突触可塑性的生物物理学基础和体视学测量研究进展

突触可塑性是神经系统生长发育、神经损伤与修复、学习与记忆的神经生物学基础。突触可塑性是指突触在形态、界面结构和功能上的可变动性和可修饰性,突触形态的可塑性表现为新突触形成、突触形状以及突触密度的变化;突触界而结构变化包括突触活性区长度、突触后致密物（postsynaptic density,PSD）厚度、突触间隙宽度以及突触界而曲率的变化;     

海马突触可塑性与神经系统相关疾病关系的研究进展

海马突触可塑性直接影响着海马功能的形成和运转过程,尤其是学习和记忆能力的建立和维持。海马突触可塑性与阿尔茨海默病(AD)抑郁症、癫痫等的发生发展存在密切关系。突触可塑性涉及多个方面,不同疾病的突触可塑性改变也不尽相同,因此,它与疾病之间的因果关系以及机制至今尚不十分明确,其影响因素也是多样的。人们已经注意到细胞移植、富集环境(EE)和体育锻炼等直接或间接影响着突触可塑性。从突触可塑性入手寻找有效治疗手段,为神经系统相关疾病防治提供新的思路。因此,改善海马突触可塑性逐渐成为神经系统相关疾病防治的重要策略。本文从海马突触可塑性相关的疾病及影响因素两个方面阐述突触可塑性的研究进展。     

穿孔突触的研究进展

1969年Peters等[1]首先报道了一种突触后致密物质含有一个或多个孔洞的突触，现在将这类突触统称为穿孔突触（perforatedsynapse，PS），并将突触后致密物质完整的突触称为非穿孔突触（non－perforatedsynapse，NPS）、穿孔突触的超微结构特征是：突触接触区面积较大，在垂直于突触后膜的切面上观察，突触后致密物质（postsynapticdensity，PSD）不连续，在平行于突触后膜的切面上观察时突触后致密物质呈环形、蹄铁形或斑片状［2］。其后许多学者对此进行了多方面的研究，目前，多数学者普遍认为穿孔突触在突触发育和可塑性过程中具有重…     

腰骶背根全切猫脊髓Ⅱ板层突触性终末的代偿性变化—电镜定…

为深入探索脊髓的可塑性变化规律，用５只单侧腰骶背根全切猫，术后存活３－４个月。发现实验侧脊髓Ⅱ板层内背根来源的复合终末数下降至正常的２４％；非背根来源的简单终末数却增加至正常的１３４％；还新发现了一类双重突触性终末，本文将之将为非典型复合终末。上述变化使突触总数仍维持在正常水平。在Ｌ６节段的简单终末中，形成对称性突触的简单终末，其增幅（７１％）显著地大于形成非对称性突触者（３６％）；含有致密核心小     

钙调蛋白激酶Ⅱ的结构及其在神经系统中的作用

钙离子（Ca²⁺ ）是通过局部信号获得特异性刺激的关键细胞内信使分子。Ca²⁺ 结合蛋白,如钙调蛋白（CaM）及其靶蛋白是Ca²⁺ 依赖性反应信号传导的关键靶点。钙/钙调蛋白依赖性蛋白酶Ⅱ（CaMKⅡ）是一种多聚体酶,它是哺乳动物前脑总蛋白的重要组成部分,并且是形成突触后致密部的主要成分。近年来国内外研究显示,CaMKⅡ包含α、β、γ 和 δ 4种亚型,其中α 和 β 主要在神经组织中表达,而 γ 和 δ 则在全身多种组织均有表达,它们参与特定的突触可塑性和记忆巩固过程,对神经系统的兴奋性及一些神经系统疾病的发生起重要作用。前期也有研究表明CaMKⅡδ在促进神经元存活中起重要作用。本文就CaMKⅡ的结构及其在神经系统中的作用和与相关神经系统疾病的关系作一综述。     

基于STDP可塑性自适应神经网络的构建及仿真研究

目的：在日益复杂的电磁环境下,生物体神经系统表现出的一定程度的可靠性、抗扰性、自适应和自修复的优势,生物的这种抗扰优势可为研究电子电路系统的电磁仿生防护提供新的思路。方法：基于神经信息传递的生理机制以及突触的可塑性机制,揭示了脉冲时间依赖突触可塑性（Spike Timing Dependent Plasticity,STDP）机制与生物自适应之间的关系,然后选取了Izhikevich神经元模型为节点,以动态STDP机制调节权值的自适应突触为桥梁。进行了四层具有自组织抗扰能力的前馈神经网络模型的构建与仿真研究,并进一步分析了所构建的神经网络的自适应抗扰能力。结果：在损伤神经元的比例小于中间层的30％时。具备STDP机制的网络抗扰能力明显优于相同损伤程度下不具备STDP机制的网络的抗扰能力。结论：所构建的基于STDP可塑性的神经网络的自适应抗扰能力与突触的STDP可塑性机制密切相关。     

突触穿孔现象及其生理意义

突触穿孔现象及其生理意义章子贵，徐晓虹，吴馥梅南京大学生物科学与技术系神经生物学研究室南京２１００９３突触是神经信息传递的关键，也是神经系统内敏感易变的部位，它具有很大的可塑性，其中突触穿孔在突触可塑性中的作用机理尤其为研究者们所关注。许多研究表明，...     

egr-1在学习记忆中的作用及机制研究进展

正学习和记忆是大脑对外界有关信息获取、处理、存储和提取的过程,其所依赖的生物学基础是神经元之间通过突触相互连接形成复杂的神经网络,启动一系列生化级联反应,导致突触可塑性变化,如长时程增强(long term potential,LTP)和长时程抑制(long term depression,LTD),其中,LTP与学习记忆的关系尤为密切。突触可塑性的功能障碍常导致与记忆力减弱或丧失等相关的一系列临床常见疾病,如癫痫、亨廷顿病、阿尔茨海默症、精神发育迟滞及进行性     

电针刺激对神经可塑性的影响

脑梗死可能导致神经功能永久性损伤,但中枢神经系统具有很强的可塑性。研究发现电针刺激通过促进神经干细胞再生、改善脑血流量及代谢、加强突触间信息传递以及调节星型胶质细胞分泌等途径对脑梗死后中枢神经系统进行修复,改变神经可塑性,实现对脑缺血的保护作用。本文归纳总结了电针刺激对神经可塑性影响的最新研究成果。     

针刺对猫部分去传入脊髓Ⅱ板层可塑性的影响──电镜定量研究

既往研究已经表明针刺能促进脊髓的可塑性变化。本研究的目的是探讨针刺引起可塑性变化的最小疗程以及是否对非针刺侧也有影响。１０只猫切断一侧Ｌ１～Ｌ５、Ｌ７～Ｓ２背根及背根节，保留Ｌ６。术后电针刺激手术侧后肢Ｌ６神经支配范围的足三里和悬钟，伏兔和三阴交穴位。用电镜定量方法计数针刺一疗程（５只）和二疗程（５只）对脊髓Ⅱ板层不同突触性终末数的影响。结果表明：两组动物对照侧两类突触性终末数与非针刺动物比无明显变化，实验侧背根来源的复合终末数分别为对照侧的４５％与８８％，二疗程组比一疗程组和非针刺动物都明显增加。非背根来源的简单终末数在二疗程组虽有增加，但增加幅度与非针刺动物一致。表明针刺促进备用根纤维可塑性变化在二疗程时才明显，而对非针刺侧却无明显影响。     

Hippocampal CA1 synaptic plasticity as a gamma transfer function

The capacity of activity-dependent synaptic modification is essential in processing and storing information, yet little is known about how synaptic plasticity alters the input-output conversion efficiency at the synapses. In the adult mouse hippocampus in vivo, we carefully compared the input-output relationship, in terms of presynaptic activity levels versus postsynaptic potentials, before and after the induction of synaptic plasticity and found that synaptic plasticity led synapses to respond more robustly to inputs, that is, synaptic gain was increased as a function of synaptic activity with an expansive, power-law nonlinearity, i.e. conforming to the so-called gamma curve. In extreme cases, long-term potentiation and depression coexist in the same synaptic pathway with long-term potentiation dominating over long-term depression at higher levels of presynaptic activity. These findings predict a novel function of synaptic plasticity, i.e. a contrast-enhancing filtering of neural information through a gamma correction-like process.     

Dynamic synapses as archives of synaptic history: state-dependent redistribution of synaptic efficacy in the rat hippocampal CA1

Plastic modifications of synaptic strength are putative mechanisms underlying information processing in the brain, including memory storage, signal integration and filtering. Here we describe a dynamic interplay between short-term and long-term synaptic plasticity. At rat hippocampal CA1 synapses, induction of both long-term potentiation (LTP) and depression (LTD) was accompanied by changes in the profile of short-term plasticity, termed redistribution of synaptic efficacy (RSE). RSE was presynaptically expressed and associated in part with a persistent alteration in hyperpolarization-activated I _h channel activity. Already potentiated synapses were still capable of showing RSE in response to additional LTP-triggering stimulation. Strikingly, RSE took place even after reversal of LTP or LTD, that is, the same synapse can display different levels of short-term plasticity without changing synaptic efficacy for the initial spike in burst presynaptic firing, thereby modulating spike transmission in a firing rate-dependent manner. Thus, the history of long-term synaptic plasticity is registered in the form of short-term plasticity, and RSE extends the information storage capacity of a synapse and adds another dimension of functional complexity to neuronal operations.     

Directionality index of neural information flow as a measure of synaptic plasticity in chronic unpredictable stress rats

This investigation examined whether the directionality of neural information flow could be used to index the measurement of synaptic plasticity in the chronic unpredictable stress (CUS) animals. Evolution map approach (EMA) was employed to determine the direction of information flow between the cortex and thalamus, while the experiment was performed by inducing long-term potentiation of the thalamocortical pathway after recording intracranial EEG at the same two positions in Wistar rats of both normal and stressed groups. The results showed that the coupling direction index was significantly diverted in stressed state compared to that in normal state, while the strength of thalamus driving frontal cortex was considerably reduced in the rats of CUS model. Moreover, the data obtained from LTP experiment exhibited that chronic stress decreased medial prefrontal cortex (mPFC) synaptic plasticity, which was certainly in accordance with the EEG findings. These results demonstrated that using EMA measurement, directionality index of neural information flow may be as a measure of synaptic plasticity.     

A role for short-term synaptic facilitation and depression in the processing of intensity information in the auditory brain stem

The nature of the synaptic connection from the auditory nerve onto the cochlear nucleus neurons has a profound impact on how sound information is transmitted. Short-term synaptic plasticity, by dynamically modulating synaptic strength, filters information contained in the firing patterns. In the sound-localization circuits of the brain stem, the synapses of the timing pathway are characterized by strong short-term depression. We investigated the short-term synaptic plasticity of the inputs to the bird's cochlear nucleus angularis (NA), which encodes intensity information, by using chick embryonic brain slices and trains of electrical stimulation. These excitatory inputs expressed a mixture of short-term facilitation and depression, unlike those in the timing nuclei that only depressed. Facilitation and depression at NA synapses were balanced such that postsynaptic response amplitude was often maintained throughout the train at high firing rates (>100 Hz). The steady-state input rate relationship of the balanced synapses linearly conveyed rate information and therefore transmits intensity information encoded as a rate code in the nerve. A quantitative model of synaptic transmission could account for the plasticity by including facilitation of release (with a time constant of approximately 40 ms), and a two-step recovery from depression (with one slow time constant of approximately 8 s, and one fast time constant of approximately 20 ms). A simulation using the model fit to NA synapses and auditory nerve spike trains from recordings in vivo confirmed that these synapses can convey intensity information contained in natural train inputs.     

“The seven sins” of the Hebbian synapse: Can the hypothesis of synaptic plasticity explain long-term memory consolidation?

Memorizing new facts and events means that entering information produces specific physical changes within the brain. According to the commonly accepted view, traces of memory are stored through the structural modifications of synaptic connections, which result in changes of synaptic efficiency and, therefore, in formations of new patterns of neural activity (the hypothesis of synaptic plasticity). Most of the current knowledge on learning and initial stages of memory consolidation ("synaptic consolidation") is based on this hypothesis. However, the hypothesis of synaptic plasticity faces a number of conceptual and experimental difficulties when it deals with potentially permanent consolidation of declarative memory ("system consolidation"). These difficulties are rooted in the major intrinsic self-contradiction of the hypothesis: stable declarative memory is unlikely to be based on such a non-stable foundation as synaptic plasticity. Memory that can last throughout an entire lifespan should be "etched in stone." The only "stone-like" molecules within living cells are DNA molecules. Therefore, I advocate an alternative, genomic hypothesis of memory, which suggests that acquired information is persistently stored within individual neurons through modifications of DNA, and that these modifications serve as the carriers of elementary memory traces.     

蓝斑突触结构衰老性变化和可塑性

本文用图象分析技术研究了老年大鼠蓝斑核内突触结构的可塑性变化。结果显示:突触数量(N/100μm~2)、平均突触厚度和剖面积等三个参数在老年组(33个月)均较成年组(6个月)明显减少(p<0.01);而突触长度两组无显著差异(p>0.05),但频数分布图显示老年组较大和较小的突触增多。老年组完整突触(A型)减少了8.54%,退化的突触(D型)增加了15.43%。本研究结果提示衰老时的蓝斑核突触膜成分丢失和数量减少,部分突触发生代偿性增大。     

Dendritic excitability and synaptic plasticity

Most synaptic inputs are made onto the dendritic tree. Recent work has shown that dendrites play an active role in transforming synaptic input into neuronal output and in defining the relationships between active synapses. In this review, we discuss how these dendritic properties influence the rules governing the induction of synaptic plasticity. We argue that the location of synapses in the dendritic tree, and the type of dendritic excitability associated with each synapse, play decisive roles in determining the plastic properties of that synapse. Furthermore, since the electrical properties of the dendritic tree are not static, but can be altered by neuromodulators and by synaptic activity itself, we discuss how learning rules may be dynamically shaped by tuning dendritic function. We conclude by describing how this reciprocal relationship between plasticity of dendritic excitability and synaptic plasticity has changed our view of information processing and memory storage in neuronal networks.     

Plasticity in the projection from the anterior thalamic nuclei to the anterior cingulate cortex in the rat in vivo: paired-pulse facilitation, long-term potentiation and short-term depression

Several neurophysiological and computational theories of the rodent navigational system suggest that the differing cortices of the frontal lobe and thalamus share information and therefore undergo changes in synaptic strength. We examine here for the first time three forms of synaptic plasticity in the projection from the anterior thalamic nuclei to the anterior cingulate cortex: we demonstrate that this projection is capable of expressing paired-pulse facilitation, long-term potentiation, and short-term depression. Furthermore, input/output curves show that field excitatory post-synaptic potential amplitude increased at all stimulus intensities following high-frequency stimulation. These findings add important information to our understanding of synaptic plasticity in this important pathway, which has been widely hypothesized to play important roles in memory and spatial representation in the rodent.     

Miniature synaptic transmission and BDNF modulate dendritic spine growth and form in rat CA1 neurones

The refinement and plasticity of neuronal connections require synaptic activity and neurotrophin signalling; their specific contributions and interplay are, however, poorly understood. We show here that brain-derived neurotrophic factor (BDNF) increased spine density in apical dendrites of CA1 pyramidal neurones in organotypic slice cultures prepared from postnatal rat hippocampal slices. This effect was observed also in the absence of action potentials, and even when miniature synaptic transmission was inhibited with botulinum neurotoxin C (BoNT/C). There were, however, marked differences in the morphology of individual spines induced by BDNF across these different levels of spontaneous ongoing synaptic activity. During both normal synaptic transmission, and when action potentials were blocked with TTX, BDNF increased the proportion of stubby, type-I spines. However, when SNARE-dependent vesicular release was inhibited with BoNT/C, BDNF increased the proportion of thin, type-III spines. Our results indicate that BDNF increases spine density irrespective of the levels of synaptic transmission. In addition, miniature synaptic transmission provides sufficient activity for the functional translation of BDNF-triggered spinogenesis into clearly defined morphological spine types, favouring those spines potentially responsible for coordinated Ca²⁺ transients thought to mediate synaptic plasticity. We propose that BDNF/TrkB signalling represents a mechanism of expression of both morphological and physiological homeostatic plasticity in the hippocampus, leading to a more efficient synaptic information transfer across widespread levels of synaptic activity.     

Stress-facilitated LTD induces output plasticity through synchronized-spikes and spontaneous unitary discharges in the CA1 region of the hippocampus

Long-term potentiation (LTP) and long-term depression (LTD) of the excitatory synaptic inputs plasticity in the hippocampus is believed to underlie certain types of learning and memory. Especially, stressful experiences, well known to produce long-lasting strong memories of the event themselves, enable LTD by low frequency stimulation (LFS, 3 Hz) but block LTP induction by high frequency stimulation (HFS, 200 Hz). However, it is unknown whether stress-affected synaptic plasticity has an impact on the output plasticity. Thus, we have simultaneously studied the effects of stress on synaptic plasticity and neuronal output in the hippocampal CA1 region of anesthetized Wistar rats. Our results revealed that stress increased basal power spectrum of the evoked synchronized-spikes and enabled LTD induction by LFS. The induction of stress-facilitated LTD but not LFS induced persistent decreases of the power spectrum of the synchronized-spikes and the frequency of the spontaneous unitary discharges; However, HFS induced LTP in non-stressed animals and increased the power spectrum of the synchronized-spikes, without affecting the frequency of the spontaneous unitary discharges, but HFS failed to induce LTP in stressed animals without affecting the power spectrum of the synchronized-spikes and the frequency of the spontaneous unitary discharges. These observations that stress-facilitated LTD induces the output plasticity through the synchronized-spikes and spontaneous unitary discharges suggest that these types of stress-related plasticity may play significant roles in distribution, amplification and integration of encoded information to other brain structures under stressful conditions.