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Chronic social defeat stress gives rise to social avoidance through fear learning 慢性社交失败压力通过恐惧学习产生社交回避。
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-09-04 DOI: 10.1016/j.bbr.2024.115245

Chronic social defeat stress (CSDS), a widely used rodent model of stress, reliably leads to decreased social interaction in stress susceptible animals. Here, we investigate a role for fear learning in this response using male 129 Sv/Ev mice, a strain that is more vulnerable to CSDS than the commonly used C57BL/6 strain. We first demonstrate that defeated 129 Sv/Ev mice avoid a CD-1 mouse, but not a conspecific, indicating that motivation to socialize is intact in this strain. CD-1 avoidance is characterized by approach behavior that results in running in the opposite direction, activity that is consistent with a threat response. We next test whether CD-1 avoidance is subject to the same behavioral changes found in traditional models of Pavlovian fear conditioning. We find that associative learning occurs across 10 days CSDS, with defeated mice learning to associate the color of the CD-1 coat with threat. This leads to the gradual acquisition of avoidance behavior, a conditioned response that can be extinguished with 7 days of repeated social interaction testing (5 tests/day). Pairing a CD-1 with a tone leads to second-order conditioning, resulting in avoidance of an enclosure without a social target. Finally, we show that social interaction with a conspecific is a highly variable response in defeated mice that may reflect individual differences in generalization of fear to other social targets. Our data indicate that fear conditioning to a social target is a key component of CSDS, implicating the involvement of fear circuits in social avoidance.

慢性社会挫败应激(CSDS)是一种广泛使用的啮齿动物应激模型,它能可靠地导致应激易感动物的社会互动减少。在这里,我们使用雄性 129Sv/Ev 小鼠研究了恐惧学习在这种反应中的作用,这种小鼠比常用的 C57BL/6 品系更容易受到 CSDS 的影响。我们首先证明,被打败的 129Sv/Ev 小鼠会躲避 CD-1 小鼠,但不会躲避同种小鼠,这表明该品系小鼠的社交动机是完整的。CD-1回避的特点是接近行为导致向相反方向奔跑,这种活动与威胁反应一致。我们接下来要测试的是,CD-1 的回避行为是否与传统巴甫洛夫恐惧条件反射模型中的行为变化相同。我们发现,联想学习发生在 10 天的 CSDS 期间,被打败的小鼠学会了将 CD-1 外衣的颜色与威胁联系起来。这导致小鼠逐渐获得回避行为,这种条件反应可以通过 7 天的重复社会互动测试(每天 5 次测试)来消除。将 CD-1 与音调配对会产生二阶条件反射,从而导致回避没有社交目标的围栏。最后,我们表明,与同种小鼠的社会互动是败育小鼠的一个高度可变的反应,这可能反映了个体在将恐惧泛化到其他社会目标方面的差异。我们的数据表明,对社交目标的恐惧条件反射是 CSDS 的关键组成部分,这意味着恐惧回路参与了社交回避。
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引用次数: 0
Interplay of MeCP2/REST/Synaptophysin-BDNF and intranasal oxytocin influence on Aβ-induced memory and cognitive impairments MeCP2/REST/Synaptophysin-BDNF和鼻内催产素对Aβ诱导的记忆和认知障碍的相互影响
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-09-03 DOI: 10.1016/j.bbr.2024.115235

Background

Alzheimer's disease (AD) is linked to the accumulation of Aβ, increased tau hyperphosphorylation, persistent neuroinflammation, and a decline in neurotrophic factors, neurogenesis, and synaptic plasticity. Oxytocin (OT) has a significant impact on memory and learning. We examined the influence of intranasal (IN) OT on synaptic plasticity, neurogenesis, histone acetylation, and spatial and cognitive memories in rats.

Methods

25–35 (5 µg/2.5 µl) was administered bilaterally in the CA1 of male Wistar rats for four consecutive days. After seven days of recovery, OT (2 µg/µl, 10 µl in each nostril) was administered IN for seven consecutive days. Working, spatial, and cognitive memories, and gene expression of neurogenesis- and synaptic plasticity-involved factors were measured in the hippocampus. Histone acetylation (H3K9 and H4K8) was also measured using western blotting.

Results

IN administration of OT significantly improved working and spatial memory impairment induced by Aβ and increased the factors involved in synaptic plasticity (MeCP2, REST, synaptophysin, and BDNF) and neurogenesis (Ki67 and DCX). We also found an enhancement in the levels of H3K9ac and H4K8ac following OT administration.

Conclusion

These findings indicated that IN OT could improve hippocampus-related behaviors by increasing synaptic plasticity, stimulating neurogenesis, and chromatin plasticity.

背景:阿尔茨海默病(AD)与 Aβ 的积累、tau 过度磷酸化的增加、持续的神经炎症以及神经营养因子、神经发生和突触可塑性的下降有关。催产素(OT)对记忆和学习有重要影响。我们研究了鼻内注射(IN)催产素对大鼠突触可塑性、神经发生、组蛋白乙酰化以及空间记忆和认知记忆的影响:方法:连续四天在雄性 Wistar 大鼠 CA1 双侧注射 Aβ25-35(5µg/2.5µl)。恢复 7 天后,连续 7 天在大鼠鼻孔内注射 OT(2µg/µl,每个鼻孔 10µl)。测量了海马的工作记忆、空间记忆和认知记忆,以及神经发生和突触可塑性相关因子的基因表达。组蛋白乙酰化(H3K9 和 H4K8)也用 Western 印迹法进行了测定:结果:IN OT明显改善了Aβ诱导的工作记忆和空间记忆损伤。结果:IN OT能明显改善Aβ诱导的工作记忆和空间记忆损伤,参与突触可塑性的因子(MeCP2、REST、突触素和BDNF)和神经发生因子(Ki67和DCX)也因IN OT的给药而明显增加。我们还发现,在服用 OT 后,H3K9ac 和 H4K8ac 的水平也有所提高:这些研究结果表明,IN OT可通过增加突触可塑性、刺激神经发生和染色质可塑性来改善海马相关行为。
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引用次数: 0
Intermittent theta burst stimulation of the left dorsolateral prefrontal cortex has no additional effect on the efficacy of virtual reality exposure therapy for acrophobia. A randomized double-blind placebo-controlled study 间歇性θ脉冲刺激左侧背外侧前额叶皮层对虚拟现实暴露疗法治疗恐高症的疗效没有额外影响。随机双盲安慰剂对照研究。
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-09-03 DOI: 10.1016/j.bbr.2024.115232

Anxiety disorders are among the most common mental disorders. Treatment guidelines recommend pharmacotherapy and cognitive behavioral therapy as standard treatment. Although cognitive behavioral therapy is an effective therapeutic approach, not all patients benefit sufficiently from it. In recent years, non-invasive brain stimulation techniques, such as transcranial magnetic stimulation, have been investigated as promising adjuncts in the treatment of affective disorders. The aim of this study is to investigate whether a combination of intermittent theta burst stimulation (iTBS) and virtual reality exposure therapy leads to a significantly greater reduction in acrophobia than virtual reality exposure with sham stimulation. In this randomized double-blind placebo-controlled study, 43 participants with acrophobia received verum or sham iTBS over the left dorsolateral prefrontal cortex prior to two sessions of virtual reality exposure therapy. Stimulation of the left dorsolateral prefrontal cortex with iTBS was motivated by an experimental study showing a positive effect on extinction memory retention. Acrophobic symptoms were assessed using questionnaires and two behavioral approach tasks one week before, after treatment and six months after the second diagnostic session. The results showed that two sessions of virtual reality exposure therapy led to a significant reduction in acrophobic symptoms, with an overall remission rate of 79 %. However, there was no additional effect of iTBS of the left dorsolateral prefrontal cortex on the therapeutic effects. Further research is needed to determine how exactly a combination of transcranial magnetic stimulation and exposure therapy should be designed to enhance efficacy.

焦虑症是最常见的精神障碍之一。治疗指南建议将药物疗法和认知行为疗法作为标准治疗方法。虽然认知行为疗法是一种有效的治疗方法,但并非所有患者都能从中充分获益。近年来,经颅磁刺激等非侵入性脑部刺激技术作为治疗情感障碍的辅助手段受到了广泛关注。本研究旨在探讨间歇性θ脉冲刺激(iTBS)与虚拟现实暴露疗法相结合是否会比虚拟现实暴露加假刺激更显著地减少恐高症。在这项随机双盲安慰剂对照研究中,43 名患有恐高症的参与者在接受两个疗程的虚拟现实暴露疗法之前,在左侧背外侧前额叶皮层接受了verum或假iTBS刺激。使用iTBS刺激左侧背外侧前额叶皮层的动机是,一项实验研究显示iTBS对消退记忆的保持有积极作用。在治疗前一周、治疗后一周以及第二次诊断治疗六个月后,使用调查问卷和两项行为接近任务对患者的恐惧症状进行了评估。结果显示,两个疗程的虚拟现实暴露疗法显著减轻了恐惧症症状,总体缓解率达到 79%。但是,左侧背外侧前额叶皮层的 iTBS 对治疗效果没有额外影响。要确定经颅磁刺激与暴露疗法的具体结合方式,以提高疗效,还需要进一步的研究。
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引用次数: 0
Complex housing in adulthood state-dependently affects the excitation-inhibition balance in the infralimbic prefrontal cortex of male C57Bl/6 mice 成年期的复杂饲养会对雄性 C57Bl/6 小鼠下边缘前额叶皮层的兴奋-抑制平衡产生状态依赖性影响。
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-09-02 DOI: 10.1016/j.bbr.2024.115233

The prefrontal cortex (PFC) plays an important role in social behavior and is sensitive to stressful circumstances. Challenging life conditions might change PFC function and put individuals at risk for maladaptive social behavior. The excitation-inhibition (EI) balance of prefrontal neurons appears to play a crucial role in this process. Here, we examined how a challenging life condition in C57BL/6JolaHsd mice, i.e. group-housing 6 mice in a complex environment for 10 days in adulthood, changes the EI-balance of infralimbic prefrontal neurons in layer 2/3, compared to standard pair-housing. Slices were prepared from “undisturbed” mice, i.e. the first mouse taken from the cage, or mice taken ∼15 min later, who were mildly aroused after removal of the first mouse. We observed a housing-condition by arousal-state interaction, with in the complex housing group an elevated EI-balance in undisturbed and reduced EI-balance in mildly aroused animals, while no differences were observed in standard housed animals. The change was explained by a shift in mIPSC and mEPSC frequency, while amplitudes remained unaffected. Female mice showed no housing-by-state interaction, but a main effect of housing was found for mIPSCs, with a higher frequency in complex- versus standard-housed females. No effects were observed in males who were complex-housed from a young age onwards. Explorative investigations support a potential mediating role of corticosterone in housing effects on the EI-balance of males. We argue that taking the arousal state of individuals into account is necessary to better understand the consequences of exposure to challenging life conditions for prefrontal function.

前额叶皮质(PFC)在社会行为中扮演着重要角色,并对压力环境十分敏感。具有挑战性的生活环境可能会改变前额叶皮质的功能,使人面临适应不良的社会行为的风险。前额叶神经元的兴奋-抑制(EI)平衡似乎在这一过程中起着至关重要的作用。在这里,我们研究了C57BL/6JolaHsd小鼠具有挑战性的生活条件(即成年后6只小鼠在复杂环境中集体饲养10天)与标准配对饲养相比如何改变第2/3层下侧前额叶神经元的EI平衡。切片取自 "未受干扰 "的小鼠,即从笼子中取出的第一只小鼠,或在取出第一只小鼠后轻度唤醒的约 15 分钟后取出的小鼠。我们观察到了饲养条件与唤醒状态之间的相互作用,在复合饲养组中,未受干扰动物的EI-平衡升高,而轻度唤醒动物的EI-平衡降低,而在标准饲养动物中未观察到差异。这种变化可以用 mIPSC 和 mEPSC 频率的变化来解释,而振幅则不受影响。雌性小鼠没有表现出饲养状态的交互作用,但发现饲养状态对 mIPSC 有主效应,复合饲养的雌性小鼠的 mIPSC 频率高于标准饲养的雌性小鼠。从幼年起就被复杂饲养的雄性小鼠则没有受到影响。探索性研究表明,皮质酮在雄性动物的情商平衡中可能起着中介作用。我们认为,要更好地理解暴露在具有挑战性的生活条件下对前额叶功能的影响,就必须考虑到个体的唤醒状态。
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引用次数: 0
Neural mechanisms underlying cognitive impairment in depression and cognitive benefits of exercise intervention 抑郁症认知障碍的神经机制和运动干预对认知的益处。
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-09-02 DOI: 10.1016/j.bbr.2024.115218

Depression is associated with functional brain impairments, although comprehensive studies remain limited. This study reviews neural mechanisms underlying cognitive impairment in depression and identifies associated activation abnormalities in brain regions. The study also explores the underlying neural processes of cognitive benefits of exercise intervention for depression. Executive function impairments, including working memory, inhibitory control and cognitive flexibility are associated with frontal cortex and anterior cingulate areas, especially dorsolateral prefrontal cortex. Depression is associated with certain neural impairments of reward processing, especially orbitofrontal cortex, prefrontal cortex, nucleus accumbens and other striatal regions. Depressed patients exhibit decreased activity in the hippocampus during memory function. Physical exercise has been found to enhance memory function, executive function, and reward processing in depression patients by increasing functional brain regions and the brain-derived neurotrophic factor (BDNF) as a nutritional factor also plays a key role in exercise intervention. The study documents neurophysiological mechanisms behind exercise intervention's improved functions. In summary, the study provides insights into neural mechanisms underlying cognitive impairments in depression and the effectiveness of exercise as a treatment.

抑郁症与大脑功能障碍有关,但全面的研究仍然有限。本研究回顾了抑郁症认知障碍的神经机制,并确定了相关脑区的激活异常。研究还探讨了运动干预对抑郁症患者认知获益的潜在神经过程。包括工作记忆、抑制控制和认知灵活性在内的执行功能障碍与额叶皮层和前扣带回区域有关,尤其是背外侧前额叶皮层。抑郁症与奖赏处理的某些神经损伤有关,尤其是眶额皮质、前额皮质、伏隔核和其他纹状体区域。抑郁症患者的海马体在发挥记忆功能时活动减少。研究发现,体育锻炼可通过增加脑功能区来增强抑郁症患者的记忆功能、执行功能和奖赏处理能力,而作为营养因子的脑源性神经营养因子(BDNF)在锻炼干预中也发挥着关键作用。研究记录了运动干预改善功能背后的神经生理学机制。总之,这项研究深入揭示了抑郁症认知障碍的神经机制以及运动作为治疗手段的有效性。
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引用次数: 0
Blunted food conditioned place preference-like behavior in adolescent-stressed male hamsters 青春期应激雄性仓鼠的食物条件性场所偏好行为减弱
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-09-02 DOI: 10.1016/j.bbr.2024.115234

Social stress during adolescence results in long lasting weight gain, obesity, and enhanced food hoarding behavior in hamsters. We wanted to determine whether stress also enhanced conditioned place preference-like behavior (CPP-like) for food reward, as would be expected from studies with substances like cocaine. Our experimental animals were exposed daily to aggressive adults for two weeks in early puberty, while also trained to explore a V-shaped maze containing a food reward at one end. They were tested for CPP-like behavior on the last day of social stress. Our results showed that while stress enhanced weight gain, food intake, food efficiency, and body fat, it caused a reduction of Place Preference as compared to controls. In fact, the correlated relationship between Place Preference and body fat was inverted by stress exposure: while it was positively correlated in controls, it was mildly negatively correlated in stressed hamsters. These unexpected data illustrate the extent of adaptive behavior in foraging animals once a resource has become untrustworthy.

青春期的社会压力会导致仓鼠长期体重增加、肥胖和囤积食物行为增强。我们想确定压力是否也会增强对食物奖赏的条件性场所偏好行为(CPP-like),正如可卡因等物质的研究预期的那样。我们的实验动物在青春期早期每天接触具有攻击性的成年仓鼠两周,同时训练它们探索一个 V 形迷宫,迷宫的一端有食物奖励。在社会压力的最后一天,我们对它们进行了类似 CPP 行为的测试。我们的结果表明,与对照组相比,虽然压力会促进体重增加、食物摄入量、食物效率和体脂增加,但却会导致位置偏好降低。事实上,场所偏好与体脂之间的相关关系因压力暴露而颠倒:在对照组中呈正相关,而在压力仓鼠中则呈轻度负相关。这些出乎意料的数据说明,一旦资源变得不可信,觅食动物的适应行为程度会有多大。
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引用次数: 0
Opioid-environment interaction: Contrasting effects of morphine administered in a novel versus familiar environment on acute and repeated morphine induced behavioral effects and on acute morphine ERK activation in reward associated brain areas 阿片类药物与环境的相互作用:在新环境和熟悉环境中施用吗啡对吗啡诱导的急性和重复行为效应以及吗啡ERK在奖赏相关脑区的急性激活效应的对比效应。
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-08-30 DOI: 10.1016/j.bbr.2024.115221

We report that environmental context can have a major impact on morphine locomotor behavior and ERK effects. We manipulated environmental context in terms of an environmental novelty/ familiarity dimension and measured morphine behavioral effects in both acute and chronic morphine treatment protocols. Wistar rats (n=7 per group) were injected with morphine 10 mg/kg or vehicle (s.c.), and immediately placed into an arena for 5 min, and locomotor activity was measured after one or 5 days. The morphine treatments were initiated either when the environment was novel or began after the rats had been familiarized with the arena by being given 5 daily nondrug tests in the arena. The results showed that acute and chronic morphine effects were strongly modified by whether the environment was novel or familiar. Acute morphine administered in a novel environment increased ERK activity more substantially in several brain areas, particularly in reward-associated areas such as the VTA in comparison to when morphine was given in a familiar environment. Repeated morphine treatments initiated in a novel environment induced a strong locomotor sensitization, whereas repeated morphine treatments initiated in a familiar environment did not induce a locomotor stimulant effect but rather a drug discriminative stimulus dis-habituation effect. The marked differential effects of environmental novelty/familiarity and ongoing dopamine activity on acute and chronic morphine treatments may be of potential clinical relevance for opioid drug addiction.

我们报告说,环境背景会对吗啡的运动行为和ERK效应产生重大影响。我们从环境新奇度/熟悉度的维度操纵了环境背景,并在急性和慢性吗啡治疗方案中测量了吗啡的行为效应。给 Wistar 大鼠(每组 7 只)注射吗啡 10 毫克/千克或吗啡载体(静脉注射),并立即将其放入竞技场中 5 分钟,然后在 1 天或 5 天后测量其运动活动。吗啡治疗要么在大鼠对环境感到陌生时开始,要么在大鼠通过每天在场内进行5次非药物测试熟悉场内环境后开始。结果表明,吗啡的急性和慢性作用会因环境是新奇的还是熟悉的而发生强烈变化。与在熟悉的环境中施用吗啡相比,在新环境中施用的急性吗啡能更大幅度地增加多个脑区的ERK活性,尤其是在与奖赏相关的区域,如VTA。在新奇环境中重复注射吗啡会诱导强烈的运动敏感化,而在熟悉环境中重复注射吗啡则不会诱导运动刺激效应,而是诱导药物分辨刺激的不习惯效应。环境的新颖性/熟悉性和持续的多巴胺活动对急性和慢性吗啡治疗的明显不同影响可能与阿片类药物成瘾有潜在的临床相关性。
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引用次数: 0
White matter correlates of cognition: A diffusion magnetic resonance imaging study 认知的白质相关性:扩散磁共振成像研究
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-08-30 DOI: 10.1016/j.bbr.2024.115222

Background

Our comprehension of the interplay of cognition and the brain remains constrained. While functional imaging studies have identified cognitive brain regions, structural correlates of cognitive functions remain underexplored. Advanced methods like Diffusion Magnetic Resonance Imaging (DMRI) facilitate the exploration of brain connectivity and White Matter (WM) tract microstructure. Therefore, we conducted connectometry method on DMRI data, to reveal WM tracts associated with cognition.

Methods

125 healthy participants from the National Institute of Mental Health Intramural Healthy Volunteer Dataset were recruited. Multiple regression analyses were conducted between DMRI-derived Quantitative Anisotropy (QA) values within WM tracts and scores of participants in Flanker Inhibitory Control and Attention Test (attention), Dimensional Change Card Sort (executive function), Picture Sequence Memory Test (episodic memory), and List Sorting Working Memory Test (working memory) tasks from National Institute of Health toolbox. The significance level was set at False Discovery Rate (FDR)<0.05.

Results

We identified significant positive correlations between the QA of WM tracts within the left cerebellum and bilateral fornix with attention, executive functioning, and episodic memory (FDR=0.018, 0.0002, and 0.0002, respectively), and a negative correlation between QA of WM tracts within bilateral cerebellum with attention (FDR=0.028). Working memory demonstrated positive correlations with QA of left inferior longitudinal and left inferior fronto-occipital fasciculi (FDR=0.0009), while it showed a negative correlation with QA of right cerebellar tracts (FDR=0.0005).

Conclusion

Our results underscore the intricate link between cognitive performance and WM integrity in frontal, temporal, and cerebellar regions, offering insights into early detection and targeted interventions for cognitive disorders.

背景:我们对认知与大脑相互作用的理解仍然受到限制。虽然功能成像研究已经确定了认知脑区,但认知功能的结构相关性仍未得到充分探索。扩散磁共振成像(DMRI)等先进方法有助于探索大脑连接性和白质(WM)束微观结构。因此,我们对 DMRI 数据进行了连接测量法,以揭示与认知相关的白质束。在WM束内的DMRI衍生定量各向异性(QA)值与美国国家卫生研究院工具箱中的Flanker抑制控制和注意力测试(注意力)、维度变化卡片分类(执行功能)、图片序列记忆测试(外显记忆)和列表分类工作记忆测试(工作记忆)任务的得分之间进行了多元回归分析。显著性水平设定为假发现率(FDR):我们发现左侧小脑和双侧穹窿内WM束的QA与注意力、执行功能和外显记忆之间存在明显的正相关(FDR分别为0.018、0.0002和0.0002),而双侧小脑内WM束的QA与注意力之间存在负相关(FDR=0.028)。工作记忆与左下纵束和左下前枕束的QA呈正相关(FDR=0.0009),而与右侧小脑束的QA呈负相关(FDR=0.0005):我们的研究结果表明,认知能力与额叶、颞叶和小脑区域的WM完整性之间存在着错综复杂的联系,这为认知障碍的早期检测和有针对性的干预提供了启示。
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引用次数: 0
Cortical high-frequency oscillations (≈ 110 Hz) in cats are state-dependent and enhanced by a subanesthetic dose of ketamine 猫的皮层高频振荡(≈ 110Hz)具有状态依赖性,亚麻醉剂量的氯胺酮会增强这种振荡。
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-08-30 DOI: 10.1016/j.bbr.2024.115231

Ketamine is an NMDA receptor antagonist that has antidepressant and anesthetic properties. At subanesthetic doses, ketamine induces transient psychosis in humans, and is used to model psychosis in experimental animals. In rodents, subanesthetic doses of ketamine increase the power of high-frequency oscillations (HFO, > 100 Hz) in the electroencephalogram (EEG), a frequency band linked to cognitive functions. However, to date, the effects of ketamine in carnivores and primates have been poorly investigated. Here, we examined in the cat, cortical HFO during wakefulness, sleep, and after administering a sub-anesthetic dose of ketamine. Four cats were prepared with cortical electrodes for chronic polysomnographic recordings in head-restrained conditions. The cortical HFO power, connectivity, direction of the information flow using Granger Causality (GC) analysis, their relationships with respiratory activity, and the effect of auditory stimulation were analyzed. During wakefulness, but not during sleep, we found that HFO were coupled with the inspiratory phase of the respiration. After ketamine administration, HFO power was enhanced and remained associated with the inspiratory phase. GC analysis suggests that ketamine-enhanced HFO originate from the olfactory bulb (OB) and stream towards the prefrontal cortex (Pf). Accordingly, occluding the nostrils significantly reduced the power of the ketamine-enhanced HFO in both the OB and Pf. Finally, auditory stimulation did not affect HFO. In conclusion, the HFO are associated with respiration during wakefulness, but not during sleep. The enhancement of this rhythm by ketamine may disrupt cortical information processing, which could contribute to some of the neuropsychiatric effects associated with ketamine.

氯胺酮是一种 NMDA 受体拮抗剂,具有抗抑郁和麻醉特性。在亚麻醉剂量下,氯胺酮会诱发人类短暂性精神病,并被用于在实验动物中建立精神病模型。在啮齿类动物中,亚麻醉剂量的氯胺酮会增加脑电图(EEG)中高频振荡(HFO,> 100Hz)的功率,这一频段与认知功能有关。然而,迄今为止,氯胺酮对食肉动物和灵长类动物的影响还鲜有研究。在这里,我们研究了猫在清醒、睡眠和注射亚麻醉剂量氯胺酮后的皮层高频脑电图。我们为四只猫准备了皮质电极,以便在头部受限的条件下进行慢性多导睡眠图记录。研究人员利用格兰杰因果关系(GC)分析法分析了大脑皮层 HFO 功率、连接性、信息流方向、它们与呼吸活动的关系以及听觉刺激的影响。我们发现,在清醒状态下,而在睡眠状态下,HFO 与呼吸的吸气阶段相关联。服用氯胺酮后,HFO的功率增强,并保持与吸气相联系。GC 分析表明,氯胺酮增强的 HFO 源自嗅球(OB)并流向前额叶皮层(Pf)。因此,闭塞鼻孔可显著降低氯胺酮增强的 HFO 在嗅球和前额叶皮层的功率。最后,听觉刺激对 HFO 没有影响。总之,HFO与清醒时的呼吸有关,但与睡眠时无关。氯胺酮增强这种节律可能会扰乱大脑皮层的信息处理,从而导致氯胺酮的一些神经精神效应。
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引用次数: 0
Excitotoxic spinal damage induced by kainic acid impairs locomotion, alters nociception, and reduces CREB nuclear translocation 凯尼酸诱导的兴奋性脊髓损伤会损害运动能力、改变痛觉并减少 CREB 的核转位
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2024-08-30 DOI: 10.1016/j.bbr.2024.115219

Our previous in vitro studies showed that excitotoxicity evoked by glutamate analogue kainate (KA) significantly decreased the number of rat spinal neurons and triggered high release of glutamate leading to locomotor network block. Our current objective was to assess the role of CREB as a predictive marker of damage following chemically-induced spinal cord injury by using in vivo and in vitro models. Thus, in vivo excitotoxicity in Balb/c adult mice was induced by KA intraspinal injection, while in vitro spinal cord excitotoxicity was produced by bath-applied KA. KA application evoked significant neuronal loss, deterioration in hindlimb motor coordination and thermal allodynia. In addition, immunohistochemical analysis showed that KA application resulted in decreased number of CREB positive nuclei in the ventral horn and in dorsal layers III-IV. Our data suggests that excitotoxic-induced neuronal loss may be potentially predicted by altered CREB nuclear translocation.

我们之前的体外研究表明,谷氨酸类似物凯恩酸盐(KA)诱发的兴奋毒性会显著减少大鼠脊髓神经元的数量,并引发谷氨酸的大量释放,导致运动网络阻滞。我们目前的目标是利用体内和体外模型评估 CREB 作为化学诱导脊髓损伤后损伤预测标志物的作用。因此,通过椎管内注射 KA 诱导 Balb/c 成年小鼠体内兴奋性中毒,而体外脊髓兴奋性中毒则是通过沐浴施加 KA 产生的。应用 KA 会诱发神经元大量缺失、后肢运动协调性恶化和热异感。此外,免疫组化分析表明,应用 KA 会导致腹侧角和背侧三至四层的 CREB 阳性核数目减少。我们的数据表明,兴奋毒性诱导的神经元损失可能是由 CREB 核转位的改变所预测的。
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Behavioural Brain Research
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