高压氧对老年小鼠记忆力及脑内Ca~(2+)的影响

观察常压（１０１．３ｋＰａ）及高压（２５３．３ｋＰａ）吸氧处理后老年小鼠学习记忆的改善情况,并测定４个主要脑区（皮层,海马,小脑,间脑）突触体内钙离子浓度,结果表明,常压及高压吸氧可明显增强老年小鼠在新异的自我活动能力,并且显著提高记忆保持力,对衰老引起的脑内高下现象具有明显的抑制效应,其中２５３．３ｋＰａ高压氧降钙效果更明显,脑内高钙与记忆衰退密切相关,提示高压氧可能是通过降钙作用而改善脑老化而     

脑内乙酰胆碱与认知活动的关系

脑内细胞外乙酰胆碱（ACh）的变化主要反映胆碱能神经元的活动,皮层和海马等脑区的ACh主要来源于基底前脑胆碱能神经元的纤维投射。应用微透析等技术在体检测清醒、自由活动动物认知过程中脑内乙酰胆碱的含量,可以研究ACh与特定行为反应和认知活动之间的关系。研究发现当机体需要对新刺激进行分析时,在学习与记忆、空间工作记忆、注意、自发运动和探究行为等认知活动中,基底前脑胆碱能神经元被激活,脑内ACh的释放也随之改变。结果提示脑内胆碱能递质系统活动与认知过程密切相关     

神经颗粒素与学习记忆关系研究进展

神经颗粒素（Neurogranin,NG）是一种新发现的脑特异性蛋白质。它分布在多个脑区,特别在对学习记忆至关重要的脑区海马。该物质自发现以来,许多学者对其生物学作用,特别是与学习记忆的关系进行了大量的研究,并取得了相当的进展。研究表明NG参与了在学习记忆功能中起核心作用的脑内几种蛋白信号传导途径、长时程增强（Long-term potentiation, LTP）和长时程抑制（Long-term depression, LTD）等突触可塑性机制。NG基因敲除后,动物出现学习记忆能力缺陷。因而它可能涉及学习记忆的形成和巩固     

慢性应激对大鼠空间学习记忆及海马和前脑皮层突触体膜流动性的影响

慢性应激对学习记忆功能的影响是神经科学的热点问题, 在脑内, 海马和前额叶是与学习记忆功能密切相关的重要脑区, 也是应激易累及损伤的主要靶区。膜流动性的改变在神经细胞功能活动中起重要作用。为探讨慢性应激对大鼠空间学习记忆功能的影响及前脑皮层和海马突触体膜流动性的作用。采用多因素慢性应激动物模型, 通过开场试验和Morris水迷宫测试大鼠行为及空间学习记忆能力; 并且测定大鼠前脑皮层和海马突触体膜流动性和突触体内游离Ca2+浓度的变化。研究结果显示, 与对照组相比, 应激组大鼠在应激后即刻, 在新异环境中的自发活动和探究行为显著降低(p<0.05, p<0.01), 空间学习记忆能力明显下降(p<0.05, p <0.01); 并且应激组大鼠前脑皮层和海马突触体膜流动性显著降低(p <0.05, p <0.01); 而突触体内游离Ca2+浓度的显著增加 (p <0.05, p <0.01)。停止应激后一周, 应激大鼠的各项指标有所恢复, 但仍未达到正常水平。研究结果提示, 慢性应激引起大鼠明显的开场行为改变和空间学习记忆功能障碍, 这些变化可能与突触体膜流动性和突触体内游离Ca2+浓度的变化密切相关。     

小鼠的记忆与脑内突触结构参数变化的相关性

比较不同月龄小鼠学习记忆力与脑内突触结构参数变化的相关性。选用１月龄和６月龄小鼠,用Ｙ－迷宫检测分辨学习能力,用一次性被动回避反应检测记忆力。然后杀鼠取脑,进行超微结构观察和定量分析测定。结果表明：（１）１月龄小鼠的分辨学习能力优于６月龄小鼠,记忆力也有优于６月龄小鼠的趋势。（２）无论在海马或大脑皮层体区,有两种结构参数有一致性增龄变化,即６月龄小鼠突触界面曲率都比１月龄小鼠显著和极显著增大;而６月龄小鼠上述两脑区的突触后致密物质厚度都极显著地小于１月龄小鼠。实验结果提示,脑内突触界面结构的增龄性变化可能是学习记忆力增龄性变化的结构基础。     

人类技巧学习的脑功能成像研究进展

近10年来的脑功能成像研究表明,人类技巧学习是一个动态过程。在这一过程中,有关脑区的活动发生了阶段性的变化。在学习的早期阶段,由于神经元选择性提高,有关脑区的活动减弱;而在晚期,由于新神经元的参与,有关脑区的活动增强。脑区活动的阶段性变化还可能与学习过程中被试对任务的意识和加工策略的转变有关。在学习过程中,不同脑区之间逐渐建立联系并组成临时任务指向性系统,这一系统受到额叶等联合皮层的调控。     

成人脑涨落图年龄变化特点的研究

该工作研究了１２０名２０－７９岁正常成人脑涨落图的年龄变化特点。结果表明：（１）从２０岁到５０岁,Ｓ系谱线活动向低频方向集中,６０岁后谱线又向高频方向有所移动;（２）部分谐振系的随龄变化表现明显,其中以Ｓ１７系变化最为敏感;（３）脑区间相干活动和各脑区的连频活动随年龄增强,脑能量分布的有序性逐渐破坏;（４）增龄性变化主要反映在优势脑区（左前脑）和优势脑轴（左前／右后脑）上,与脑高级机能活动密切相关的左前脑的退行性变化最为明显。上述结果反映了脑功能的减退是一个非线性的多层次的复杂过程。     

人类超常记忆的认知神经科学研究综述

借助脑成像技术,人类超常记忆研究揭示出:世界记忆大师与常人存在显著的脑功能差异,如海马等区域的激活;随着领域内训练增加,知识与经验逐渐取代一般能力来影响记忆活动,如在空间记忆任务上相关脑区激活量减少且集中;行为层面的记忆理论找到了相应的电生理基础,如国际象棋记忆的"组块"位于颞叶,音乐领域的"长时工作记忆"与脑区负波有关.同时,期待更多从生理层面上来揭示人类超常记忆能力实质的研究.     

脑内原癌基因c—fos与大鼠本能行为的研究

随着分子生物学技术的发展,原癌基因的发现冲击了生命科学的研究进程。Ｓ－ｆｏｓ基因作为数十种原癌基因中的一种,由于其在受到刺激时能作出迅速而短暂的反应（刺激后数十分钟内即开始表达,数十小时后就恢复正常水平）,且其表达产物ｍＲＮＡ和核磷蛋白（ｐ~５５ｃ－ｆｏｓ,简称Ｆｏｓ）位于神经元的胞浆或胞核内,所以,人们常将其视作神经元激活的一个重要指标。再之,由于不同性质和强度的刺激,Ｓ－ｆｏｓ表达的脑区、时程及强度不同,用原位杂交或免疫组织化学方法显示在备种刺激条件下ｃ－ｆｏｓ表达产物所在的脑区和强度并结合…     

学习和记忆的神经生物学

学习和记忆的神经生物学研究正处于非常令人振奋的阶段。人们以动物的行为研究来表明学习和记忆的特征和类别;用哺乳动物模型澄清和确定脑的基本记忆痕迹环路;根据人类记忆和脑研究的成果识别参与记忆的神经元系统;在无脊推动物和脊推动物中,对于记忆的神经元、神经化学、分子和生物物理的基础的了解已经有了良好的开端;基本的联想学习和神经元网络的理论研究和数学分析也进展迅速。因此,对于学习和记忆神经基础的这种新见解有可能在教育、治疗学习能力丧失和设计新的人工智能系统等方面都得到应用。     

Behavioral alterations in mice lacking the translation repressor 4E-BP2

The requirement for de novo protein synthesis during multiple forms of learning, memory and behavior is well-established; however, we are only beginning to uncover the regulatory mechanisms that govern this process. In order to determine how translation initiation is regulated during neuroplasticity we engineered mutant C57Bl/6J mice that lack the translation repressor eukaryotic initiation factor 4E-binding protein 2 (4E-BP2) and have previously demonstrated that 4E-BP2 plays a critical role in hippocampus-dependent synaptic plasticity and memory. Herein, we examined the 4E-BP2 knockout mice in a battery of paradigms to address motor activity and motor skill learning, anxiety and social dominance behaviors, working memory and conditioned taste aversion. We found that the 4E-BP2 knockout mice demonstrated altered activity in the rotating rod test, light/dark exploration test, spontaneous alternation T-maze and conditioned taste aversion test. The information gained from these studies builds a solid foundation for future studies on the specific role of 4E-BP2 in various types of behavior, and for a broader, more detailed examination of the mechanisms of translational control in the brain.     

Insulin receptor substrate 2 is a negative regulator of memory formation

Insulin has been shown to impact on learning and memory in both humans and animals, but the downstream signaling mechanisms involved are poorly characterized. Insulin receptor substrate-2 (Irs2) is an adaptor protein that couples activation of insulin- and insulin-like growth factor-1 receptors to downstream signaling pathways. Here, we have deleted Irs2, either in the whole brain or selectively in the forebrain, using the nestin Cre- or D6 Cre-deleter mouse lines, respectively. We show that brain- and forebrain-specific Irs2 knockout mice have enhanced hippocampal spatial reference memory. Furthermore, NesCreIrs2KO mice have enhanced spatial working memory and contextual- and cued-fear memory. Deletion of Irs2 in the brain also increases PSD-95 expression and the density of dendritic spines in hippocampal area CA1, possibly reflecting an increase in the number of excitatory synapses per neuron in the hippocampus that can become activated during memory formation. This increase in activated excitatory synapses might underlie the improved hippocampal memory formation observed in NesCreIrs2KO mice. Overall, these results suggest that Irs2 acts as a negative regulator on memory formation by restricting dendritic spine generation.     

Attenuation of Morphine-Induced Behavioral Changes in Rodents byd-andl-Glucose

Administration ofd-glucose enhances learning and memory in several tasks and also attenuates memory impairments and other behavioral effects of several drugs, including morphine. The present experiment compared the effects of peripherally administeredd-glucose with those ofl-glucose, a stereoisomer ofd-glucose that is not metabolized and does not readily cross the blood–brain barrier. Liked-glucose, though at somewhat different doses, peripherally administeredl-glucose attenuated morphine-induced deficits in spontaneous alternation performance in rats and mice and attenuated morphine-induced hyperactivity in mice.l-Glucose did not raise circulating levels of plasmad-glucose, suggesting that the effects ofl-glucose are not secondary to increased availability ofd-glucose. Using direct injections ofd- andl-glucose and morphine into the medial septum of rats, the findings indicate thatd-glucose but notl-glucose attenuated morphine-induced deficits in spontaneous alternation performance; indeed, intraseptal injections ofl-glucose alone impaired spontaneous alternation performance. These findings suggest that peripherall-glucose antagonizes morphine-induced behavioral effects by a peripheral signaling mechanism, one distinct from the mechanisms that mediate at least some of the effects ofd-glucose on brain function.     

Individual differences in the functional neuroanatomy of verbal discrimination learning revealed by positron emission tomography

Why do some people have better memory abilities than others? This issue has been of long-standing interest to scientists and lay people. However, using purely behavioral methods, psychologists have made little progress in illuminating it. Now that functional brain imaging techniques have become available to study mind/brain relations, there is a new promise of understanding individual differences in learning and memory in terms of corresponding differences in brain activity. In this paper, we will present a positron emission tomography (PET) study designed to examine individual differences in learning and memory abilities. The basic assumption is that different patterns of brain activity serve as strong predictors of memory performance. Two specific questions were addressed in this study: (i) Can PET illuminate the relations between memory processes and their neuroanatomical correlates among individual learners and rememberers? and (ii) if so, how are these relations affected by the stage of practice on a given memory task? Our PET study examined individual differences in the neuroanatomical correlates of multi-trial verbal discrimination learning in 16 young healthy subjects. The results identified patterns of brain regions in which blood flow correlated with subjects' retrieval performance. However, these regions did not correlate with performance during all learning trials. Instead, a gradual shift was observed from one pattern of brain regions to another over the course of learning. These results suggest that individual differences in memory performance are related to differences in neural activity within specific brain circuits.     

Emotional responses and memory performance of middle-aged CD1 mice in a 3D maze: effects of low infrared light

Non-thermal near infra-red (IR) has been shown to have many beneficial photobiological effects on a range of cell types, including neurons. In the present study, a pretreatment with a daily 6 min exposure to IR1072 for 10 days yielded a number of significant behavioral effects on middle-aged female CD-1 mice (12-months) tested in a 3D-maze. Middle-aged mice show significant deficits in a working memory test and IR treatment reversed this deficit. Interestingly, the IR treated middle-aged group despite making less memory errors than sham middle-aged group spent longer time in different parts of the maze than both the young group (3-months) and sham-middle-aged group (12-months). Young mice appeared more anxious than middle-aged mice in the first sessions of the test. Exposure to IR appeared to have no significant effects upon exploratory activity or anxiety responses. However, it elicited significant effects on working memory, with the IR middle-aged mice being more considerate in their decision making, which results in an overall improved cognitive performance which is comparable to that of young CD-1 mice. The present study describes a novel method for assessing emotional responses and memory performance in a 3D spatial navigation task and demonstrates the validity of our new all-in-one test and its sensitivity to ageing and non-invasive beneficial IR treatment.     

Testosterone fails to reverse spatial memory decline in aged rats and impairs retention in young and middle-aged animals

Recently, the vasopressin (AVP) innervation in the rat brain was shown to be restored in senescent rats following long-term testosterone administration. In order to investigate whether this restoration is accompanied by an improvement in learning and memory, both sham- and testosterone-treated young (4.5 months), middle-aged (20 months), and aged (31 months) male Brown-Norway rats were tested in a Morris water maze. All animals learned to localize a cued platform equally well, indicating that the ability to learn this task was not affected by sensory, motoric, or motivational changes with aging or testosterone treatment. There were no significant differences in retention following cue training. Subsequent training with a hidden platform in the opposite quadrant of the pool (place training) revealed impaired spatial learning in middle-aged and aged animals. Retention following place training was significantly impaired in the sham-treated aged rats as compared with sham-treated young rats. Testosterone treatment did not improve spatial learning nor retention of spatial information, but, on the contrary, impaired retention in young and middle-aged animals. The present results confirm earlier reports on an impairment of spatial learning and memory in senescent rats but fail to support a role of decreased plasma testosterone levels and central AVP innervation in this respect.     

血糖水平对STZ鼠探究行为及学习记忆的影响

为了解不同血糖水平下链脲佐菌素诱导鼠（STZ鼠）探究行为与学习和记忆的变化情况,把60只STZ鼠按血糖水平分成高血糖组、良好血糖组和低血糖组3组,进行延迟时间、探究时间测定和小鼠跳台试验,并与正常对照组比较。结果发现,良好血糖组与正常对照组各检测指标均相近;3组STZ鼠延迟时间、完成迷津作业时间均按血糖值递增;组间差异显著;小鼠跳台试验中高血糖组的错误数最多,24小时后错误数最少,前后差值有组间差异;延迟时间、探究时间与血糖呈显著正相关,错误数差值与血糖呈显著负相关。结果表明,高血糖鼠的探究行为和学习能力最差,但对被动回避学习的记忆保持相对较好。     

Histidine-decarboxylase knockout mice show deficient nonreinforced episodic object memory, improved negatively reinforced water-maze performance, and increased neo- and ventro-striatal dopamine turnover

The brain's histaminergic system has been implicated in hippocampal synaptic plasticity, learning, and memory, as well as brain reward and reinforcement. Our past pharmacological and lesion studies indicated that the brain's histamine system exerts inhibitory effects on the brain's reinforcement respective reward system reciprocal to mesolimbic dopamine systems, thereby modulating learning and memory performance. Given the close functional relationship between brain reinforcement and memory processes, the total disruption of brain histamine synthesis via genetic disruption of its synthesizing enzyme, histidine decarboxylase (HDC), in the mouse might have differential effects on learning dependent on the task-inherent reinforcement contingencies. Here, we investigated the effects of an HDC gene disruption in the mouse in a nonreinforced object exploration task and a negatively reinforced water-maze task as well as on neo- and ventro-striatal dopamine systems known to be involved in brain reward and reinforcement. Histidine decarboxylase knockout (HDC-KO) mice had higher dihydrophenylacetic acid concentrations and a higher dihydrophenylacetic acid/dopamine ratio in the neostriatum. In the ventral striatum, dihydrophenylacetic acid/dopamine and 3-methoxytyramine/dopamine ratios were higher in HDC-KO mice. Furthermore, the HDC-KO mice showed improved water-maze performance during both hidden and cued platform tasks, but deficient object discrimination based on temporal relationships. Our data imply that disruption of brain histamine synthesis can have both memory promoting and suppressive effects via distinct and independent mechanisms and further indicate that these opposed effects are related to the task-inherent reinforcement contingencies.     

Long-term continuous, but not daily, environmental enrichment reduces spatial memory decline in aged male mice

Although environmental enrichment improves spatial memory and alters synaptic plasticity in aged rodents, it is unclear whether all types of enrichment treatments yield similar benefits. The present study examined the effects in aged male mice of three types of enrichment on spatial memory in Morris water maze and radial arm maze tasks, and on levels of the presynaptic protein synaptophysin in several brain regions. Non-enriched young and aged males were compared with males exposed to one of the following treatments for 10 weeks: 5 min of daily handling, 3 h of daily basic enrichment, or 24 h of continuous complex enrichment. Young controls outperformed aged controls in both tasks. Neither daily handling nor daily enrichment affected spatial memory or synaptophysin levels. In contrast, continuous enrichment significantly reduced age-related spatial memory decline in both tasks, such that this group was statistically indistinguishable from young controls in most measures of performance. Continuously enriched mice were also significantly better than other aged mice in several spatial memory measures. Despite these improvements, synaptophysin levels in the continuous enrichment group were significantly lower than those of young and aged controls in the frontoparietal cortex, hippocampus, and striatum, suggesting a negative relationship between synaptophysin levels and spatial memory in aged males. These data demonstrate that different types of enrichment in aged male mice have disparate effects on spatial memory, and that the relationship between enrichment-induced changes in synaptophysin levels and spatial memory in aged males differs from that we have previously reported in aged female mice.