to synaptic plasticity, and consequent depression-like behavior in mother rats experiencing MS-induced PPD, paving the way for new preventive and therapeutic strategies for PPD.

妊娠压力会加重产后抑郁症(PPD),但治疗方法仍然有限。环境富集(EE)可能是治疗包括抑郁症在内的神经精神疾病的一种干预措施,但环境富集可能影响产后抑郁症的具体机制仍不清楚。在这里,我们研究了在通过母鼠分离(MS)建立的稳定 PPD 模型中,EE 对行为、分子和细胞的影响。接受 MS 的母体大鼠会出现抑郁样行为和认知功能障碍,并伴有明显的神经炎症,包括小胶质细胞活化、神经元凋亡和突触可塑性受损。将 EE 的持续时间延长至整个孕期和哺乳期,我们观察到 EE 可逆转 MS 诱导的抑郁表型,抑制神经炎症和神经元凋亡,并改善母体大鼠的突触可塑性。因此,EE能有效缓解神经炎症、神经元凋亡、突触可塑性损伤以及MS诱导的母鼠抑郁样行为,为PPD的预防和治疗新策略铺平道路。
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引用次数: 0
The neurocomputational signature of decision-making for unfair offers in females under acute psychological stress 急性心理压力下女性对不公平报价决策的神经计算特征
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-06 DOI: 10.1016/j.ynstr.2024.100622
Guangya Wang , Jun Tang , Zhouqian Yin , Siyu Yu , Xindi Shi , Xiurong Hao , Zhudele Zhao , Yafeng Pan , Shijia Li

Stress is a crucial factor affecting social decision-making. However, its impacts on the behavioral and neural processes of females’ unfairness decision-making remain unclear. Combining computational modeling and functional near-infrared spectroscopy (fNIRS), this study attempted to illuminate the neurocomputational signature of unfairness decision-making in females. We also considered the effect of trait stress coping styles. Forty-four healthy young females (20.98 ± 2.89 years) were randomly assigned to the stress group (n = 21) and the control group (n = 23). Acute psychosocial stress was induced by the Trier Social Stress Test (TSST), and participants then completed the one-shot ultimatum game (UG) as responders. The results showed that acute psychosocial stress reduced the adaptability to fairness and lead to more random decision-making responses. Moreover, in the stress group, a high level of negative coping style predicted more deterministic decision. fNIRS results showed that stress led to an increase of oxy-hemoglobin (HbO) peak in the right temporoparietal junction (rTPJ), while decreased the activation of left middle temporal gyrus (lMTG) when presented the moderately unfair (MU) offers. This signified more involvement of the mentalization and the inhibition of moral processing. Moreover, individuals with higher negative coping scores showed more deterministic decision behaviors under stress. Taken together, our study emphasizes the role of acute psychosocial stress in affecting females’ unfairness decision-making mechanisms in social interactions, and provides evidences for the “tend and befriend” pattern based on a cognitive neuroscience perspec

压力是影响社会决策的一个重要因素。然而,压力对女性不公平决策的行为和神经过程的影响仍不清楚。本研究结合计算建模和功能性近红外光谱(fNIRS),试图揭示女性不公平决策的神经计算特征。我们还考虑了特质压力应对方式的影响。44 名健康的年轻女性(20.98 ± 2.89 岁)被随机分配到压力组(21 人)和对照组(23 人)。通过特里尔社会压力测试(TSST)诱发急性社会心理压力,然后参与者以应答者的身份完成一次性最后通牒游戏(UG)。结果表明,急性社会心理压力降低了参与者对公平的适应性,并导致他们做出更多随机决策反应。fNIRS结果表明,当被试提出中度不公平(MU)的提议时,压力导致右侧颞顶交界处(rTPJ)的氧血红蛋白(HbO)峰值升高,而左侧颞中回(lMTG)的激活程度降低。这表明更多的心智化参与和道德处理的抑制。此外,消极应对得分较高的个体在压力下表现出更多的决定性决策行为。综上所述,我们的研究强调了急性社会心理压力对女性在社会交往中的不公平决策机制的影响,并从认知神经科学的角度为 "倾向和结交 "模式提供了证据。
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引用次数: 0
SNX27: A trans-species cognitive modulator with implications for anxiety and stress susceptibility SNX27:一种跨物种认知调节器,对焦虑和压力易感性有影响
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-05 DOI: 10.1016/j.ynstr.2024.100619
Gisela Armada , Susana Roque , Cláudia Serre-Miranda , Liliana Ferreira , Ana Vale , Ana João Rodrigues , Wanjin Hong , Margarida Correia-Neves , Neide Vieira

Sorting Nexin 27 (SNX27) is a brain-enriched endosome-associated cargo adaptor that shapes excitatory control, being relevant for cognitive and reward processing, and for several neurological conditions. Despite this, SNX27's role in the nervous system remains poorly explored. To further understand SNX27 function, we performed an extensive behavioral characterization comprising motor, cognitive and emotional dimensions of SNX27+/− mice. Furthermore, attending on the recently described association between SNX27 function and cellular stress signaling mechanisms in vitro, we explored SNX27-stress interplay using a Caenorhabditis elegans Δsnx-27 mutant and wild-type (WT) rodents after stress exposure.

SNX27+/− mice, as C. elegans Δsnx-27 mutants, present cognitive impairments, highlighting a conserved role for SNX27 in cognitive modulation across species. Interestingly, SNX27 downmodulation leads to anxiety-like behavior in mice evaluated in the Elevated Plus Maze (EPM). This anxious phenotype is associated with increased dendritic complexity of the bed nucleus of the stria terminalis (BNST) neurons, and increased complexity of the basolateral amygdala (BLA) pyramidal neurons. These findings highlight the still unknown role of SNX27 in anxiety regulation.

Moreover, we uncovered a direct link between SNX27 dysfunction and stress susceptibility in C. elegans and found that stress-exposed rodents display decreased SNX27 levels in stress-susceptible brain regions.

Altogether, we provided new insights on SNX27's relevance in anxiety-related behaviors and neuronal structure in stress-associated brain regions.

分选内含蛋白 27(SNX27)是一种脑内富集的内含体相关货物适配体,它能影响兴奋控制,与认知和奖赏处理以及多种神经系统疾病有关。尽管如此,SNX27 在神经系统中的作用仍然鲜为人知。为了进一步了解 SNX27 的功能,我们对 SNX27+/- 小鼠的运动、认知和情绪等方面进行了广泛的行为特征描述。此外,根据最近描述的SNX27功能与体外细胞应激信号转导机制之间的联系,我们利用草履虫Δsnx-27突变体和野生型(WT)啮齿动物在应激暴露后探索了SNX27与应激之间的相互作用。有趣的是,SNX27 下调会导致小鼠在高架迷宫(EPM)中出现类似焦虑的行为。这种焦虑表型与纹状体末端床核(BNST)神经元树突复杂性的增加以及杏仁基底外侧(BLA)锥体神经元复杂性的增加有关。这些发现突显了SNX27在焦虑调控中仍未知的作用。此外,我们还发现了SNX27功能障碍与优雅鼠的应激易感性之间的直接联系,并发现应激暴露的啮齿类动物在应激易感脑区的SNX27水平降低。
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引用次数: 0
Social isolation postweaning alters reward-related dopamine dynamics in a region-specific manner in adolescent male rats 断奶后的社会隔离会以特定区域的方式改变青春期雄性大鼠与奖赏相关的多巴胺动态变化
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-02 DOI: 10.1016/j.ynstr.2024.100620
Valeria Lallai , Cristina Congiu , Giulia Craig , Letizia Manca , Yen-Chu Chen , Angeline J. Dukes , Christie D. Fowler , Laura Dazzi

Early development is characterized by dynamic transitions in brain maturation, which may be impacted by environmental factors. Here, we sought to determine the effects of social isolation from postweaning and during adolescence on reward behavior and dopaminergic signaling in male rats. Subjects were socially isolated or group housed at postnatal day 21. Three weeks later, extracellular dopamine concentrations were examined in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (NAc) during a feeding bout. Surprisingly, opposing effects were found in which increased mPFC dopamine concentrations were observed in group housed, but not isolated, rats. In stark contrast, increased dopamine levels were found in the NAc of isolated, but not group housed, rats. Moreover, the absence of an effect in the mPFC of the isolated rats could not be reversed by subsequent group housing, demonstrating the remarkable long-term effects on dopamine signaling dynamics. When provided a highly palatable food, the isolated subjects exhibited a dramatic increase in mPFC dopamine levels when the chocolate was novel, but no effects following chronic chocolate consumption. In contrast, the group housed subjects showed significantly increased dopamine levels only with chronic chocolate consumption. The dopamine changes were correlated with differences in behavioral measures. Importantly, the deficit in reward-related behavior during isolation could be reversed by microinjection of either dopamine or cocaine into the mPFC. Together, these data provide evidence that social isolation from postweaning and during adolescence alters reward-induced dopamine levels in a brain region-specific manner, which has important functional implications for reward-related behavior.

早期发育的特点是大脑成熟的动态过渡,这可能会受到环境因素的影响。在此,我们试图确定断奶后和青春期的社会隔离对雄性大鼠奖励行为和多巴胺能信号传导的影响。受试者在出生后第 21 天被隔离或集体饲养。三周后,在喂食过程中检测内侧前额叶皮层(mPFC)和伏隔核(NAc)的细胞外多巴胺浓度。令人惊讶的是,研究人员发现,分组饲养的大鼠(而非隔离饲养的大鼠)mPFC多巴胺浓度增加,而分组饲养的大鼠(而非隔离饲养的大鼠)则相反。与此形成鲜明对比的是,隔离饲养的大鼠多巴胺水平升高,而非分组饲养的大鼠多巴胺水平升高。此外,隔离大鼠的 mPFC 没有受到影响,但随后的分组饲养却无法逆转,这表明多巴胺信号动态受到了显著的长期影响。当提供一种高适口性食物时,当巧克力是一种新奇的食物时,隔离受试者表现出 mPFC 多巴胺水平的急剧上升,但长期食用巧克力后则没有任何影响。相比之下,群居受试者只有在长期食用巧克力时多巴胺水平才会显著增加。多巴胺的变化与行为测量的差异相关。重要的是,在多巴胺或可卡因显微注射到mPFC后,隔离期间奖赏相关行为的缺失可以逆转。总之,这些数据提供了证据,表明从断奶后到青春期的社会隔离会以特定脑区的方式改变奖赏诱导的多巴胺水平,这对奖赏相关行为具有重要的功能影响。
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引用次数: 0
The role of brain serotonin signaling in excessive alcohol consumption and withdrawal: A call for more research in females 大脑血清素信号在过度饮酒和戒酒中的作用:呼吁对女性进行更多研究
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-20 DOI: 10.1016/j.ynstr.2024.100618
Megan E. Castle, Meghan E. Flanigan

Alcohol Use Disorder (AUD) is a leading cause of death and disability worldwide, but current treatments are insufficient in fully addressing the symptoms that often lead to relapses in alcohol consumption. The brain's serotonin system has been implicated in AUD for decades and is a major regulator of stress-related behaviors associated with increased alcohol consumption. This review will discuss the current literature on the association between neurobiological adaptations in serotonin systems and AUD in humans as well as the effectiveness of serotonin receptor manipulations on alcohol-related behaviors like consumption and withdrawal. We will further discuss how these findings in humans relate to findings in animal models, including a comparison of systemic pharmacological manipulations modulating alcohol consumption. We next provide a detailed overview of brain region-specific roles for serotonin and serotonin receptor signaling in alcohol-related behaviors in preclinical animal models, highlighting the complexity of forming a cohesive model of serotonin function in AUD and providing possible avenues for more effective therapeutic intervention. Throughout the review, we discuss what is known about sex differences in the sequelae of AUD and the role of serotonin in these sequelae. We stress a critical need for additional studies in women and female animals so that we may build a clearer path to elucidating sex-specific serotonergic mechanisms and develop better treatments.

酒精使用障碍(AUD)是导致全球死亡和残疾的一个主要原因,但目前的治疗方法不足以完全解决经常导致酒精消费复发的症状。几十年来,大脑的血清素系统一直与 AUD 有关,它是与酒精消费增加有关的压力相关行为的主要调节器。本综述将讨论血清素系统的神经生物学适应性与人类 AUD 之间关联的现有文献,以及操纵血清素受体对酒精相关行为(如饮酒和戒酒)的有效性。我们将进一步讨论这些人类研究结果与动物模型研究结果之间的关系,包括对调节酒精消耗的系统药理作用进行比较。接下来,我们将详细概述临床前动物模型中血清素和血清素受体信号传导在酒精相关行为中的脑区特异性作用,突出强调在 AUD 中形成血清素功能凝聚模型的复杂性,并为更有效的治疗干预提供可能的途径。在整篇综述中,我们讨论了有关 AUD 后遗症的性别差异以及血清素在这些后遗症中的作用的已知情况。我们强调亟需在女性和雌性动物中开展更多研究,从而为阐明性别特异性血清素能机制和开发更好的治疗方法开辟一条更清晰的道路。
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引用次数: 0
Sex-specific threat responding and neuronal engagement in carbon dioxide associated fear and extinction: Noradrenergic involvement in female mice 与二氧化碳相关的恐惧和消退中的性别特异性威胁反应和神经元参与:雌性小鼠去甲肾上腺素能的参与
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-20 DOI: 10.1016/j.ynstr.2024.100617
Rebecca Ahlbrand , Allison Wilson , Patrick Woller , Yuv Sachdeva , Jayden Lai , Nikki Davis , James Wiggins , Renu Sah

Difficulty in appropriately responding to threats is a key feature of psychiatric disorders, especially fear-related conditions such as panic disorder (PD) and posttraumatic stress disorder (PTSD). Most prior work on threat and fear regulation involves exposure to external threatful cues. However, fear can also be triggered by aversive, within-the-body, sensations. This interoceptive signaling of fear is highly relevant to PD and PTSD but is not well understood, especially in the context of sex. Using female and male mice, the current study investigated fear-associated spontaneous and conditioned behaviors to carbon dioxide (CO2) inhalation, a potent interoceptive threat that induces fear and panic. We also investigated whether behavioral sensitivity to CO2 is associated with delayed PTSD-relevant behaviors. CO2 evoked heterogenous freezing behaviors in both male and female animals. However, active, rearing behavior was significantly reduced in CO2-exposed male but not female mice. Interestingly, behavioral sensitivity to CO2 was associated with compromised fear extinction, independent of sex. However, in comparison to CO2-exposed males, females elicited less freezing and higher rearing during extinction suggesting an engagement of active versus passive defensive coping. Persistent neuronal activation marker ΔFosB immuno-mapping revealed attenuated engagement of infralimbic-prefrontal areas in both sexes but higher activation of brain stem locus coeruleus (LC) area in females. Inter-regional co-activation mapping revealed sex-independent disruptions in the infralimbic-amygdala associations but altered LC associations only in CO2-exposed female mice. Lastly, dopamine β hydroxylase positive (DβH + ve) noradrenergic neuronal cell counts in the LC correlated with freezing and rearing behaviors during CO2 inhalation and extinction only in female but not male mice. Collectively, these data provide evidence for higher active defensive responding to interoceptive threat CO2-associated fear in females that may stem from increased recruitment of the brainstem noradrenergic system. Our findings reveal distinct contributory mechanisms that may promote sex differences in fear and panic associated pathologies.

难以对威胁做出适当反应是精神疾病的一个主要特征,尤其是与恐惧相关的疾病,如惊恐障碍(PD)和创伤后应激障碍(PTSD)。之前关于威胁和恐惧调节的研究大多涉及暴露于外部威胁线索的情况。然而,身体内部的厌恶感觉也会引发恐惧。这种恐惧的感知间信号与帕金森病和创伤后应激障碍高度相关,但人们对其了解不多,尤其是在性别背景下。本研究使用雌性和雄性小鼠,调查了吸入二氧化碳(CO2)时与恐惧相关的自发行为和条件行为。我们还研究了对二氧化碳的行为敏感性是否与创伤后应激障碍相关的延迟行为有关。二氧化碳会诱发雄性和雌性动物出现不同的冻结行为。然而,暴露于二氧化碳的雄性小鼠的主动饲养行为明显减少,而雌性小鼠则没有。有趣的是,对二氧化碳的行为敏感性与恐惧消退能力受损有关,与性别无关。然而,与暴露于二氧化碳的雄性小鼠相比,雌性小鼠在熄灭过程中引起的冻结更少,饲养程度更高,这表明雌性小鼠参与了主动与被动的防御应对。持续性神经元激活标记物ΔFosB免疫图谱显示,雌雄动物的下边缘-前额叶区的参与程度都有所降低,但雌性动物的脑干定位区(LC)的激活程度更高。区域间共同激活图谱显示,下边缘-杏仁核关联的中断与性别无关,但只有暴露于二氧化碳的雌性小鼠的LC关联发生了改变。最后,LC 中多巴胺 β 羟化酶阳性(DβH + ve)去甲肾上腺素能神经元细胞数量与吸入二氧化碳时的冻结和饲养行为相关,只有雌性小鼠与之相关,雄性小鼠则不然。总之,这些数据提供了证据,证明雌性小鼠对二氧化碳相关恐惧的感知威胁做出了更高的主动防御反应,这可能源于脑干去甲肾上腺素能系统招募的增加。我们的研究结果揭示了可能导致恐惧和恐慌相关病症的性别差异的不同机制。
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引用次数: 0
Isolation of the differential effects of chronic and acute stress in a manner that is not confounded by stress severity 以不受压力严重程度影响的方式隔离慢性和急性压力的不同影响
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-10 DOI: 10.1016/j.ynstr.2024.100616
Michael A. Conoscenti , Daniel B. Weatherill , Yuqing Huang , Raphael Tordjman , Michael S. Fanselow

Firm conclusions regarding the differential effects of the maladaptive consequences of acute versus chronic stress on the etiology and symptomatology of stress disorders await a model that isolates chronicity as a variable for studying the differential effects of acute versus chronic stress. This is because most previous studies have confounded chronicity with the total amount of stress. Here, we have modified the stress-enhanced fear learning (SEFL) protocol, which models some aspects of posttraumatic stress disorder (PTSD) following an acute stressor, to create a chronic variant that does not have this confound. Comparing results from this new protocol to the acute protocol, we found that chronic stress further potentiates enhanced fear-learning beyond the nonassociative enhancement induced by acute stress. This additional component is not observed when the unconditional stimulus (US) used during subsequent fear learning is distinct from the US used as the stressor, and is enhanced when glucose is administered following stressor exposure, suggesting that it is associative in nature. Furthermore, extinction of stressor-context fear blocks this additional associative component of SEFL as well as reinstatement of generalized fear, suggesting reinstatement of generalized fear may underlie this additional SEFL component.

关于急性和慢性压力对应激障碍的病因学和症状学所产生的不良后果的不同影响,还有待于建立一个模型,将慢性化作为研究急性和慢性压力的不同影响的一个变量。这是因为之前的大多数研究都将慢性应激与应激总量混为一谈。在这里,我们修改了应激增强恐惧学习(SEFL)方案(该方案模拟了急性应激后创伤后应激障碍(PTSD)的某些方面),创建了一个没有这种混淆的慢性变体。将这种新方案的结果与急性方案的结果进行比较后,我们发现,慢性应激进一步增强了恐惧学习能力,超出了急性应激引起的非联想增强。如果在随后的恐惧学习过程中使用的无条件刺激(US)与作为应激源的US不同,就不会观察到这种额外的成分,而如果在暴露于应激源后给予葡萄糖,这种额外的成分就会增强,这表明它在本质上是联想性的。此外,应激源-情境恐惧的消退会阻止 SEFL 的这种额外联想成分以及泛化恐惧的恢复,这表明泛化恐惧的恢复可能是 SEFL 这种额外成分的基础。
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引用次数: 0
Integrating and fragmenting memories under stress and alcohol 压力和酒精下的记忆整合与碎片化
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-08 DOI: 10.1016/j.ynstr.2024.100615
Krystian B. Loetscher , Elizabeth V. Goldfarb

Stress can powerfully influence the way we form memories, particularly the extent to which they are integrated or situated within an underlying spatiotemporal and broader knowledge architecture. These different representations in turn have significant consequences for the way we use these memories to guide later behavior. Puzzlingly, although stress has historically been argued to promote fragmentation, leading to disjoint memory representations, more recent work suggests that stress can also facilitate memory binding and integration. Understanding the circumstances under which stress fosters integration will be key to resolving this discrepancy and unpacking the mechanisms by which stress can shape later behavior. Here, we examine memory integration at multiple levels: linking together the content of an individual experience, threading associations between related but distinct events, and binding an experience into a pre-existing schema or sense of causal structure. We discuss neural and cognitive mechanisms underlying each form of integration as well as findings regarding how stress, aversive learning, and negative affect can modulate each. In this analysis, we uncover that stress can indeed promote each level of integration. We also show how memory integration may apply to understanding effects of alcohol, highlighting extant clinical and preclinical findings and opportunities for further investigation. Finally, we consider the implications of integration and fragmentation for later memory-guided behavior, and the importance of understanding which type of memory representation is potentiated in order to design appropriate interventions.

压力会有力地影响我们形成记忆的方式,尤其是记忆在多大程度上被整合或置于潜在的时空和更广泛的知识架构中。这些不同的表征反过来又会对我们利用这些记忆指导以后行为的方式产生重大影响。令人费解的是,虽然压力在历史上一直被认为会促进记忆的分裂,导致记忆表征的脱节,但最近的研究表明,压力也能促进记忆的结合和整合。了解压力在何种情况下会促进记忆整合,将是解决这一差异并揭示压力影响日后行为的机制的关键。在这里,我们将从多个层面来研究记忆整合:将单个经验的内容联系在一起,在相关但不同的事件之间建立联系,以及将经验与预先存在的图式或因果结构感结合在一起。我们将讨论每种整合形式背后的神经和认知机制,以及有关压力、厌恶学习和负面情绪如何调节每种整合形式的研究结果。在这一分析中,我们发现压力确实可以促进每种形式的整合。我们还展示了记忆整合如何应用于理解酒精的影响,强调了现有的临床和临床前研究结果以及进一步研究的机会。最后,我们探讨了整合和分裂对以后记忆引导行为的影响,以及了解哪种类型的记忆表征会被强化以设计适当干预措施的重要性。
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引用次数: 0
Does sleep promote adaptation to acute stress: An experimental study 睡眠是否能促进对急性压力的适应:一项实验研究
IF 5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-02-04 DOI: 10.1016/j.ynstr.2024.100613
Emil Hein , Risto Halonen , Thomas Wolbers , Tommi Makkonen , Markus Kyllönen , Liisa Kuula , Ilmari Kurki , Philipp Stepnicka , Anu-Katriina Pesonen

Objectives

Evidence of the impact of chronic stress on sleep is abundant, yet experimental sleep studies with a focus on acute stress are scarce and the results are mixed. Our study aimed to fill this gap by experimentally investigating the effects of pre-sleep social stress on sleep dynamics during the subsequent night, as measured with polysomnography (PSG).

Methods

Thirty-four healthy individuals (65% females, Mage = 25.76 years SD = 3.35) underwent a stress-inducing (SC) or neutral control condition (CC) in virtual reality (VR). We used overnight EEG measurements to analyze the basic sleep parameters and power spectral density (PSD) across the sleep cycles, and measured heart rate and its variability (HRV), skin electrodermal activity (EDA), and salivary cortisol to capture physiological arousal during the VR task and the pre-sleep period.

Results

Following acute stress (SC), the amount of slow-wave sleep (SWS) was higher and N2 sleep lower relative to CC, specifically in the first sleep cycle. In SC, PSD was elevated in the beta-low (16–24 Hz) and beta-high (25–35 Hz) frequency ranges during both stages N2 and SWS over the entire night.

Conclusions

Sleep promoted adaptation to acute social stress by a longer duration of SWS in the subsequent sleep period, especially in early sleep. A similar homeostatic effect towards restorative sleep is well-evidenced in animal model stress studies but has not been previously reported in experimental human studies. Whether the high-frequency PSD activity during stages N2 and SWS also serves in the resolution of transient stress, remains open.

目的有大量证据表明慢性压力对睡眠有影响,但以急性压力为重点的实验性睡眠研究却很少,而且结果也不尽相同。我们的研究旨在通过多导睡眠图(PSG)的测量,实验性地研究睡前社会压力对随后一夜睡眠动态的影响,从而填补这一空白。方法34名健康人(65%为女性,年龄:25.76岁,平均年龄:3.35岁)在虚拟现实(VR)中接受了压力诱导(SC)或中性控制条件(CC)。我们使用通宵脑电图测量来分析各睡眠周期的睡眠结构和功率谱密度(PSD),并测量了心率及其变异性(HRV)、皮肤电活动(EDA)和唾液皮质醇,以捕捉 VR 任务期间和睡眠前的生理唤醒。在SC中,整夜N2和SWS阶段的β-低(16-24Hz)和β-高(25-35Hz)频率范围内的PSD都升高了。结论在随后的睡眠期,尤其是在早期睡眠中,睡眠通过延长SWS的持续时间促进了对急性社会压力的适应。类似的恢复性睡眠平衡效应在动物应激模型研究中得到了充分证实,但在人类实验研究中却未见报道。N2和SWS阶段的高频PSD活动是否也能起到缓解瞬时压力的作用,目前尚无定论。
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引用次数: 0
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Neurobiology of Stress
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