一种对动物学习记忆能力突变筛查的新途径

本文详细描述了一种全自动化的行为检测方案.在自然饲养环境/检测环境(24/7)中,我们测量了小鼠针对两个给食器中获得食物的比例与它们在相应给食器停留时长的比例进行匹配的精确性与准确性.该方案是对传统条件性习得(trials-to-acquisition)行为测验设备的改进,可以检测动物时间间隔能力的精确性与准确性,对定时目标选择的相关概率的效果,以及记忆一天中从不同给食器中获得食物次数的精确性与准确性.该压缩系统避免了在整个实验过程中对小鼠的持握操作,可忽略实验者/技术员的实验操作时间,而且可以递送小鼠置入实验环境后,7～9个实验日中全部3组实验流程产生的大量结果.其中,第一个实验流程为单个24小时周期内完成的时间匹配能力的筛查,它对动物的时间、空间估计能力的记忆机制进行精确检测.因此,该系统允许在有限的实验空间、较短的实验周期内,对大量的实验小鼠进行有可能存在的学习记忆能力缺陷进行大规模筛查.此外,该系统运行所依赖的软件可以在公共开放平台获得.     

长期双酚A暴露对成年小鼠恐惧记忆的影响

双酚A (bisphenol, BPA)是一种广泛应用于塑料制品的环境内分泌干扰物, 具有弱雌激素和抗雄激素活性, 与雌激素受体有一定的亲和力。本实验探讨长期BPA暴露对成年小鼠恐惧记忆的影响及其神经机制。将9周龄雄性小鼠暴露于BPA (0.4、4、40 mg/kg/d) 90 d, 建立小鼠亚慢性BPA暴露模型后, 进行场景性条件恐惧训练, 然后分别在电击后1 hr及24 hr检测小鼠的僵立时间, 同时在电击前、电击后1 hr及24 hr检测海马相关蛋白表达变化。结果表明, BPA (4、40 mg/kg/d)暴露延长小鼠场景性条件恐惧训练后1 hr及24 hr的僵立时间。Western blot蛋白检测结果显示, 行为训练前, BPA降低了小鼠NMDA受体NR1亚基表达水平, 上调组蛋白去乙酰化酶2表达。行为训练后1 hr及24 hr, BPA促进海马NMDA受体亚基NR1和组蛋白H3乙酰化表达, 抑制组蛋白去乙酰化酶2表达, 同时促进ERK1/2磷酸化水平。以上结果表明, 长期BPA暴露提高成年小鼠恐惧记忆获得的同时延长恐惧记忆的保持; 该作用可能通过激活海马的ERK1/2通路而改变核内组蛋白乙酰化和NMDA受体水平进行。     

四种不同品系小鼠旷场行为和记忆的比较研究

本文以生理心理学研究中常用的几种实验方法,对三种标准化国际通用品系的实验小鼠与我国特有的昆明系小鼠的行为活动特征和记忆进行比较研究。结果表明,三种国际通用品系小鼠的一般行为活动较昆明系小鼠明显活跃．旷场行为实验结果有显著差异。但在记忆保持方面,四个品系间无明显差异。实验提示．昆明系小鼠可适用于研究动物的高级心理功能。     

基于客体工作记忆的保持对时间判断的影响（英文）

本研究探讨工作记忆内容的保持能否影响时间判断,采用难以用言语编码和保持的抽象客体作为刺激材料,操作记忆内容与时间任务中刺激的关联程度。实验1将工作记忆中的变化觉察范式和时间判断任务结合,具体来讲,要求被试首先记忆一个客体,然后在每个trial的最后判断测试刺激是否与记忆项相同;在延迟阶段,被试完成时间判断任务,即判断相继出现的两个刺激的时距哪个更长(或更短)。记忆匹配条件下,时间任务中的一个刺激与记忆内容完全相同,相应的另一个刺激与记忆内容在形状和颜色上都不同,记忆匹配和记忆不匹配各占一半。匹配刺激先短后长、先长后短的顺序在被试内充分平衡;记忆不匹配条件下,时间任务中的两个刺激均与记忆项无关。结果发现,记忆匹配刺激不存在顺序效应;相比无记忆匹配条件,记忆匹配延长了时间判断的时间;进一步分析发现记忆匹配刺激与长时距对应时,正确率更低,反应时更长。为了进一步探讨实验1的结果是由对记忆内容的保持造成的,还是由刺激的重复出现造成的,实验2要求被试忽略第一个刺激,仅完成时间判断任务。结果发现,知觉匹配和知觉不匹配条件在时间判断的正确率和反应时上都无显著差异。研究说明记忆内容的保持引起了注意定向,影响了人们对时间信息的判断和决策。     

基于客体工作记忆内容的保持对时间判断的影响

本研究通过操作工作记忆内容的有效性,探讨了记忆内容的保持对时间判断的影响。采用不规则的客体作为实验材料,使时间任务中的刺激与工作记忆内容匹配或不匹配。实验1采用工作记忆和时间判断的双任务范式,要求被试首先记忆一个客体,然后在每个试次的最后判断测试刺激是否与记忆项相同。在延迟阶段,被试判断连续出现的两个刺激的时距哪个更长（或更短）。实验2中,要求被试忽略第一个刺激,仅完成时间判断任务。结果发现,相比单任务的计时,双任务条件下,工作记忆内容的保持延长了时间判断的时间。而且,在记忆匹配和知觉匹配条件下,匹配刺激呈现的时间越长,正确率越低,反应时越长。这说明记忆内容的保持增加了决策的难度,工作记忆内容对时间判断的可能是由记忆内容引起的注意定向造成的。     

适应性记忆：方位记忆的生存优势

采用“间接学习—回忆”实验范式,考查方位记忆的生存优势及生存记忆的性别差异。在电脑屏幕上下左右4个方位随机呈现动物或食物图片,被试相对于中央点对捕获动物或采集食物的难易程度进行评价,然后进行方位回忆测验。实验1和实验2为2（情境：生存情境vs.比赛情境）×2（性别：男vs.女）的被试间设计,发现当狩猎动物或采集食物活动与生存相关时,图片方位回忆的正确率较大;实验3为2（情境：生存狩猎情境vs.生存采集情境）×2（性别：男vs.女）的混合设计,发现不同性别被试在两种生存情境中的图片回忆正确率存在差异。表明方位记忆具有生存优势,生存记忆存在性别差异。     

樟柳碱所致学习和记忆障碍动物模型的探讨

本实验采用水迷津法、步下法和步入法,用樟柳碱制备学习和记忆障碍的动物模型。结果表明,樟柳碱(10毫克/公斤)可使小鼠引起学习障碍,其表现为通过水迷津全程的时间延长,而且小鼠进入盲路的错误次数明显增多。樟柳碱(10毫克/公斤)可使小鼠引起记忆障碍,在樟柳碱的影响下,小鼠步下平台或步入暗箱的潜伏期明显缩短,并使它们的错误次数增多。本实验结果进一步表明,测定小鼠的记忆障碍,步入法似乎比步下法更为敏感。     

催产素对学习和记忆的调节效应：来自动物与人类的研究证据

作为一种神经肽, 催产素对于个体社会认知和情绪加工有着非常重要的调节作用, 其中就包括对在人们工作和生活中扮演着关键角色的学习和记忆活动的影响。采用不同模态技术的动物和人类研究一致表明了外源性催产素对于学习和记忆具有重要的调节作用, 这一作用可能是外源性催产素通过与多巴胺奖赏通路、边缘系统等学习和记忆关键脑网络中广泛分布的催产素受体相结合, 进而调整其功能状态实现的; 但与此同时, 催产素对学习和记忆的促进或抑制作用会因实验范式、刺激材料、给药时间、位置和剂量等因素的不同而存在差异。未来需要协同动物和人类研究的各自优势, 采用规范化的实验任务设置和给药程序克服当前该领域的研究局限, 并积极发掘催产素在干预相关精神疾病患者学习和记忆加工缺陷中的应用潜力。     

负性情绪对压抑遗忘记忆的影响

该实验使用Think/No-think(T/NT)任务,从外显和内隐记忆两个方面探讨负性情绪、测试时间对压抑遗忘的影响。实验结果表明:在外显记忆成绩中情绪与T/NT任务的交互作用显著,在NT条件下中性词回忆的成绩优于负性词,同时,情绪的主效应显著,被试对中性词的记忆显著高于负性词。但是T/NT任务的主效应不显著,情绪×T/NT任务×测试时间的交互不显著。在内隐记忆成绩中,在所有条件下的记忆成绩均无显著性差异。     

小鼠新颖寻求特质对酒精的运动激活效应的影响

新颖寻求(或感觉寻求)特质与许多成瘾药物的易感性密切相关。例如, 高、低新颖寻求动物对可卡因、苯丙胺和吗啡等成瘾药物的奖赏、运动激活、强化效应的反应存在差异。长期饮用酒精也容易成瘾, 但尚未发现关于新颖寻求特质影响酒精成瘾的报道。本实验采用药物成瘾研究中常用的自发活动模型, 考察了高、低新颖寻求动物在酒精急性处理、慢性处理和激发过程中的行为表现。实验过程中首先采用两种新颖寻求模型, 即新颖环境中自发活动模型和新颖客体偏爱模型, 将昆明小鼠分别区分为高、低自发活动组和高、低新颖客体偏爱组, 连续10天给予酒精(2g/kg/d, i.p.)或等量盐水处理, 戒断2天后所有小鼠接受酒精(2g/kg)激发。实验结果表明, 新颖环境低自发活动小鼠比新颖环境高自发活动小鼠对酒精急性、慢性处理导致的运动激活效应更敏感; 在酒精激发期前者的自发活动水平也高于后者。本实验结果说明新颖环境中自发活动特质影响动物对酒精导致的运动激活效应的反应。     

Sudden Death and Gradual Decay in Visual Working Memory

ABSTRACT— General Douglas MacArthur remarked that "old soldiers never die; they just fade away." For decades, researchers have concluded that visual working memories, like old soldiers, fade away gradually, becoming progressively less precise as they are retained for longer periods of time. However, these conclusions were based on threshold-estimation procedures in which the complete termination of a memory could artifactually produce the appearance of lower precision. Here, we use a recall-based visual working memory paradigm that provides separate measures of the probability that a memory is available and the precision of the memory when it is available. Using this paradigm, we demonstrate that visual working memory representations may be retained for several seconds with little or no loss of precision, but that they may terminate suddenly and completely during this period.     

Are three-sample tasks less sensitive than two-sample tasks? Memory effects in the testing of taste discrimination

In order to provide insights into why discrimination protocols with three stimuli sometimes tend to be less sensitive than protocols with two stimuli, two experiments were conducted. In these experiments, the relative effects of memory decay and memory interference were investigated. Both experiments involved purified water and/or solutions of low NaCl concentration. In Experiment 1, three protocols were compared: the traditional same-different test (Protocol 1), the same protocol with a rinse between the two samples (Protocol 2), and Protocol 2 with an added time delay between the first sample and the intermediate rinse (Protocol 3.) The decrease in measured d' values as time delay increased indicated that memory decay might be a factor for tests with three stimuli, such as the triangle method, rendering it less sensitive than tests with two stimuli, such as the same-different method. In Experiment 2, four protocols were compared: the traditional same-different test, the two-rinse same-different test, the triangle test, and what will be called duo same-different test. The experimental design allowed the individual consideration of memory decay and interference effects. From this last experiment, the substantial effect of memory interference was uncovered. Further experimentation will be necessary to estimate the exact relative effects of memory interference and memory decay.     

The inhibitory avoidance test optimized for discovery of cognitive enhancers

In the present article, we describe a new protocol for the inhibitory avoidance test, with a dual purpose: (1) to provide a leß variable and more reliable aßeßment of the efficacy of potential cognitive enhancers in antagonizing scopolamine-induced long-term-memory deficits, and (2) to secure a high throughput for pharmacological screening of cognitive enhancers. The new protocol consists of two acquisition trials that are followed 24 h later by a single retention trial. In the present study, this protocol clearly dißociated the frequency distributions of retention latencies between scopolamine- and vehicle-treated groups and allowed validation by means of two acetylcholinesterase inhibitors—tacrine and donepezil—that proved to be active in counteracting the scopolamine-induced memory deficit. This protocol also produced stability of the behavioral response to pharmacological agents over a 3-year period. A statistical power analysis indicated that, depending on the efficacy of the drug/dose, a sample size of 5–12 mice was required in order to show a reversal of the scopolamineinduced memory deficit. The double-trial acquisition protocol is suitable for testing cognitive enhancers, while also providing a clearly enhanced throughput.     

Methodological issues in judgment and decision-making research: Concurrent verbal protocol validity and simultaneous traces of process

This paper examines two dimensions of concurrent verbal protocol validity. First, whether verbalization affects process and outcome (reactivity) was examined by comparing concurrent verbal protocol traces with those from a computer search process tracing method, the latter being a complete trace of information acquisition from experimental materials. Earlier findings that verbalization affects time were confirmed. However, verbalization did not affect amount and pattern of acquisition or accuracy of judgments. Second, whether concurrent verbal protocols are complete was examined by comparing concurrent verbal protocol and computer traces that were simultaneously obtained in a treatment in which subjects verbalized as they acquired information from the computer. The verbal traces less completely captured information acquisition behavior than computer search. This suggests that, although concurrent verbal protocols provide greater insight into decision behavior than computer search, the latter is a more reliable information-acquisition trace. Thus, if information acquisition is of primary interest and if computer search activities can be naturally integrated into performing the primary task, computer search is preferred to concurrent verbal protocols. However, if information use or retrieval from long-term memory is of primary interest, concurrent verbal protocols are preferred to computer search. Finally, this paper examined whether the simultaneous use of concurrent verbal protocols and computer search provides traces of information acquisition and use that are as complete as when each method is independently applied. Although computer search tended to limit subjects verbalizations of evaluative operators, this effect may be eliminated by practice on the computer prior to collecting data.     

Integrated memory for objects, places, and temporal order: evidence for episodic-like memory in mice

Human episodic memory refers to the recollection of an unique past experience in terms of what happened, and where and when it happened. Factoring out the issue of conscious recollection, episodic memory, even at the behavioral level, has been difficult to demonstrate in non-human mammals. Although, it was previously shown that rodents can associate what and when or what and where information given on unique trials, it proved to be difficult to demonstrate memory for what, where, and when simultaneously in mammals, without using extensive training procedures, which might induce semantic rather than episodic memory recall. Towards the goal of an animal model of human episodic memory we designed an three-trial object exploration task in which different versions of the novelty-preference paradigm were combined to subsume (a) object recognition memory, (b) the memory for locations in which objects were explored, and (c) the temporal order memory for object presented at distinct time points. We found that mice spent more time exploring two "old familiar" objects relative to two "recent familiar" objects, reflecting memory for what and when and concomitantly directed more exploration at a spatially displaced "old familiar" object relative to a stationary "old familiar" object, reflecting memory for what and where. These results suggest that during a single test trial the mice were able to (a) recognize previously explored objects, (b) remember the location in which particular objects were previously encountered, and (c) to discriminate the relative recency in which different objects were presented. According to the currently discussed behavioral criteria for episodic-like memory in animals, our results suggest that mice are capable to form such higher order memories.     

Extinction memory in the crab Chasmagnathus: recovery protocols and effects of multi-trial extinction training

A decline in the frequency or intensity of a conditioned behavior following the withdrawal of the reinforcement is called experimental extinction. However, the experimental manipulation necessary to trigger memory reconsolidation or extinction is to expose the animal to the conditioned stimulus in the absence of reinforcement. Recovery protocols were used to reveal which of these two processes was developed. By using the crab contextual memory model (a visual danger stimulus associated with the training context), we investigated the dynamics of extinction memory in Chasmagnathus. Here, we reveal the presence of three recovery protocols that restore the original memory: the old memory comes back 4 days after the extinction training, or when a weak training is administered later, or once the VDS is presented in a novel context 24 h after the extinction session. Another objective was to evaluate whether the administration of multi-trial extinction training could trigger an extinction memory in Chasmagnathus. The results evince that the extinction memory appears only when the total re-exposure time is around 90 min independently of the number of trials employed to accumulate it. Thus, it is feasible that the mechanisms described for the case of the extinction memory acquired through a single training trial are valid for multi-trial extinction protocols. Finally, these results are in agreement with those reports obtained with models phylogenetically far apart from the crab. Behind this attempt is the idea that in the domain of studies on memory, some principles of behavior organization and basic mechanisms have universal validity.     

Of mice and men: virtual Hebb-Williams mazes permit comparison of spatial learning across species

We developed a computer-generated virtual environment to test humans, for the first time, on the Hebb-Williams mazes. The goal was to provide a standardized test that could be used to directly compare human performance with that of C57BL/6J mice performing in real versions of the mazes. Such a comparison seems crucial if conclusions regarding genetic manipulations of rodents are to be mapped onto human cognitive disorders. The learning curves across species were strikingly similar, lending support to the rodent model of human spatial memory. Humans learned faster than rodents in both the acquisition and the test portions of the protocol, and females of both species were less efficient in solving these problems than males. These results represent the first modern comparison of human and rodent learning that uses the same test of spatial problem solving.     

PC-PVT: A platform for psychomotor vigilance task testing,analysis, and prediction

Using a personal computer (PC) for simple visual reaction time testing is advantageous because of the relatively low hardware cost, user familiarity, and the relative ease of software development for specific neurobehavioral testing protocols. However, general-purpose computers are not designed with the millisecond-level accuracy of operation required for such applications. Software that does not control for the various sources of delay may return reaction time values that are substantially different from the true reaction times. We have developed and characterized a freely available system for PC-based simple visual reaction time testing that is analogous to the widely used psychomotor vigilance task (PVT). In addition, we have integrated individualized prediction algorithms for near-real-time neurobehavioral performance prediction. We characterized the precision and accuracy with which the system as a whole measures reaction times on a wide range of computer hardware configurations, comparing its performance with that of the “gold standard” PVT-192 device. We showed that the system is capable of measuring reaction times with an average delay of less than 10 ms, a margin of error that is comparable to that of the gold standard. The most critical aspect of hardware selection is the type of mouse used for response detection, with gaming mice showing a significant advantage over standard ones. The software is free to download from http://bhsai.org/downloads/pc-pvt/.