Selective inactivation of adenosine A(2A) receptors in striatal neurons enhances working memory and reversal learning

The adenosine A(2A) receptor (A(2A)R) is highly enriched in the striatum where it is uniquely positioned to integrate dopaminergic, glutamatergic, and other signals to modulate cognition. Although previous studies support the hypothesis that A(2A)R inactivation can be pro-cognitive, analyses of A(2A)R's effects on cognitive functions have been restricted to a small subset of cognitive domains. Furthermore, the relative contribution of A(2A)Rs in distinct brain regions remains largely unknown. Here, we studied the regulation of multiple memory processes by brain region-specific populations of A(2A)Rs. Specifically, we evaluated the cognitive impacts of conditional A(2A)R deletion restricted to either the entire forebrain (i.e., cerebral cortex, hippocampus, and striatum, fb-A(2A)R KO) or to striatum alone (st-A(2A)R KO) in recognition memory, working memory, reference memory, and reversal learning. This comprehensive, comparative analysis showed for the first time that depletion of A(2A)R-dependent signaling in either the entire forebrain or striatum alone is associated with two specific phenotypes indicative of cognitive flexibility-enhanced working memory and enhanced reversal learning. These selective pro-cognitive phenotypes seemed largely attributed to inactivation of striatal A(2A)Rs as they were captured by A(2A)R deletion restricted to striatal neurons. Neither spatial reference memory acquisition nor spatial recognition memory were grossly affected, and no evidence for compensatory changes in striatal or cortical D(1), D(2), or A(1) receptor expression was found. This study provides the first direct demonstration that targeting striatal A(2A)Rs may be an effective, novel strategy to facilitate cognitive flexibility under normal and pathologic conditions.     

Emergent Simple Discrimination via Transfer from Differentially Reinforced S+ Stimuli: A Further Test of the Stimulus-Response Interaction Model

This study examined emergent form discrimination through contiguity of the forms (B stimuli) with colours (A stimuli) associated with different magnitudes of reinforcement. In Experiment 1, children were trained on two colour discriminations. In both, the colour stimuli had the same form: A1B1/A2B1 and A3B1/A2B1. Responding to A1/B1 was followed by three units of reinforcement, to A3B1 by one unit of reinforcement, and to A2B1 by no reinforcement. There followed five tests in which stimuli were presented without programmed consequences. These assessed: (1) the maintenance of accurate performance on the training tasks; (2) S+ preference (A1B1/A3B1); (3) stimulus generalization (A1B2/A2B3, A3B4/A2B5); (4) S+ preference again (A1B6/A3B6); and (5) transfer from the S+ colours to the forms (A4B2/A4B4). On the final test, seven of the eight subjects selected A4B2. Experiment 2 demonstrated that a preference for A4B2 also occurred when the S+ preference tests were omitted. This preference was also found when the total amounts of reinforcement associated with the S+ colours (A1 and A3) were the same (Experiment 3). These findings: (a) indicate that children can acquire new discriminations under non-reinforced conditions through contiguity with differentially reinforced S+ stimuli; (b) support the Stimulus-Response Interaction model (Smeets, 1993) for specifying transfer.     

A derived transfer of functions and the implicit association test

Participants were trained in a series of interrelated conditional discriminations that aimed to establish four 4-member equivalence classes (i.e., A1-B1-C1-D1, A2-B2-C2-D2, A3-B3-C3-D3, A4-B4-C4-D4). During this training, the four A stimuli (i.e., A1, A2, A3, and A4) were compounded with pictures containing positive or negative evaluative functions (A1/A2 negative & A3/A4 positive). The transfer of evaluative functions to directly and indirectly related members of the equivalence classes (i.e., B, C, and D stimuli) was measured using an Implicit Association Test (IAT). During consistent test blocks, participants were required to press the same response key for target words that were related to those A stimuli that possessed similar evaluative functions (A1/A2-left key & A3/A4-right key). During inconsistent test blocks, target words that were related to those A stimuli with different evaluative functions were assigned to the same response key (A1/A4-left key & A2/A3-right key). Results showed that all 8 participants, who passed a matching-to-sample equivalence test following the IAT, responded more rapidly on consistent relative to inconsistent test blocks. This typical IAT effect was not observed for those participants who did not pass the equivalence test. The results suggest that the IAT effect may arise from formally untested derived relations, and supports the argument that such relations could provide a valid behavioral model of semantic categories in natural language.     

一个含有原子的自然模型∑（A）

1989年A.Blass和A.Scedrov构造了含有原子的模型V（A）（A是所有原子的集合,参见文献[1]）并证明了V（A）是ZFA（ZFA=ZF＋A,公理A断言：存在所有原子的集合）的模型。由于集合论的公理系统GB是ZF的一个保守扩充,因此,集合论的公理系统GBA（GBA=GB＋A,其中GB是集合论的含有集合和类的哥德尔－贝奈斯公理系统）也是ZFA的一个保守扩充。本文的目的是在集合论的含有原子和集合的公理系统ZFA的自然模型V（A）的基础上,为集合论的含有原子、集合和类的公理系统GBA建立模型。因此,我们首先介绍了A.Blass和A.Scedrov的含有原子的模型V（A）;第二,给出并证明V（A）具有的一些基本性质;第三,扩充了集合论的公理系统ZFA的形式语言LZFA并定义含有原子和集合的类C;第四,构造含有原子、集合和类的模型∑（A）,称它为自然模型,最后,证明了∑（A）是GBA的模型。     

Gender differences in the relationship between hostility and the type A behavior pattern

A group of 97 male and 111 female undergraduates completed the Jenkins Activity Survey, the Framingham Type A Scale, the Adjective Checklist Type A Scale, the Spielberger State-Trait Anxiety Inventory, and the Buss-Durkee Hostility Inventory. A factor analysis revealed three dimensions: Anger-Emotionality, Anger-Aggression, and Residual Pattern A. All Type A measures loaded highly on the Type A factor, with the Jenkins Activity Survey loading the highest. The Framingham Type A Scale was related to Anger-Emotionality, the Adjective Checklist Type A Scale was related to Anger-Aggression, and the Jenkins Activity Survey was related to neither of the anger dimensions. Women scored higher than men on Anger-Emotionality and the Guilt, Resentment, and Irritability subscales and lower than men on the Assaultiveness subscale. Women showed higher correlations between Type A and the Guilt subscale, and men between Type A and the Suspiciousness subscale. We conclude that Type A is a multidimensional construct that manifests itself differently in men and women.     

Activation of adenosine receptors in the posterior cingulate cortex impairs memory retrieval in the rat

Adenosine A1 and A2A receptor agonists and antagonists have been reported to alter learning and memory. The aim of our study was to investigate the involvement of adenosinergic system in memory retrieval into posterior cingulate cortex (PCC) of Wistar rats. To clarify this question, we tested specifics agonist and antagonists of adenosine A1 and A2A receptors in rats submitted to a one-trial inhibitory avoidance task. The stimulation of adenosine A1 and A2A receptors by CPA and CGS21680, respectively, impaired memory retrieval for inhibitory avoidance task, into PCC. These findings provide behavioral evidence for the role of adenosinergic system in the memory retrieval into PCC.     

A role for the perceptual representation memory system in category learning

There is growing evidence that working memory, episodic/semantic memory, and procedural memory all play important roles in at least some types of category learning. Little is known, however, about the role of the perceptual representation memory system (PRS). Two experiments are reported that provide evidence that under certain conditions, the PRS, by itself, is sufficient to mediate category learning. Both experiments compared performance in (A, not A) and (A, B) prototype distortion category-learning tasks, in which category exemplars are created by randomly distorting one category prototype in the (A, not A) conditions or two prototypes in the (A, B) conditions. Results showed that (A, not A) performance was more sensitive to prototype similarity and less affected by the removal of feedback than (A, B) performance. These results support the hypothesis that (A, not A) performance was mediated by the PRS, but that (A, B) performance recruited other memory systems.     

真核双基因表达载体p1RES-Rb94-E1A的构建与鉴定

以pE1A质粒为模板,扩增E1A基因,然后将E1AcDNA片段插入前期已经构建好的真核表达载体pIRES-Rb94的MCSB的SalI与NotI之间,获得真核双基因表达质粒p1RES-Rb94-E1A,转染肺腺癌A549细胞后,采用RT—PCR和Westernblot方法检测Rb94和E1A在A549细胞中的表达,为研...     

The utility of the A1 and A2 criteria in the diagnosis of PTSD

In the field of posttraumatic stress disorder (PTSD), the revisions to the DSM-IV definition of a potentially traumatic event are contentious. Proponents praise the subjective emphasis, while others contend that the changes to the criterion broadened the conceptualization of PTSD. This study examined the predictive utility of Criterion A events, examining the stressor (A1) and subjective emotional response (A2) components of the definition of a traumatic event. Rates of Criterion A events and PTSD were calculated for three diverse samples, and predictive power, sensitivity, specificity, and ROC curves were computed to determine the predictive utility of Criterion A requirements for PTSD symptom, duration, and functional impairment diagnostic criteria. Across all samples, the current Criterion A requirements did not predict much better than chance. Specifically, A2 reports added little to the predictive ability of an A1 stressor, though the absence of A2 predicted the absence of PTSD-related symptoms, their duration, and impairment. Notably, the combination of three A1 and A2 criteria showed the best prediction. Confronted events also showed less predictive ability than experienced events, with more variable performance across samples. These results raise fundamental questions about the threshold or "gate" that Criterion A ought to play in our current nosology.     

Working memory deficits in transgenic rats overexpressing human adenosine A2A receptors in the brain

Adenosine receptors in the central nervous system have been implicated in the modulation of different behavioural patterns and cognitive functions although the specific role of A(2A) receptor (A(2A)R) subtype in learning and memory is still unclear. In the present work we establish a novel transgenic rat strain, TGR(NSEhA2A), overexpressing adenosine A(2A)Rs mainly in the cerebral cortex, the hippocampal formation, and the cerebellum. Thereafter, we explore the relevance of this A(2A)Rs overexpression for learning and memory function. Animals were behaviourally assessed in several learning and memory tasks (6-arms radial tunnel maze, T-maze, object recognition, and several Morris water maze paradigms) and other tests for spontaneous motor activity (open field, hexagonal tunnel maze) and anxiety (plus maze) as modification of these behaviours may interfere with the assessment of cognitive function. Neither motor performance and emotional/anxious-like behaviours were altered by overexpression of A(2A)Rs. TGR(NSEhA2A) showed normal hippocampal-dependent learning of spatial reference memory. However, they presented working memory deficits as detected by performance of constant errors in the blind arms of the 6 arm radial tunnel maze, reduced recognition of a novel object and a lack of learning improvement over four trials on the same day which was not observed over consecutive days in a repeated acquisition paradigm in the Morris water maze. Given the interdependence between adenosinic and dopaminergic function, the present results render the novel TGR(NSEhA2A) as a putative animal model for the working memory deficits and cognitive disruptions related to overstimulation of cortical A(2A)Rs or to dopaminergic prefrontal dysfunction as seen in schizophrenic or Parkinson's disease patients.     

The relation between type A behavior and chronic emotional distress: a meta-analysis

A meta-analysis was conducted of studies examining the relation between Type A behavior and chronic emotional distress as measured by standard psychological scales. Aggregating across all studies, the average effect size was .27, indicating a positive association between Type A and chronic dysphoria; however, there was considerable variability in the size of the relation among studies. Partitioning by Type A measure revealed that Structured Interview-assessed Type A was unrelated to chronic dysphoric emotions; however, most of the self-report measures of Type A behavior were moderately correlated with upset. The Framingham Type A Scale and the Bortner Scale showed the strongest relations. Thus, contrary to the traditional view, Type A measured by self-report does have some emotional concomitants, although they are not in the pathological range. Also discussed are how the results bear on the proposal that the maladjusted personality confers coronary risk, the implications for reported associations between Type A and illness complaints, and for the study of the Type A as a social psychological construct.     

Reviews

C arotenuto , A ldo . A Secret Symmetry: Sabina Spiclrein Between Jung and Freud
S chwartz-salant , N. Narcissism and Character Transformation
M attoon , M. A. Jungian Psychology in Perspective
J affé , A niela . Aufsätze zur Psychologic C. G. Jungs
S tevens , A. A Natural History of the Self
S teele , R. Freud and Jung: Conflicts of Interpretation
G ould , E ric . Mythical Intentions in Modern Literature     

Relational discrimination by pigeons in a go/no-go procedure with compound stimuli: a methodological note

A go/no‐go procedure with compound stimuli typically establishes emergent behavior that parallels in structure and typical outcome that of conventional tests for symmetric, transitive, and equivalence relations in normally capable adults. The present study employed a go/no‐go compound stimulus procedure with pigeons. During training, pecks to two‐component compounds A1B1, A2B2, B1C1, and B2C2 were followed by food. Pecks to compounds A1B2, A2B1, B1C2, and B2C1 re‐started the 30‐s stimulus presentation interval. The absence of pecking to those compounds for 30 s ended the trial. Subsequent tests presented these components in new spatial arrangements and/or in recombinative compounds that together corresponded to conventional tests of symmetry, transitivity, and equivalence: B1A1, B2A2, C1B1, C2B2, A1C1, A2C2, C1A1, C2A2 vs. B1A2, B2A1, C1B2, C2B1, A1C2, A2C1, C1A2, C2A1 (positive vs. negative instances of symmetric, transitive, and equivalence relations). On tests for symmetric relations, all pigeons behaved in a manner consistent with training on both positive instances (i.e., by responding) and on negative instances (i.e., by not responding). By contrast, the pigeons' behavior on tests for transitivity and equivalence was inconsistent with baseline training, thus failing to show the recombinative discrimination performance that is typical of normally capable humans when trained and tested using the go/no‐go procedure with compound stimuli.     

Protein kinase C mediates amyloid β-protein fragment 31–35-induced suppression of hippocampal late-phase long-term potentiation in vivo

Amyloid β-protein (Aβ) in the brain of Alzheimer’s disease (AD) plays a detrimental role in synaptic plasticity and cognitive function. The effects of Aβ on the early-phase long-term potentiation (E-LTP) have been reported widely. However, whether the late-phase long-term potentiation (L-LTP), which differs from E-LTP mechanistically, is also affected by Aβ is still an open question. The present study examined the effects of intracerebraventricular injection of Aβ fragments 25–35 and 31–35 on the L-LTP in the CA1 area of rat hippocampus in vivo, and further investigated its possible underlying mechanism. Our results showed that: (1) Aβ25–35 (6.25–25 nmol) did not affect the baseline field excitatory postsynaptic potentials, but dose-dependently suppressed multiple high-frequency stimuli-induced L-LTP; (2) Aβ31–35, a shorter Aβ fragment than Aβ25–35, also significantly suppressed L-LTP, with the same suppressive effects as Aβ25–35; (3) pretreatment with PMA (6 nmol/5 μl), a membrane permeable PKC agonist, effectively prevented Aβ31–35-induced deficits in the early and the late components of L-LTP; (4) co-application of Aβ31–35 and chelerythrine (12 nmol/5 μl), a PKC antagonist, caused no additive suppression of L-LTP. These results indicate that both Aβ25–35 and Aβ31–35 can impair hippocampal synaptic plasticity in vivo by suppressing the maintenance of L-LTP, and PKC probably mediates the Aβ-induced suppression of hippocampal L-LTP. In addition, the similar efficacy of Aβ31–35 and Aβ25–35 in L-LTP suppression supports the hypothesis we suggested previously that the sequence 31–35 in Aβ might be the shortest active sequence responsible for the neuronal toxicity induced by full length of Aβ molecules.     

Remembering change: The critical role of recursive remindings in proactive effects of memory

In three experiments, we examined the role of the detection and recollection of change in proactive effects of memory in a classic A–B, A–D paradigm. Participants studied two lists of word pairs that included pairs repeated across lists (A–B, A–B), pairs with the same cue but a changed response (A–B, A–D) in the second list, and control pairs (A–B, C–D). The results revealed that performance on A–B, A–D pairs reflected a mixture of facilitation and interference effects. Proactive facilitation occurred when changes in responses were detected and recollected, whereas proactive interference occurred when change was not detected or when it was not recollected. We describe detecting change as involving recursive remindings that result in memory for the List 1 response being embedded in the representation of memory for the List 2 response. These embedded representations preserve the temporal order of the responses. Our findings highlight the importance of detection and recollection of change for proactive effects of memory.     

Family characteristics and school achievements of type A children

We examined the familial characteristics of Type A children and the consequences of Type A behaviors for children's classroom achievements. A maximum of 156 boys and 190 girls enrolled in elementary and middle schools and their parents participated in various aspects of the data collection procedures and analyses reported in this article. Results showed that Type A children were not more likely to have families with a history of cardiovascular-related diseases or families of upper socioeconomic status. Young Type A boys, but not girls, had Type A mothers and fathers, suggesting an early modeling of Type A behaviors by boys. Competitive boys and girls and Type A girls had higher achievement test scores and classroom grades, independent of IQ test scores, than did relatively noncompetitive children and Type B girls, respectively. Thus, the competitive aspect of Type A leads to important early achievements, independent of ability, perhaps because care givers and teachers respond to Type A behaviors of children by encouraging them to continue to strive to achieve. Gender differences in the findings were also discussed and related to the adult literature.     

CONDITIONAL DISCRIMINATION VS. MATCHING TO SAMPLE: AN EXPANSION OF THE TESTING PARADIGM

A subject's performance under a conditional-discrimination procedure defines conditional relations between stimuli: “If A1, then B1; if A2, then B2.” The procedure may also generate matching to sample. If so, the stimuli will be related not only by conditionality, but by equivalence: A1 and B1 will become equivalent members of one stimulus class, A2 and B2 of another. One paradigm for testing whether a conditional-discrimination procedure has generated equivalence relations uses three sets of stimuli, A, B, and C, three stimuli per set. Subjects learn to select Set-B and Set-C comparisons conditionally upon Set-A samples. Having been explicitly taught six sample-comparison relations, A1B1, A1C1, A2B2, A2C2, A3B3, and A3C3, subjects prove immediately capable of matching the B- and C-stimuli; six new relations emerge (B1C1, B2C2, B3C3, C1B1, C2B2, C3B3). The 12 stimulus relations, six taught and six emergent, define the existence of three three-member stimulus classes, A1B1C1, A2B2C2, and A3B3C3. This paradigm was expanded by introducing three more stimuli (Set D), and teaching eight children not only the AB and AC relations but DC relations also—selecting Set-C comparisons conditionally upon Set-D samples. Six of the children proved immediately capable of matching the B- and D-stimuli to each other. By selecting appropriate Set-B comparisons conditionally upon Set-D samples, and Set-D comparisons conditionally upon Set-B samples, they demonstrated the existence of three four-member stimulus classes, A1B1C1D1, A2B2C2D2, and A3B3C3D3. These larger classes were confirmed by the subjects' success with the prerequisite lower-level conditional relations; they were also able to select Set-D comparisons conditionally upon samples from Sets A and C, and to do the BC and CB matching that defined the original three-member classes. Adding the three DC relations therefore generated 12 more, three each in BD, DB, AD, and CD. Enlarging each class by one member brought about a disproportionate increase in the number of emergent relations. Ancillary oral naming tests suggested that the subject's application of the same name to each stimulus was neither necessary nor sufficient to establish classes of equivalent stimuli.     

Assessing Type A behavior in children: a longitudinal exploration of the overlap between Type A behavior and hyperactivity

Child Type A behavior and its relation to hyperactivity were investigated developmentally using a longitudinal normal sample of 91 children (46 boys and 45 girls) between the ages of 4 and 8-9. In light of the overlap found in several studies between Type A behavior, as measured by the Matthews Youth Test for Health (MYTH) questionnaire, and hyperactivity measured by questionnaires, an attempt was made to measure Type A behavior as distinct from hyperactivity using behavioral observations. The MYTH questionnaire and behavioral observations were used to assess Type A behavior and questionnaire-based measures and behavioral observations were used to assess hyperactivity. Predictions were made regarding individual stability in phenomena and in measures. The results indicated considerable stability in the respective Type A and hyperactivity measures over time, and further, that behavioral observations make it possible to measure Global Type A behavior and Type A Competitiveness as distinct from hyperactivity, although the status of Type A Impatience at early ages is not yet settled. The MYTH and the observed Type A behavior showed differential relations to external criteria, such as achievement measures and problem behavior. This has implications for future measurement and perhaps conceptualization of Type A behavior in children, and thereby also for studying the developmental aspects of Type A behavior.     

Superconditioning from a reduced reinforcer

In four autoshaping experiments pigeons received conditioned inhibition training of the form A++, AB-, where ++ is a strong reinforcer and - is nonreinforcement. Subsequent AB+ training, in which + is a moderate reinforcer, resulted in enhanced conditioning of A, relative to an A stimulus receiving no treatment, one receiving A+ treatment, and one receiving A++ treatment. This enhancement of conditioning to Aconstitutes a demonstration of “superconditioning”. The presence of the inhibitory B sufficiently enhanced the reinforcing power of the moderate reinforcer (+) that it was able to further increase the excitation controlled by A. This occurred even though A had previously been paired with a stronger reinforcer (++). Superconditioning was also observed when A and B were extinguished prior to treatment with + or were originally neutral stimuli followed by + in the presence of an inhibitor trained elsewhere.     

心理弹性儿童的压力/逆境认知

心理弹性儿童是如何看待其曾经历的或正在经历的严重压力/逆境的?解读这一问题或可促进对聚焦于儿童自身的心理弹性机制的探查。为考察心理弹性儿童压力/逆境认知特点,利用Visual FoxPro 8.0平台自编计算机程序和故事测验法,分别从压力/逆境的敏感程度、觉知到的压力/逆境严重程度、觉知到的压力/逆境影响持久程度和觉知到的压力/逆境可应对程度四个方面对心理弹性组儿童和缺乏心理弹性组儿童进行测量。结果发现:(1)心理弹性儿童的压力/逆境敏感程度高于缺乏心理弹性儿童,表现为前者在压力/逆境指标回忆量、压力/逆境再认敏感性指标和模糊情境下压力/逆境偏向性上的得分均比后者高,而且,前者的压力/逆境指标再认击中平均反应时比后者短,反应标准亦比后者宽松。(2)心理弹性儿童在觉知到的压力/逆境严重程度、影响持久程度和可应对程度上两亚类实验任务(你认为主人公如何看?和若你是主人公如何看?)上的得分与反应时,除设身处地的压力/逆境影响持久程度认知外,其余与缺乏心理弹性儿童之间差异均不显著,提示,心理弹性儿童所觉知到的严重压力/逆境影响远没有缺乏心理弹性儿童所认为的更为持久。文章探讨了儿童更为敏感的压力/逆境觉知和相对而言认为严...