水通道蛋白-4在突触可塑性及学习记忆中的作用

水通道蛋白-4(aquaporin-4,AQP-4)作为水通道蛋白家族之一,在中枢神经系统具有广泛的分布,且在星形胶质细胞终足上高表达。研究表明,AQP-4可通过调节星形胶质细胞的功能在维持脑内水稳态、脑体积和神经元兴奋性等方面发挥重要的作用。但是AQP-4在突触可塑性、学习记忆及认知等方面所发挥的作用还不明了。突触功能可塑性的变化按其性质的不同可分为长时程增强(long term potentiation,LTP)和长时程抑制(long term depression,LTD),两者被公认为是学习记忆的神经生物学基础。海马区是调节学习记忆过程的核心脑区,其突触可塑性与学习记忆有密切的关系。本文旨在综述AQP-4与海马区突触可塑性及相关学习记忆的关系研究进展,并展望AQP-4作为新的靶点在认知功能障碍中的可能作用,为临床治疗相关神经系统疾病提供新的思路与方向。     

我国首次发现胶质细胞突触具有可塑性

今年6月9日出版的美国《科学》杂志发表了中国科学院上海生命科学研究院神经科学研究所段树民研究员领导的研究小组有关胶质细胞突触具有可塑性这一最新研究成果。近年的研究发现神经元与NG2胶质细胞之间有直接的突触联系。但这类突触的意义是什么?是否具有可塑性?产生可     

星形胶质细胞

目录一、星形胶质细胞的生物学特性(一 )星形胶质细胞的异质性(二 )胶质网络二、星形胶质细胞的功能(一 )分泌功能(二 )星形胶质细胞与神经的发育及再生(三 )星形胶质细胞具有对神经元微环境调控的能力(四 )免疫功能与血脑屏障调控三、星形胶质细胞功能的新近进展(一 )星形胶质细胞也具有可兴奋性(二 )星形胶质细胞与神经元的通讯或对话(三 )在突触形成和突触可塑性中的作用(四 )星形胶质细胞与神经发生胶质细胞是神经系统内数量众多的一大类细胞群体 ,约占中枢神经系统 (CNS)细胞总数的 90 % ,星形胶质细胞 (astrocyte)是其中主要的组成…     

胶质细胞介导性激素的神经系统作用

性激素在神经系统的作用包括调节突触可塑性,参与脑的性别分化,衰老过程和神经损伤修复等,胶质细胞表达性激素受体,是性激素的靶细胞,性激素通过对胶质细胞的作用,再影响神经系统的功能,胶质细胞成为性激素对神经系统作用的中间环节。     

再可塑性在学习记忆中作用的研究进展

突触可塑性是学习记忆功能的重要细胞机制,也是神经科学领域的研究热点之一,其中长时程增强(long-term potentiation,LTP)与长时程抑制(long-term depression,LTD)是突触可塑性的两种主要表现形式。作为突触可塑性高级形式的再可塑性(metaplasticity),是指突触可塑性的可塑性,即突触活动的过往史对后继的突触可塑性产生影响,这表明突触的可塑性依赖于当前的突触"状态",因此对探究大脑学习记忆功能与疾病对认知的影响具有重要意义。自再可塑性的概念提出以来,便引起了广泛关注,大量的实验现象与细胞机制的研究成果已经使再可塑性的理论体系逐渐完善。尤其是近年来,人们发现再可塑性调节不仅可以影响突触可塑性,在个体水平上,再可塑性调节也可以提高动物的学习记忆能力,并且可以调控神经网络对特定信息的编码。这些研究成果不仅极大地丰富了再可塑性的理论体系,也为人们探究学习记忆功能开辟了新的道路。本文从以下三个方面对再可塑性调节的研究进展进行了概括与总结:(1)再可塑性的主要分子机制;(2)再可塑性对学习记忆功能的影响;(3)再可塑性领域的研究展望。     

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。     

上海生科院神经科学研究所一项成果入选2006年度“中国基础研究十大新闻”

中科院上海生科院神经科学研究所的一项研究成果“研究发现神经元——胶质细胞问的突触具有长时程可塑性”入选2006年度“中国基础研究十大新闻”。     

neurexin家族在突触发生和突触传递中作用的研究进展

neurexin家族属于神经细胞表面蛋白,参与细胞识别和细胞黏附,可能介导细胞信号转导。最近研究表明,neurexins在突触发生和突触传递等过程中发挥重要作用,并可能影响学习记忆功能。这些研究进展对于进一步揭示neurexins在神经突触可塑性及其在学习记忆过程中的可能作用具有重要意义。本文主要对neurexin家族的研究概况、NRXN1在突触发生和突触传递中的功能及其在学习记忆功能中的可能作用进行简要综述。     

胶质细胞在突触形成及突触传导中的作用

近年来,对胶质细胞功能的研究迅速发展.诸多研究都表明胶质细胞不仅为神经元功能发挥提供良好环境,而且还直接影响突触形成及其功能完善.此外胶质细胞也可以通过自身释放化学递质与神经元形成突触联系,参与对神经元兴奋性及突触传导的调节.     

突触蛋白在学习记忆过程中的作用

学习和记忆是脑的高级功能。学习指人和动物获得外界知识的神经过程;记忆指将获得的知识储存和读出的神经过程。突触蛋白(synapsin)是一种与突触结构和功能密切相关的膜蛋白,在突触的可塑性以及长时程增强(long-timepotentiation,LTP)中起着重要作用。而突触可塑性是突触对内外环境变化作出反应的能力,是学习记忆的神经生物学基础。LTP一直被认为是学习记忆的神经基础之一,是突触可塑性的功能指标,也是研究学习记忆的理想模型。该文介绍突触蛋白在学习记忆过程中的作用及机制、突触蛋白在学习记忆研究中的应用。     

Glial cells in synaptic plasticity.

Plasticity of synaptic transmission is believed to be the cellular basis for learning and memory, and depends upon different pre- and post-synaptic neuronal mechanisms. Recently, however, an increasing number of studies have implicated a third element in plasticity; the perisynaptic glial cell. Originally glial cells were thought to be important for metabolic maintenance and support of the nervous system. However, work in the past decade has clearly demonstrated active involvement of glia in stability and overall nervous system function as well as synaptic plasticity. Through specific modulation of glial cell function, a wide variety of roles for glia in synaptic plasticity have been uncovered. Furthermore, interesting circumstantial evidence suggests a glial involvement in multiple other types of plasticity. We will discuss recent advances in neuron-glial interactions that take place during synaptic plasticity and explore different plasticity phenomena in which glial cells may be involved.     

Interrogating structural plasticity among synaptic engrams

Our daily experiences and learnings are stored in the form of memories. These experiences trigger synaptic plasticity and persistent structural and functional changes in neuronal synapses. Recently, cellular studies of memory storage and engrams have emerged over the last decade. Engram cells reflect interconnected neurons via modified synapses. However, we were unable to observe the structural changes arising from synaptic plasticity in the past, because it was not possible to distinguish the synapses between engram cells. To overcome this barrier, dual-eGRASP (enhanced green fluorescent protein reconstitution across synaptic partners) technology can label specific synapses among multiple synaptic ensembles. Selective labeling of engram synapses elucidated their role by observing the structural changes in synapses according to the memory state. Dual-eGRASP extends cellular level engram studies to introduce the era of synaptic level studies. Here, we review this concept and possible applications of the dual-eGRASP, including recent studies that provided visual evidence of structural plasticity at the engram synapse.     

A critical role for the glial-derived neuromodulator D-serine in the age-related deficits of cellular mechanisms of learning and memory

Age-associated deficits in learning and memory are closely correlated with impairments of synaptic plasticity. Analysis of N-methyl-D-aspartate receptor (NMDAr)-dependent long-term potentiation (LTP) in CA1 hippocampal slices indicates that the glial-derived neuromodulator D-serine is required for the induction of synaptic plasticity. During aging, the content of D-serine and the expression of its synthesizing enzyme serine racemase are significantly decreased in the hippocampus. Impaired LTP and NMDAr-mediated synaptic potentials in old rats are rescued by exogenous D-serine. These results highlight the critical role of glial cells and presumably astrocytes, through the availability of D-serine, in the deficits of synaptic mechanisms of learning and memory that occur in the course of aging.     

Cadherins and synaptic plasticity

Given their trans-synaptic localization, their persistent expression at mature synapses and their distinct biochemical and adhesive properties, cadherins are uniquely poised at the synapse to mediate synaptic plasticity, the ability to change synaptic function thought to underlie learning and memory. For example recent work suggests that cadherins may recruit and stabilize AMPA receptors at the synapse via direct interactions or through complex formation, revealing cross talk between postsynaptic signaling and adhesion. Moreover, the use of small interfering RNA knockdown of cadherin, the availability of N-cadherin-deficient embryonic stem cells and the acute disruption of cadherin function with peptide application in vivo have allowed for more precise dissection of the molecular mechanisms by which cadherins function in both structural and functional plasticity.     

Assembly and plasticity of the glutamatergic postsynaptic specialization

Glutamate mediates most excitatory synaptic transmission in the brain. Synaptic strength at glutamatergic synapses shows a remarkable degree of use-dependent plasticity and such modifications may represent a physiological correlate to learning and memory. Glutamate receptors and downstream enzymes are organized at synapses by cytoskeletal proteins containing multiple protein-interacting domains. Recent studies demonstrate that these 'scaffolding' proteins within the postsynaptic specialization have the capacity to promote synaptic maturation, influence synapse size, and modulate glutamate receptor function.     

Activity-induced Notch signaling in neurons requires Arc/Arg3.1 and is essential for synaptic plasticity in hippocampal networks

Notch signaling in the nervous system has been most studied in the context of cell fate specification. However, numerous studies have suggested that Notch also regulates neuronal morphology, synaptic plasticity, learning, and memory. Here we show that Notch1 and its ligand Jagged1 are present at the synapse, and that Notch signaling in neurons occurs in response to synaptic activity. In addition, neuronal Notch signaling is positively regulated by Arc/Arg3.1, an activity-induced gene required for synaptic plasticity. In Arc/Arg3.1 mutant neurons, the proteolytic activation of Notch1 is disrupted both in vivo and in vitro. Conditional deletion of Notch1 in the postnatal hippocampus disrupted both long-term potentiation (LTP) and long-term depression (LTD), and led to deficits in learning and short-term memory. Thus, Notch signaling is dynamically regulated in response to neuronal activity, Arc/Arg3.1 is a context-dependent Notch regulator, and Notch1 is required for the synaptic plasticity that contributes to memory formation.     

Huntingtin Is Critical Both Pre- and Postsynaptically for Long-Term Learning-Related Synaptic Plasticity in Aplysia

Patients with Huntington’s disease exhibit memory and cognitive deficits many years before manifesting motor disturbances. Similarly, several studies have shown that deficits in long-term synaptic plasticity, a cellular basis of memory formation and storage, occur well before motor disturbances in the hippocampus of the transgenic mouse models of Huntington’s disease. The autosomal dominant inheritance pattern of Huntington’s disease suggests the importance of the mutant protein, huntingtin, in pathogenesis of Huntington’s disease, but wild type huntingtin also has been shown to be important for neuronal functions such as axonal transport. Yet, the role of wild type huntingtin in long-term synaptic plasticity has not been investigated in detail. We identified a huntingtin homolog in the marine snail Aplysia, and find that similar to the expression pattern in mammalian brain, huntingtin is widely expressed in neurons and glial cells. Importantly the expression of mRNAs of huntingtin is upregulated by repeated applications of serotonin, a modulatory transmitter released during learning in Aplysia. Furthermore, we find that huntingtin expression levels are critical, not only in presynaptic sensory neurons, but also in the postsynaptic motor neurons for serotonin-induced long-term facilitation at the sensory-to-motor neuron synapse of the Aplysia gill-withdrawal reflex. These results suggest a key role for huntingtin in long-term memory storage.     

Translational control of synaptic plasticity

Synapses, points of contact between axons and dendrites, are conduits for the flow of information in the circuitry of the central nervous system. The strength of synaptic transmission reflects the interconnectedness of the axons and dendrites at synapses; synaptic strength in turn is modified by the frequency with which the synapses are stimulated. This modulation of synaptic strength, or synaptic plasticity, probably forms the cellular basis for learning and memory. RNA metabolism, particularly translational control at or near the synapse, is one process that controls long-lasting synaptic plasticity and, by extension, memory formation and consolidation. In the present paper, I review some salient features of translational control of synaptic plasticity.