Vulnerability of conditional NCAM-deficient mice to develop stress-induced behavioral alterations

Previous studies in rodents showed that chronic stress induces structural and functional alterations in several brain regions, including shrinkage of the hippocampus and the prefrontal cortex, which are accompanied by cognitive and emotional disturbances. Reduced expression of the neural cell adhesion molecule (NCAM) following chronic stress has been proposed to be crucially involved in neuronal retraction and behavioral alterations. Since NCAM gene polymorphisms and altered expression of alternatively spliced NCAM isoforms have been associated with bipolar depression and schizophrenia in humans, we hypothesized that reduced expression of NCAM renders individuals more vulnerable to the deleterious effects of stress on behavior. Here, we specifically questioned whether mice in which the NCAM gene is inactivated in the forebrain by cre-recombinase under the control of the calcium-calmodulin-dependent kinase II promoter (conditional NCAM-deficient mice), display increased vulnerability to stress. We assessed the evolving of depressive-like behaviors and spatial learning and memory impairments following a subchronic stress protocol (2 weeks) that does not result in behavioral dysfunction, nor in altered NCAM expression, in wild-type mice. Indeed, while no behavioral alterations were detected in wild-type littermates after subchronic stress, conditional NCAM-deficient mice showed increased immobility in the tail suspension test and deficits in reversal spatial learning in the water maze. These findings indicate that diminished NCAM expression might be a critical vulnerability factor for the development of behavioral alterations by stress and further support a functional involvement of NCAM in stress-induced cognitive and emotional disturbances.     

Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction

There is much interest to understand the mechanisms leading to the establishment, maintenance, and extinction of fear memories. The amygdala has been critically involved in the processing of fear memories and a number of molecular changes have been implicated in this brain region in relation to fear learning. Although neural cell adhesion molecules (NCAMs) have been hypothesized to play a role, information available about their contribution to fear memories is scarce. We investigate here whether polysialylated NCAM (PSA-NCAM) contributes to auditory fear conditioning in the amygdala. First, PSA-NCAM expression was evaluated in different amygdala nuclei after auditory fear conditioning at two different shock intensities. Results showed that PSA-NCAM expression was increased 24 h post-training only in animals subjected to the highest shock intensity (1mA). Second, PSA-NCAM was cleaved in the basolateral amygdaloid complex through micro-infusions of the enzyme endoneuraminidase N, and the consequences of such treatment were investigated on the acquisition, consolidation, remote memory expression, and extinction of conditioned fear memories. Intra-amygdaloid cleavage of PSA-NCAM did not affect acquisition, consolidation or expression of remote fear memories. However, intra-amygdaloid PSA-NCAM cleavage enhanced fear extinction processes. These results suggest that upregulation of PSA-NCAM is a correlate of fear conditioning that is not necessary for the establishment of fear memory in the amygdala, but participates in mechanisms precluding fear extinction. These findings point out PSA-NCAM as a potential target for the treatment of psychopathologies that involve impairment in fear extinction.     

Post-training intrahippocampal injection of synthetic poly-alpha-2,8-sialic acid-neural cell adhesion molecule mimetic peptide improves spatial long-term performance in mice

Several data have shown that the neural cell adhesion molecule (NCAM) is necessary for long-term memory formation and might play a role in the structural reorganization of synapses. The NCAM, encoded by a single gene, is represented by several isoforms that differ with regard to their content of alpha-2,8-linked sialic acid residues (PSA) on their extracellular domain. The carbohydrate PSA is known to promote plasticity, and PSA-NCAM isoforms remain expressed in the CA3 region of the adult hippocampus. In the present study, we investigated the effect on spatial memory consolidation of a PSA gain of function by injecting a PSA mimetic peptide (termed pr2) into the dorsal hippocampus. Mice were subjected to massed training in the spatial version of the water maze. Five hours after the last training session, experimental mice received an injection of pr2, whereas control mice received PBS or reverse peptide injections in the hippocampal CA3 region. Memory retention was tested at different time intervals: 24 h, 1 wk, and 4 wk. The results showed that the post-training infusion of pr2 peptide significantly increases spatial performance whenever it was assessed after the training phase. By contrast, administration of the control reverse peptide did not affect retention performance. These findings provide evidence that (1) PSA-NCAM is involved in memory consolidation processes in the CA3 hippocampal region, and (2) PSA mimetic peptides can facilitate the formation of long-term spatial memory when injected during the memory consolidation phase.     

Neurobiological and endocrine correlates of individual differences in spatial learning ability

The polysialylated neural cell adhesion molecule (PSA-NCAM) has been implicated in activity-dependent synaptic remodeling and memory formation. Here, we questioned whether training-induced modulation of PSA-NCAM expression might be related to individual differences in spatial learning abilities. At 12 h posttraining, immunohistochemical analyses revealed a learning-induced up-regulation of PSA-NCAM in the hippocampal dentate gyrus that was related to the spatial learning abilities displayed by rats during training. Specifically, a positive correlation was found between latency to find the platform and subsequent activated PSA levels, indicating that greater induction of polysialylation was observed in rats with the slower acquisition curve. At posttraining times when no learning-associated activation of PSA was observed, no such correlation was found. Further experiments revealed that performance in the massed water maze training is related to a pattern of spatial learning and memory abilities, and to learning-related glucocorticoid responsiveness. Taken together, our findings suggest that the learning-related neural circuits of fast learners are better suited to solving the water maze task than those of slow learners, the latter relying more on structural reorganization to form memory, rather than the relatively economic mechanism of altering synaptic efficacy that is likely used by the former.     

The effects of non-contingent extrinsic and intrinsic rewards on memory consolidation

Emotional and arousing treatments given shortly after learning enhance delayed memory retrieval in animal and human studies. Positive affect and reward induced prior to a variety of cognitive tasks enhance performance, but their ability to affect memory consolidation has not been investigated before. Therefore, we investigated the effects of a small, non-contingent, intrinsic or extrinsic reward on delayed memory retrieval. Participants (n=108) studied and recalled a list of 30 affectively neutral, imageable nouns. Experimental groups were then given either an intrinsic reward (e.g., praise) or an extrinsic reward (e.g., US 1 dollar). After a one-week delay, participants' retrieval performance for the word list was significantly better in the extrinsic reward groups, whether the reward was expected or not, than in controls. Those who received the intrinsic reward performed somewhat better than controls, but the difference was not significant. Thus, at least some forms of arousal and reward, even when semantically unrelated to the learned material, can effectively modulate memory consolidation. These types of treatments might be useful for the development of new memory intervention strategies.     

Service job lawyers are happier than money job lawyers,despite their lower income

Giving too much emphasis to extrinsic values and too little emphasis to intrinsic values is known to depress well-being. But is simply working in an extrinsic job also risky, even if that job delivers the money? We compared 1414 ‘Money’ (extrinsic) lawyers, 1145 ‘Service’ (intrinsic) lawyers, and 3415 ‘Other’ lawyers as to their income, values, well-being, and drinking behavior. Although service lawyers had much lower incomes, they also experienced more well-being and less negative affect compared to money lawyers, and drank less and less often. ANCOVAs showed that the intrinsic vs. extrinsic job-type effects were independent of rated intrinsic vs. extrinsic values, current income, years of work experience, and class rank at graduation, suggesting that the job-contexts themselves were operative. We discuss the difficult choice that pre-professional students face, between two versions of the American dream: one emphasizing wealth and status, and the other, service and personal development.     

内外动机对青少年记忆的影响及其神经机制

动机是一切行为的核心, 动机可分为外在和内在动机。青少年时期既是记忆的关键期, 也是动机发展的特殊时期。然而, 目前关于内外动机影响青少年记忆的研究才刚刚起步, 尚不清楚外在和内在动机影响青少年记忆的规律和机制是否一致, 也不清楚二者如何交互影响记忆。本研究将结合认知范式和脑成像技术, 考察外在和内在动机如何分别影响以及交互影响青少年记忆。这将有助于更加全面、深刻理解内外动机影响青少年记忆的独特规律和机制, 为科学提升青少年动机和记忆效果提供研究证据。     

Reflecting on being an effective teacher in an age of measurement

This reflective study examines what effective means in terms of teaching in secondary schools in England. The article questions whether quality assurance and observations produce better teachers or better ‘fabricators’. The study explores the pressures of performativity and the resulting fabrication: the ‘ticking of boxes’ in order to be classed as ‘outstanding’ and ‘effective’. A journey to recapture the pleasure in teaching and learning through reflective diaries will be considered. Here the process leads to the outcome without an overemphasis on assessment criteria and performativity or extrinsic motivators which can counter intrinsic motivation and professional judgement.     

Motivated semantic control: Exploring the effects of extrinsic reward and self-reference on semantic retrieval in semantic aphasia

Recent insights show that increased motivation can benefit executive control, but this effect has not been explored in relation to semantic cognition. Patients with deficits of controlled semantic retrieval in the context of semantic aphasia (SA) after stroke may benefit from this approach since ‘semantic control’ is considered an executive process. Deficits in this domain are partially distinct from the domain-general deficits of cognitive control. We assessed the effect of both extrinsic and intrinsic motivation in healthy controls and SA patients. Experiment 1 manipulated extrinsic reward using high or low levels of points for correct responses during a semantic association task. Experiment 2 manipulated the intrinsic value of items using self-reference, allocating pictures of items to the participant (‘self’) or researcher (‘other’) in a shopping game before participants retrieved their semantic associations. These experiments revealed that patients, but not controls, showed better performance when given an extrinsic reward, consistent with the view that increased external motivation may help ameliorate patients’ semantic control deficits. However, while self-reference was associated with better episodic memory, there was no effect on semantic retrieval. We conclude that semantic control deficits can be reduced when extrinsic rewards are anticipated; this enhanced motivational state is expected to support proactive control, for example, through the maintenance of task representations. It may be possible to harness this modulatory impact of reward to combat the control demands of semantic tasks in SA patients.     

The neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo

The neural cell adhesion molecule (NCAM) is known to play a role in developmental and structural processes but also in synaptic plasticity and memory of the adult animal. Recently, FGL, a NCAM mimetic peptide that binds to the Fibroblast Growth Factor Receptor 1 (FGFR-1), has been shown to have a beneficial impact on normal memory functioning, as well as to rescue some pathological cognitive impairments. Whether its facilitating impact may be mediated through promoting neuronal plasticity is not known. The present study was therefore designed to test whether FGL modulates the induction and maintenance of synaptic plasticity in the dentate gyrus (DG) in vivo. For this, we first assessed the effect of the FGL peptide on synaptic functions at perforant path-dentate gyrus synapses in the anesthetized rat. FGL, or its control inactive peptide, was injected locally 60 min before applying high-frequency stimulation (HFS) to the medial perforant path. The results suggest that although FGL did not alter basal synaptic transmission, it facilitated both the induction and maintenance of LTP. Interestingly, FGL also modified the heterosynaptic plasticity observed at the neighboring lateral perforant path synapses. The second series of experiments, using FGL intracerebroventricular infusion in the awake animal, confirmed its facilitating effect on LTP for up to 24 h. Our data also suggest that FGL could alter neurogenesis associated with LTP. In sum, these results show for the first time that enhancing NCAM functions by mimicking its heterophilic interaction with FGFR facilitates hippocampal synaptic plasticity in the awake, freely moving animal.     

内外部线索对不同类型学习判断的影响

以Koriat的线索模型理论为基础,在前人研究的基础上探讨两种学习判断的差异,并进一步考察内外部线索对即时学习判断和延迟学习判断的不同影响。研究结果发现：（1）延迟学习判断的相对准确性显著高于即时学习判断,验证了延迟学习判断效应的存在。（2）不同的线索类型对学习判断的影响不同,学习判断对内部线索更加敏感。（3）相同的线索在不同的学习判断条件下影响不同。（4）即时学习判断条件下的JOL值分布呈现逐渐上升的趋势;延迟学习判断条件下的JOL值分布呈“U”型曲线。     

Unitization mitigates interference by intrinsic negative emotion in familiarity and recollection of associative memory: Electrophysiological evidence

Emotion exerts varied influences on memory. While task-relevant item memory is often enhanced by emotion, associative memory is generally impaired. Unitization is known to improve associative memory, but its effects and mechanisms in protecting associative memory from emotional interference are rather obscure. The current study investigated associative memory by employing experimental manipulation of unitization (vs. nonunitization) encoding strategy and stimulus emotion (neutral, intrinsic negative, and extrinsic negative), combined with event-related potential (ERP) signatures of familiarity (FN400 old/new effects) and recollection (parietal late positive component/LPC old/new effects) in memory recognition. Both behavioral and ERP indices of associative recognition from the nonunitization group confirmed emotional interference in associative memory. Importantly, it was primarily intrinsic (vs. extrinsic) emotion that impeded associative memory. Unitization encoding improved memory performance in general, accompanied by enhanced recollection process and induction of familiarity process, which is typically not involved in associative memory recognition and was indeed absent in the nonunitization group. Importantly, unitization helped to preserve behavioral performance (specifically, response speed though not recognition strength) from interference by intrinsic emotion while largely reversed the detriment of intrinsic emotion on ERP indices of familiarity and recollection processes. Interestingly, a synergy between intrinsic emotion and unitization encoding was observed, which could underpin the facilitation of familiarity process in associative recognition of emotional pairs. Overall, current findings highlight interference by intrinsic emotion in associative memory, which is nonetheless responsive to mitigation by unitization encoding.     

工作记忆对知觉类别学习的影响:问题与构想

人们学习将感知到的客体按照不同的标准或规则分类存储,即类别学习。而工作记忆作为多种认知加工的基础,对类别学习具有重要作用。基于已有研究,分别梳理了言语工作记忆和视空工作记忆对基于规则和信息整合类别结构的影响。目前,执行功能是否影响内隐类别学习系统、工作记忆负荷对内隐外显类别学习系统的影响是否一致还存在争议。此外,工作记忆影响知觉类别学习的认知加工阶段尚不清晰。未来的研究还需明确工作记忆负荷对内隐和外显类别学习的影响,进一步验证工作记忆影响类别学习的认知加工阶段假设的合理性。     

材料呈现方式和复习与否对中文电子笔记学习学习效果的影响

笔记策略的“转换假说”指出：将听觉材料写下来比将视觉材料写下来的学习效果更好。本研究以此为基础,以104名大学生为被试,采用多元方差分析的方法,探讨了材料呈现方式和复习与否对拼音键入的中文电子笔记的即时和延时学习效果的影响。结果发现,电子笔记在视觉材料上比在听觉材料上的即时学习效果更优;在间隔一周后的延时重测中,复习后的延时学习效果显著优于不复习,但复习在视觉材料组和听觉材料组中的促进作用无显著差异。     

Disentangling component learning and executive processes in hidden pathway maze learning in children: A process-based approach

Identification of cognitive processes that affect children’s ability to manage complex information is critical to understanding the development of executive functions. However, characterization of these processes is hampered by a lack of appropriate tasks and reliance on single outcome measures that are unsuitable for studying complex aspects of executive function. The current study aimed to circumvent these limitations by employing a hidden maze learning paradigm (Groton Maze Learning Test; independence of component cognitive GMLT) to evaluate the processes—spatial memory and rule use—that underlie hidden pathway maze learning in children. Specifically, we investigated the impact of withholding rule instructions (Study 1) and nonrepeating pathways on each trial (Study 2) on the ability to use rules and to locate pathways in 10 × 10 mazes in a sample of 8-year-old children. Results of these studies suggested that manipulations of task rules did not affect spatial memory and that manipulations of the maze pathway did not affect rule use. These findings demonstrate the independence of spatial memory and rule use on the GMLT and provide evidence of a “double dissociation” of cognitive processes that underlie hidden maze learning in children. Implications for understanding the coordination of component cognitive processes that underlie executive function in childhood are discussed.     

Reelin supplementation enhances cognitive ability, synaptic plasticity, and dendritic spine density

Apolipoprotein receptors belong to an evolutionarily conserved surface receptor family that has intimate roles in the modulation of synaptic plasticity and is necessary for proper hippocampal-dependent memory formation. The known lipoprotein receptor ligand Reelin is important for normal synaptic plasticity, dendritic morphology, and cognitive function; however, the in vivo effect of enhanced Reelin signaling on cognitive function and synaptic plasticity in wild-type mice is unknown. The present studies test the hypothesis that in vivo enhancement of Reelin signaling can alter synaptic plasticity and ultimately influence processes of learning and memory. Purified recombinant Reelin was injected bilaterally into the ventricles of wild-type mice. We demonstrate that a single in vivo injection of Reelin increased activation of adaptor protein Disabled-1 and cAMP-response element binding protein after 15 min. These changes correlated with increased dendritic spine density, increased hippocampal CA1 long-term potentiation (LTP), and enhanced performance in associative and spatial learning and memory. The present study suggests that an acute elevation of in vivo Reelin can have long-term effects on synaptic function and cognitive ability in wild-type mice.     

Heterogeneity in generalized reinforcement learning and its relation to cognitive ability

In this paper, we study the connections between working memory capacity (WMC) and learning in the context of economic guessing games. We apply a generalized version of reinforcement learning, popularly known as the experience-weighted attraction (EWA) learning model, which has a connection to specific cognitive constructs, such as memory decay, the depreciation of past experience, counterfactual thinking, and choice intensity. Through the estimates of the model, we examine behavioral differences among individuals due to different levels of WMC. In accordance with ‘Miller’s magic number’, which is the constraint of working memory capacity, we consider two different sizes (granularities) of strategy space: one is larger (finer) and one is smaller (coarser). We find that constraining the EWA models by using levels (granules) within the limits of working memory allows for a better characterization of the data based on individual differences in WMC. Using this level-reinforcement version of EWA learning, also referred to as the EWA rule learning model, we find that working memory capacity can significantly affect learning behavior. Our likelihood ratio test rejects the null that subjects with high WMC and subjects with low WMC follow the same EWA learning model. In addition, the parameter corresponding to ‘counterfactual thinking ability’ is found to be reduced when working memory capacity is low.     

Serotonin Depletion Does Not Prevent Intrinsic Sensitization in the Leech

Intrinsic sensitization is a form of behavioral facilitation that is distinct from the extrinsic sensitization normally studied. To examine whether intrinsic and extrinsic sensitization are mediated by different physiological processes, the effects of 5,7-dihydroxytryptamine-induced serotonin (5-HT) depletion on intrinsic sensitization of the leech whole-body shortening response were observed. Previous experiments have shown that 5-HT depletion disrupts dishabituation and extrinsic sensitization of this behavior in the leech. Intrinsic sensitization was observed in preparations from both control and 5-HT-depleted animals, indicating that this form of behavioral facilitation was not affected by 5-HT depletion. The differences in the effects of 5-HT depletion on intrinsic versus extrinsic sensitization suggest that there are distinct neurophysiological processes mediating these two forms of behavioral facilitation. In addition, 5-HT depletion appeared to disrupt a putative extrinsic form of habituation of the shortening reflex. These data support the hypothesis that both intrinsic and extrinsic processes of neuromodulation mediate habituation and sensitization.     

A Controlled Study of Clicker‐Assisted Memory Enhancement in College Classrooms

Personal response systems, commonly called ‘clickers’, are widely used in secondary and post‐secondary classrooms. Although many studies show they enhance learning, experimental findings are mixed, and methodological issues limit their conclusions. Moreover, prior work has not determined whether clickers affect cognitive change or simply alert students to information likely to be on tests. The present investigation used a highly controlled methodology that removed subject and item differences from the data to explore the effect of clicker questions on memory for targeted facts in a live classroom and to gain a window on the cognitive processes affecting the outcome. We found that in‐class clicker questions given in a university psychology class augmented performance on delayed exam questions by 10–13%. Experimental results and a class survey indicate that it is unlikely that the observed effects can be attributed solely to attention grabbing. Rather, the data suggest the technology invokes the testing effect. Copyright © 2012 John Wiley & Sons, Ltd.     

How many dimensions underlie judgments of learning and recall? Evidence from state-trace methodology

The authors used state-trace methodology to investigate whether a single dimension (e.g., strength) is sufficient to account for recall and judgments of learning (JOLs) or whether multiple dimensions (e.g., intrinsic and extrinsic factors) are needed. The authors separately manipulated the independent variables of intrinsic and extrinsic cues, determining their state traces for recall and JOLs. In contrast to the supposition that intrinsic cues have similar effects on both recall and JOLs whereas extrinsic cues affect JOLs less strongly than recall (i.e., 2 dimensions underlying recall and JOLs), the authors found repeated support for the sufficiency of a single dimension for both recall and JOLs (not only immediate JOLs but also delayed JOLs) across a variety of intrinsic and extrinsic cues.