Behavioural Brain Research最新文献_第5页

Xiaochaihu decoction alleviates chronic stress-induced depressive-like behavior in mice by modulating the gut microbiota-brain axis 小柴胡汤通过调节肠道菌群-脑轴减轻小鼠慢性应激性抑郁样行为

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2026-01-15 DOI: 10.1016/j.bbr.2026.116046

Xiangwei Zhao , Jing Liang , Ting Zhou , Jun Hou , Jingzi Yu , Jinfu Shi , Jun Du , Haitao Wang , Xiujun Zhang , Xueliang Shang

Background

Xiaochaihu Decoction (XCHD) has shown potential in treating neurological disorders, but its mechanisms in alleviating depression remain unclear.

Aim of the study

The aim of this study was to examine if the XCHD was able to alleviate depressive-like impairment in a mouse model of chronic mild stress.

Materials and methods

Fifty male C57BL/6 mice were divided into five groups: control (CON), stress (CUMS), stress with low and high XCHD doses (CUMS+L-XCHD, CUMS+H-XCHD), and fluoxetine (CUMS+FLX). The deprssion model was established using chronic unpredictable mild stress (CUMS) and isolated feeding. Animal behavior was assessed using the sucrose preference and open-field tests. Neuroplasticity, inflammation, and gut microbiota were analyzed using Western blotting, immunofluorescence, and 16S rRNA sequencing.

Results

XCHD increased sucrose consumption and improved spatial learning and memory in stressed mice. It also alleviated anxiety and behavioral despair, restored hippocampal neuroplasticity, and reduced inflammation. XCHD modulated the Nogo-A/S1P2R-Gαq-PKC signaling pathway and enhanced tight junction proteins in the colon. Additionally, XCHD restored gut microbiota balance, increasing Firmicutes and reducing Bacteroides and Proteobacteria.

Conclusion

XCHD ameliorates depressive-like symptoms by modulating the gut microbiota-brain axis, enhancing neuroplasticity, and reducing inflammation, suggesting its potential as an antidepressant therapy.

小柴胡汤（XCHD）已显示出治疗神经系统疾病的潜力，但其缓解抑郁症的机制尚不清楚。本研究的目的是研究XCHD是否能够减轻慢性轻度应激小鼠模型的抑郁样损伤。材料与方法将50只雄性C57BL/6小鼠分为5组：对照组（CON）、应激组（CUMS）、XCHD低、高剂量应激组（CUMS+L-XCHD、CUMS+H-XCHD）和氟西汀（CUMS+FLX）。采用慢性不可预测轻度应激（CUMS）和隔离饲养建立抑郁模型。采用蔗糖偏好试验和野外试验评估动物行为。使用Western blotting、免疫荧光和16S rRNA测序分析神经可塑性、炎症和肠道微生物群。结果xchd增加应激小鼠的蔗糖消耗，改善小鼠的空间学习记忆能力。它还能减轻焦虑和行为绝望，恢复海马神经可塑性，减少炎症。XCHD调节Nogo-A/S1P2R-Gαq-PKC信号通路，增强结肠紧密连接蛋白。此外，XCHD恢复了肠道菌群平衡，增加了厚壁菌门，减少了拟杆菌门和变形菌门。结论xchd可通过调节肠道菌群-脑轴、增强神经可塑性、减轻炎症等机制改善抑郁样症状，提示xchd具有抗抑郁治疗的潜力。

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引用次数: 0

Prediction bias for physical exertion in chronic fatigue: Evidence from an observational paradigm 慢性疲劳中体力消耗的预测偏差：来自观察范式的证据

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2026-01-15 DOI: 10.1016/j.bbr.2026.116043

Vallilath V.M. Ramakrishnan , Yakeen Hafouda , Joe Butler , Paul Mullins , Hans-Peter Kubis

Many clinical conditions are associated with a high incidence of chronic fatigue. While some physiological causes for chronic fatigue are established, e.g., processes connected to inflammation, psychological factors may also contribute. The metacognitive theory of dyshomeostasis proposes that a mismatch between cognitive predictions and sensory evidence for actions undermines self-efficacy and perception of control, contributing to chronic fatigue. We aimed to investigate alterations in prediction for physical exertion in participants with chronic fatigue using a new paradigm based on observation, therefore avoiding sensory feedback from the periphery. Participants watched randomised sets of videos with people exercising at different physical exertion levels. Participants had to predict the rate of physical exertion (RPE) of the individuals observed in the videos. Additionally, questionnaires for chronic fatigue, disability, mood, clinical history and body characteristics were assessed. 49 complete data sets from participants with chronic fatigue and 74 data sets from control subjects were analysed in this study. Compared with the control group, participants with chronic fatigue predicted a significantly higher RPE for the observed exercising individuals across all exertion levels. Multiple linear regression models revealed that in the control group, the variance of the bias in the prediction of exertion was significantly explained by the characteristics of the individuals observed in the videos. However, in the chronic fatigue group, the variance of bias in the prediction of exertion was strongly explained by the characteristics of the observer, i.e. fatigue levels and disability. Outcomes revealed that participants with chronic fatigue predicted higher exertion levels during observations and that levels were strongly influenced by their clinical symptoms, suggesting a prediction bias for exertion being present even without performing physical tasks.

许多临床状况都与慢性疲劳的高发有关。虽然已经确定了慢性疲劳的一些生理原因，例如与炎症有关的过程，但心理因素也可能起作用。动态失调的元认知理论提出，认知预测和感觉证据之间的不匹配会破坏自我效能感和控制感，从而导致慢性疲劳。我们的目的是研究慢性疲劳参与者体力消耗预测的变化，使用基于观察的新范式，从而避免来自外周的感觉反馈。参与者观看了一组随机的视频，视频中人们以不同的体力消耗水平进行锻炼。参与者必须预测视频中观察到的个体的体力消耗率（RPE）。此外，对慢性疲劳、残疾、情绪、临床病史和身体特征进行问卷调查。本研究分析了来自慢性疲劳受试者的49组完整数据集和来自对照受试者的74组数据集。与对照组相比，慢性疲劳的参与者预测，在所有运动水平下，观察到的运动个体的RPE都明显更高。多元线性回归模型显示，在对照组中，运动强度预测偏差的方差显著地被视频中观察到的个体特征所解释。然而，在慢性疲劳组中，预测运动的偏差方差可以用观察者的特征（即疲劳水平和残疾）来解释。结果显示，慢性疲劳的参与者在观察期间预测了更高的运动水平，而运动水平受到他们的临床症状的强烈影响，这表明即使没有进行体力劳动，运动水平也存在预测偏差。

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引用次数: 0

Tackling the interplay between the brain and kidneys: CYP2C19 mice as a preclinical tool for studying cognitive impairment in kidney disease? 解决大脑和肾脏之间的相互作用：CYP2C19小鼠作为研究肾脏疾病认知障碍的临床前工具？

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2026-01-15 DOI: 10.1016/j.bbr.2026.116047

Dušanka Stanić , Jelena Petrović , Miloš Ilić , Jelena Nedeljković , Ana Ivanović , Neda Milinković , Marin M. Jukić , Sophie Ferlicot , Gaye Hafez , Ziad Massy , Vesna Pešić

Chronic kidney disease (CKD) is a global health issue, often associated with cognitive and behavioural disturbances. The cytochrome P450 enzyme CYP2C19 has previously been associated with neurobehavioural changes. Humanised transgenic CYP2C19 mice show emotional changes, and abnormalities in locomotion and in brain regions involved in memory and stress response. This study aimed to investigate whether cognitive impairments in CYP2C19 transgenic mice are related to impaired renal function or structure. Adult male and female wild-type and CYP2C19 mice (total N = 41) were included in the study. Behavioural phenotyping was performed by examining short-term memory in Novel Object Recognition Test (NORT) and social interaction in Social Recognition Test (SRT). After 24 h, urine was collected, animals were sacrificed, and blood samples and kidneys were collected and used for biochemical assays and histological assessment. NORT and SRT revealed cognitive deficits and possible social anxiety in CYP2C19 mice compared to wild-type controls, as no difference was observed in time CYP2C19 mice spent interacting with novel objects or unfamiliar animals. Biochemical analysis showed no significant differences in total protein, albumin, urea, creatinine and uric acid between experimental groups. Histological evaluation confirmed that there was no structural kidney damage in CYP2C19 mice. Our findings indicate that in CYP2C19 mice, cognitive and behavioural changes described here are independent of renal dysfunction. Therefore, CYP2C19 mouse model represents a valuable tool to study cognitive impairment without concomitant kidney disease and could serve as a suitable control in studies investigating the interplay between cognitive decline and CKD.

慢性肾脏疾病（CKD）是一个全球性的健康问题，通常与认知和行为障碍有关。细胞色素P450酶CYP2C19先前与神经行为改变有关。人源化的转基因CYP2C19小鼠表现出情绪变化、运动异常以及与记忆和应激反应有关的大脑区域异常。本研究旨在探讨CYP2C19转基因小鼠的认知障碍是否与肾功能或结构受损有关。选取成年雄性和雌性野生型小鼠及CYP2C19小鼠共41只。行为表型通过新对象识别测试（NORT）中的短期记忆和社会识别测试（SRT）中的社会互动进行。24h后采集尿液，处死动物，采集血液和肾脏，进行生化分析和组织学评估。与野生型对照相比，NORT和SRT显示CYP2C19小鼠的认知缺陷和可能的社交焦虑，因为CYP2C19小鼠与新物体或不熟悉的动物互动的时间没有差异。生化分析显示，各试验组间总蛋白、白蛋白、尿素、肌酐、尿酸均无显著差异。组织学评价证实CYP2C19小鼠无结构性肾损害。我们的研究结果表明，在CYP2C19小鼠中，这里描述的认知和行为变化与肾功能障碍无关。因此，CYP2C19小鼠模型是研究无并发肾脏疾病的认知功能障碍的有价值的工具，可以作为研究认知能力下降与CKD相互作用的合适对照。

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引用次数: 0

Anodal HD-tDCS of vmPFC facilitates learning of monosemous and polysemous words: A computational modeling study vmPFC的阳极HD-tDCS促进单义和多义单词的学习：一个计算模型研究

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2026-01-15 DOI: 10.1016/j.bbr.2026.116042

Yufeng Zhou , Fanghui Ge , Weiwei Zhang , Mengjie Lv , John W. Schwieter , Huanhuan Liu

Vocabulary learning requires learners to establish stable mappings between symbols and meanings. Reinforcement learning (RL) principles, through feedback-based value computation, provide a compelling framework supporting such mappings, with the ventromedial prefrontal cortex (vmPFC) playing a key role in value-based learning and decision-making. In this study, we combined artificial pseudowords with a probabilistic reversal learning paradigm and applied high-definition transcranial direct current stimulation (HD-tDCS) in the vmPFC to investigate its role in vocabulary acquisition. Computational modeling revealed that anodal HD-tDCS led to more stable integration of feedback and greater choice consistency. Parametric fMRI further showed enhanced value coding in the putamen and postcentral gyrus for monosemous words, along with strengthened frontostriatal connectivity that supported the acquisition of polysemous words. Collectively, these findings demonstrate that anodal HD-tDCS over the vmPFC, along with RL mechanisms, effectively facilitates vocabulary acquisition, advancing our understanding of the neural basis of language learning.

词汇学习要求学习者在符号和意义之间建立稳定的映射关系。强化学习（RL）原理通过基于反馈的价值计算，为这种映射提供了一个令人信服的框架，腹内侧前额叶皮层（vmPFC）在基于价值的学习和决策中起着关键作用。在本研究中，我们将人工假词与概率反转学习范式相结合，采用高分辨率经颅直流电刺激（HD-tDCS）在vmPFC中研究其在词汇习得中的作用。计算模型表明，阳极HD-tDCS使反馈集成更稳定，选择一致性更强。参数化功能磁共振成像进一步显示，壳核和中央后回对单字的价值编码增强，额纹状体连接增强，支持多义词的习得。总的来说，这些发现表明，在vmPFC上的无节点HD-tDCS，以及RL机制，有效地促进了词汇习得，促进了我们对语言学习神经基础的理解。

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引用次数: 0

Corrigendum to: “Maternal antibiotic administration during a critical developmental window has enduring neurobehavioural effects in offspring mice” [Behav. Brain Res. 404 (2021) 113156] 更正：“在一个关键的发育窗口期间，母体抗生素给药对后代小鼠有持久的神经行为影响”[行为学杂志]。中国生物医学工程学报，2004(5):349 - 349。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2026-01-14 DOI: 10.1016/j.bbr.2026.116041

Rory O’Connor , Gerard M. Moloney , Christine Füllling , Ken O’Riordan , Pat Fitzgerald , Harriët Schellekens , Timothy G. Dinan , John F. Cryan

引用次数: 0

Sex and estrous phase influence functional connectivity during fear extinction 性和发情期影响恐惧消退过程中的功能连接。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2026-01-11 DOI: 10.1016/j.bbr.2026.116039

Alyssa A. Hohorst , Jessica D. Westerman , Carolina Sanchez-Mendoza , Margaret K. Tanner , Miles Q. Dryden , Juliet R. Freund , Remla A. Abdul , Kevin M. Crombie , Benjamin N. Greenwood

Female rats exposed to fear extinction during the proestrus and estrus phases (Pro/Est) or following estradiol administration in ovariectomized females show enhanced extinction memory and reduced fear relapse relative to males and females extinguished during the metestrus and diestrus phases (Met/Di). In Pro/Est females, this effect requires activity of the substantia nigra-to-dorsolateral striatum (SN-DLS) dopamine (DA) pathway during extinction. Although elevated ovarian hormones can enhance SN-DLS DA activity, it remains unclear whether estrous phase also influences activity of catecholaminergic neurons in regions beyond the SN during extinction. Furthermore, how the nigrostriatal pathway interacts with traditional extinction networks during extinction has not yet been investigated. To address these questions, we examined sex- and estrous phase-dependent differences in neural activation and functional connectivity during extinction across a distributed network including midbrain catecholaminergic regions, traditional fear extinction networks, and striatal subregions. During extinction, Pro/Est females froze less than males and Met/Di females, exhibited less cFos in the prelimbic cortex and cingulate gyrus compared to males, had greater cFos in the medial amygdala relative to males, and displayed greater cFos within ventral tegmental area DA neurons compared to males and Met/Di females. Furthermore, functional connectivity during extinction was highest in Pro/Est females, with the DLS identified as a hub, indicating high influence over network connectivity. These findings provide new insight into how sex and estrous phase influence extinction processing and suggest the DLS may be a key region influencing extinction learning in Pro/Est females.

在发情前期和发情期（Pro/Est）暴露于恐惧消退的雌性大鼠，或在去卵巢的雌性大鼠服用雌二醇后，相对于在发情期和发情期（Met/Di）消失的雄性和雌性大鼠，表现出更强的恐惧消退记忆和更少的恐惧复发。在Pro/Est雌性中，这种效应需要在灭绝期间黑质-背外侧纹状体（SN-DLS）多巴胺（DA）通路的活动。尽管卵巢激素升高可增强SN- dls DA活性，但尚不清楚发情期是否也影响SN外区域儿茶酚胺能神经元的活性。此外，黑质纹状体通路在灭绝过程中如何与传统的灭绝网络相互作用尚未得到研究。为了解决这些问题，我们研究了一个分布式网络，包括中脑儿茶酚胺能区、传统的恐惧消退网络和纹状体亚区，在消退过程中，性别和动情期相关的神经激活和功能连接差异。在灭绝过程中，Pro/Est雌性比雄性和Met/Di雌性更少冻结，与雄性相比，前边缘皮层和扣带回的cFos更少，内侧杏仁核的cFos比雄性更大，腹侧被盖区DA神经元的cFos比雄性和Met/Di雌性更大。此外，灭绝期间的功能连通性在Pro/Est雌性中最高，DLS被确定为枢纽，表明对网络连通性的影响很大。这些发现为性别和发情期如何影响消去加工提供了新的见解，并表明DLS可能是影响Pro/Est雌性消去学习的关键区域。

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引用次数: 0

GLB regulates microglial M1/M2 polarization after cerebral ischemic injury via the TLR4 signaling pathway GLB通过TLR4信号通路调控脑缺血损伤后小胶质细胞M1/M2极化。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2026-01-11 DOI: 10.1016/j.bbr.2026.116038

Guanghong Shen , Jianbo Xu , Jiansong Chen , Irum Naz Abbasi , Xia Yuan , Fei Wu , Javaria Sundus , Qining Yang , Marong Fang , Nashwa Amin

Inflammatory injury after ischemic stroke (IS) severely limits the treatment of stroke. Microglial polarization involved in the regulation of neuroinflammatory responses and brain injury related to IS. Glibenclamide (GLB) has been proven to inhibit microglial activation and alleviate neuroinflammation. However, the effect of GLB on microglial polarization and its mechanism remain unclear in IS. Here, we study the neuroprotective effect of GLB and its possible mechanism. In this study, the area of infarction, blood-brain barrier (BBB) permeability, and zea longa score of the mice were detected. Neurobehavioral functions were evaluated using the Rota-Rod and Open Field Test (OFT). Western blotting was performed to assess the protein levels of Sur1, Trpm4, TLR4, NF-κB, IL-1β, and TGF-β, while immunofluorescence (IF) was used to detect Iba-1, iNOS, and Arg-1. Our results demonstrated that GLB-mediated inhibition of the Sur1-Trpm4 channel reduced infarct size, preserved BBB integrity, and improved neurological function. GLB upregulated TGF-β and Arg-1 expression while downregulating TLR4, NF-κB, IL-1β, Iba-1, and iNOS in IS mice. It exerted neuroprotective effects and alleviated neuroinflammation. In summary, GLB may mitigate IS by modulating microglial M1/M2 polarization and suppressing TLR4/NF-κB pathway activation.

缺血性脑卒中后的炎症损伤严重限制了脑卒中的治疗。小胶质细胞极化参与IS相关的神经炎症反应和脑损伤的调节。格列本脲（GLB）已被证明可以抑制小胶质细胞的激活和减轻神经炎症。然而，GLB对IS小胶质细胞极化的影响及其机制尚不清楚。在此，我们研究GLB的神经保护作用及其可能的机制。本研究检测小鼠脑梗死面积、血脑屏障通透性、zelonga评分。采用Rota-Rod and Open Field Test （OFT）评估神经行为功能。Western blotting检测Sur1、Trpm4、TLR4、NF-κB、IL-1β、TGF-β蛋白水平，免疫荧光（IF）检测Iba-1、iNOS、Arg-1蛋白水平。我们的研究结果表明，glb介导的Sur1-Trpm4通道抑制减少了梗死面积，保留了血脑屏障的完整性，改善了神经功能。GLB上调IS小鼠TGF-β和Arg-1的表达，下调TLR4、NF-κB、IL-1β、Iba-1和iNOS的表达。发挥神经保护作用，减轻神经炎症。综上所述，GLB可能通过调节小胶质细胞M1/M2极化和抑制TLR4/NF-κB通路激活来缓解IS。

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引用次数: 0

Does telencephalic lateralization modulate anxiety? Effects of unilateral ablation assessed in the light-dark and open field tests in Nile tilapia (Oreochromis niloticus) 端脑侧化调节焦虑吗？在尼罗罗非鱼（Oreochromis niloticus）的光暗和野外试验中评估单侧消融的影响。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2026-01-11 DOI: 10.1016/j.bbr.2026.116036

Jaqueline Alves de Souza , Gabrielle Araujo Pimentel , Luiz Henrique Florindo

Functional brain lateralization is widespread among vertebrates, including teleost fish, and plays a key role in emotional regulation, particularly in anxiety. However, the contribution of each telencephalic hemisphere to anxiety-like behavior remains poorly understood in most fish species. This study investigated whether unilateral telencephalic ablation affects anxiety-like responses in Nile tilapia, a species of ecological and economic relevance that is increasingly used in neurobehavioral research. Eighty-four fish were assigned to four groups: left ablation, right ablation, sham-operated, and intact controls. After behavioral performance was assessed using the light–dark test (n = 37) and the open field test (n = 35). Telencephalic ablation did not alter preference for the dark compartment; however, fish with right-hemisphere ablation showed increased avoidance of the light compartment, suggesting a potential lateralized contribution to threat evaluation. Across repeated exposures, freezing and erratic swimming decreased in all groups, including those with ablations, indicating preserved habituation despite telencephalic damage. In the open field test, no group differences were detected in freezing, thigmotaxis, or spatial distribution, although erratic swimming was more frequent in ablated animals, with the left-lesioned group differing significantly from both control groups. Overall, these findings indicate that telencephalic lateralization in Nile tilapia does not exclusively govern anxiety-like behavior but may influence specific components, such as light avoidance and motor reactivity. The preserved habituation and subtle lateralized effects highlight compensatory neural plasticity and the involvement of extra-telencephalic circuits. This study provides new evidence for emotional lateralization in teleost and reinforces the value of Nile tilapia as a model for investigating the neural basis of lateralized emotional processing.

功能性脑侧化在包括硬骨鱼在内的脊椎动物中普遍存在，并在情绪调节，特别是焦虑方面起着关键作用。然而，在大多数鱼类中，每个端脑半球对焦虑样行为的贡献仍然知之甚少。这项研究调查了单侧端脑消融是否会影响尼罗罗非鱼的焦虑样反应，尼罗罗非鱼是一种生态和经济相关的物种，越来越多地用于神经行为研究。84条鱼被分为四组：左消融组、右消融组、假手术组和完整对照组。采用明暗测试（n = 37）和野外测试（n = 35）评估行为表现。端脑消融术没有改变对暗室的偏好；然而，右半球消融的鱼显示出对光室的回避增加，这表明潜在的侧化对威胁评估有贡献。经过反复暴露，所有组（包括消融组）的冻结和不稳定游泳都减少了，这表明尽管端脑损伤，但仍保持了习惯化。在野外测试中，虽然在消融动物中不稳定的游动更为频繁，但在冻结、移动性或空间分布方面没有发现组间差异，左侧病变组与对照组有显著差异。总的来说，这些发现表明，尼罗罗非鱼的端脑侧化并不完全控制焦虑样行为，但可能影响特定的成分，如避光和运动反应性。保留的习惯化和微妙的侧化效应突出了代偿性神经可塑性和端外脑回路的参与。本研究为硬骨鱼的情绪偏侧化提供了新的证据，并强化了尼罗罗非鱼作为研究偏侧化情绪加工神经基础的模型的价值。

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引用次数: 0

Interactions of vitamins and gut microbiota in neurodevelopmental disorders 神经发育障碍中维生素和肠道菌群的相互作用。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2026-01-10 DOI: 10.1016/j.bbr.2026.116028

Lizhi Liu , Zhuoliang Gu , Boyu Guo , Yanan Wang , Tatiana V. Kirichenko , Yuliya V. Markina , Alexander M. Markin , Huiming Hua , Dahong Li , Anthony Yiu-Ho Woo

Good nutritional status in early life is vital for neurodevelopment, but eating disorders like picky eating heighten risks of nutritional imbalance and dysbiosis. Dysregulated gut microbiomes are increasingly linked to gastrointestinal issues and neurodevelopmental disorders. Vitamin deficiency may aggravate these conditions, emphasizing the need for focused nutritional care. The gut microbiota plays a key role in brain function and development, offering potential as a therapeutic target. At present, supplementation of probiotics, prebiotics, vitamins and other nutrients is presumed to produce some benefits to neurodevelopmental disorders though robust data on their effectiveness remain scarce. We propose that vitamin deficiency and dysbiosis interact, influencing neurodevelopment and brain function. Our review identifies key substrates such as vitamins, short-chain fatty acids, cytokines, neurotransmitters, and tryptophan metabolites in this network and provides mechanistic insights into their roles in the pathogenesis of neurodevelopmental disorders, paving the way for personalized strategies to address these conditions.

生命早期良好的营养状况对神经发育至关重要，但挑食等饮食失调会增加营养失衡和生态失调的风险。肠道微生物群失调越来越多地与胃肠道问题和神经发育障碍联系在一起。维生素缺乏可能会加重这些情况，强调需要重点营养护理。肠道微生物群在大脑功能和发育中起着关键作用，提供了作为治疗靶点的潜力。目前，益生菌、益生元、维生素和其他营养素的补充被认为对神经发育障碍有一定的益处，尽管关于其有效性的可靠数据仍然很少。我们认为维生素缺乏和生态失调相互作用，影响神经发育和脑功能。我们的综述确定了该网络中的关键底物，如维生素、短链脂肪酸、细胞因子、神经递质和色氨酸代谢物，并提供了它们在神经发育障碍发病机制中的作用的机制见解，为解决这些疾病的个性化策略铺平了道路。

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引用次数: 0

The mPFC-PAG in defensive coping: A correlational but not causal role in shifting strategy 防御应对中的mPFC-PAG回路：在策略转移中起相关而非因果作用。

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2026-01-10 DOI: 10.1016/j.bbr.2026.116037

Meijuan Li , Qian Wang , Xiaoxue Li , Zhixin Wu , Wenjun Li , Yvbo Ning , Juanjuan Zhang , Xiao Jiang , Kai Wang , Liang Jing

Defensive behaviors under threat are fundamental for survival, and their dysregulation contributes to psychiatric disorders. The medial prefrontal cortex (mPFC) and periaqueductal gray (PAG) pathway are implicated in regulating defensive behaviors, but their specific role in choosing between coping strategies remains unclear. Here, we investigated these brain regions using the two-way active avoidance (TWAA) task in male rats. Anatomical tracing confirmed a robust unidirectional projection from layer V neurons of mPFC subregions (including ACC, PL, IL) to the PAG. Using c-Fos immunohistochemistry, we found significantly higher neuronal activation in the infralimbic cortex (IL), but not other mPFC subregions or the PAG, in rats exhibiting active avoidance (AA, active avoidance rate > 80 %) compared to those showing reactive escape (RE, active avoidance rate ＜50 %). However, combining retrograde tracing with c-Fos labeling showed no differences in activation of PAG projecting neurons between AA groups and RE groups across all mPFC subregions. Furthermore, optogenetic activation of IL neurons or PAG neurons did not alter established AA/RE coping preferences in the TWAA task, nor did it affect baseline locomotion in the open field test. These findings reveal a critical dissociation between regional neuronal activity and the causal control of defensive behaviors. While IL activity correlates with AA, acute global activation of the mPFC or PAG is insufficient to override established coping preferences. This suggests that adaptive strategy switching likely requires precisely timed, cell-type-specific activation or modulation during learning phase, rather than broad activation after strategies are consolidated.

Significance statement

This study demonstrates that while infralimbic cortex activity correlates with active avoidance behavior, acute optogenetic activation of the mPFC or PAG is insufficient to shift established defensive coping strategies. These findings reveal a critical dissociation between regional neural activity patterns and the causal control of defensive behaviors.

威胁下的防御行为是生存的基础，其失调会导致精神疾病。内侧前额叶皮层（mPFC）和导水管周围灰质通路（PAG）参与调节防御行为，但它们在应对策略选择中的具体作用尚不清楚。在这里，我们使用双向主动回避（TWAA）任务来研究雄性大鼠的这些大脑区域。解剖示迹证实mPFC亚区（包括ACC、PL、IL）的V层神经元向PAG有强大的单向投射。通过c-Fos免疫组化，我们发现主动回避（AA，主动回避率为80%）的大鼠与反应性逃避（RE，主动回避率<50%）的大鼠相比，边缘下皮层（IL）的神经元活化明显更高，但其他mPFC亚区或PAG的神经元活化则没有。然而，将逆行示踪与c-Fos标记相结合，在所有mPFC亚区AA组和RE组之间PAG投射神经元的激活没有差异。此外，IL神经元或PAG神经元的光遗传激活不会改变TWAA任务中既定的AA/RE应对偏好，也不会影响开阔场测试中的基线运动。这些发现揭示了区域神经元活动和防御行为的因果控制之间的关键分离。虽然IL活性与AA相关，但mPFC或PAG的急性全局激活不足以覆盖已建立的应对偏好。这表明适应性策略转换可能需要在学习阶段精确定时、细胞类型特异性激活或调节，而不是在策略巩固后广泛激活。意义声明：本研究表明，虽然边缘下皮层活动与主动回避行为相关，但mPFC或PAG的急性光遗传激活不足以改变既定的防御应对策略。这些发现揭示了区域神经活动模式和防御行为的因果控制之间的关键分离。

{"title":"The mPFC-PAG in defensive coping: A correlational but not causal role in shifting strategy","authors":"Meijuan Li , Qian Wang , Xiaoxue Li , Zhixin Wu , Wenjun Li , Yvbo Ning , Juanjuan Zhang , Xiao Jiang , Kai Wang , Liang Jing","doi":"10.1016/j.bbr.2026.116037","DOIUrl":"10.1016/j.bbr.2026.116037","url":null,"abstract":"<div><div>Defensive behaviors under threat are fundamental for survival, and their dysregulation contributes to psychiatric disorders. The medial prefrontal cortex (mPFC) and periaqueductal gray (PAG) pathway are implicated in regulating defensive behaviors, but their specific role in choosing between coping strategies remains unclear. Here, we investigated these brain regions using the two-way active avoidance (TWAA) task in male rats. Anatomical tracing confirmed a robust unidirectional projection from layer V neurons of mPFC subregions (including ACC, PL, IL) to the PAG. Using c-Fos immunohistochemistry, we found significantly higher neuronal activation in the infralimbic cortex (IL), but not other mPFC subregions or the PAG, in rats exhibiting active avoidance (AA, active avoidance rate > 80 %) compared to those showing reactive escape (RE, active avoidance rate ＜50 %). However, combining retrograde tracing with c-Fos labeling showed no differences in activation of PAG projecting neurons between AA groups and RE groups across all mPFC subregions. Furthermore, optogenetic activation of IL neurons or PAG neurons did not alter established AA/RE coping preferences in the TWAA task, nor did it affect baseline locomotion in the open field test. These findings reveal a critical dissociation between regional neuronal activity and the causal control of defensive behaviors. While IL activity correlates with AA, acute global activation of the mPFC or PAG is insufficient to override established coping preferences. This suggests that adaptive strategy switching likely requires precisely timed, cell-type-specific activation or modulation during learning phase, rather than broad activation after strategies are consolidated.</div></div><div><h3>Significance statement</h3><div>This study demonstrates that while infralimbic cortex activity correlates with active avoidance behavior, acute optogenetic activation of the mPFC or PAG is insufficient to shift established defensive coping strategies. These findings reveal a critical dissociation between regional neural activity patterns and the causal control of defensive behaviors.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"502 ","pages":"Article 116037"},"PeriodicalIF":2.3,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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