星形胶质细胞功能障碍在抑郁症发病中的作用研究进展

星型胶质细胞在突触形成、神经元代谢、神经递质传递等方面起重要作用,其退行性病变可引起突触蛋白水平降低、神经元体积减小及神经递质传递异常,进而引起神经精神性疾病的发生。抑郁症患者前额叶皮层、海马、杏仁核以及前扣带回等多个脑区均有星型胶质细胞密度减低,提示星形胶质细胞与抑郁症发病密切相关。研究表明,能量和营养支持、谷氨酸(glutamate,Glu)转运和代谢、N-甲基-D-天(门)冬氨酸(N-methyl-D-aspartate,NMDA)受体活性调节以及炎症反应异常等星形胶质细胞功能障碍参与抑郁症的发生。本文就星形胶质细胞功能障碍在抑郁症发病机理中的作用进行综述。     

星形胶质细胞诱导成年神经干细胞的神经发生

在中枢神经系统 ,成年后新神经元发生主要见于两个脑区 ,即室管下区 (ｓｕｂｖｅｎｔｒｉｃｕｌａｒｚｏｎｅ)与海马的颗粒下区 (ｓｕｂｇｒａｎｕｌａｒｚｏｎｅ)。正常情况下 ,除上述脑区外的其它脑区能够产生神经胶质细胞 ,但是不能产生神经元。为了研究神经元和 /或神经胶质细胞对来源于成年的神经干细胞分化的影响 ,Ｓｏｎｇ等分离了成年大鼠海马的神经元和星形胶质细胞 ,将其分别或联合与来自成年的、依赖ＦＧＦ 2的神经干细胞共培养 ,意外地发现神经元促进神经干细胞分化为少突胶质细胞 ,而星形胶质细胞则促进神经干细胞分化为神经…     

小脑皮质结构年龄相关变化的研究进展

衰老过程中小脑皮质出现明显的形态学变化,包括体积萎缩、重量减轻、皮层厚度下降、神经元数量减少,树突丢失、细胞超微结构改变、神经递质紊乱以及胶质细胞增生等。神经元数量丢失与结构退变以及神经递质改变可能会导致老年小脑皮质神经环路破坏和信息传输紊乱,与老年个体运动调节功能及运动学习能力下降有关;神经胶质活动增强对维持老年小脑皮质的形态和功能可能起保护作用。     

脊髓以上水平疼痛相关神经通路机制的研究进展

疼痛是一种多维度的情感体验,痛感觉和痛情绪是其最主要的两个组分。关于疼痛,以往研究只专注于痛觉传递通路的某个环节或某个关键脑区,缺乏行为个体脑区与脑区连接在整体状态下参与疼痛或调节疼痛的证据。新的实验工具和实验技术的诞生,为痛感觉和痛情绪的神经通路研究带来了曙光。本文综述了近年来脊髓水平以上的神经系统(包括丘脑、杏仁核、中脑导水管周围灰质、臂旁核和内侧前额叶皮层)参与形成痛感觉和调节痛情绪的神经通路结构和功能基础,为疼痛的深入研究提供线索。     

BAX敲除对小鼠大脑皮层和海马星形胶质细胞分布的影响

星形胶质细胞是大脑中一类高度异质的重要大胶质细胞,不仅在脑的发育和功能中起到重要作用,也参与多种神经病理生理学过程。多项研究表明B淋巴细胞瘤-2相关X蛋白(B-cell lymphoma-2 associated X protein,BAX)依赖性凋亡通路参与调控正常发育过程中脑内神经元的数量与分布,但是对其调控星形胶质细胞的研究则较为匮乏。本文旨在研究BAX是否参与不同脑区星形胶质细胞分布的调控。以纯合子和杂合子BAX敲除小鼠为研究对象,用SOX9免疫荧光染色法检测6周龄小鼠的大脑皮层和海马中星形胶质细胞的密度。结果显示,星形胶质细胞的密度在不同皮层分区之间以及皮层和海马之间存在显著差异,并且BAX敲除导致海马中星形胶质细胞的密度显著降低,皮层中GABA能抑制神经元密度显著升高,而皮层中星形胶质细胞的密度则未受显著影响。以上结果提示,BAX差异调控皮层星形胶质细胞与神经元,也差异调控皮层与海马中的星形胶质细胞。这项研究为了解星形胶质细胞的区域异质性和BAX在大脑发育中的功能提供了重要信息。     

小鼠不同脑区星形胶质细胞小分子诱导转分化和基因表达差异的研究

该文旨在比较小分子化合物诱导小鼠不同脑区星形胶质细胞向神经元转分化的特性,并利用转录组测序技术分析小鼠不同脑区星形胶质细胞的基因表达差异。以新生小鼠皮层和海马的星形胶质细胞作为起始细胞,通过小分子化合物VCR诱导其向神经元转分化,利用免疫荧光染色检测转分化过程中细胞形态的变化以及神经元的比例,通过转录组测序比较两种星形胶质细胞的基因表达差异,并对差异基因进行荧光定量PCR验证及GO富集分析。结果表明,皮层星形胶质细胞经VCR诱导转分化为神经元的能力要显著优于海马星形胶质细胞;转录组测序发现,两种星形胶质细胞有12 658个基因存在差异表达,GO分析结果表明,在皮层星形胶质细胞中高表达的基因更多地参与细胞分裂的过程,推测差异显著基因GAD2、EYA2、GSX2、INSM1以及GNG3是与转分化相关的基因。该研究对星形胶质细胞向神经元转分化的机制研究具有借鉴意义。     

吗啡与安定对清醒猕猴前额叶皮层神经元自发放电活动的影响

本实验采用慢性微电极技术,对清醒猕猴前额叶皮层神经元自发放电活动进行了观察。并结合动物行为观察了吗啡与安定对该脑区电活动的影响。在14只对伤害性刺激有反应的神经元中,观察了9只神经元对静脉注射吗啡的效应,其中8只被激活;对伤害性有反应的7只神经元,注射安定后,仅有2只神经元的活动受到抑制,其它无变化。看来吗啡与安定对前额叶皮层的活动在一定的影响。     

前边缘皮质生长激素抑制素神经元在吗啡引起的行为学改变中的作用

药物成瘾是一种由药物滥用所引起的慢性、复发性的精神疾病,主要特征是不计后果的强迫性用药。药物成瘾涉及多个脑区的神经可塑性改变。前边缘皮质(prelimbic cortex, PrL)是背内侧前额叶皮质的主要区域,有大量的锥体神经元,其兴奋性神经投射可以促进可卡因觅药行为。PrL还存在少量GABA能中间神经元,对PrL的兴奋性神经元功能、信息整合和传递起到重要的调控作用,而这一部分神经元在药物成瘾过程中的作用并不清楚。小清蛋白(parvalbumin, PV)和生长激素抑制素(somatostatin, SST)神经元是前额叶皮质中分布广泛的两类主要的抑制性GABA能中间神经元。本研究利用PV-Cre和SSTCre的转基因小鼠,结合化学遗传学的方法探究PrL中间神经元在吗啡引起的行为学改变中的作用。结果显示,特异性抑制PrL脑区SST神经元可以显著增加小鼠的焦虑水平,但不影响小鼠的运动能力;抑制PrL脑区SST神经元降低小鼠吗啡诱导的活动性增强及条件位置偏爱;而抑制PrL脑区PV神经元则对小鼠的运动能力、焦虑水平及吗啡引起的行为学改变均没有显著影响。本研究通过对PrL脑区PV及SST中间神经元在吗啡诱导的行为学改变中作用的研究,为成瘾药物作用的细胞及神经基础提供了依据。     

多巴胺调节海马神经元可塑性的研究进展

多巴胺是脑内重要的信息传递物质,不仅可以作为递质释放到前额叶、伏隔核等脑区,直接进行信息传递,也可以作为调质调节其它突触递质的传递,并影响神经元可塑性。海马参与构成边缘系统,受多巴胺能神经支配,执行着有关学习记忆以及空间定位的功能。海马神经元的可塑性是学习记忆的细胞分子基础。研究表明,多巴胺对海马神经元的突触可塑性和兴奋性可塑性都具有重要的调节作用。本文扼要综述多巴胺对海马神经元突触可塑性和兴奋性可塑性的调节机制的研究进展,以期为DA系统参与海马区学习记忆功能的研究提供新思路,更深入地了解学习记忆的神经机制。     

猫运动皮层神经元和S100、GFAP阳性细胞的年龄相关性变化

比较了青、老年猫运动皮层神经元与S100、GFAP免疫阳性胶质细胞的形态学变化,并探讨其与衰老过程中运动功能衰退的关系。采用Nissl染色显示青、老年猫运动皮层分层结构和神经元。免疫组织化学方法（SABC法）显示青、老年猫运动皮层S100免疫反应阳性(S100-immunoreactive, S100-IR)细胞及胶质纤维酸性蛋白免疫反应阳性(GFAP-immunoreactive, GFAP-IR)细胞。在Olympus 显微镜下,用Moitcam 5000数码成像与分析系统计数运动皮层各层神经元、S100-IR细胞及GFAP-IR细胞的数量,并随机抽样测量S100-IR、GFAP-IR细胞的胞体直径。与青年猫相比,老年猫运动皮层Ⅴ、Ⅵ层神经元密度显著下降(P < 0.01),老年猫运动皮层中S100-IR和GFAP-IR细胞密度与胞体直径均显著增加(P < 0.01),且细胞的免疫阳性反应较强。研究结果表明,猫运动皮层的神经元密度在衰老过程中Ⅴ、Ⅵ层神经元密度显著下降,有可能会降低老年个体运动皮层对运动的调控能力;随着衰老、运动皮层的星形胶质细胞出现明显的反应性活化与增生,这对维持大脑运动皮层神经元的活性和神经元之间的通讯联系,从而延缓老年性运动功能衰退具有重要意义。     

Know your place: neural processing of social hierarchy in humans

Social hierarchies guide behavior in many species, including humans, where status also has an enormous impact on motivation and health. However, little is known about the underlying neural representation of social hierarchies in humans. In the present study, we identify dissociable neural responses to perceived social rank using functional magnetic resonance imaging (fMRI) in an interactive, simulated social context. In both stable and unstable social hierarchies, viewing a superior individual differentially engaged perceptual-attentional, saliency, and cognitive systems, notably dorsolateral prefrontal cortex. In the unstable hierarchy setting, additional regions related to emotional processing (amygdala), social cognition (medial prefrontal cortex), and behavioral readiness were recruited. Furthermore, social hierarchical consequences of performance were neurally dissociable and of comparable salience to monetary reward, providing a neural basis for the high motivational value of status. Our results identify neural mechanisms that may mediate the enormous influence of social status on human behavior and health.     

Transcranial Direct Current Stimulation of Right Dorsolateral Prefrontal Cortex Does Not Affect Model-Based or Model-Free Reinforcement Learning in Humans

There is broad consensus that the prefrontal cortex supports goal-directed, model-based decision-making. Consistent with this, we have recently shown that model-based control can be impaired through transcranial magnetic stimulation of right dorsolateral prefrontal cortex in humans. We hypothesized that an enhancement of model-based control might be achieved by anodal transcranial direct current stimulation of the same region. We tested 22 healthy adult human participants in a within-subject, double-blind design in which participants were given Active or Sham stimulation over two sessions. We show Active stimulation had no effect on model-based control or on model-free (‘habitual’) control compared to Sham stimulation. These null effects are substantiated by a power analysis, which suggests that our study had at least 60% power to detect a true effect, and by a Bayesian model comparison, which favors a model of the data that assumes stimulation had no effect over models that assume stimulation had an effect on behavioral control. Although we cannot entirely exclude more trivial explanations for our null effect, for example related to (faults in) our experimental setup, these data suggest that anodal transcranial direct current stimulation over right dorsolateral prefrontal cortex does not improve model-based control, despite existing evidence that transcranial magnetic stimulation can disrupt such control in the same brain region.     

Theta burst stimulation of the human motor cortex

It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices. With its relevance to processes such as learning and memory, the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models. To date, the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation (rTMS), a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp. However, effects on synaptic plasticity reported are often weak, highly variable between individuals, and rarely last longer than 30 min. Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable, consistent, long-lasting, and powerful effect on motor cortex physiology and behavior after an application period of only 20-190 s.     

Transcranial Direct Current Stimulation of the Left Dorsolateral Prefrontal Cortex Shifts Preference of Moral Judgments

Attitude to morality, reflecting cultural norms and values, is considered unique to human social behavior. Resulting moral behavior in a social environment is controlled by a widespread neural network including the dorsolateral prefrontal cortex (DLPFC), which plays an important role in decision making. In the present study we investigate the influence of neurophysiological modulation of DLPFC reactivity by means of transcranial direct current stimulation (tDCS) on moral reasoning. For that purpose we administered anodal, cathodal, and sham stimulation of the left DLPFC while subjects judged the appropriateness of hard moral personal dilemmas. In contrast to sham and cathodal stimulation, anodal stimulation induced a shift in judgment of personal moral dilemmas towards more non-utilitarian actions. Our results demonstrate that alterations of left DLPFC activity can change moral judgments and, in consequence, provide a causal link between left DLPFC activity and moral reasoning. Most important, the observed shift towards non-utilitarian actions suggests that moral decision making is not a permanent individual trait but can be manipulated; consequently individuals with boundless, uncontrollable, and maladaptive moral behavior, such as found in psychopathy, might benefit from neuromodulation-based approaches.     

Dynamic social adaptation of motion-related neurons in primate parietal cortex

Social brain function, which allows us to adapt our behavior to social context, is poorly understood at the single-cell level due largely to technical limitations. But the questions involved are vital: How do neurons recognize and modulate their activity in response to social context? To probe the mechanisms involved, we developed a novel recording technique, called multi-dimensional recording, and applied it simultaneously in the left parietal cortices of two monkeys while they shared a common social space. When the monkeys sat near each other but did not interact, each monkey's parietal activity showed robust response preference to action by his own right arm and almost no response to action by the other's arm. But the preference was broken if social conflict emerged between the monkeys-specifically, if both were able to reach for the same food item placed on the table between them. Under these circumstances, parietal neurons started to show complex combinatorial responses to motion of self and other. Parietal cortex adapted its response properties in the social context by discarding and recruiting different neural populations. Our results suggest that parietal neurons can recognize social events in the environment linked with current social context and form part of a larger social brain network.     

内侧前额叶与社会认知

早期的研究表明杏仁核、前额叶、颞上沟、前扣带回等与人类的社会认知活动有关;随着多种新技术的应用。越来越多的研究发现其它一些脑区结构(如岛叶、基底节、白质等)也与社会认知和行为有关。本文综述了内侧前额叶在社会认知中的作用,重点介绍了内侧前额叶在心灵理论、情绪认知、社会推理与决策、道德判断、自我认知等社会认知活动中的作用。未来研究希望能从整体和动态上认识内侧前额叶在社会认知活动中的作用。     

Brain lipid changes after repetitive transcranial magnetic stimulation: potential links to therapeutic effects?

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used in the management of neurologic disorders such as depression and chronic pain, but little is known about how it could affect brain lipids, which play important roles in membrane structure and cellular functions. The present study was carried out to examine the effects of rTMS on brain lipids at the individual molecular species level using the novel technique of lipidomics. Rats were subjected to high frequency (15 Hz) stimulation of the left hemisphere with different intensities and pulses of rTMS. The prefrontal cortex, hippocampus and striatum were harvested 1 week after rTMS and lipid profiles analyzed by tandem mass spectrometry. rTMS resulted in changes mainly in the prefrontal cortex. There were significant alterations in plasmalogen phosphatidylethanolamines, phosphatidylcholines, and increases in sulfated galactosylceramides or sulfatides. Plasmalogen species with long chain polyunsaturated fatty acids (PUFAs) showed decrease in abundance together with corresponding increase in lysophospholipid species suggesting endogenous release of long chain fatty acids such as docosahexaenoic acid (DHA) in brain tissue. The hippocampus showed no significant changes, whilst changes in the striatum were often opposite to that of the prefrontal cortex. It is postulated that changes in brain lipids may underlie some of the clinical effects of rTMS.     

Stimulation of the left dorsolateral prefrontal cortex with slow rTMS enhances verbal memory formation

Encoding of episodic memories relies on stimulus-specific information processing and involves the left prefrontal cortex. We here present an incidental finding from a simultaneous EEG-TMS experiment as well as a replication of this unexpected effect. Our results reveal that stimulating the left dorsolateral prefrontal cortex (DLPFC) with slow repetitive transcranial magnetic stimulation (rTMS) leads to enhanced word memory performance. A total of 40 healthy human participants engaged in a list learning paradigm. Half of the participants (N = 20) received 1 Hz rTMS to the left DLPFC, while the other half (N = 20) received 1 Hz rTMS to the vertex and served as a control group. Participants receiving left DLPFC stimulation demonstrated enhanced memory performance compared to the control group. This effect was replicated in a within-subjects experiment where 24 participants received 1 Hz rTMS to the left DLPFC and vertex. In this second experiment, DLPFC stimulation also induced better memory performance compared to vertex stimulation. In addition to these behavioural effects, we found that 1 Hz rTMS to DLPFC induced stronger beta power modulation in posterior areas, a state that is known to be beneficial for memory encoding. Further analysis indicated that beta modulations did not have an oscillatory origin. Instead, the observed beta modulations were a result of a spectral tilt, suggesting inhibition of these parietal regions. These results show that applying 1 Hz rTMS to DLPFC, an area involved in episodic memory formation, improves memory performance via modulating neural activity in parietal regions.

Encoding of episodic memories relies on stimulus-specific information processing and involves the left prefrontal cortex. An incidental finding from a simultaneous EEG-TMS experiment reveals that applying 1-Hz repetitive transcranial magnetic stimulation to this area of the brain improves memory performance by modulating neural activity in parietal regions.     

The Neural Basis of Responsibility Attribution in Decision-Making

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent’s emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context.     

mGluR5 Ablation in Cortical Glutamatergic Neurons Increases Novelty-Induced Locomotion

The group I metabotropic glutamate receptor 5 (mGluR5) has been implicated in the pathology of various neurological disorders including schizophrenia, ADHD, and autism. mGluR5-dependent synaptic plasticity has been described at a variety of neural connections and its signaling has been implicated in several behaviors. These behaviors include locomotor reactivity to novel environment, sensorimotor gating, anxiety, and cognition. mGluR5 is expressed in glutamatergic neurons, inhibitory neurons, and glia in various brain regions. In this study, we show that deleting mGluR5 expression only in principal cortical neurons leads to defective cannabinoid receptor 1 (CB1R) dependent synaptic plasticity in the prefrontal cortex. These cortical glutamatergic mGluR5 knockout mice exhibit increased novelty-induced locomotion, and their locomotion can be further enhanced by treatment with the psychostimulant methylphenidate. Despite a modest reduction in repetitive behaviors, cortical glutamatergic mGluR5 knockout mice are normal in sensorimotor gating, anxiety, motor balance/learning and fear conditioning behaviors. These results show that mGluR5 signaling in cortical glutamatergic neurons is required for precisely modulating locomotor reactivity to a novel environment but not for sensorimotor gating, anxiety, motor coordination, several forms of learning or social interactions.