小鼠视网膜神经节细胞树突在出生后不同发育时期的生长特点

目前,神经元发育过程中树突的生长特点备受关注.利用体外视网膜培养,森林脑炎病毒(SFV)转染和适时观察的实验方法,对出生后不同发育时期神经节细胞树突生长情况进行了研究.结果显示,随着出生后发育的进行,视网膜神经节细胞的树突经历了一个从活跃到比较稳定的生长过程,即小鼠出生时(P0)树突处于非常活跃的状态中,而P13时树突则比较稳定,P3和P8时处于前两者的一种中间状态.对同一发育时期不同种类节细胞树突生长情况的分析表明,不同种类神经节细胞之间树突生长的特点没有明显差别.由于小鼠是目前应用最广泛的哺乳动物模型,本实验为进一步研究视网膜神经节细胞树突发育的调控机制提供了基础.     

利用工程树突细胞定向的纳米颗粒增强免疫应答的简单策略

在这项研究中,作者证实了一种简单的能够增强免疫应答的策略,这种策略是使用两组分树突细胞定向抗原投递系统。一种组分是由用于树突细胞导向的双功能性融合蛋白所构成,另一组分是由生物素化的PLGA纳米颗粒（NPs）制备而成,     

分形动力系统中Fibonacci过程的若干性质

作者在文「」１中讨论了一种生命期有限,存活率和繁殖率有随机统计性的“泛广义Ｆｉｂｏｎａｃｃｉ数列”,并正式定义它为Ｆｉｂｏｎａｃｃｉ过程。Ａｒｎｅｏｄｏ等自１９９３年以来多次报导了一种适用于神经树突,毛细管,叶序,视网膜和海藻等增生的分形ＤＬＡ在增长过程中是准Ｆｉｂｏｎａｃｃｉ的。     

RCS大鼠视网膜变性过程中二级神经元形态学变化的研究

用免疫组织化学方法研究RCS大鼠(Royal College of Surgeon's rat,RCS rat)视网膜变性过程中早、中、晚期二级神经元形态的变化。结果发现,P1MRCS大鼠各二级神经元未见明显的形态改变。P2M RCS大鼠视网膜外核层萎缩约85%,视杆双极细胞顶端树突萎缩;水平细胞的树突与轴突在外网状层的分层未见改变。P3M RCS大鼠视网膜外核层萎缩近95%,RCS大鼠视杆双极细胞顶端萌生新的神经突起;水平细胞的树突分支明显丢失,轴突在外网状层的分层发生改变,出现新生神经突起;无长突细胞的树突在内网状层的分层至变性晚期也未见改变。该研究表明RCS大鼠视网膜二级神经元形态的改变是继发性改变,是感光细胞变性后对传入缺失的一种反应,即重构反应。在进行视网膜功能救治时需要考虑重构反应带来的影响。     

猫丘脑腹后外侧核的超微结构

采用电镜技术观察了猫丘脑腹后外侧核的超微结构。该核内的神经元可分为大小两种类型，大型直径在１５—４０μｍ，小型小于１５μｍ，其胞质内容无明显差别。树突较多见，直径从１—１０μｍ不等。轴突可分为三种类型：含圆形小泡的小终末、终末及扁平小泡的终末。突触类型主要为轴树突触，此外还可见到轴体、轴轴、轴轴树、树树突触以及以树突为中心的突触复合体。在树突之间、树突与胞体之间还存在有非突触的丝状连接。     

青蛙视网膜神经节细胞分类的研究

关于视网膜神经节细胞分类的研究,到现在已有几十年的历史。许多研究者对不同动物进行了观察,但他们分类的根据不完全一致。在早期,Cajal(1893)以树突分枝在内网织层的分布做为根据。后来,将视网膜做整铺片,能够观察到神经节细胞的整个形态。这样,分类的依据也增加了,逐渐把神经节细胞胞体的大小、树突野的范围和树突分枝数目等做为分类标准(Kalinina,1974;Boycott er al.,1974)。从分类的趋势来看,有从复杂到简单的倾向,如早期研究中,Cajal(引自Kalinina,1974)将神经节细胞分为11类,后来,Lettvin和他的同事(1961)以及Kalinina(1974)分为五类,Shibkova(1970)分为三类。随着电生理研究的发展,对神经节细胞的分类开始把细胞形态和生理机能联系起来。近年来,在哺乳动物中,用电生理方法发现有三种反应特性不同的神经节细胞,分别叫做X.Y.W细胞。Boycott等(1974)根据神经节细胞的形态特点,将它们分为α.β.γ三种类型,并且发现这三类细胞分别与X.Y.W细胞对应,从而使组织学研究具有了新的意义。     

一种新的视网膜神经元——网间细胞

网间细胞是近年来新发现的一种视网膜神经元,其胞体位于内核层的内缘,突起在内、外网状层中广泛伸展。在内网状层,它仅从无足细胞接收输入;而在外网状层,它总是突触前的,其突起在外水平细胞和双极细胞的树突上形成突触,从而为视信息在视网膜中的传递提供了一条离心反馈通路。其主要生理作用似乎是阻遏水平细胞的侧向抑制效应。     

群落内物种多样性发生与维持的一个假说

本文根据作者对竞争排除法则的研究而提出了一个新的群落多样性假说。按照作者的观点,占用相同生态位的物种可以稳定共存;这样,群落内物种多样性将受到４个基本因子所控制。它们分别是：（Ⅰ）生态位的数量;（Ⅱ）区域物种库的大小;（Ⅲ）物种迁入速率,以及（Ⅳ）物种灭绝速率。该假说强调区域生物地理过程与局域生态过程共同决定了群落内种多样性的大小及分布模式。     

一种基于视网膜主血管方向的视盘定位及提取方法

为分割出眼底图像中的视盘,构建基于眼底图像的计算机辅助诊断系统,提出了一种基于视网膜主血管方向的视盘定位及提取方法。首先,利用Otsu阈值分割眼底图像R通道获取视盘候选区域;然后利用彩色眼底图像的HSV空间的H通道提取视网膜主血管并确定主血管方向;在此基础上,通过在方向图内寻找出对加权匹配滤波器响应值最高的点确定视盘中心位置;最后,利用该位置信息从视盘候选区域中"挑选"出真正的视盘。利用该方法对100幅不同颜色、不同亮度的眼底图像进行视盘分割,得到准确率98%,平均每幅图像处理时间1.3 s。结果表明:该方法稳定可靠,能快速、有效分割出眼底图像中的视盘。     

赢家通吃:神经环路修剪的竞争机制

人类的大脑约由一千亿个神经元组成,它们通过位于树突棘结构上的突触相互连接,形成庞大的神经网络,主宰着人们的感觉、运动、记忆与情感。这个神经网络并不是一成不变的。发育早期,神经元之间的连接迅速建立;而在个体经由青少年期向成年期转变的过程中,多余的连接经由树突棘的修剪得到清除,神经环路得到优化,从而达到最佳的信息传递与储存效果。树突棘修剪对于大脑的正常功能至关重要,在多种发育性神经系统疾病中均发现了树突棘修剪的异常,但介导该过程的分子机制是基本未知的。中国科学院神经科学研究所于翔研究组的工作发现,发育过程中小鼠感觉皮层的树突棘修剪和被保留树突棘的成熟同时受到感觉经验的双向调控,并协同变化。通过在单个树突棘的水平精细操控细胞黏附水平和神经电活动水平,于翔实验室进一步发现这种协同的成熟/修剪变化是由相邻树突棘间对一类细胞黏附分子——cadherin/catenin复合物——的竞争所介导:竞争到更多此类复合物的树突棘变得稳定、成熟,而失败的一方则被修剪。这一"赢家通吃"的竞争模型为发育过程中神经网络的优化提供了分子机制的解释,拓展了人们对于大脑可塑性的理解,并可能代表了生物系统发育的普遍策略。鉴于树突棘修剪的异常与孤独症、精神分裂症等发育性神经系统疾病密切相关,阐明其分子机制对解析上述疾病的致病机理有重要的理论与临床意义。     

Morphological characteristics of different types of neurons in the ventrooralis anterior,ventrooralis internus,and ventrooralis posterior nuclei in the human thalamus

1. Golgi-Kopsch preparations of the oral ventral nuclei of human thalamus were analyzed in an attempt to classify the neuronal types. 2. Three types of neurons are described for the first time in humans. Type I neurons are large or medium in size and bear dendrites with protrusions, spines, and short hair-like appendages. Some have a radiate dendritic arbor and others have dendrites grouped in tufts. The dendritic trees of these neurons are dense. 3. Type II neurons are medium or small in size with less dense dendritic trees. These cells have somatic as well as dendritic appendages of different forms. 4. Relatively rare is a type of very small neurons, type III, with few and sparsely branching dendrites.     

More than just synaptic building blocks: scaffolding proteins of the post-synaptic density regulate dendritic patterning

The dendritic arbor is responsible for receiving and consolidating neuronal input. Outgrowth and morphogenesis of the arbor are complex stages of development that are poorly understood. However, recent findings have identified synaptic scaffolding proteins as novel regulators of these important events. Scaffolding proteins are enriched in the post-synaptic density where they bind and bring into close proximity neurotransmitter receptors, signaling molecules, and regulators of the actin cytoskeleton. This property is important for dendritic spine morphogenesis and maintenance in the mature neuron. Scaffolding proteins are now being described as key regulators of neurite outgrowth, dendritic development, and pattern formation in immature neurons. These proteins, which include post-synaptic-95, Shank and Densin-180, as well as many of their interacting partners, appear to regulate both the microtubule and actin cytoskeleton to influence dendrite morphology. Through a large array of protein-protein interaction domains, scaffolding proteins are able to form large macromolecular complexes that include cytoskeletal motor proteins as well as microtubule and actin regulatory molecules. Together, the new findings form a persuasive argument that scaffolding proteins deliver critical regulatory elements to sites of dendritic outgrowth and branching to modulate the formation and maintenance of the dendritic arbor.     

Structural homeostasis: compensatory adjustments of dendritic arbor geometry in response to variations of synaptic input

As the nervous system develops, there is an inherent variability in the connections formed between differentiating neurons. Despite this variability, neural circuits form that are functional and remarkably robust. One way in which neurons deal with variability in their inputs is through compensatory, homeostatic changes in their electrical properties. Here, we show that neurons also make compensatory adjustments to their structure. We analysed the development of dendrites on an identified central neuron (aCC) in the late Drosophila embryo at the stage when it receives its first connections and first becomes electrically active. At the same time, we charted the distribution of presynaptic sites on the developing postsynaptic arbor. Genetic manipulations of the presynaptic partners demonstrate that the postsynaptic dendritic arbor adjusts its growth to compensate for changes in the activity and density of synaptic sites. Blocking the synthesis or evoked release of presynaptic neurotransmitter results in greater dendritic extension. Conversely, an increase in the density of presynaptic release sites induces a reduction in the extent of the dendritic arbor. These growth adjustments occur locally in the arbor and are the result of the promotion or inhibition of growth of neurites in the proximity of presynaptic sites. We provide evidence that suggest a role for the postsynaptic activity state of protein kinase A in mediating this structural adjustment, which modifies dendritic growth in response to synaptic activity. These findings suggest that the dendritic arbor, at least during early stages of connectivity, behaves as a homeostatic device that adjusts its size and geometry to the level and the distribution of input received. The growing arbor thus counterbalances naturally occurring variations in synaptic density and activity so as to ensure that an appropriate level of input is achieved.     

Development of morphological diversity of dendrites in Drosophila by the BTB-zinc finger protein abrupt

Morphological diversity of dendrites contributes to specialized functions of individual neurons. In the present study, we examined the molecular basis that generates distinct morphological classes of Drosophila dendritic arborization (da) neurons. da neurons are classified into classes I to IV in order of increasing territory size and/or branching complexity. We found that Abrupt (Ab), a BTB-zinc finger protein, is expressed selectively in class I cells. Misexpression of ab in neurons of other classes directed them to take the appearance of cells with smaller and/or less elaborated arbors. Loss of ab functions in class I neurons resulted in malformation of their typical comb-like arbor patterns and generation of supernumerary branch terminals. Together with the results of monitoring dendritic dynamics of ab-misexpressing cells or ab mutant ones, all of the data suggested that Ab endows characteristics of dendritic morphogenesis of the class I neurons.     

A phenomenological theory of spatially structured local synaptic connectivity

The structure of local synaptic circuits is the key to understanding cortical function and how neuronal functional modules such as cortical columns are formed. The central problem in deciphering cortical microcircuits is the quantification of synaptic connectivity between neuron pairs. I present a theoretical model that accounts for the axon and dendrite morphologies of pre- and postsynaptic cells and provides the average number of synaptic contacts formed between them as a function of their relative locations in three-dimensional space. An important aspect of the current approach is the representation of a complex structure of an axonal/dendritic arbor as a superposition of basic structures—synaptic clouds. Each cloud has three structural parameters that can be directly estimated from two-dimensional drawings of the underlying arbor. Using empirical data available in literature, I applied this theory to three morphologically different types of cell pairs. I found that, within a wide range of cell separations, the theory is in very good agreement with empirical data on (i) axonal–dendritic contacts of pyramidal cells and (ii) somatic synapses formed by the axons of inhibitory interneurons. Since for many types of neurons plane arborization drawings are available from literature, this theory can provide a practical means for quantitatively deriving local synaptic circuits based on the actual observed densities of specific types of neurons and their morphologies. It can also have significant implications for computational models of cortical networks by making it possible to wire up simulated neural networks in a realistic fashion.     

Homer proteins shape Xenopus optic tectal cell dendritic arbor development in vivo

Considerable evidence suggests that the Homer family of scaffolding proteins contributes to synaptic organization and function. We investigated the role of both Homer 1b, the constitutively expressed, and developmentally regulated form of Homer, and Homer 1a, the activity-induced immediate early gene, in dendritic arbor elaboration and synaptic function of developing Xenopus optic tectal neurons. We expressed exogenous Homer 1a or Homer 1b in developing Xenopus tectal neurons. By collecting in vivo time lapse images of individual, EGFP-labeled and Homer-expressing neurons over 3 days, we found that Homer 1b leads to a significant decrease in dendritic arbor growth rate and arbor size. Synaptic transmission was also altered in developing neurons transfected with Homer 1b. Cells expressing exogenous Homer 1b over 3 days had a significantly greater AMPA to NMDA ratios, and increased AMPA mEPSC frequency. These data suggest that increasing Homer 1b expression increases excitatory synaptic inputs, increases synaptic maturation, and slows dendritic arbor growth rate. Exogenous Homer 1a expression increases AMPA mEPSC frequency, but did not significantly affect tectal cell dendritic arbor development. Changes in the ratio of Homer 1a to Homer 1b may signal the neuron that overall activity levels in the cell have changed, and this in turn could affect protein interactions at the synapse, synaptic transmission, and structural development of the dendritic arbor.     

Developmental shaping of dendritic arbors in Drosophila relies on tightly regulated intra-neuronal activity of protein kinase A (PKA)

Dendrites develop morphologies characterized by multiple levels of complexity that involve neuron type specific dendritic length and particular spatial distribution. How this is developmentally regulated and in particular which signaling molecules are crucial in the process is still not understood. Using Drosophila class IV dendritic arborization (da) neurons we test in vivo the effects of cell-autonomous dose-dependent changes in the activity levels of the cAMP-dependent Protein Kinase A (PKA) on the formation of complex dendritic arbors. We find that genetic manipulations of the PKA activity levels affect profoundly the arbor complexity with strongest impact on distal branches. Both decreasing and increasing PKA activity result in a reduced complexity of the arbors, as reflected in decreased dendritic length and number of branching points, suggesting an inverted U-shape response to PKA. The phenotypes are accompanied by changes in organelle distribution: Golgi outposts and early endosomes in distal dendritic branches are reduced in PKA mutants. By using Rab5 dominant negative we find that PKA interacts genetically with the early endosomal pathway. We test if the possible relationship between PKA and organelles may be the result of phosphorylation of the microtubule motor dynein components or Rab5. We find that Drosophila cytoplasmic dynein components are direct PKA phosphorylation targets in vitro, but not in vivo, thus pointing to a different putative in vivo target. Our data argue that tightly controlled dose-dependent intra-neuronal PKA activity levels are critical in determining the dendritic arbor complexity, one of the possible ways being through the regulation of organelle distribution.     

Mammalian Target of Rapamycin Complex 1 (mTORC1) and 2 (mTORC2) Control the Dendritic Arbor Morphology of Hippocampal Neurons

Dendrites are the main site of information input into neurons. Their development is a multistep process controlled by mammalian target of rapamycin (mTOR) among other proteins. mTOR is a serine/threonine protein kinase that forms two functionally distinct complexes in mammalian cells: mTORC1 and mTORC2. However, the one that contributes to mammalian neuron development remains unknown. This work used short hairpin RNA against Raptor and Rictor, unique components of mTORC1 and mTORC2, respectively, to dissect mTORC involvement in this process. We provide evidence that both mTOR complexes are crucial for the proper dendritic arbor morphology of hippocampal neurons. These two complexes are required for dendritic development both under basal conditions and upon the induction of mTOR-dependent dendritic growth. We also identified Akt as a downstream effector of mTORC2 needed for proper dendritic arbor morphology, the action of which required mTORC1 and p70S6K1.