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。     

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。     

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。     

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。     

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。     

长时程突触可塑性中的突触标识

神经元长时程突触可塑性是学习和记忆的基础,神经元长时程突触可塑性的维持依赖于基因的转录和蛋白质合成.然而,这些转录产物和新合成的蛋白质是如何从胞体运输到突触点,还不甚清楚.近年来的研究显示,当长时程突触可塑性发生时,被激活的突触能通过建立突触标记(synaptic tag)来识别、捕捉和利用其所需要的基因产物,以维持突触可塑性的长时程变化.这一过程或现象被称为突触标识(synaptic tagging).本文就近年来突触标识的研究进展作一概述.     

短时程突触可塑性研究概况

突触可塑性是神经系统所具有的重要特征,也是神经系统实现其功能的重要保障。按照持续的时间划分,突触可塑性可分为短时程突触可塑性和长时程突触可塑性。短时程突触可塑性包括短时程增强和短时程压抑两种类型。与长时程突触可塑性不同,短时程突触可塑性的产生主要依赖于神经递质释放概率的变化,其往往决定神经回路的信息处理和反应模式,不仅直接参与了对输入信号的识别和处理,而且还可对长时程突触可塑性的表达产生重要影响。     

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。     

突触可塑性与脑疾病的神经发育基础

大脑神经回路高度有序的神经元活动是高级脑功能的基础,神经元之间的突触联结是神经回路的关键功能节点。神经突触根据神经元活动调整其传递效能的能力,亦即突触可塑性,被认为是神经回路发育和学习与记忆功能的基础。其异常则可能导致如抑郁症和阿尔茨海默病等精神、神经疾病。将介绍这两种疾病与突触可塑性的关系,聚焦于相关分子和细胞机制以及新的研究、治疗手段等进展。     

突触后致密结构的可塑性

突触后致密结构（ＰＳＤ） 约由３０ 多种蛋白质组成, 大多数是与突触传递有紧密联系的蛋白质, 它的形态结构, 生化组分及生理功能都具很大的可塑性。ＰＳＤ是ＬＴＰ发生的结构基础之一, ＰＳＤ的可塑性易受突触前传入信息及机体内、外环境因素的影响, ＰＳＤ是实现突触传递功能的重要形态结构基础。     

The role of myosin V in exocytosis and synaptic plasticity

In neuroscience, myosin V motor proteins have attracted attention since they are highly expressed in brain, and absence of myosin Va in man leads to a severe neurological disease called Griscelli syndrome. While in some cells myosin V is described to act as a vesicle transport motor, an additional role in exocytosis has emerged recently. In neurons, myosin V has been linked to exocytosis of secretory vesicles and recycling endosomes. Through these functions, it is implied in regulating important brain functions including the release of neuropeptides by exocytosis of large dense-core vesicles and the insertion of neurotransmitter receptors into post-synaptic membranes. This review focuses on the role of myosin V in (i) axonal transport and stimulated exocytosis of large dense-core vesicles to regulate the secretion of neuroactive substances, (ii) tethering of the endoplasmic reticulum at cerebellar synapses to permit long-term depression, (iii) recycling of α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors at hippocampal synapses during long-term potentiation, and (iv) recycling of nicotinic acetylcholine receptors at the neuromuscular junction. Myosin V is thus discussed as an important modulator of synaptic plasticity.     

Spike-timing-dependent BDNF secretion and synaptic plasticity

In acute hippocampal slices, we found that the presence of extracellular brain-derived neurotrophic factor (BDNF) is essential for the induction of spike-timing-dependent long-term potentiation (tLTP). To determine whether BDNF could be secreted from postsynaptic dendrites in a spike-timing-dependent manner, we used a reduced system of dissociated hippocampal neurons in culture. Repetitive pairing of iontophoretically applied glutamate pulses at the dendrite with neuronal spikes could induce persistent alterations of glutamate-induced responses at the same dendritic site in a manner that mimics spike-timing-dependent plasticity (STDP)—the glutamate-induced responses were potentiated and depressed when the glutamate pulses were applied 20 ms before and after neuronal spiking, respectively. By monitoring changes in the green fluorescent protein (GFP) fluorescence at the dendrite of hippocampal neurons expressing GFP-tagged BDNF, we found that pairing of iontophoretic glutamate pulses with neuronal spiking resulted in BDNF secretion from the dendrite at the iontophoretic site only when the glutamate pulses were applied within a time window of approximately 40 ms prior to neuronal spiking, consistent with the timing requirement of synaptic potentiation via STDP. Thus, BDNF is required for tLTP and BDNF secretion could be triggered in a spike-timing-dependent manner from the postsynaptic dendrite.     

受体酪氨酸激酶依赖的信号转导在突触可塑性中的研究

突触可塑性对于脑发育过程中的神经环路重构以及学习记忆等脑的高级功能是非常重要的。许多受体酪氨酸激酶家族成员,包括TrkB、ErbB和Eph在神经连接的建立和重构过程中起到核心作用。比如,突触后EphB依赖的信号会导致树突棘的产生和神经递质受体的聚集,而ephrinA引起的EphA4激活可以导致树突棘的回缩。但是,目前对EphA4依赖的树突棘重组和对神经递质受体的调节背后的机制还知之甚少。本文将集中探讨EphA4及其下游的信号通路在神经肌肉接头和中枢神经的突触中,对神经递质受体的调节功能。     

Spike-based synaptic plasticity and the emergence of direction selective simple cells: simulation results

Direction selectivity (DS) of simple cells in the primary visual cortex was recently suggested to arise from short-term synaptic depression in thalamocortical afferents (Chance F, Nelson S, Abbott L (1998), J. Neuroscience 18(12): 4785–4799). In the model, two groups of afferents with spatially displaced receptive fields project through either depressing and non-depressing synapses onto the V1 cell. The degree of synaptic depression determines the temporal phase advance of the response to drifting gratings. We show that the spatial displacement and the appropriate degree of synaptic depression required for DS can develop within an unbiased input scenario by means of temporally asymmetric spike-timing dependent plasticity (STDP) which modifies both the synaptic strength and the degree of synaptic depression. Moving stimuli of random velocities and directions break any initial receptive field symmetry and produce DS. Frequency tuning curves and subthreshold membrane potentials akin to those measured for non-directional simple cells are thereby changed into those measured for directional cells. If STDP is such that down-regulation dominates up-regulation the overall synaptic strength adapts in a self-organizing way such that eventually the postsynaptic response for the non-preferred direction becomes subthreshold. To prevent unlearning of the acquired DS by randomly changing stimulus directions an additional learning threshold is necessary. To further protect the development of the simple cell properties against noise in the stimulus, asynchronous and irregular synaptic inputs are required.     

Translational switch for long‐term maintenance of synaptic plasticity

Memory can last a lifetime, yet synaptic contacts that contribute to the storage of memory are composed of proteins that have much shorter lifetimes. A physiological model of memory formation, long‐term potentiation (LTP), has a late protein‐synthesis‐dependent phase (L‐LTP) that can last for many hours in slices or even for days in vivo. Could the activity‐dependent synthesis of new proteins account for the persistence of L‐LTP and memory? Here, we examine the proposal that a self‐sustaining regulation of translation can form a bistable switch that can persistently regulate the on‐site synthesis of plasticity‐related proteins. We show that an αCaMKII–CPEB1 molecular pair can operate as a bistable switch. Our results imply that L‐LTP should produce an increase in the total amount of αCaMKII at potentiated synapses. This study also proposes an explanation for why the application of protein synthesis and αCaMKII inhibitors at the induction and maintenance phases of L‐LTP result in very different outcomes.     

Dynamics underlying synaptic gain between pairs of cortical pyramidal neurons

Changes in connectivity between pairs of neurons can serve as a substrate for information storage and for experience-dependent changes in neuronal circuitry. Early in development, synaptic contacts form and break, but how these dynamics influence the connectivity between pairs of neurons is not known. Here we used time-lapse imaging to examine the synaptic interactions between pairs of cultured cortical pyramidal neurons, and found that the axon-dendrite contacts between each neuronal pair were composed of both a relatively stable and a more labile population. Under basal conditions, loss and gain of contacts within this labile population was well balanced and there was little net change in connectivity. Selectively increasing the levels of activated CaMKII in the postsynaptic neuron increased connectivity between pairs of neurons by increasing the rate of gain of new contacts without affecting the probability of contact loss, or the proportion of stable and labile contacts, and this increase required Calcium/calmodulin binding to CaMKII. Our data suggest that activating CaMKII can increase synaptic connectivity through a CaM-dependent increase in contact formation, followed by stabilization of a constant fraction of new contacts.