催产素对产后抑郁症患者母性行为的调节作用

产后抑郁症是指女性分娩后一段时间内出现的严重抑郁发作现象。研究表明, 催产素不仅参与分娩过程和正常的母性行为表达, 也在调节产后抑郁的发病及患者的母性行为中起到了重要的作用。产后抑郁症患者的情绪和认知功能受损, 这可能导致了母性行为表达质量的下降; 催产素可以通过中脑边缘多巴胺系统来调控母性行为, 作用于内侧视前区(MPOA)来激活中脑腹侧被盖区(VTA)-伏隔核(NAc)环路从而影响伏隔核内多巴胺的分泌; 催产素对产后抑郁症中母性行为的调节机制可能是通过调节五羟色胺系统的功能来发挥抗焦虑作用, 也可能是通过与其它激素的交互作用来加速母性行为的表达。未来研究进一步明确催产素在中枢神经环路中的功能差异, 以及社会支持对产后抑郁症患者催产素的使用带来的影响。     

急性心理应激影响记忆效果：心理韧性的调节作用

研究选取56名大学生被试,通过特里尔社会应激测验、记忆和心理韧性测验来探究急性心理应激对大学生记忆效果的影响,以及心理韧性在二者关系中的调节作用。结果表明相对于非应激组,应激组大学生的整体记忆成绩更差,且应激组中的高应激反应大学生的记忆成绩比低应激反应者的记忆成绩更差;心理韧性可以调节应激反应与记忆成绩之间的关系,表现为高心理韧性者的记忆成绩显著好于低心理韧性者。研究进一步从认知加工资源分配与再分配的视角讨论了心理应激、心理韧性与记忆功能三者间的关系与启示。     

母性应激对母性行为和心理功能的影响

成为母亲对女性而言是人生经历的特殊阶段, 她们在这个阶段发生的生理和心理的适应性改变对其自身和子代健康具有重要意义。母性应激是阻碍母亲适应性改变顺利进行的重要因素。母性应激会破坏人类母亲和雌性哺乳动物的母性行为、认知功能和情绪调节, 这种影响与糖皮质激素、催产素、催乳素等内分泌系统的调节失常; 母性环路、边缘系统及前额叶皮质等神经环路对刺激的神经反应改变以及神经发生、树突和突触重塑的可塑性变化有关。     

青少年心理韧性与恶意创造性行为倾向的关系

恶意创造力因其独特的“危害性”而与一般创造力有所区分。积极的人格特质如心理韧性由于可以促进一般创造力但对恶意有所抑制, 故其对恶意创造力的影响尚不清楚。通过2个研究考察心理韧性与恶意创造力的关系及其作用机制, 以及心理韧性与应激对恶意创造力的共同作用。结果表明：心理韧性水平能够显著负向预测青少年的恶意创造性行为, 且主要通过积极应对方式对恶意创造性行为起作用; 心理韧性对恶意创造性行为的影响也会受到应激环境的调节, 即相对于非应激条件, 应激条件下削弱了积极应对方式对恶意创造性行为的抑制作用。这些结果表明有必要注重培养青少年的心理韧性以抵御外界环境的不良影响, 并正确引导其创造力的发展。     

情景变换诱发已消退恐惧记忆重现的神经环路

暴露疗法是治疗创伤后应激障碍的主要行为疗法。当被试反复暴露于可引起恐惧反应的条件刺激(如白噪音), 但却不伴有非条件刺激(如足底电击)时, 恐惧记忆将被消退, 形成消退记忆。但恐惧记忆并未从根本上被擦除, 当被试在消退训练以外的情景暴露于条件刺激时, 已消退的恐惧记忆将会重现。海马、内侧前额叶皮层、杏仁核等脑区及其相互连接的神经环路是情景诱发恐惧记忆重现的生理基础。情景变化诱发恐惧记忆重现过程中, 海马可能是通过直接投射至杏仁核基底核、杏仁核外侧核或通过边缘前皮质间接调控杏仁核基底核、杏仁核外侧核的功能, 产生恐惧反应。     

慢性应激对大鼠空间学习记忆及海马和前脑皮层突触体膜流动性的影响

慢性应激对学习记忆功能的影响是神经科学的热点问题, 在脑内, 海马和前额叶是与学习记忆功能密切相关的重要脑区, 也是应激易累及损伤的主要靶区。膜流动性的改变在神经细胞功能活动中起重要作用。为探讨慢性应激对大鼠空间学习记忆功能的影响及前脑皮层和海马突触体膜流动性的作用。采用多因素慢性应激动物模型, 通过开场试验和Morris水迷宫测试大鼠行为及空间学习记忆能力; 并且测定大鼠前脑皮层和海马突触体膜流动性和突触体内游离Ca2+浓度的变化。研究结果显示, 与对照组相比, 应激组大鼠在应激后即刻, 在新异环境中的自发活动和探究行为显著降低(p<0.05, p<0.01), 空间学习记忆能力明显下降(p<0.05, p <0.01); 并且应激组大鼠前脑皮层和海马突触体膜流动性显著降低(p <0.05, p <0.01); 而突触体内游离Ca2+浓度的显著增加 (p <0.05, p <0.01)。停止应激后一周, 应激大鼠的各项指标有所恢复, 但仍未达到正常水平。研究结果提示, 慢性应激引起大鼠明显的开场行为改变和空间学习记忆功能障碍, 这些变化可能与突触体膜流动性和突触体内游离Ca2+浓度的变化密切相关。     

慢性应激损害大鼠学习记忆且抑制海马及额叶FGF2蛋白表达

慢性应激能够影响学习和记忆等认知功能。海马和额叶是与学习和记忆联系密切的脑区, 参与信息的获得、保持及提取。碱性成纤维生长因子(FGF2)对神经元发生、存活以及损伤修复具有重要促进作用, 目前成为神经系统退行性疾病相关研究的热点。本研究旨在探索慢性应激如何影响大鼠学习和记忆能力, 以及这一过程中FGF2蛋白在海马和额叶中表达的改变。实验中将16只雄性SD大鼠随机分为对照组和慢性应激组, 采用慢性不可预见温和刺激建立大鼠慢性应激模型, 通过Morris水迷宫实验及Y迷宫实验检测学习与记忆功能的改变, 并对海马及额叶中FGF2蛋白的表达情况进行Western blot及免疫组织化学检测。结果发现, 5周慢性应激导致大鼠学习和记忆能力受损, 海马及额叶FGF2蛋白表达下调。因此认为, FGF2蛋白可能参与慢性应激损害学习记忆能力的机制, 提示FGF2可能是诊断和治疗神经系统退行性病变的分子靶目标。     

创伤后应激障碍的动物模型及其神经生物学机制

创伤后应激障碍是指个体由于经历对生命具有威胁的事件或严重的创伤,导致症状长期持续的精神障碍。研究创伤后应激障碍的主要动物模型为条件性恐惧和应激敏感化模型。研究表明,创伤后应激障碍中长时程留存的恐惧性记忆、高唤醒等症状与大脑杏仁核、内侧前额叶皮层和海马三个脑区及下丘脑-垂体-肾上腺轴负反馈功能增强密切相关。其中杏仁核活动增强是条件性恐惧记忆获得、保持和表达的关键神经基础。内侧前额叶皮层对杏仁核的去抑制及海马向杏仁核传递的威胁性环境信息,促进创伤后应激障碍症状的出现。在经历创伤应激后糖皮质激素受体的上调及多巴胺活动的增强是创伤后应激障碍产生的主要神经基础。对创伤后应激障碍的药物治疗研究证明多巴胺D2受体在改善患者症状中的作用比较重要,但仍需作更深入的探索     

神经颗粒素与脑老化、疾病及应激关系

神经颗粒素是一种神经元特异性、Ca2＋敏感性的鈣调蛋白（CaM）结合蛋白,是蛋白激酶C的突触后底物,与信号传导和长时程增强（LTP）有关。这是一种新发现的脑特异性蛋白质。主要分布在前脑和海马,在皮质、海马CA1-CA3区、齿状回、纹状体和杏仁核中高表达。在大脑发育的不同阶段,神经颗粒素在脑内的含量和分布区域会发生变化,其生物学作用受到国内外学者的关注。近年来国外学者开始对神经颗粒素与脑老化、疾病及应激关系进行考查。该文将着重介绍对神经颗粒素在脑老化、疾病和应激过程中所扮演的角色的研究工作及其新发现,目的是对脑与行为关系的理解及有关的脑机制的研究提供一个新的视点。     

应激对记忆影响的脑科学研究及其教育启示

大量脑科学的研究揭示,应激对与海马相关的陈述性记忆的调节主要通过应激激素,尤其是糖皮质激素的分泌而发生作用,而影响的方向取决于一些调节变量,包括糖皮质激素升高的水平以及记忆的不同阶段等。研究发现基底外侧杏仁核是糖皮质激素对记忆不同阶段产生差异性影响的关键部位。因此,在教育过程中,既要科学地认识应激对记忆的消极影响,又要有效利用应激对记忆产生的调节作用,来提高学生的学习效率。     

Endurance factors improve hippocampal neurogenesis and spatial memory in mice

Physical activity improves learning and hippocampal neurogenesis. It is unknown whether compounds that increase endurance in muscle also enhance cognition. We investigated the effects of endurance factors, peroxisome proliferator-activated receptor δ agonist GW501516 and AICAR, activator of AMP-activated protein kinase on memory and neurogenesis. Mice were injected with GW for 7 d or AICAR for 7 or 14 d. Two weeks thereafter mice were tested in the Morris water maze. AICAR (7 d) and GW improved spatial memory. Moreover, AICAR significantly, and GW modestly, elevated dentate gyrus neurogenesis. Thus, pharmacological activation of skeletal muscle may mediate cognitive effects.     

A study of the contribution of hippocampal-accumbens-subpallidal projections to locomotor activity

Locomotor activity recorded in an automated open-field apparatus was increased substantially by unilateral injections of carbachol, a cholinergic agonist, into the dentate gyrus of the hippocampus. Hyperactivity elicited in this way was reduced significantly when glutamate antagonists were injected into the ipsilateral nucleus accumbens. Injecting gamma-aminobutyric acid into the ipsilateral subpallidal region also reduced the hyperactivity from injections of carbachol into the dentate gyrus. When these compounds were injected into the contralateral accumbens and subpallidal region, respectively, there was little or no reduction in the carbachol-elicited locomotor activity. These observations suggest that neural pathways fom hippocampus to accumbens to subpallidal region may contribute to locomotor activity.     

Unpacking the cognitive map: the parallel map theory of hippocampal function

In the parallel map theory, the hippocampus encodes space with 2 mapping systems. The bearing map is constructed primarily in the dentate gyrus from directional cues such as stimulus gradients. The sketch map is constructed within the hippocampus proper from positional cues. The integrated map emerges when data from the bearing and sketch maps are combined. Because the component maps work in parallel, the impairment of one can reveal residual learning by the other. Such parallel function may explain paradoxes of spatial learning, such as learning after partial hippocampal lesions, taxonomic and sex differences in spatial learning, and the function of hippocampal neurogenesis. By integrating evidence from physiology to phylogeny, the parallel map theory offers a unified explanation for hippocampal function.     

NT-3 facilitates hippocampal plasticity and learning and memory by regulating neurogenesis

In the adult brain, the expression of NT-3 is largely confined to the hippocampal dentate gyrus (DG), an area exhibiting significant neurogenesis. Using a conditional mutant line in which the NT-3 gene is deleted in the brain, we investigated the role of NT-3 in adult neurogenesis, hippocampal plasticity, and memory. Bromodeoxyuridine (BrdU)-labeling experiments demonstrated that differentiation, rather than proliferation, of the neuronal precursor cells (NPCs) was significantly impaired in DG lacking NT-3. Triple labeling for BrdU, the neuronal marker NeuN, and the glial marker GFAP indicated that NT-3 affects the number of newly differentiated neurons, but not glia, in DG. Field recordings revealed a selective impairment in long-term potentiation (LTP) in the lateral, but not medial perforant path-granule neuron synapses. In parallel, the NT-3 mutant mice exhibited deficits in spatial memory tasks. In addition to identifying a novel role for NT-3 in adult NPC differentiation in vivo, our study provides a potential link between neurogenesis, dentate LTP, and spatial memory.     

Neurogenesis decreases with age in the canine hippocampus and correlates with cognitive function

New neurons are continually produced in the adult mammalian brain from progenitor cells located in specific brain regions, including the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. We hypothesized that neurogenesis occurs in the canine brain and is reduced with age. We examined neurogenesis in the hippocampus of five young and five aged animals using doublecortin (DCX) and bromodeoxyuridine (BrdU) immunostaining. The total unilateral number of new neurons in the canine SGZ and granule cell layer (GCL) was estimated using stereological techniques based upon unbiased principles of systematic uniformly random sampling. Animals received 25mg/kg of BrdU once a day for 5 days and were euthanized 9 days after the last injection. We found evidence of neurogenesis in the canine brain and that cell genesis and neurogenesis are greatly reduced in the SGZ/GCL of aged animals compared to young. We further tested the hypothesis that an antioxidant fortified food or behavioral enrichment would improve neurogenesis in the aged canine brain and neurogenesis may correlate with cognitive function. Aged animals were treated for 2.8 years and tissue was available for six that received the antioxidant food, five that received the enrichment and six receiving both treatments. There were no significant differences in the absolute number of DCX or DCX-BrdU neurons or BrdU nuclei between the treatment groups compared to control animals. The number of DCX-positive neurons and double-labeled DCX-BrdU-positive neurons, but not BrdU-positive nuclei alone, significantly correlated with performance on several cognitive tasks including spatial memory and discrimination learning. These results suggest that new neurons in the aged canine dentate gyrus may participate in modulating cognitive functions.     

Running is the neurogenic and neurotrophic stimulus in environmental enrichment

Environmental enrichment (EE) increases dentate gyrus (DG) neurogenesis and brain-derived neurotrophic factor (BDNF) levels. However, running is considered an element of EE. To dissociate effects of physical activity and enrichment on hippocampal neurogenesis and BDNF levels, young female C57Bl/6 mice were housed under control, running, enrichment, or enrichment plus running conditions, and injected with bromodeoxyuridine. Cell genesis was assessed after 12 d and differentiation was analyzed 1 mo later. In addition, locomotor activity in the open field and hippocampal mature BDNF peptide levels were measured. Open-field adaptation was improved in all groups, compared to controls, but more so with running. New cell proliferation, survival, neuron number, and neurotrophin levels were enhanced only when running was accessible. We conclude that exercise is the critical factor mediating increased BDNF levels and adult hippocampal neurogenesis.     

Learning and adult neurogenesis: survival with or without proliferation?

Recent high quality papers have renewed interest in the phenomenon of neurogenesis within the adult mammalian brain. Many studies now show that neurogenesis can be modulated by environmental factors including physical activity, stress, and learning. These findings have considerable implications for neuroscience in general, including the study of learning and memory, neural network plasticity, aging, neurodegeneration, and the recovery from brain injury. Although new light has been shed on this field, many contradictory findings have been reported. Here we propose two principle issues which underlie these inconsistencies, with particular focus on the interaction between learning and neurogenesis. The first issue relates to the basic methodology of measuring the generation of new brain cells, i.e., proliferation, as compared to survival of the newly made cells. Mostly, measures of neurogenesis reported are a combination of proliferation and survival, making it impossible to distinguish between these separate processes. The second aspect is in regards to the role of environmental factors which can affect both proliferation and survival independently. Especially the interaction between stress and learning is of importance since these might counteract each other in some circumstances. Reviewing the literature while taking these issues into account indicates that, in contrast to some findings, cell proliferation in the dentate gyrus of the hippocampus as a result of learning cannot be ruled out yet. On the other hand, increased survival of granule cells in the dentate gyrus as a result of hippocampal-dependent learning has been clearly demonstrated. Moreover, this learning-induced survival of granule cells, which were born before the actual learning experience, might provide a molecular mechanism for the 'use it or lose it' principle.     

Neurogenesis and the spacing effect: learning over time enhances memory and the survival of new neurons

Information that is spaced over time is better remembered than the same amount of information massed together. This phenomenon, known as the spacing effect, was explored with respect to its effect on learning and neurogenesis in the adult dentate gyrus of the hippocampal formation. Because the cells are generated over time and because learning enhances their survival, we hypothesized that training with spaced trials would rescue more new neurons from death than the same number of massed trials. In the first experiment, animals trained with spaced trials in the Morris water maze outperformed animals trained with massed trials, but there was not a direct effect of trial spacing on cell survival. Rather, animals that learned well retained more cells than animals that did not learn or learned poorly. Moreover, performance during acquisition correlated with the number of cells remaining in the dentate gyrus after training. In the second experiment, the time between blocks of trials was increased. Consequently, animals trained with spaced trials performed as well as those trained with massed, but remembered the location better two weeks later. The strength of that memory correlated with the number of new cells remaining in the hippocampus. Together, these data indicate that learning, and not mere exposure to training, enhances the survival of cells that are generated 1 wk before training. They also indicate that learning over an extended period of time induces a more persistent memory, which then relates to the number of cells that reside in the hippocampus.     

c-Fos expression reveals aberrant neural network activity during cued fear conditioning in APPswe transgenic mice

The neural circuitry underlying emotional learning and memory is known to involve both the amygdala and hippocampus. Both of these structures undergo anatomical and functional changes during the course of Alzheimer's disease. The present study used expression of the immediate early gene c-Fos to examine the effect of amyloid-induced synaptic pathology on neural activity in the hippocampus and amygdala immediately following Pavlovian fear conditioning. Tg2576 mice underwent cued fear conditioning and the regional interdependencies of c-Fos expression in the hippocampus and the amygdala were assessed using structural equation modelling. Tg2576 mice displayed normal acquisition of conditioned freezing to a punctate auditory cue paired with shock. However, the analysis of c-Fos expression indicated abnormal regional activity in the hippocampal dentate gyrus of Tg2576 mice. Structural equation modelling also supported the view that activity within the amygdala was independent of hippocampal activity in Tg2576 mice (unlike control mice) and regional interaction between the dentate gyrus and CA3 region was disrupted. The results provide novel insight into the effects of excess amyloid production on brain region interdependencies underpinning emotional learning.