中枢学习记忆功能相关基因

近几年随着遗传学和分子生物学等技术的迅速发展,使我们从基因水平对构成学习记忆基础的分子机制有了进一步的认识.这些研究表明,学习记忆过程所必需的许多分子和分子机制在进化过程中得到保存,多种基因及其产物可在细胞膜受体、胞质内信号转导通路级联成分、胞核内基因表达的转录调节以及细胞生长发育等多个层次与学习记忆的调控有关.本文仅就来自海兔、果蝇和啮齿类动物的与中枢学习记忆功能有关的基因进行综述.     

颞叶癫痫与学习、记忆障碍

颞叶癫痫的发作与海马等边缘系统的病变密切相关,而海马等结构又参与了学习、记忆等认知功能的形成。最近有关颞叶癫痫发作后引起的学习、记忆功能障碍逐渐得到人们的认识和重视。学习记忆的神经生物学机制是十分复杂的,本文从学习、记忆的解剖基础、突触修饰理论、长时程增强、神经细胞内钙离子等方面,对颞叶癫痫发作后引起的学习记忆障碍的机制进行了综述。     

中枢毒蕈碱受体与学习记忆

毒蕈碱受体对学习记忆具有重要的调节作用，本文从学习记忆的基本概念、毒蕈碱受体的结构特征及在脑内的功能定位、毒蕈碱受体调节学习记忆的分子生物学机制及其与其它神经递质系统的相互作用等方面总结了毒蕈碱受体调节学习记忆的机制。     

学习和记忆的影像学研究进展

人们渴望学习，更希望牢固地记住学过的知识及看过、听过或经历过的事。科学家们则不断地探索有关学习和记忆的奥秘，包括学习和记忆的过程，记忆的存储和提取，不同类型的记忆功能在大脑的准确解剖位置，如何永葆良好的学习和记忆能力等。随着解剖学和神经生理学等的发展，人们发现学习和记忆主要与边缘系统结构有关，但这远不能解释     

SORL1基因与阿尔茨海默病相关性的研究现状

<正>阿尔茨海默病(Alzheimer's disease,AD)是最常见的痴呆类型,该病是与多基因有关的中枢神经系统的退行性疾病。AD的发病机制目前认为与遗传因素、细胞凋亡、自由基损伤等因素有关。AD的病理改变主要是累及前基底部发出至大脑皮质和海马的胆碱能神经通路,已知这些通路与注意、学习、记忆及其他认知过程有关。近年来研究发现,利用分子生物学技术,从DNA/RNA水平检测基因,分析基因结构变异和     

成瘾行为形成过程中学习记忆的参与及其相关的脑机制

多种学习记忆系统参与了成瘾行为形成的长时程适应过程，中脑奖党通路腹侧被盖区－伏核投射多巴胺能神经纤维至前额叶，海马，杏仁核等有重要学习记忆功能的结构和核团，同时又接受这些区域发现的谷氨酸能传入纤维，提示多巴胺，谷氨酸等相对独立又互相关联的神经递质系统共同参与成瘾行为的学习记忆调控过程，不同的成瘾药物介导细胞外递质及相关受体作用，激活细胞内信号转导及基因的转录和表达，从而产生突触可塑的变化，这一变化过程可能是成瘾行为获得和保持的主要生物基础。cAMP反应原件结合蛋白、即刻早基因△fosB可能是成瘾长过程适应的分子开关。     

离子型谷氨酸受体在长时程增强产生机制中的研究进展

长时程增强(Long-term potentiation,LTP)是一种发生在神经细胞信号传输中持久的增强现象。在分子水平研究学习和记忆能力,反应海马功能可塑性的长时程增强是常用的指标,其作用的改变与学习记忆密切相关。长时程增强增加会促进学习记忆能力,而长时程增强减弱会导致学习记忆能力的下降。诱导长时程增强发生的相关机制非常复杂,迄今尚未完全阐明,而关于离子型谷氨酸受体在其中的作用研究相对较少。因此,本文对离子型谷氨酸受体在长时程增强形成条件、分子机制等方面进行了综述。     

中枢毒蕈碱受体与学习记忆

毒蕈碱受体对学习记忆具有重要的调节作用 ,本文从学习记忆的基本概念、毒蕈碱受体的结构特征及在脑内的功能定位、毒蕈碱受体调节学习记忆的分子生物学机制及其与其它神经递质系统的相互作用等方面总结了毒蕈碱受体调节学习记忆的机制     

神经营养因子研究进展(2)

退行性变、死亡 ,此区与人类记忆有关 ,给予ＮＧＦ可使该区胆碱能神经元胞体增大、功能改善 ,从而提高其学习记忆能力。最近的研究开始阐明介导ＮＧＦ促进电兴奋 ,增强神经元存活等功能的新通路 ,即通过调控离子通道基因转录来增强Ｐｃ12细胞兴奋〔5〕。1 1 2　ＢＤＮＦ :主要在中枢神经系统中表达 ,以海马、皮质、杏仁核等脑区含量最高 ,在海马中ＢＤＮＦｍＲＮＡ含量高出ＮＧＦｍ ＲＮＡ2 0～ 30倍。也见于心、肺和骨骼肌等外周组织中 ,但其表达水平较低 ,与ＮＧＦ相当。在脑发育过程中 ,ＢＤＮＦ初为低水平表达 ,后期增加 ,成为脑内各不…     

β-catenin蛋白在肝细胞癌中表达的意义

β-连环蛋白是一种重要的胞内蛋白,它具有双重功能,一是介导细胞粘附的E钙粘连素的重要结构分子,其异常改变在肿瘤浸润、转移过程中发挥重要作用;二是WNT信号传导途径的关键信号分子,降解障碍致使胞质内游离的β-连环蛋白积累,并与T细胞因子/淋巴细胞增强因子(TCF/LEF)结合进入细胞核,激活下游靶基因cmyc转录,引起细胞增殖和分化失控,导致肿瘤发生.     

Finding new candidate genes for learning and memory

The genetic mechanisms underlying learning and memory remain mysterious, but many of the genes are likely to be expressed in the hippocampus, a region pivotal to this process. We used a 9,000 gene microarray to examine differences in hippocampal gene expression between two F1 hybrid mouse strains that perform well on the Morris water maze and two inbred strains that perform poorly. This resulted in identification of 27 differentially expressed genes, which could be used to place the F1 hybrid and inbred strains into separate clusters based on singular value decomposition. Most of the genes have unknown function, but those with known functions may provide clues to the molecular mechanisms of learning. Using multiple strains to narrow down the number of candidate genes should be a useful general approach to genome-wide studies of behavioral and other complex traits.     

Combined neuroimaging and gene expression analysis of the genetic basis of brain plasticity indicates across species homology

Brain plasticity and memory formation depend on the expression of a large number of genes. This relationship had been studied using several experimental approaches and researchers have identified genes regulating plasticity through a variety of mechanisms. Despite this effort, a great deal remains unknown regarding the role of different genes in brain plasticity. Previous studies usually focused on specific brain structures and many of the genes influencing plasticity have yet to be identified. In this work, we integrate results of in vivo neuroimaging studies of plasticity with whole‐brain gene expression data for the study of neuroplasticity. Brain regions, found in the imaging study to be involved in plasticity, are first spatially mapped to the anatomical framework of the genetic database. Feature ranking methods are then applied to identify genes that are differentially expressed in these regions. We find that many of our highly ranked genes are involved in synaptic transmission and that some of these genes have been previously associated with learning and memory. We show these results to be consistent when applying our method to gene expression data from four human subjects. Finally, by performing similar experiments in mice, we reveal significant cross species correlation in the ranking of genes. In addition to the identification of plasticity related candidate genes, our results also demonstrate the potential of data integration approaches as a tool to link high level phenomena such as learning and memory to underlying molecular mechanisms. Hum Brain Mapp 35:5888–5902, 2014. © 2014 Wiley Periodicals, Inc.     

Molecular and cellular mechanisms of cognitive function: implications for psychiatric disorders.

Recent studies on the molecular and cellular basis of learning and memory have brought us closer than ever to understanding the mechanisms of synaptic plasticity and their relevance to memory formation. Genetic approaches have played a central role in these new findings because the same mutant mice can be studied with molecular, cellular, circuit, and behavioral tools. Therefore, the results can be used to construct models that cut across levels of analytical complexity, forging connections from the biochemistry of the modified protein to the behavior of the mutant mice. These findings are not only improving our understanding of learning and memory, they are also enriching our understanding of cognitive disorders, such as neurofibromatosis type I. Mechanisms underlying long-term changes in synaptic function are likely to be at the heart of many cognitive and emotional processes in humans. Therefore, molecular and cellular insights into learning and memory undoubtedly will have a profound impact on the understanding and treatment of psychiatric disorders.     

Gene expression profiles--a new dynamic and functional dimension to the exploration of learning and memory

Many experiments in the past have demonstrated the requirement of de novo gene expression during the long-term retention of learning and memory. Although previous studies implicated individual genes or genetic pathways in learning and memory they did not uncover the collective behaviors of the genes. In view of the broad variety of genes and the cross-talk of genetic pathways, gene expression profiles offer a new dynamic and functional dimension to the exploration of learning and memory. This review illustrates how DNA microarray-based gene expression profiling may help to dissect and analyze the complex mechanisms involved in gene regulation during the acquisition and storage of memory.     

Long-term depression: multiple forms and implications for brain function

Long-term potentiation (LTP) and long-term depression (LTD) remain widely accepted vertebrate models for the cellular and molecular mechanisms that underlie synaptic changes during learning and memory. Although LTD is a phenomenon that occurs in many regions of the CNS, it is clear that the mechanisms recruited in its induction and expression can vary, depending on many factors, including brain region and developmental time point. LTD in the hippocampus and cerebellum is probably the best characterized, although there are also other brain areas where mechanisms of LTD are well understood, and where it is thought to have a functional role.     

Hippocampal gene expression profiles in passive avoidance conditioning

Many experiments in the past have demonstrated the requirement of de novo gene expression during the long‐term retention of learning and memory. Although previous studies implicated individual genes or genetic pathways in learning and memory, the collective behaviours of the genes is mostly unknown. We have used genome‐scale screening by microarray analysis to examine the hippocampal expression of more than 1200 genes relevant to neurobiology during instrumental conditioning. Training rats on a step‐through passive avoidance task led to unique patterns of gene expression when compared to naïve animals or those exposed to the conditioned or the unconditioned stimulus alone. The newly identified genes afford a quantitative view of the changes which accompany conditioning at the genomic level and enable deeper insights into the molecular basis underlying learning and memory.     

Is LTP in the hippocampus a useful model for learning-related alterations in gene expression?

It is well established that the formation of long-term memory requires de novo protein synthesis. Altered gene expression is therefore critical in the signal transduction cascade activated by the learning experience. Long-term potentiation (LTP) is a mnemonic model in which particular patterns of activation of incoming excitatory fibers (representing the learning experience) may induce long-lasting enhancement of the communication between the involved pre- and post-synapses (representing the memory). Therefore, cellular and molecular mechanisms of LTP have been extensively studied under the assumption that their understanding will contribute to our comprehension of the mechanisms underlying memory formation. In recent years, however, this analogy has been challenged by reports of inconsistency between LTP and memory. Here we assess LTP in the hippocampus as a model system to study spatial memory-related alterations in gene expression. We focus on three molecular families that are likely to play a role in synaptic plasticity: (1) synaptic communication related proteins; (2) signal transduction machinery; and (3) growth factors. Reviewing first the literature on LTP and then behavioral research we found both consistent and inconsistent findings regarding the LTP/memory linkage. The importance of restricting the discussion to both a learning phase and a brain (sub)structure, as well as of incorporating more physiological LTP stimulation protocols, is discussed. We conclude that while LTP is indeed limited as a model of memory, a careful use of it as a model system of synaptic plasticity is fruitful and productive in screening out candidate memory-related genes.     

Genes regulated by learning in the hippocampus

The enduring changes in long-term memory probably depend on regulation of gene expression in the hippocampus. To seek genes regulated by learning, we used microarray technology to compare hippocampal gene expression in mice undergoing training in the Morris water maze and control mice forced to swim for the same period in the absence of a hidden platform. ANOVA was employed to prioritize genes for further study, and three genes were confirmed by real-time PCR as being regulated during learning. One of the genes was the alpha subunit of the platelet-derived growth factor receptor (Pdgfra); another showed homology to DnaJ and cAMP response element-binding protein 2 (CREB2); and a third was novel. These genes may provide useful insights into the molecular mechanisms of hippocampal learning.     

Neuromodulatory pathways in learning and memory: Lessons from invertebrates

In an ever‐changing environment, animals have to continuously adapt their behaviour. The ability to learn from experience is crucial for animals to increase their chances of survival. It is therefore not surprising that learning and memory evolved early in evolution and are mediated by conserved molecular mechanisms. A broad range of neuromodulators, in particular monoamines and neuropeptides, have been found to influence learning and memory, although our knowledge on their modulatory functions in learning circuits remains fragmentary. Many neuromodulatory systems are evolutionarily ancient and well‐conserved between vertebrates and invertebrates. Here, we highlight general principles and mechanistic insights concerning the actions of monoamines and neuropeptides in learning circuits that have emerged from invertebrate studies. Diverse neuromodulators have been shown to influence learning and memory in invertebrates, which can have divergent or convergent actions at different spatiotemporal scales. In addition, neuromodulators can regulate learning dependent on internal and external states, such as food and social context. The strong conservation of neuromodulatory systems, the extensive toolkit and the compact learning circuits in invertebrate models make these powerful systems to further deepen our understanding of neuromodulatory pathways involved in learning and memory.