与突触可塑性相关的神经振荡和信息流研究

作为一种有节律的神经活动,神经振荡现象发生在所有的神经系统中,例如大脑皮层、海马、皮层下神经核团以及感觉器官.本综述首先给出了已有的研究结果,即基于theta和gamma频段的同步神经振荡揭示了认知过程的起源与本质,如学习与记忆.然后介绍了关于神经振荡分析的新技术和算法,如表征神经元突触可塑性的神经信息流方向指数,并例...     

神经胶质细胞与突触可塑性研究新进展

突触的可塑性是研究学习与记忆的基础,很长时间以来人们对突触的可塑性研究主要集中在神经元和突触上;而胶质细胞的作用较少受到注意。最近的研究发现胶质细胞也参与突触的构成并影响突触的活动。研究表明中枢神经系统中的胶质细胞包括星形胶质细胞、小胶质细胞和少突胶质细胞可分别通过谷氨酸、丝氨酸、甘氨酸、ATP等信号调节突触的可塑性,从而为突触的可塑性研究提供了新的思路和方向,并有助于阐明突触的发生以及学习与记忆的机制。     

突触可塑性的数学公式

提出突触可塑性的一个可能的数学公式,尝试用这个公式统一地描述突触长时程增强效应和突触长时程抑制效应。     

Eph-ephrin与突触可塑性

Eph受体酪氨酸激酶及其配体ephrin广泛参与神经系统的发育,如轴突导向、细胞迁移、体节形成和血管生成。最近研究显示的Ephephrin在突触的定位提示其与突触可塑性有关。Ephephrin对成年神经系统的可塑性、学习和记忆,以及神经损伤后的再生可能具有重要的调节作用。     

非常规肌球蛋白与突触可塑性

突触可塑性是学习记忆的基础,其分子机制是理解记忆形成和维持的关键,也为神经退行性疾病的预防与治疗提供了新靶点。肌球蛋白超家族广泛存在于人体各种组织细胞中,主要分为常规肌球蛋白和非常规肌球蛋白。越来越多的研究发现,非常规肌球蛋白参与了许多重要的生命活动,尤其是在神经系统对突触可塑性的调节中,起到了十分重要的作用。     

突触的可塑性与学习,记忆机制

位于哺乳动物海马、小脑皮层的不同类型的可塑性突触,分别具有突触传递的长时程强化(LTP)或抑制(LTD)现象,它们可能是某些经典条件反射形成的基础。以LTD型突触为记忆装置的小脑局部神经网络,具有典型的适应控制能力。突触可塑性的另一类表现是突触前纤维长芽,有证据表明,伴随大脑—红核系统条件反射的建立,在红核神经元胞体附近有新的突触形成,这可能是长期记忆的基础。     

钙依赖性突触的可塑性

突触前和突触后细胞内钙离子（[Ca^2 ]i)在短时程和长时程突触的可塑性中,发挥着重要的住处传递作用。兴奋后残留[Ca^2 ]i,可以激发短时程突触增强。突触前[Ca^2 ]i可以影响被抑制的突触前膜囊泡的更新,并准确编码突前和突触后信息,产生截然相反的长时程突触修（ＬＴＰ或ＬＴＤ）。     

AMPA受体的磷酸化与突触可塑性

突触可塑性在学习记忆中发挥了重要作用,AMPA(α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid,AMPA)受体功能和运输的调节是突触可塑性机制研究的重要环节。在突触可塑性发生过程中,激酶和磷酸酶能够调节AMPA受体C末端的磷酸化水平,进而影响AMPA受体运输。对于AMPA受体磷酸化的研究能够加深我们对突触可塑性机制的理解。     

牛磺酸与突触可塑性研究进展

牛磺酸是哺乳动物中枢神经系统中含量最为丰富的自由氨基酸之一,具有许多认定的神经生理功能。最新的研究结果表明,用牛磺酸孵育脑片可以诱导兴奋性突触传递的持久增强效应。虽然牛磺酸引起的这种持久增强不是由于活动或经验所导致的突触效能的改变,但与反映突触可塑性的长时程增强具有许多共同特征,分享部分共同机制。同时,药理学实验提示,神经元对牛磺酸的摄取可能是长时程增强诱导的关键步骤。     

神经元突触前可塑性的结构及分子基础

突触可塑性是神经元间信息传递的重要生理调控机制,它包括突触前可塑性和突触后可塑性.突触前可塑性是指通过对神经递质释放过程的干预、修饰,调节突触强度的过程.突触强度的变化,是通过影响量子的大小,活动区的个数和囊泡释放概率来实现的.而突触前囊泡活动尤为重要：从转运、搭靠、融合至内吞进入下一轮循环,每一步都是由一群互相作用的蛋白质共同完成的.     

Synaptic plasticity in health and disease: introduction and overview

We summarize the reviews and research papers submitted by speakers at a discussion meeting on Synaptic Plasticity in Health and Disease held at the Royal Society, London on 2–3 December 2013, and a subsequent satellite meeting convened at the Royal Society/Kavli Centre at Chicheley Hall on 4–5 December 2013. Together, these contributions give an overview of current research and controversies in a vibrant branch of neuroscience with important implications for the understanding of many forms of learning and memory, and a wide spectrum of neurological and cognitive disorders.     

老年痴呆症的突触和神经环路机制

老年痴呆症的主要临床表现为认知功能严重受损,其原因可能是皮层与海马内的突触结构或功能障碍及神经环路活动异常所致。可溶性Aβ尤其是Aβ寡聚体(而不是沉积在脑组织中的淀粉样斑块)可能首先选择性地攻击GABA能抑制性神经元,使海马或皮层内兴奋性神经元由于所受抑制减弱而过度兴奋,进而导致神经环路或网络活动异常。神经网络异常又通过一系列的代偿反应引起突触传递和突触可塑性受损。正常生理水平的tau通过不同的机制在介导Aβ的突触及神经环路毒性中扮演重要角色。     

The lysosome and neurodegenerative diseases

It has long been believed that the lysosome is an important digestive organelle. There is increasing evidence that the lysosome is also involved in pathogenesis of a variety of neurodegenerative diseases, including Alzheimer＇s disease, Parkinson＇s disease, Huntington＇s disease, and amyotrophic lateral sclerosis. Abnormal protein degradation and deposition induced by iysosomal dysfunction may be the primary contributor to age-related neurodegeneration. In this review, the possible relationship between lysosome and various neurodegenerative diseases is described.     

Synaptic diversity and differentiation: Crustacean neuromuscular junctions

Crustacean motor neurons exhibit a wide range of synaptic responses. Tonically active neurons generally produce small excitatory postsynaptic potentials (EPSPs) at low impulse frequencies, and are able to release much more transmitter as the impulse frequency increases. Phasic neurons typically generate large EPSPs in their target cells, but have less capability for frequency facilitation, and undergo synaptic depression during maintained activity. These differences depend in part upon the neuron's ongoing levels of activity; phasic neurons acquire physiological and morphological features of tonic neurons when their activity level is altered. Molecules responsible for adaptation to activity can be sought in single identified phasic neurons with current techniques. The fact that both phasic and tonic neurons innervate the same target muscle fibers is evidence for presynaptic determination of synaptic properties, but there is also evidence for postsynaptic determination of specific properties of different endings of a single neuron. The occurrence of high- and low-output endings of the same tonic motor neurons on different muscle fibers suggests a target-specific influence on synaptic properties. Structural variation of synapses on individual terminal varicosities leads to the hypothesis that individual synapses have different probabilities for release of transmitter. We hypothesize that structurally complex synapses have a higher probability for release than the less complex synapses. This provides an explanation for the larger quantal contents of high-output terminals (where the proportion of complex synapses is higher), and also a mechanism for progressive recruitment of synapses during frequency facilitation.     

Homeostatic plasticity of GABA-ergic synaptic transmission in rat hippocampal cell cultures

It has been shown recently that prolonged blockade of neuronal firing activates several homeostatic mechanisms in neocortical networks, including alteration of glutamatergic and GABA-ergic synaptic transmission, and postsynaptic changes are involved in both cases. We studied whether such treatment also affects GABA-ergic synaptic transmission in hippocampal cell cultures. Using whole-cell voltage-clamp recording and local extracellular stimulation, we investigated evoked inhibitory postsynaptic currents (IPSC) in cultured rat hippocampal neurons grown with the sodium channel blocker tetrodotoxin (TTX) and under control conditions. We found that chronic TTX treatment significantly decreased the amplitude of evoked IPSC. This decrease was accompanied by an increase in the coefficient of variation of the above parameter, which is suggestive of a presynaptic mechanism. In contrast, no changes in the IPSC reversal potential or paired-pulse depression were observed in TTX-treated cultures. We conclude that alteration of GABA-ergic synaptic transmission contributes to the homeostatic plasticity in hippocampal neuronal networks, and this change is at least in part due to a presynaptic mechanism.Neirofiziologiya/Neurophysiology, Vol. 36, Nos. 5/6, pp. 432–437, September–December, 2004.This revised version was published online in April 2005 with a corrected cover date and copyright year.     

Inhibition of phagocytosis reduced the classical activation of BV2 microglia induced by amyloidogenic fragments of beta-amyloid and prion proteins

The inflammatory responses in Alzheimer＇s disease and prion diseases are dominated by microglia activation. Three different phenotypes of microglial activation, namely classical activation, alternative activation, and acquired deactivation, have been described. In this study, we investigated the effect of amyloido- genic fragments of amyloid 13 and prion proteins （Aβ1_42 and PrP106-126） on various forms of microglial activation. We first examined the effect of Aβ1_42 and PrP106-126 stimulation on the mRNA expression levels of several markers of microglial activation, as well as the effect of cytochalasin D, a phagocytosis inhibitor, on microgllal activation in Aβ1_42- and PrP106-126- stimulated BV2 microglla. Results showed that Aβ1-42 and PrPlo6_126 induced the classical activation of BV2 microglia, decreased the expression level of alternative expression markers, and had no effect on the expression of acquired de- activation markers. Cytochalasin D treatment significantly reduced Aβ1_42- and PrP106-26-induced up-regulation of proinflammatory factors, but did not change the expression profile of the markers of alternative activation or acquired de- activation in BV2 cells which were exposed to Aβ1-42 and PrPlo6_126. Our results suggested that microglia interact with amyloidogenic peptides in the extraceilular milieu-stimulated microglial classical activation and reduce its alternative activa- tion, and that the uptake of amyloidogenic peptides from the extracellular milieu amplifies the classical microglial activation.     

阿尔兹海默症转基因小鼠模型研究进展及评价

随着世界人口的老龄化,阿尔兹海默症已经成为严重威胁老年人健康的主要疾病之一,研究并建立可靠的阿尔兹海默症动物模型对于探明疾病的病因、发病机制及防治药物的开发均具有重要意义。本文就目前使用最为广泛和研究最为深入的转基因小鼠模型的病理、行为学变化特点及其在阿尔兹海默症研究中的应用和发现作一介绍。     

阿尔茨海默病与雌激素和褪黑素的相关性研究进展

阿尔茨海默病（AD）是引起痴呆的第一病因,其发病机制尚不十分明确。目前尚无特效的药物可逆转脑功能缺损或阻止病情进展,临床上用胆碱乙酰转移酶抑制剂、抗精神症状药物、维生素E等均只能轻微改善症状。雌激素和褪黑素在基础和临床研究中都显示对AD有治疗作用,且二者的疗效与AD的病程有明显相关性。     

阿托伐他汀治疗阿尔茨海默病疗效观察

目的：研究他汀类药物在改善阿尔茨海默病患者认知功能障碍的作用。方法：将阿尔茨海默痛患者40例,随机分成治疗组（阿托伐他汀钙20mg1次／d口服）和对照组（茴拉西坦0．2g3次／天口服）,连续用药90d,在30d、60d、90d分别对两组病人进行认知功能评分（简易精神量表）。结果：利用t检验的方法计算t值,30d比较,t=-0．938（P〉0．05,差异无统计学意义）;60d比较,t=1．333（P〉0．05,差异无统计学意义）;90d比较t=2．356（P〈0．05,差异具有统计学意义）,提示90天后治疗组改善认知功能障碍优于对照组,且随着用药时间的延长,优势显现可能越为明显。结论：阿托伐他汀可能有助于阿尔茨海默病的治疗。