17β-Estradiol: Effect on CA1 Hippocampal Synaptic Plasticity

An understanding of synaptic plasticity in the mammalian brain has been one of R. F. Thompson's major pursuits throughout his illustrious career. A current series of experiments of significant interest to R. F. Thompson is an examination of the interactions between sex hormones, synaptic plasticity, aging, and stress. This research is contained within a broader project whose aim is to investigate animal models that evaluate estrogen interactions with Alzheimer's disease. This paper reviews the recent results that have led to a better understanding of how the sex hormone estrogen influences synaptic plasticity in an important structure within the mammalian brain responsible for learning and memory: the hippocampus. In this review, a number of experiments have been highlighted that investigate the molecular mechanisms that underlie estrogen's effect on two specific forms of synaptic plasticity commonly studied in neurophysiology and the behavioral neurosciences: long-term potentiation and long-term depression.     

Memory Maintenance

ABSTRACT— Change in the synaptic communication between neurons—known as synaptic plasticity—plays a key role in learning and memory. It is not yet clear, however, whether the properties of synaptic plasticity are sufficient to account for long-term-memory maintenance. Recent studies have revealed that synaptic plasticity can indeed persist for weeks or months, as might be expected of a long-term-memory mechanism. However, memories encoded by neural systems are not static; they continue to evolve as new learning occurs. Furthermore, neural-network modeling has shown that synapses must be able to reconfigure their connection strengths during new learning if old information is to be preserved. Recent tests confirm that synapses, once modified, retain their capacity for further modification, indicating that they can indeed operate in the manner predicted to be necessary for memory maintenance in a dynamic learning network.     

同一学习中海马不同区的习得性长时程突触增强的形成

本研究探查大鼠分辨学习中海马齿状回(DG)和CA_3区突触效应的变化及其相互关系,以探讨同一学习中海马不同区突触可塑性变化的特点及其相互关系,进一步论证习得性长时程增强(LTP)是学习和记忆的神经基础。发现:(1)穿通纤维的单个刺激可在DG和CA_3同时记录到潜伏期、峰值和波形各异的群体峰电位(PS);在一定范围内PS随刺激强度的增加而增大,但DG的PS增大程度比CA_3的小;据此,检测刺激的强度应选在该范围内。(2)随着行为训练,DG和CA_3区的突触传递同时产生LTP,两者LTP的发展是显著正相关关系(P<0.01),PS峰值同时达到最高水平,且先于分辨反应达学会标准,首次表明在同一学习中大鼠海马的DG和CA_3的习得性LTP是同时产生的。本研究还表明,在慢性实验下同时记录和分析行为学习中海马两个区突触效应的变化及其相互关系是可能的,这给从神经环路角度研究学习和记忆的突触机制提供了有用的模型。     

Neural Plasticity and Human Development

In this article, I argue that experience-induced changes in the brain may be a useful way of viewing the course of human development. Work from the neurosciences supports the claim that most of the behavioral phenomena of interest to psychologists (e.g., cognition, perception, language, emotion) are instantiated by the process of neural plasticity. When development is viewed in this manner, the fallaciousness of the long-standing and often contentious debate over nature versus nurture becomes apparent. Moreover, by utilizing theneuroscientific tools used to examine the effects of experience on brain and behavioral development (e.g., functional neuroimaging), we may improve how we conceptualize our notions of intervention, competence, and resilience.     

The Effects of Estrogen Replacement Therapy on Neuropsychological Functioning in Postmenopausal Women With and Without Dementia: A Critical and Theoretical Review

We review 42 studies examining the effects of estrogen replacement therapy (ERT) on memory and cognition in nondemented postmenopausal women. Although there are an appreciable number of nonsignificant findings, the number of significant findings favoring ERT users considerably outnumbers the rare findings of better performance in controls. Experimental studies demonstrate a consistent beneficial effect on verbal memory, but these are short-term studies of the more acute effects of ERT. The observational studies suggest that there may be a long-lasting effect of continued ERT on cognitive functioning, but these studies need to be interpreted with caution because of the lack of random assignment and a possible healthy user bias. We also summarize findings from studies on the effects of ERT on Alzheimer's disease (AD). ERT is associated with a decreased risk for dementia, but there is little evidence for a positive effect on cognition in women with AD. Definitive answers to questions about the long-term effects of ERT on cognitive aging and risk of developing AD should be provided by 3 ongoing clinical trials.     

Ovarian steroids and cognitive function

The ovarian steroids, estrogen and progesterone, not only govern reproductive events in mammalian females but also influence an array of other processes. Of particular clinical interest is the potential of ovarian steroids to facilitate storage of new memories and to protect neurons from various threats. Research during the past decade confirms that estrogen and progesterone influence the biochemical, electrical, and structural properties of neurons in brain regions that subserve learning and memory. These mechanisms form the biological foundations for the complex effects of ovarian steroids on cognitive functions in various species, including humans. Despite significant progress in our understanding of the roles of hormonal factors in cognitive function and neuronal survival, the value of hormone replacement as a treatment and deterrent for cognitive impairments associated with age, disease, and injury remains uncertain as we enter the new century.     

工作记忆训练对认知功能和大脑神经系统的影响

工作记忆训练成为近年来提升个体认知绩效的一种有效方式。工作记忆训练主要是指采用工作记忆广度任务、刷新任务以及各种复杂工作记忆任务在计算机上以循序渐进的方式进行训练。近年来的研究发现, 工作记忆训练能提升工作记忆、流体智力、抑制、注意、阅读和数学等认知功能。神经机制的研究发现：工作记忆训练引起大脑额-顶区域激活减弱, 而皮层下结构包括纹状体和尾状核区域的激活增强; 工作记忆训练减少了大脑灰质的数量, 增强了大脑白质的功能连通性; 工作记忆训练引起尾状核上多巴胺受体的变化。未来的研究需要在研究设计、被试人群、研究手段上进一步确认和扩展工作记忆训练的有效性和内在认知神经机制。     

老年执行功能的认知可塑性和神经可塑性

执行衰退假说认为执行功能的特异性衰退是引起认知年老化的主要原因, 近年来越来越多的研究表明, 老年人的执行功能及其相关脑区(主要为前额叶)存在可塑性, 通过训练执行功能的衰退可得到缓解, 且相关脑区的激活水平、脑容量或神经递质都可发生改变; 部分研究还发现执行功能训练对其它认知能力有一定的迁移效应。这些发现对于认知年老化理论的继续探索和认知干预研究的实践应用都具有重要意义。     

工作记忆刷新功能的可塑性

从工作记忆刷新功能的训练入手, 以不同人群为研究对象, 采用活动记忆任务, 从行为层面和认知神经层面探讨工作记忆刷新功能的可塑性。结果发现, 工作记忆刷新功能具有可塑性。具体表现为, 通过刷新功能训练, 个体在工作记忆刷新任务上的成绩提高。工作记忆刷新功能训练使得个体对刺激的识别能力增强, 对无关信息的抑制能力提高, 进而促使工作记忆中的更新能力得到提升。通过工作记忆刷新训练可以提高个体其它认知功能, 但是, 相对于认知能力稳定以及衰退的个体, 这种迁移效应在工作记忆能力发展个体中的表现更为明显。     

自动情绪调节的神经机制及其可塑性

自动情绪调节无需意识决定、注意加工及有意控制, 改变着情绪轨迹。迄今为止, 研究仅限于证实其确能低耗高效地改变情绪过程, 尚未对其如何改变情绪过程进行研究。以自动情绪调节的神经机制作为研究对象具有可操作性, 可从行为和心理生理层面, 对自动情绪调节改变情绪过程的机制进行实验研究。研究问题包括：1)通过EEG技术检验自动情绪调节是否影响预备阶段行为反应倾向; 2)自动情绪调节对注意的注意觉醒、注意朝向和注意执行三个阶段的作用机制; 3)自动情绪调节对评价和反应的作用机制; 4)自动情绪调节的可塑性在脑活动上的体现。最终确定自动情绪调节的加工规律, 构建其预备-注意-评价-反应模型, 并为有效控制情绪紊乱和研究出高效的情绪调节干预方案提供理论和实证依据。     

基于中央执行功能的儿童工作记忆可塑性机制

近期的研究发现儿童的工作记忆能力具有一定的可塑性。研究者采用双盲对照实验设计, 通过改编的工作记忆广度、N-back、活动记忆和GO-NOGO等任务对15岁以下的正常儿童和特殊儿童(多动症、智力低下等)的工作记忆能力进行训练, 训练的周期一般为15~30天不等, 每天训练时长约15~25分钟。研究结果发现, 工作记忆训练不仅可以提高儿童的工作记忆能力, 而且还可以迁移至其它高级认知功能(流体智力、数学能力等), 甚至可以改善多动症儿童的临床症状。研究者还发现这种训练效应可以保持3~6个月。通过工作记忆中央执行功能的训练, 是否可以促进儿童认知功能的发展？儿童认知功能的可塑性表现为短暂的提高还是促进认知发展？中央执行功能的训练如何影响儿童认知加工过程的发展？这些问题的回答对于近一步探索认知活动和认知神经的可塑性具有一定的理论意义。可以为工作记忆缺陷儿童的临床干预和治疗提供有效的工具, 具有实践意义。     

去甲肾上腺素对习得性长时程突触增强的影响

在大鼠条件性饮水反应的建立和巩固过程中,在每天训练之前,通过预先与记录电极一起埋植在海马齿状回的注药管,微量注射去甲肾上腺素(NE),观察其对海马齿状回的习得性长时程突触增强的影响。结果表明:NE能增强突触效应;训练作业前注NE易化了习得性长时程突触增强的形成,但对其巩固无影响;同时相应地易化了动物条件反应的建立。提示NE参与海马齿状回的习得性长时程增强的形成。本文对其可能的作用机制进行了讨论。     

Alzheimer病人记忆损害特征的研究

目的了解AD病人记忆损害的特征。方法采用多维记忆评估量表中的12个分测验对30例临床诊断可能的Alzheimer病患者及与病人组相匹配的30例正常受试进行记忆功能的测定。结果AD组几乎在所有的分测验和指数分上均差于对照组。AD轻度组仅在自由组词、残图命名、空间广度、常识记忆等4个分测验及记忆广度、内隐记忆等2个指数分上与对照组之间无明显差异。中重度组则在所有分测验和指数分均差于对照组。经以教育年限为协变量校正后,轻度与中重度组在自由组词、残图命名、经历定向、常识记忆、自由回忆、内隐记忆、日常记忆等分测验和指数分上存在明显差异。12个分测验成绩的比较发现,负荷外显记忆的各个分测验的成绩均较差,负荷内隐记忆的两个分测验的成绩较好。结论轻度AD病人存在着广泛的外显记忆障碍,中重度AD病人除了存在外显记忆障碍外还表现出内隐记忆和日常生括记忆的障碍。这一结果提示人类大脑中存在着多个记忆系统,不同系统受损所导致的记忆障碍不同。     

乳头体对海马齿状回习得性长时程突触增强的影响

用高频电脉冲刺激大鼠乳头体（ＭＢ）,可一过性抑制由刺激穿通纤维（ＰＰ）诱发的海马齿状回（ＤＧ）群体锋电位（ＰＳ）。训练作业前先刺激ＭＢ,导致ＤＧ的习得性长时程突触增强（ＬＤＬＴＰ）的形成显著延缓,相应地延缓了条件性饮水反应的建立。电刺激ＭＢ对ＰＰ─ＤＧＰＳ的这种抑制作用在训练所产生的ＰＳ增大达最高水平时显著减弱,刺激ＭＢ对ＬＤＬＴＰ的保持及相应地对条件反应的巩固没有明显影响。结果表明ＭＢ对ＤＧＬＤＬＴＰ的形成有抑制性调制作用。     

从神经可塑性的视角看压力与疾病的关系

压力致病是一个复杂的过程,涉及到与多种致病因素的相互作用、多个器官系统的激活和反馈、不同发育阶段对疾病的易感性等。这个过程中,神经可塑性起着重要的调节作用。本文以神经可塑性为切入点,阐述了压力、发育阶段、个人发展、疾病发生之间的关系。     

轻度阿尔茨海默症患者的前瞻记忆

轻度阿尔茨海默症往往伴随着不同程度的前瞻记忆衰退。已有研究以轻度阿尔茨海默症与前瞻记忆衰退的关联程度为主线, 对比了这一关联与“其他认知缺陷疾病-前瞻记忆衰退”、“轻度阿尔茨海默症-回溯记忆衰退”以及“轻度阿尔茨海默症-遗传表达”这三种关联的类似程度。此外, 也有研究涉及到了如何促进轻度阿尔茨海默症患者的前瞻记忆。将来的研究应引入病情程度、前瞻记忆任务类型等变量, 深入探讨轻度阿尔茨海默症与前瞻记忆衰退的关联, 并使用ERP、fMRI等神经生理技术确定轻度阿尔茨海默症患者前瞻记忆衰退的机制。     

Remote Odor Memory in Alzheimer's Disease: Deficits as Measured by Familiarity

Deficit in olfaction and remote nonolfactory memory in Alzheimer's disease (AD) motivated the present study of remote memory for odors and faces, operationally defined as rated familiarity, in patients with AD and controls. Uncommon engineering symbols were rated for familiarity to ensure task comprehension. Results showed that patients with AD rate odors, but not faces, as significantly less familiar than do controls, which is indicative of deficit in remote odor memory. Follow-up testing 1 year later again showed this result. Poor odor-detection sensitivity in patients, with AD, but lack of significant correspondence between sensitivity and familiarity, suggests an existing but limited effect of sensitivity on familiarity. The findings provide further evidence that olfaction may be a useful modality for early identification of AD.     

主观记忆减退老年人情节记忆的行为表现及其脑机制

情节记忆是个体对特定时间,特定地点所经历的特定事件的记忆.主观报告情节记忆下降是主观记忆减退老年人最典型的表现.与健康对照组老年人相比, 主观记忆减退老年人情节记忆下降的速率更快, 罹患老年性痴呆的风险更高, 但其情节记忆加工的脑机制尚不明确.前人研究提示, 主观记忆减退老年人在外在记忆行为尚未出现损伤的情况下, 其大脑情节记忆相关脑区的神经活动已经出现异常.探究主观记忆减退的记忆神经环路关键节点和路径的异常, 揭示神经环路在老年痴呆发生发展中的变化规律, 对深入理解老年痴呆的发病机制有重要的科学意义.同时, 主观记忆减退老年人作为特殊的记忆损伤群体, 对其神经环路的深入探究, 也必将为揭示人类记忆的神经机制做出独特的贡献.     

Cognitive Plasticity and Cortical Modules

ABSTRACT— Some organisms learn to calculate, accumulate knowledge, and communicate in ways that others do not. What factors determine which intellectual abilities a particular species or individual can easily acquire? I propose that cognitive-skill learning capacity reflects (a) the availability of specialized cortical circuits, (b) the flexibility with which cortical activity is coordinated, and (c) the customizability of cortical networks. This framework can potentially account for differences in learning capacity across species, individuals, and developmental stages. Understanding the mechanisms that constrain cognitive plasticity is fundamental to developing new technologies and educational practices that maximize intellectual advancements.