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  1. Sleep Spindles as Facilitators of Memory Formation and Learning

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    Daniel Ulrich

    2016-01-01

    Full Text Available Over the past decades important progress has been made in understanding the mechanisms of sleep spindle generation. At the same time a physiological role of sleep spindles is starting to be revealed. Behavioural studies in humans and animals have found significant correlations between the recall performance in different learning tasks and the amount of sleep spindles in the intervening sleep. Concomitant neurophysiological experiments showed a close relationship between sleep spindles and other sleep related EEG rhythms as well as a relationship between sleep spindles and synaptic plasticity. Together, there is growing evidence from several disciplines in neuroscience for a participation of sleep spindles in memory formation and learning.

  2. Transcription factor ABF-1 suppresses plasma cell differentiation but facilitates memory B cell formation.

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    Chiu, Yi-Kai; Lin, I-Ying; Su, Shin-Tang; Wang, Kuan-Hsiung; Yang, Shii-Yi; Tsai, Dong-Yan; Hsieh, Yi-Ting; Lin, Kuo-I

    2014-09-01

    Ag-primed B cells that result from an immune response can form either memory B cells or Ab-secreting plasma cells; however, the molecular machinery that controls this cellular fate is poorly understood. In this study, we show that activated B cell factor-1 (ABF-1), which encodes a basic helix-loop-helix transcriptional repressor, participates in this regulation. ABF-1 was prevalently expressed in purified memory B cells and induced by T follicular helper cell-mediated signals. ABF-1 expression declined by the direct repression of B lymphocyte-induced maturation protein-1 during differentiation. Ectopic expression of ABF-1 reduced the formation of Ab-secreting cells in an in vitro differentiation system of human memory B cells. Accordingly, knockdown of ABF-1 potentiates the formation of Ab-secreting cells. A transgenic mouse that expresses inducible ABF-1 in a B cell-specific manner was generated to demonstrate that the formation of germinal center and memory B cells was augmented by induced ABF-1 in an immune response, whereas the Ag-specific plasma cell response was dampened. This effect was associated with the ability of ABF-1 to limit cell proliferation. Together, our results demonstrate that ABF-1 facilitates formation of memory B cells but prevents plasma cell differentiation.

  3. Fasting launches CRTC to facilitate long-term memory formation in Drosophila.

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    Hirano, Yukinori; Masuda, Tomoko; Naganos, Shintaro; Matsuno, Motomi; Ueno, Kohei; Miyashita, Tomoyuki; Horiuchi, Junjiro; Saitoe, Minoru

    2013-01-25

    Canonical aversive long-term memory (LTM) formation in Drosophila requires multiple spaced trainings, whereas appetitive LTM can be formed after a single training. Appetitive LTM requires fasting prior to training, which increases motivation for food intake. However, we found that fasting facilitated LTM formation in general; aversive LTM formation also occurred after single-cycle training when mild fasting was applied before training. Both fasting-dependent LTM (fLTM) and spaced training-dependent LTM (spLTM) required protein synthesis and cyclic adenosine monophosphate response element-binding protein (CREB) activity. However, spLTM required CREB activity in two neural populations--mushroom body and DAL neurons--whereas fLTM required CREB activity only in mushroom body neurons. fLTM uses the CREB coactivator CRTC, whereas spLTM uses the coactivator CBP. Thus, flies use distinct LTM machinery depending on their hunger state.

  4. 6-hydroxy-L-nicotine from Arthrobacter nicotinovorans facilitate spatial memory formation in rats

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    Lucian Hritcu; Marius Stefan; Marius Mihasan; Roderich Brandsch

    2010-01-01

    Effects of 6-hydroxy-L-nicotine derived from nicotine catabolism in Arthrobacter nicotinovorans on learning and memory processes were examined in adult male Wistar rats. 6-hydroxy-L-nicotine (0.3 mg/kg, i.p., 7 consecutive days chronic administration) significantly increased spontaneous alternation in Y-maze task and working memory in radial arm-maze task, suggesting effects on short-term memory, without affecting long-term memory, explored by reference memory in radial arm-maze t...

  5. Anodal tDCS over the Primary Motor Cortex Facilitates Long-Term Memory Formation Reflecting Use-Dependent Plasticity.

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    Orjon Rroji

    Full Text Available Previous research suggests that anodal transcranial direct current stimulation (tDCS over the primary motor cortex (M1 modulates NMDA receptor dependent processes that mediate synaptic plasticity. Here we test this proposal by applying anodal versus sham tDCS while subjects practiced to flex the thumb as fast as possible (ballistic movements. Repetitive practice of this task has been shown to result in performance improvements that reflect use-dependent plasticity resulting from NMDA receptor mediated, long-term potentiation (LTP-like processes. Using a double-blind within-subject cross-over design, subjects (n=14 participated either in an anodal or a sham tDCS session which were at least 3 months apart. Sham or anodal tDCS (1 mA was applied for 20 min during motor practice and retention was tested 30 min, 24 hours and one week later. All subjects improved performance during each of the two sessions (p < 0.001 and learning gains were similar. Our main result is that long term retention performance (i.e. 1 week after practice was significantly better when practice was performed with anodal tDCS than with sham tDCS (p < 0.001. This effect was large (Cohen's d=1.01 and all but one subject followed the group trend. Our data strongly suggest that anodal tDCS facilitates long-term memory formation reflecting use-dependent plasticity. Our results support the notion that anodal tDCS facilitates synaptic plasticity mediated by an LTP-like mechanism, which is in accordance with previous research.

  6. Why it's easier to remember seeing a face we already know than one we don't: preexisting memory representations facilitate memory formation.

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    Reder, Lynne M; Victoria, Lindsay W; Manelis, Anna; Oates, Joyce M; Dutcher, Janine M; Bates, Jordan T; Cook, Shaun; Aizenstein, Howard J; Quinlan, Joseph; Gyulai, Ferenc

    2013-03-01

    In two experiments, we provided support for the hypothesis that stimuli with preexisting memory representations (e.g., famous faces) are easier to associate to their encoding context than are stimuli that lack long-term memory representations (e.g., unknown faces). Subjects viewed faces superimposed on different backgrounds (e.g., the Eiffel Tower). Face recognition on a surprise memory test was better when the encoding background was reinstated than when it was swapped with a different background; however, the reinstatement advantage was modulated by how many faces had been seen with a given background, and reinstatement did not improve recognition for unknown faces. The follow-up experiment added a drug intervention that inhibited the ability to form new associations. Context reinstatement did not improve recognition for famous or unknown faces under the influence of the drug. The results suggest that it is easier to associate context to faces that have a preexisting long-term memory representation than to faces that do not.

  7. Nicotine facilitates memory consolidation in perceptual learning.

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    Beer, Anton L; Vartak, Devavrat; Greenlee, Mark W

    2013-01-01

    Perceptual learning is a special type of non-declarative learning that involves experience-dependent plasticity in sensory cortices. The cholinergic system is known to modulate declarative learning. In particular, reduced levels or efficacy of the neurotransmitter acetylcholine were found to facilitate declarative memory consolidation. However, little is known about the role of the cholinergic system in memory consolidation of non-declarative learning. Here we compared two groups of non-smoking men who learned a visual texture discrimination task (TDT). One group received chewing tobacco containing nicotine for 1 h directly following the TDT training. The other group received a similar tasting control substance without nicotine. Electroencephalographic recordings during substance consumption showed reduced alpha activity and P300 latencies in the nicotine group compared to the control group. When re-tested on the TDT the following day, both groups responded more accurately and more rapidly than during training. These improvements were specific to the retinal location and orientation of the texture elements of the TDT suggesting that learning involved early visual cortex. A group comparison showed that learning effects were more pronounced in the nicotine group than in the control group. These findings suggest that oral consumption of nicotine enhances the efficacy of nicotinic acetylcholine receptors. Our findings further suggest that enhanced efficacy of the cholinergic system facilitates memory consolidation in perceptual learning (and possibly other types of non-declarative learning). In that regard acetylcholine seems to affect consolidation processes in perceptual learning in a different manner than in declarative learning. Alternatively, our findings might reflect dose-dependent cholinergic modulation of memory consolidation. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

  8. The formation of flashbulb memories.

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    Conway, M A; Anderson, S J; Larsen, S F; Donnelly, C M; McDaniel, M A; McClelland, A G; Rawles, R E; Logie, R H

    1994-05-01

    A large group of subjects took part in a multinational test-retest study to investigate the formation of flashbulb (FB) memories for learning the news of the resignation of the British prime minister, Margaret Thatcher. Over 86% of the U.K. subjects were found to have FB memories nearly 1 year after the resignation; their memory reports were characterized by spontaneous, accurate, and full recall of event details, including minutiae. In contrast, less than 29% of the non-U.K. subjects had FB memories 1 year later; memory reports in this group were characterized by forgetting, reconstructive errors, and confabulatory responses. A causal analysis of secondary variables showed that the formation of FB memories was primarily associated with the level of importance attached to the event and level of affective response to the news. These findings lend some support to the study by R. Brown and Kulik (1977), who suggest that FB memories may constitute a class of autobiographical memories distinguished by some form of preferential encoding.

  9. Audiovisual integration facilitates monkeys' short-term memory.

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    Bigelow, James; Poremba, Amy

    2016-07-01

    Many human behaviors are known to benefit from audiovisual integration, including language and communication, recognizing individuals, social decision making, and memory. Exceptionally little is known about the contributions of audiovisual integration to behavior in other primates. The current experiment investigated whether short-term memory in nonhuman primates is facilitated by the audiovisual presentation format. Three macaque monkeys that had previously learned an auditory delayed matching-to-sample (DMS) task were trained to perform a similar visual task, after which they were tested with a concurrent audiovisual DMS task with equal proportions of auditory, visual, and audiovisual trials. Parallel to outcomes in human studies, accuracy was higher and response times were faster on audiovisual trials than either unisensory trial type. Unexpectedly, two subjects exhibited superior unimodal performance on auditory trials, a finding that contrasts with previous studies, but likely reflects their training history. Our results provide the first demonstration of a bimodal memory advantage in nonhuman primates, lending further validation to their use as a model for understanding audiovisual integration and memory processing in humans.

  10. Learned Interval Time Facilitates Associate Memory Retrieval

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    van de Ven, Vincent; Kochs, Sarah; Smulders, Fren; De Weerd, Peter

    2017-01-01

    The extent to which time is represented in memory remains underinvestigated. We designed a time paired associate task (TPAT) in which participants implicitly learned cue-time-target associations between cue-target pairs and specific cue-target intervals. During subsequent memory testing, participants showed increased accuracy of identifying…

  11. Verifying Visual Properties in Sentence Verification Facilitates Picture Recognition Memory

    NARCIS (Netherlands)

    D. Pecher (Diane); K. Zanolie (Kiki); R. Zeelenberg (René)

    2007-01-01

    textabstractAccording to the perceptual symbols theory (Barsalou, 1999), sensorimotor simulations underlie the representation of concepts. We investigated whether recognition memory for pictures of concepts was facilitated by earlier representation of visual properties of those concepts. During stud

  12. Short-term facilitation may stabilize parametric working memory trace

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    Vladimir eItskov

    2011-10-01

    Full Text Available Networks with continuous set of attractors are considered to be a paradigmatic model for parametric working memory, but require fine-tuning of connections and are thus structurally unstable. Here we analyzed the network with ring attractor, where connections are not perfectly tuned and the activity state therefore drifts in the absence of the stabilizing stimulus. We derive an analytical expression for the drift dynamics and conclude that the network cannot function as working memory for a period of several seconds, a typical delay time in monkey memory experiments. We propose that short-term synaptic facilitation in recurrent connections significantly improves the robustness of the model by slowing down the drift of activity bump. Extending the calculation of the drift velocity to network with synaptic facilitation, we conclude that facilitation can slow down the drift by a large factor, rendering the network suitable as a model of working memory.

  13. Facilitating memory with hypnosis, focused meditation, and eye closure.

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    Wagstaff, Graham F; Brunas-Wagstaff, Jo; Cole, Jon; Knapton, Luke; Winterbottom, James; Crean, Vicki; Wheatcroft, Jacqueline

    2004-10-01

    Three experiments examined some features of hypnotic induction that might be useful in the development of brief memory-facilitation procedures. The first involved a hypnosis procedure designed to facilitate face identification; the second employed a brief, focused-meditation (FM) procedure, with and without eye closure, designed to facilitate memory for an emotional event. The third experiment was a check for simple motivation and expectancy effects. Limited facilitation effects were found for hypnosis, but these were accompanied by increased confidence in incorrect responses. However, eye closure and FM were effective in facilitating free recall of an event without an increase in errors. FM reduced phonemic fluency, suggesting that the effectiveness of FM was not due to simple changes in expectancy or motivation.

  14. Memory Facilitation effect in Interaction between Video Clips and Music

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    吉岡, 賢治; 岩永, 誠

    2007-01-01

    Previous studies examined memories of video clips under the condition of affects combination of pictures and music. Video clips, which were combined with music in same impressions, were easy to remember their contents. The present study aimed to examine the memory facilitation about pictures in two perspectives, the strength of affects and the distribution of the processing recourses. Participants were 39 undergraduate volunteers, who were divided into three experimental conditions randomly. ...

  15. Glucocorticoids boost stimulus-response memory formation in humans.

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    Guenzel, Friederike M; Wolf, Oliver T; Schwabe, Lars

    2014-07-01

    Stress affects memory beyond hippocampus-dependent spatial or episodic memory processes. In particular, stress may influence also striatum-dependent stimulus-response (S-R) memory processes. Rodent studies point to an important role of glucocorticoids in the modulation of S-R memory. However, whether glucocorticoids influence S-R memory processes in humans is still unknown. Therefore, we examined in the current experiment the impact of glucocorticoids on the formation of S-R memories in humans. For this purpose, healthy men and women received either hydrocortisone or a placebo 45 min before completing an S-R association learning task and an S-R navigation task. In addition, participants performed also a virtual spatial navigation task and a spatial navigation task in a real environment. Memory of all four learning tasks was tested one week later. Our data showed that hydrocortisone before learning enhanced memory of the S-R association learning task. Moreover, hydrocortisone enhanced the memory of the virtual spatial navigation task, mainly in women. Memory performance in the other tasks remained unaffected by hydrocortisone. These findings provide first evidence that glucocorticoids may facilitate S-R memory formation processes in humans.

  16. Social facilitation of long-lasting memory retrieval in Drosophila.

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    Chabaud, Marie-Ange; Isabel, Guillaume; Kaiser, Laure; Preat, Thomas

    2009-10-13

    Recent studies demonstrate that social interactions can have a profound influence on Drosophila melanogaster behavior and cuticular pheromone patterns. Olfactory memory performance has mostly been investigated in groups, and previous studies have reported that grouped flies do not interact with each other and behave in the same way as individual flies during short-term memory retrieval. However, the influence of social effects on the two known forms of Drosophila long-lasting associative memory, anesthesia-resistant memory (ARM) and long-term memory (LTM), has never been reported. We show here that ARM is displayed by individual flies but is socially facilitated; flies trained for ARM interact within a group to improve their conditioned performance. In contrast, testing shows LTM improvement in individual flies rather than in a group. We show that the social facilitation of ARM during group testing is independent of the social context of training and does not involve nonspecific aggregation. Furthermore, we demonstrate that social interactions facilitate ARM retrieval. We also show that social interactions necessary for this facilitation are specifically generated by trained flies: when single flies trained for ARM are mixed with groups of naive flies, they display poor retrieval, whereas mixing with groups trained either for ARM or LTM enhances performance.

  17. Paradoxical facilitation of working memory after basolateral amygdala damage.

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    Barak Morgan

    Full Text Available Working memory is a vital cognitive capacity without which meaningful thinking and logical reasoning would be impossible. Working memory is integrally dependent upon prefrontal cortex and it has been suggested that voluntary control of working memory, enabling sustained emotion inhibition, was the crucial step in the evolution of modern humans. Consistent with this, recent fMRI studies suggest that working memory performance depends upon the capacity of prefrontal cortex to suppress bottom-up amygdala signals during emotional arousal. However fMRI is not well-suited to definitively resolve questions of causality. Moreover, the amygdala is neither structurally or functionally homogenous and fMRI studies do not resolve which amygdala sub-regions interfere with working memory. Lesion studies on the other hand can contribute unique causal evidence on aspects of brain-behaviour phenomena fMRI cannot "see". To address these questions we investigated working memory performance in three adult female subjects with bilateral basolateral amygdala calcification consequent to Urbach-Wiethe Disease and ten healthy controls. Amygdala lesion extent and functionality was determined by structural and functional MRI methods. Working memory performance was assessed using the Wechsler Adult Intelligence Scale-III digit span forward task. State and trait anxiety measures to control for possible emotional differences between patient and control groups were administered. Structural MRI showed bilateral selective basolateral amygdala damage in the three Urbach-Wiethe Disease subjects and fMRI confirmed intact functionality in the remaining amygdala sub-regions. The three Urbach-Wiethe Disease subjects showed significant working memory facilitation relative to controls. Control measures showed no group anxiety differences. Results are provisionally interpreted in terms of a 'cooperation through competition' networks model that may account for the observed paradoxical

  18. Generalizing memories over time: sleep and reinforcement facilitate transitive inference.

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    Werchan, Denise M; Gómez, Rebecca L

    2013-02-01

    The use of reinforcement and rewards is known to enhance memory retention. However, the impact of reinforcement on higher-order forms of memory processing, such as integration and generalization, has not been directly manipulated in previous studies. Furthermore, there is evidence that sleep enhances the integration and generalization of memory, but these studies have only used reinforcement learning paradigms and have not examined whether reinforcement impacts or is critical for memory integration and generalization during sleep. Thus, the aims of the current study were to examine: (1) whether reinforcement during learning impacts the integration and generalization of memory; and (2) whether sleep and reinforcement interact to enhance memory integration and generalization. We investigated these questions using a transitive inference (TI) task, which is thought to require the integration and generalization of disparate relational memories in order to make novel inferences. To examine whether reinforcement influences or is required for the formation of inferences, we compared performance using a reinforcement or an observation based TI task. We examined the impact of sleep by comparing performance after a 12-h delay containing either wake or sleep. Our results showed that: (1) explicit reinforcement during learning is required to make transitive inferences and that sleep further enhances this effect; (2) sleep does not make up for the inability to make inferences when reinforcement does not occur during learning. These data expand upon previous findings and suggest intriguing possibilities for the mechanisms involved in sleep-dependent memory transformation.

  19. Externalising the autobiographical self: sharing personal memories online facilitated memory retention.

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    Wang, Qi; Lee, Dasom; Hou, Yubo

    2017-07-01

    Internet technology provides a new means of recalling and sharing personal memories in the digital age. What is the mnemonic consequence of posting personal memories online? Theories of transactive memory and autobiographical memory would make contrasting predictions. In the present study, college students completed a daily diary for a week, listing at the end of each day all the events that happened to them on that day. They also reported whether they posted any of the events online. Participants received a surprise memory test after the completion of the diary recording and then another test a week later. At both tests, events posted online were significantly more likely than those not posted online to be recalled. It appears that sharing memories online may provide unique opportunities for rehearsal and meaning-making that facilitate memory retention.

  20. What Do They Understand? Using Technology to Facilitate Formative Assessment

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    Mitten, Carolyn; Jacobbe, Tim; Jacobbe, Elizabeth

    2017-01-01

    Formative assessment is so important to inform teachers' planning. A discussion of the benefits of using technology to facilitate formative assessment explains how four primary school teachers adopted three different apps to make their formative assessment more meaningful and useful.

  1. Stabilization of memory States by stochastic facilitating synapses.

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    Miller, Paul

    2013-12-06

    Bistability within a small neural circuit can arise through an appropriate strength of excitatory recurrent feedback. The stability of a state of neural activity, measured by the mean dwelling time before a noise-induced transition to another state, depends on the neural firing-rate curves, the net strength of excitatory feedback, the statistics of spike times, and increases exponentially with the number of equivalent neurons in the circuit. Here, we show that such stability is greatly enhanced by synaptic facilitation and reduced by synaptic depression. We take into account the alteration in times of synaptic vesicle release, by calculating distributions of inter-release intervals of a synapse, which differ from the distribution of its incoming interspike intervals when the synapse is dynamic. In particular, release intervals produced by a Poisson spike train have a coefficient of variation greater than one when synapses are probabilistic and facilitating, whereas the coefficient of variation is less than one when synapses are depressing. However, in spite of the increased variability in postsynaptic input produced by facilitating synapses, their dominant effect is reduced synaptic efficacy at low input rates compared to high rates, which increases the curvature of neural input-output functions, leading to wider regions of bistability in parameter space and enhanced lifetimes of memory states. Our results are based on analytic methods with approximate formulae and bolstered by simulations of both Poisson processes and of circuits of noisy spiking model neurons.

  2. Cannabinoid facilitation of fear extinction memory recall in humans

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    Rabinak, Christine A.; Angstadt, Mike; Sripada, Chandra S.; Abelson, James L.; Liberzon, Israel; Milad, Mohammed R.; Phan, K. Luan

    2012-01-01

    A first-line approach to treat anxiety disorders is exposure-based therapy, which relies on extinction processes such as repeatedly exposing the patient to stimuli (conditioned stimuli; CS) associated with the traumatic, fear-related memory. However, a significant number of patients fail to maintain their gains, partly attributed to the fact that this inhibitory learning and its maintenance is temporary and conditioned fear responses can return. Animal studies have shown that activation of the cannabinoid system during extinction learning enhances fear extinction and its retention. Specifically, CB1 receptor agonists, such as Δ9-tetrahydrocannibinol (THC), can facilitate extinction recall by preventing recovery of extinguished fear in rats. However, this phenomenon has not been investigated in humans. We conducted a study using a randomized, double-blind, placebo-controlled, between-subjects design, coupling a standard Pavlovian fear extinction paradigm and simultaneous skin conductance response (SCR) recording with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo (PBO) 2 hours prior to extinction learning in 29 healthy adult volunteers (THC = 14; PBO = 15) and tested extinction retention 24 hours after extinction learning. Compared to subjects that received PBO, subjects that received THC showed low SCR to a previously extinguished CS when extinction memory recall was tested 24 hours after extinction learning, suggesting that THC prevented the recovery of fear. These results provide the first evidence that pharmacological enhancement of extinction learning is feasible in humans using cannabinoid system modulators, which may thus warrant further development and clinical testing. PMID:22796109

  3. Epigenetic Regulation of Memory Formation and Maintenance

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    Zovkic, Iva B.; Guzman-Karlsson, Mikael C.; Sweatt, J. David

    2013-01-01

    Understanding the cellular and molecular mechanisms underlying the formation and maintenance of memories is a central goal of the neuroscience community. It is well regarded that an organism's ability to lastingly adapt its behavior in response to a transient environmental stimulus relies on the central nervous system's capability for structural…

  4. Piracetam, an AMPAkine drug, facilitates memory consolidation in the day-old chick.

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    Samartgis, Jodi R; Schachte, Leslie; Hazi, Agnes; Crowe, Simon F

    2012-12-01

    Piracetam is an AMPAkine drug that may have a range of different mechanisms at the cellular level, and which has been shown to facilitate memory, amongst its other effects. This series of experiments demonstrated that a 10mg/kg dose of piracetam facilitated memory consolidation in the day-old chick when injected from immediately until 120min after weak training (i.e. using a 20% v/v concentration of methyl anthranilate) with the passive avoidance learning task. Administration of piracetam immediately after training led to memory facilitation which lasted for up to 24h following training. This dose of the AMPAkine was not shown to facilitate memory reconsolidation. These findings support the contention that application of the AMPAkine piracetam facilitates memory using a weak training task, and extend the range of actions previously noted with NMDA-related agents to those which also facilitate the AMPA receptor. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Learning under stress impairs memory formation.

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    Schwabe, Lars; Wolf, Oliver T

    2010-02-01

    Converging lines of evidence indicate that stress either before or after learning influences memory. Surprisingly little is known about how memory is affected when people learn while they are stressed. Here, we examined the impact of learning under stress in 48 healthy young men and women. Participants were exposed to stress (socially evaluated cold pressor test) or a control condition while they learned emotional words and neutral words that were either conceptually associated with or unrelated to the stressor. Memory was assessed in free recall and recognition tests 24h after learning. Learning under stress reduced both free recall and recognition performance, irrespective of the emotionality and the stress context relatedness of the words. While the effect of stress was comparable in men and women, women outperformed men in the free recall test. These findings show a memory impairing effect of learning under stress in humans and challenge some assumptions of current theories about the impact of stress around the time of learning on memory formation.

  6. Sleep deprivation increases formation of false memory.

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    Lo, June C; Chong, Pearlynne L H; Ganesan, Shankari; Leong, Ruth L F; Chee, Michael W L

    2016-12-01

    Retrieving false information can have serious consequences. Sleep is important for memory, but voluntary sleep curtailment is becoming more rampant. Here, the misinformation paradigm was used to investigate false memory formation after 1 night of total sleep deprivation in healthy young adults (N = 58, mean age ± SD = 22.10 ± 1.60 years; 29 males), and 7 nights of partial sleep deprivation (5 h sleep opportunity) in these young adults and healthy adolescents (N = 54, mean age ± SD = 16.67 ± 1.03 years; 25 males). In both age groups, sleep-deprived individuals were more likely than well-rested persons to incorporate misleading post-event information into their responses during memory retrieval (P sleep in optimal cognitive functioning, reveal the vulnerability of adolescents' memory during sleep curtailment, and suggest the need to assess eyewitnesses' sleep history after encountering misleading information. © 2016 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

  7. Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation.

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    Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert; Michaelevski, Izhak

    2016-02-01

    Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein

  8. Sleep-dependent facilitation of episodic memory details.

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    Els van der Helm

    Full Text Available While a role for sleep in declarative memory processing is established, the qualitative nature of this consolidation benefit, and the physiological mechanisms mediating it, remain debated. Here, we investigate the impact of sleep physiology on characteristics of episodic memory using an item- (memory elements and context- (contextual details associated with those elements learning paradigm; the latter being especially dependent on the hippocampus. Following back-to-back encoding of two word lists, each associated with a different context, participants were assigned to either a Nap-group, who obtained a 120-min nap, or a No Nap-group. Six hours post-encoding, participants performed a recognition test involving item-memory and context-memory judgments. In contrast to item-memory, which demonstrated no between-group differences, a significant benefit in context-memory developed in the Nap-group, the extent of which correlated both with the amount of stage-2 NREM sleep and frontal fast sleep-spindles. Furthermore, a difference was observed on the basis of word-list order, with the sleep benefit and associated physiological correlations being selective for the second word-list, learned last (most proximal to sleep. These findings suggest that sleep may preferentially benefit contextual (hippocampal-dependent aspects of memory, supported by sleep-spindle oscillations, and that the temporal order of initial learning differentially determines subsequent offline consolidation.

  9. What Kind of Knowledge Facilitates Memory of Melodies?

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    Oura, Yoko

    Melodic memory appears to be founded on building blocks that are memorized in terms of style-specific ordering rules, melodic prototypes, and memory strategies. Ordering rules concern musical form and construction, while melodic strategies involve sequences of several notes. This paper reports on research studies undertaken to test these concepts…

  10. MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function.

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    Barbosa, Ana C; Kim, Mi-Sung; Ertunc, Mert; Adachi, Megumi; Nelson, Erika D; McAnally, John; Richardson, James A; Kavalali, Ege T; Monteggia, Lisa M; Bassel-Duby, Rhonda; Olson, Eric N

    2008-07-08

    Learning and memory depend on the activity-dependent structural plasticity of synapses and changes in neuronal gene expression. We show that deletion of the MEF2C transcription factor in the CNS of mice impairs hippocampal-dependent learning and memory. Unexpectedly, these behavioral changes were accompanied by a marked increase in the number of excitatory synapses and potentiation of basal and evoked synaptic transmission. Conversely, neuronal expression of a superactivating form of MEF2C results in a reduction of excitatory postsynaptic sites without affecting learning and memory performance. We conclude that MEF2C limits excessive synapse formation during activity-dependent refinement of synaptic connectivity and thus facilitates hippocampal-dependent learning and memory.

  11. Histone Deacetylase Inhibition Facilitates Massed Pattern-Induced Synaptic Plasticity and Memory

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    Pandey, Kiran; Sharma, Kaushik P.; Sharma, Shiv K.

    2015-01-01

    Massed training is less effective for long-term memory formation than the spaced training. The role of acetylation in synaptic plasticity and memory is now well established. However, the role of this important protein modification in synaptic plasticity induced by massed pattern of stimulation or memory induced by massed training is not well…

  12. Differential effects of ongoing EEG beta and theta power on memory formation

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    Scholz, Sebastian; Schneider, Signe Luisa

    2017-01-01

    Recently, elevated ongoing pre-stimulus beta power (13–17 Hz) at encoding has been associated with subsequent memory formation for visual stimulus material. It is unclear whether this activity is merely specific to visual processing or whether it reflects a state facilitating general memory formation, independent of stimulus modality. To answer that question, the present study investigated the relationship between neural pre-stimulus oscillations and verbal memory formation in different sensory modalities. For that purpose, a within-subject design was employed to explore differences between successful and failed memory formation in the visual and auditory modality. Furthermore, associative memory was addressed by presenting the stimuli in combination with background images. Results revealed that similar EEG activity in the low beta frequency range (13–17 Hz) is associated with subsequent memory success, independent of stimulus modality. Elevated power prior to stimulus onset differentiated successful from failed memory formation. In contrast, differential effects between modalities were found in the theta band (3–7 Hz), with an increased oscillatory activity before the onset of later remembered visually presented words. In addition, pre-stimulus theta power dissociated between successful and failed encoding of associated context, independent of the stimulus modality of the item itself. We therefore suggest that increased ongoing low beta activity reflects a memory promoting state, which is likely to be moderated by modality-independent attentional or inhibitory processes, whereas high ongoing theta power is suggested as an indicator of the enhanced binding of incoming interlinked information. PMID:28192459

  13. Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory.

    Science.gov (United States)

    Penke, Zsuzsa; Morice, Elise; Veyrac, Alexandra; Gros, Alexandra; Chagneau, Carine; LeBlanc, Pascale; Samson, Nathalie; Baumgärtel, Karsten; Mansuy, Isabelle M; Davis, Sabrina; Laroche, Serge

    2014-01-05

    It is well established that Zif268/Egr1, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memory; however, it is as yet uncertain whether increasing expression of Zif268 in neurons can facilitate memory formation. Here, we used an inducible transgenic mouse model to specifically induce Zif268 overexpression in forebrain neurons and examined the effect on recognition memory and hippocampal synaptic transmission and plasticity. We found that Zif268 overexpression during the establishment of memory for objects did not change the ability to form a long-term memory of objects, but enhanced the capacity to form a long-term memory of the spatial location of objects. This enhancement was paralleled by increased long-term potentiation in the dentate gyrus of the hippocampus and by increased activity-dependent expression of Zif268 and selected Zif268 target genes. These results provide novel evidence that transcriptional mechanisms engaging Zif268 contribute to determining the strength of newly encoded memories.

  14. Relational memory: a daytime nap facilitates the abstraction of general concepts.

    Directory of Open Access Journals (Sweden)

    Hiuyan Lau

    Full Text Available It is increasingly evident that sleep strengthens memory. However, it is not clear whether sleep promotes relational memory, resultant of the integration of disparate memory traces into memory networks linked by commonalities. The present study investigates the effect of a daytime nap, immediately after learning or after a delay, on a relational memory task that requires abstraction of general concept from separately learned items. Specifically, participants learned English meanings of Chinese characters with overlapping semantic components called radicals. They were later tested on new characters sharing the same radicals and on explicitly stating the general concepts represented by the radicals. Regardless of whether the nap occurred immediately after learning or after a delay, the nap participants performed better on both tasks. The results suggest that sleep--even as brief as a nap--facilitates the reorganization of discrete memory traces into flexible relational memory networks.

  15. The Role of Actin Cytoskeleton in Memory Formation in Amygdala

    Directory of Open Access Journals (Sweden)

    Raphael eLamprecht

    2016-03-01

    Full Text Available The central, lateral and basolateral amygdala nuclei are essential for the formation of long-term memories including emotional and drug-related memories. The study of cellular and molecular mechanisms underpinning memory in amygdala may shed light on the formation of memory and on fear and addiction-related disorders. A challenge is to identify molecules activated by learning that subserve cellular changes needed for memory formation and maintenance in amygdala. Recent studies show that activation of synaptic receptors during fear and drug-related learning leads to alteration in actin cytoskeleton dynamics and structure in amygdala. Such changes in actin cytoskeleton in amygdala are essential for fear and drug-related memories formation. Moreover, the actin cytoskeleton subserves, after learning, changes in neuronal morphogenesis and glutamate receptors trafficking in amygdala. These cellular events are involved in fear and drug-related memories formation. Actin polymerization is also needed for the maintenance of drug-associated memories in amygdala. Thus, the actin cytoskeleton is a key mediator between receptor activation during learning and cellular changes subserving long-term memory in amygdala. The actin cytoskeleton may serve as a target for pharmacological treatment of fear memory associated with fear and anxiety disorders and drug addiction to prevent the debilitating consequences of these diseases.

  16. Rhinal-hippocampal connectivity determines memory formation during sleep.

    NARCIS (Netherlands)

    Fell, J.; Fernandez, G.; Lutz, M.T.; Kockelmann, E.; Burr, W.; Schaller, C.; Elger, C.E.; Helmstaedter, C.

    2006-01-01

    Compared with waking state attention, volition and semantic processing play a minor role during sleep. Thus, investigating declarative memory formation during sleep may allow us to isolate mnemonic core processes. The most feasible approach to memory formation during sleep is the analysis of dream

  17. Noise facilitation in associative memories of exponential capacity.

    Science.gov (United States)

    Karbasi, Amin; Salavati, Amir Hesam; Shokrollahi, Amin; Varshney, Lav R

    2014-11-01

    Recent advances in associative memory design through structured pattern sets and graph-based inference algorithms have allowed reliable learning and recall of an exponential number of patterns that satisfy certain subspace constraints. Although these designs correct external errors in recall, they assume neurons that compute noiselessly, in contrast to the highly variable neurons in brain regions thought to operate associatively, such as hippocampus and olfactory cortex. Here we consider associative memories with boundedly noisy internal computations and analytically characterize performance. As long as the internal noise level is below a specified threshold, the error probability in the recall phase can be made exceedingly small. More surprising, we show that internal noise improves the performance of the recall phase while the pattern retrieval capacity remains intact: the number of stored patterns does not reduce with noise (up to a threshold). Computational experiments lend additional support to our theoretical analysis. This work suggests a functional benefit to noisy neurons in biological neuronal networks.

  18. Connected Classroom Technology Facilitates Multiple Components of Formative Assessment Practice

    Science.gov (United States)

    Shirley, Melissa L.; Irving, Karen E.

    2015-02-01

    Formative assessment has been demonstrated to result in increased student achievement across a variety of educational contexts. When using formative assessment strategies, teachers engage students in instructional tasks that allow the teacher to uncover levels of student understanding so that the teacher may change instruction accordingly. Tools that support the implementation of formative assessment strategies are therefore likely to enhance student achievement. Connected classroom technologies (CCTs) include a family of devices that show promise in facilitating formative assessment. By promoting the use of interactive student tasks and providing both teachers and students with rapid and accurate data on student learning, CCT can provide teachers with necessary evidence for making instructional decisions about subsequent lessons. In this study, the experiences of four middle and high school science teachers in their first year of implementing the TI-Navigator™ system, a specific type of CCT, are used to characterize the ways in which CCT supports the goals of effective formative assessment. We present excerpts of participant interviews to demonstrate the alignment of CCT with several main phases of the formative assessment process. CCT was found to support implementation of a variety of instructional tasks that generate evidence of student learning for the teacher. The rapid aggregation and display of student learning evidence provided teachers with robust data on which to base subsequent instructional decisions.

  19. Neuropeptide S interacts with the basolateral amygdala noradrenergic system in facilitating object recognition memory consolidation.

    Science.gov (United States)

    Han, Ren-Wen; Xu, Hong-Jiao; Zhang, Rui-San; Wang, Pei; Chang, Min; Peng, Ya-Li; Deng, Ke-Yu; Wang, Rui

    2014-01-01

    The noradrenergic activity in the basolateral amygdala (BLA) was reported to be involved in the regulation of object recognition memory. As the BLA expresses high density of receptors for Neuropeptide S (NPS), we investigated whether the BLA is involved in mediating NPS's effects on object recognition memory consolidation and whether such effects require noradrenergic activity. Intracerebroventricular infusion of NPS (1nmol) post training facilitated 24-h memory in a mouse novel object recognition task. The memory-enhancing effect of NPS could be blocked by the β-adrenoceptor antagonist propranolol. Furthermore, post-training intra-BLA infusions of NPS (0.5nmol/side) improved 24-h memory for objects, which was impaired by co-administration of propranolol (0.5μg/side). Taken together, these results indicate that NPS interacts with the BLA noradrenergic system in improving object recognition memory during consolidation.

  20. Muscarinic acetylcholine receptors act in synergy to facilitate learning and memory.

    Science.gov (United States)

    Leaderbrand, Katherine; Chen, Helen J; Corcoran, Kevin A; Guedea, Anita L; Jovasevic, Vladimir; Wess, Jurgen; Radulovic, Jelena

    2016-11-01

    Understanding how episodic memories are formed and retrieved is necessary if we are to treat disorders in which they malfunction. Muscarinic acetylcholine receptors (mAChR) in the hippocampus and cortex underlie memory formation, but there is conflicting evidence regarding their role in memory retrieval. Additionally, there is no consensus on which mAChR subtypes are critical for memory processing. Using pharmacological and genetic approaches, we found that (1) encoding and retrieval of contextual memory requires mAChR in the dorsal hippocampus (DH) and retrosplenial cortex (RSC), (2) memory formation requires hippocampal M3 and cooperative activity of RSC M1 and M3, and (3) memory retrieval is more impaired by inactivation of multiple M1-M4 mAChR in DH or RSC than inactivation of individual receptor subtypes. Contrary to the view that acetylcholine supports learning but is detrimental to memory retrieval, we found that coactivation of multiple mAChR is required for retrieval of both recently and remotely acquired context memories. Manipulations with higher receptor specificity were generally less potent than manipulations targeting multiple receptor subtypes, suggesting that mAChR act in synergy to regulate memory processes. These findings provide unique insight into the development of therapies for amnestic symptoms, suggesting that broadly acting, rather than receptor-specific, mAchR agonists and positive allosteric modulators may be the most effective therapeutic approach. © 2016 Leaderbrand et al.; Published by Cold Spring Harbor Laboratory Press.

  1. Memory formation, amnesia, improved memory and reversed amnesia: 5-HT role.

    Science.gov (United States)

    Perez-Garcia, G; Meneses, A

    2008-12-16

    Traditionally, the search for memory circuits has been focused on examinations of amnesic and AD patients, cerebral lesions and neuroimaging. A complementary alternative has become the use of autoradiography with radioligands, aiming to identify neurobiological markers associated with memory formation, amnesia states and (more recently) recovery from memory deficits. Indeed, ex vivo autoradiographic studies offer the advantage of detecting functionally active receptors altered by pharmacological tools during memory formation, amnesia states and memory recovery. Moreover, serotonin (5-hydroxytryptamine, 5-HT) systems have become a pharmacological and genetic target in the treatment of memory disorders. Herein evidence from studies involving expression of 5-HT(1A), 5-HT(2A), 5-HT(4), and 5-HT(6) receptors in memory formation, amnesia conditions (e.g., pharmacological models or aging) and recovery of memory is reviewed. Thus, specific 5-HT receptors were expressed in trained animals relative to untrained in brain areas such as cortex, hippocampus and amygdala. However, relative to the control group, rats showing amnesia or recovered memory, showed in the hippocampus, region where explicit memory is formed, a complex pattern of 5-HT receptor expression. An intermediate expression occurred in amygdala, septum and some cortical areas in charge of explicit memory storage. Even in brain areas thought to be in charge of procedural memory such as basal ganglia, animals showing recovered memory displayed an intermediate expression, while amnesic groups, depending on the pharmacological amnesia model, showed up- or down-regulation. In conclusion, evidence indicates that autoradiography, by using specific radioligands, offers excellent opportunities to map dynamic changes in brain areas engaged in these cognitive processes. The 5-HT modulatory role strengthens or suppresses memory is critically depend on the timing of the memory formation.

  2. The role of sleep in false memory formation.

    Science.gov (United States)

    Payne, Jessica D; Schacter, Daniel L; Propper, Ruth E; Huang, Li-Wen; Wamsley, Erin J; Tucker, Matthew A; Walker, Matthew P; Stickgold, Robert

    2009-10-01

    Memories are not stored as exact copies of our experiences. As a result, remembering is subject not only to memory failure, but to inaccuracies and distortions as well. Although such distortions are often retained or even enhanced over time, sleep's contribution to the development of false memories is unknown. Here, we report that a night of sleep increases both veridical and false recall in the Deese-Roediger-McDermott (DRM) paradigm, compared to an equivalent period of daytime wakefulness. But while veridical memory deteriorates across both wake and sleep, false memories are preferentially preserved by sleep, actually showing a non-significant improvement. The same selectivity of false over veridical memories was observed in a follow-up nap study. Unlike previous studies implicating deep, slow-wave sleep (SWS) in declarative memory consolidation, here veridical recall correlated with decreased SWS, a finding that was observed in both the overnight and nap studies. These findings lead to two counterintuitive conclusions - that under certain circumstances sleep can promote false memories over veridical ones, and SWS can be associated with impairment rather than facilitation of declarative memory consolidation. While these effects produce memories that are less accurate after sleep, these memories may, in the end, be more useful.

  3. Increasing top-down suppression from prefrontal cortex facilitates tactile working memory.

    Science.gov (United States)

    Hannula, Henri; Neuvonen, Tuomas; Savolainen, Petri; Hiltunen, Jaana; Ma, Yuan-Ye; Antila, Hanne; Salonen, Oili; Carlson, Synnöve; Pertovaara, Antti

    2010-01-01

    Navigated transcranial magnetic stimulation (TMS) combined with diffusion-weighted magnetic resonance imaging (DW-MRI) and tractography allows investigating functional anatomy of the human brain with high precision. Here we demonstrate that working memory (WM) processing of tactile temporal information is facilitated by delivering a single TMS pulse to the middle frontal gyrus (MFG) during memory maintenance. Facilitation was obtained only with a TMS pulse applied to a location of the MFG with anatomical connectivity to the primary somatosensory cortex (S1). TMS improved tactile WM also when distractive tactile stimuli interfered with memory maintenance. Moreover, TMS to the same MFG site attenuated somatosensory evoked responses (SEPs). The results suggest that the TMS-induced memory improvement is explained by increased top-down suppression of interfering sensory processing in S1 via the MFG-S1 link. These results demonstrate an anatomical and functional network that is involved in maintenance of tactile temporal WM.

  4. Hormonal regulation of AMPA receptor trafficking and memory formation

    Directory of Open Access Journals (Sweden)

    Harmen J Krugers

    2009-10-01

    Full Text Available Humans and rodents retain memories for stressful events very well. The facilitated retention of these memories is normally very useful. However, in susceptible individuals a variety of pathological conditions may develop in which memories related to stressful events remain inappropriately present, such as in post-traumatic stress disorder. The memory enhancing effects of stress are mediated by hormones, such as norepinephrine and glucocorticoids which are released during stressful experiences. Here we review recently identified molecular mechanisms that underlie the effects of stress hormones on synaptic efficacy and learning and memory. We discuss AMPA receptors as major target for stress hormones and describe a model in which norepinephrine and glucocorticoids are able to strengthen and prolong different phases of stressful memories.

  5. Dose-response investigation into glucose facilitation of memory performance and mood in healthy young adults.

    Science.gov (United States)

    Sünram-Lea, Sandra I; Owen, Lauren; Finnegan, Yvonne; Hu, Henglong

    2011-08-01

    It has been suggested that the memory enhancing effect of glucose follows an inverted U-shaped curve, with 25 g resulting in optimal facilitation in healthy young adults. The aim of this study was to further investigate the dose dependency of the glucose facilitation effect in this population across different memory domains and to assess moderation by interindividual differences in glucose regulation and weight. Following a double-blind, repeated measures design, 30 participants were administered drinks containing five different doses of glucose (0 g, 15 g, 25 g, 50 g, and 60 g) and were tested across a range of memory tasks. Glycaemic response and changes in mood state were assessed following drink administration. Analysis of the data showed that glucose administration did not affect mood, but significant glucose facilitation of several memory tasks was observed. However, dose-response curves differed depending on the memory task with only performance on the long-term memory tasks adhering largely to the previously observed inverted U-shaped dose-response curve. Moderation of the response profiles by interindividual differences in glucose regulation and weight was observed. The current data suggest that dose-response function and optimal dose might depend on cognitive domain and are moderated by interindividual differences in glucose regulation and weight.

  6. Dynamin 1 is required for memory formation.

    Directory of Open Access Journals (Sweden)

    Mauro Fà

    Full Text Available Dynamin 1-3 isoforms are known to be involved in endocytotic processes occurring during synaptic transmission. No data has directly linked dynamins yet with normal animal behavior. Here we show that dynamin pharmacologic inhibition markedly impairs hippocampal-dependent associative memory. Memory loss was associated with changes in synaptic function occurring during repetitive stimulation that is thought to be linked with memory induction. Synaptic fatigue was accentuated by dynamin inhibition. Moreover, dynamin inhibition markedly reduced long-term potentiation, post-tetanic potentiation, and neurotransmitter released during repetitive stimulation. Most importantly, the effect of dynamin inhibition onto memory and synaptic plasticity was due to a specific involvement of the dynamin 1 isoform, as demonstrated through a genetic approach with siRNA against this isoform to temporally block it. Taken together, these findings identify dynamin 1 as a key protein for modulation of memory and release evoked by repetitive activity.

  7. Stressed memories: How acute stress affects memory formation in humans

    NARCIS (Netherlands)

    Henckens, M.J.A.G.; Hermans, E.J.; Pu, Z.; Joels, M.; Fernandez, G.S.E.

    2009-01-01

    Stressful, aversive events are extremely well remembered. Such a declarative memory enhancement is evidently beneficial for survival, but the same mechanism may become maladaptive and culminate in mental diseases such as posttraumatic stress disorder (PTSD). Stress hormones are known to enhance

  8. Human declarative memory formation: segregating rhinal and hippocampal contributions.

    NARCIS (Netherlands)

    Fernandez, G.S.E.; Klaver, P.; Fell, J.; Grunwald, T.; Elger, C.E.

    2002-01-01

    The medial temporal lobe (MTL) is the core structure of the declarative memory system, but which specific operation is performed by anatomically defined MTL substructures? One hypothesis proposes that the hippocampus carries out an exclusively mnemonic operation during declarative memory formation

  9. Fear memory formation can affect a different memory: fear conditioning affects the extinction, but not retrieval, of conditioned taste aversion (CTA) memory

    OpenAIRE

    2014-01-01

    The formation of fear memory to a specific stimulus leads to subsequent fearful response to that stimulus. However, it is not apparent whether the formation of fear memory can affect other memories. We study whether specific fearful experience leading to fear memory affects different memories formation and extinction. We revealed that cued fear conditioning, but not unpaired or naïve training, inhibited the extinction of conditioned taste aversion (CTA) memory that was formed after fear condi...

  10. Fear memory formation can affect a different memory: fear conditioning affects the extinction, but not retrieval, of conditioned taste aversion (CTA) memory

    OpenAIRE

    2014-01-01

    The formation of fear memory to a specific stimulus leads to subsequent fearful response to that stimulus. However, it is not known whether the formation of fear memory can affect other memories. We study whether specific fearful experience leading to fear memory affects different memories formation and extinction. We revealed that cued fear conditioning, but not unpaired or naïve training, inhibited the extinction of CTA memory that was formed after fear conditioning training in rats. Fear ...

  11. Neural activity supporting the formation of associative memory versus source memory.

    Science.gov (United States)

    Park, Heekyeong; Shannon, Vale; Biggan, John; Spann, Catherine

    2012-08-30

    The ability to form a new association with discontiguous elements constitutes the very crux of episodic memory. However, it is not fully understood whether different types of associations rely on common neural correlates for encoding associations. In the present study, we investigated whether the formation of associative memory (associations between items) and source memory (associations between an item and its context) recruits common neural activity during encoding, or whether each type of association requires different neural activity for subsequent memory. During study, participants were visually presented a list of object pairs in the scanner while the names of objects were simultaneously presented either in a male or female voice. Participants completed a post-scan recognition test for associative and source memories for object pairs and their contexts. Associative memory was predicted in the left inferior prefrontal cortex, the fusiform gyrus and the medial temporal lobe including both perirhinal and parahippocampal cortices and the posterior hippocampus. Encoding activity for source memory was identified in the right insula and the right anterior hippocampus. Further, neural activity in the right posterior hippocampus was recruited for successful formation of both associative and source memories. Collectively, these findings highlight the pivotal role of the hippocampus in successful encoding of associative and source memories and add more weight to the role of the perirhinal cortex in associative encoding of objects. The present findings have implications for roles of the medial temporal lobe sub-regions for successful formation of associative and source memories.

  12. Endogenous cortisol elevations are related to memory facilitation only in individuals who are emotionally aroused.

    Science.gov (United States)

    Abercrombie, Heather C; Speck, Nicole S; Monticelli, Roxanne M

    2006-02-01

    Animal research suggests that cortisol facilitates memory only during emotional arousal. Thus, we predicted that during mild emotion and stress elicitation, endogenous cortisol elevations would predict memory facilitation only in individuals who report high stress-related negative affect. Thirty-one men viewed neutral and emotional stimuli and then were subjected to a public speaking stress task. Area under the curve for overall cortisol output during the speech was computed. Negative affect (NA) using the PANAS state version [Watson, D., Clark, L.A., Tellegen, A., 1988. Development and validation of brief measures of positive and negative affect: the PANAS scales. J. Personality Social Psychol. 54, 1063-1070.] was measured at baseline and immediately after the speech stressor. Cortisol output during the speech and change in NA interactively predicted free recall performance assessed 2 days later. This interaction was due to the finding that higher cortisol output was related to memory facilitation only in subjects who reported high stress-related negative affect (i.e. only in those individuals whose NA increased compared to baseline). This relation was especially prominent for recall of unpleasant pictures. Subjects who reported low stress-related negative affect, no relation was found between cortisol output during the speech and memory performance. Thus, the relation between cortisol and memory appears to depend on an increase in negative affect related to stress.

  13. Memory for Lectures: How Lecture Format Impacts the Learning Experience.

    Directory of Open Access Journals (Sweden)

    Trish L Varao-Sousa

    Full Text Available The present study investigated what impact the presentation style of a classroom lecture has on memory, mind wandering, and the subjective factors of interest and motivation. We examined if having a professor lecturing live versus on video alters the learning experience of the students in the classroom. During the lectures, students were asked to report mind wandering and later complete a memory test. The lecture format was manipulated such that all the students received two lectures, one live and one a pre-recorded video. Results indicate that lecture format affected memory performance but not mind wandering, with enhanced memory in the live lectures. Additionally, students reported greater interest and motivation in the live lectures. Given that a single change to the classroom environment, professor presence, impacted memory performance, as well as motivation and interest, the present results have several key implications for technology-based integrations into higher education classrooms.

  14. Memory for Lectures: How Lecture Format Impacts the Learning Experience.

    Science.gov (United States)

    Varao-Sousa, Trish L; Kingstone, Alan

    2015-01-01

    The present study investigated what impact the presentation style of a classroom lecture has on memory, mind wandering, and the subjective factors of interest and motivation. We examined if having a professor lecturing live versus on video alters the learning experience of the students in the classroom. During the lectures, students were asked to report mind wandering and later complete a memory test. The lecture format was manipulated such that all the students received two lectures, one live and one a pre-recorded video. Results indicate that lecture format affected memory performance but not mind wandering, with enhanced memory in the live lectures. Additionally, students reported greater interest and motivation in the live lectures. Given that a single change to the classroom environment, professor presence, impacted memory performance, as well as motivation and interest, the present results have several key implications for technology-based integrations into higher education classrooms.

  15. Chunk formation in immediate memory and how it relates to data compression.

    Science.gov (United States)

    Chekaf, Mustapha; Cowan, Nelson; Mathy, Fabien

    2016-10-01

    This paper attempts to evaluate the capacity of immediate memory to cope with new situations in relation to the compressibility of information likely to allow the formation of chunks. We constructed a task in which untrained participants had to immediately recall sequences of stimuli with possible associations between them. Compressibility of information was used to measure the chunkability of each sequence on a single trial. Compressibility refers to the recoding of information in a more compact representation. Although compressibility has almost exclusively been used to study long-term memory, our theory suggests that a compression process relying on redundancies within the structure of the list materials can occur very rapidly in immediate memory. The results indicated a span of about three items when the list had no structure, but increased linearly as structure was added. The amount of information retained in immediate memory was maximal for the most compressible sequences, particularly when information was ordered in a way that facilitated the compression process. We discuss the role of immediate memory in the rapid formation of chunks made up of new associations that did not already exist in long-term memory, and we conclude that immediate memory is the starting place for the reorganization of information. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Stable panoramic views facilitate snap-shot like memories for spatial reorientation in homing pigeons.

    Directory of Open Access Journals (Sweden)

    Tommaso Pecchia

    Full Text Available Following spatial disorientation, animals can reorient themselves by relying on geometric cues (metric and sense specified both by the macroscopic surface layout of an enclosed space and prominent visual landmarks in arrays. Whether spatial reorientation in arrays of landmarks is based on explicit representation of the geometric cues is a matter of debate. Here we trained homing pigeons (Columba livia to locate a food-reward in a rectangular array of four identical or differently coloured pipes provided with four openings, only one of which allowed the birds to have access to the reward. Pigeons were trained either with a stable or a variable position of the opening on pipes, so that they could view the array either from the same or a variable perspective. Explicit mapping of configural geometry would predict successful reorientation irrespective of access condition. In contrast, we found that a stable view of the array facilitated spatial learning in homing pigeons, likely through the formation of snapshot-like memories.

  17. Working memory binding and episodic memory formation in aging, mild cognitive impairment, and Alzheimer's dementia

    NARCIS (Netherlands)

    Geldorp, B. van; Heringa, S.M.; Berg, E. van den; Olde Rikkert, M.G.M.; Biessels, G.J.; Kessels, R.P.

    2015-01-01

    INTRODUCTION: Recent studies indicate that in both normal and pathological aging working memory (WM) performance deteriorates, especially when associations have to be maintained. However, most studies typically do not assess the relationship between WM and episodic memory formation. In the present

  18. Protein synthesis inhibition in the basolateral nucleus of amygdala facilitates extinction of auditory fear memory

    Institute of Scientific and Technical Information of China (English)

    JIN XinChun; QI XueLian; YANG XiaoFei; LI BaoMing

    2007-01-01

    It is known that consolidation of fear conditioning requires de novo protein synthesis in the amygdala. However, there is controversy about the role of protein synthesis in post-retrieval extinction of fear memory. The present study investigated the effect of protein synthesis inhibition (PSI) in the basolateral nucleus of amygdala (BLA) on post-retrieval extinction of auditory fear memory. Intra-BLA infusion of the protein synthesis inhibitor anisomycin '0' h post-retrieval facilitated the extinction, but was ineffective if the memory was not retrieved. Anisomycin had no effect on the extinction when it was infused 6 h post-retrieval. The present results suggest that there exists a protein-synthesis-dependent mechanism in the BLA that retards extinction of auditory fear memory.

  19. Covalent Modification of DNA Regulates Memory Formation

    National Research Council Canada - National Science Library

    Miller, Courtney A; Sweatt, J. David

    2007-01-01

    ... during mitosis. The mechanisms that accomplish this are a set of posttranslational modifications of DNA and chromatin that alter gene expression patterns. Rapidly accumulating evidence suggests that the nervous system has co-opted these epigenetic mechanisms utilized during development for the generation of long-term behavioral memories in adulthood ( S...

  20. Functional Neuroanatomy of "Drosophila" Olfactory Memory Formation

    Science.gov (United States)

    Guven-Ozkan, Tugba; Davis, Ronald L.

    2014-01-01

    New approaches, techniques and tools invented over the last decade and a half have revolutionized the functional dissection of neural circuitry underlying "Drosophila" learning. The new methodologies have been used aggressively by researchers attempting to answer three critical questions about olfactory memories formed with appetitive…

  1. CLIP-170 facilitates the formation of kinetochore-microtubule attachments.

    Science.gov (United States)

    Tanenbaum, Marvin E; Galjart, Niels; van Vugt, Marcel A T M; Medema, René H

    2006-01-11

    CLIP-170 is a microtubule 'plus end tracking' protein involved in several microtubule-dependent processes in interphase. At the onset of mitosis, CLIP-170 localizes to kinetochores, but at metaphase, it is no longer detectable at kinetochores. Although RNA interference (RNAi) experiments have suggested an essential role for CLIP-170 during mitosis, the molecular function of CLIP-170 in mitosis has not yet been revealed. Here, we used a combination of high-resolution microscopy and RNAi-mediated depletion to study the function of CLIP-170 in mitosis. We found that CLIP-170 dynamically localizes to the outer most part of unattached kinetochores and to the ends of growing microtubules. In addition, we provide evidence that a pool of CLIP-170 is transported along kinetochore-microtubules by the dynein/dynactin complex. Interference with CLIP-170 expression results in defective chromosome congression and diminished kinetochore-microtubule attachments, but does not detectibly affect microtubule dynamics or kinetochore-microtubule stability. Taken together, our results indicate that CLIP-170 facilitates the formation of kinetochore-microtubule attachments, possibly through direct capture of microtubules at the kinetochore.

  2. BAF53b, a Neuron-Specific Nucleosome Remodeling Factor, Is Induced after Learning and Facilitates Long-Term Memory Consolidation.

    Science.gov (United States)

    Yoo, Miran; Choi, Kwang-Yeon; Kim, Jieun; Kim, Mujun; Shim, Jaehoon; Choi, Jun-Hyeok; Cho, Hye-Yeon; Oh, Jung-Pyo; Kim, Hyung-Su; Kaang, Bong-Kiun; Han, Jin-Hee

    2017-03-29

    Although epigenetic mechanisms of gene expression regulation have recently been implicated in memory consolidation and persistence, the role of nucleosome-remodeling is largely unexplored. Recent studies show that the functional loss of BAF53b, a postmitotic neuron-specific subunit of the BAF nucleosome-remodeling complex, results in the deficit of consolidation of hippocampus-dependent memory and cocaine-associated memory in the rodent brain. However, it is unclear whether BAF53b expression is regulated during memory formation and how BAF53b regulates fear memory in the amygdala, a key brain site for fear memory encoding and storage. To address these questions, we used viral vector approaches to either decrease or increase BAF53b function specifically in the lateral amygdala of adult mice in auditory fear conditioning paradigm. Knockdown of Baf53b before training disrupted long-term memory formation with no effect on short-term memory, basal synaptic transmission, and spine structures. We observed in our qPCR analysis that BAF53b was induced in the lateral amygdala neurons at the late consolidation phase after fear conditioning. Moreover, transient BAF53b overexpression led to persistently enhanced memory formation, which was accompanied by increase in thin-type spine density. Together, our results provide the evidence that BAF53b is induced after learning, and show that such increase of BAF53b level facilitates memory consolidation likely by regulating learning-related spine structural plasticity.SIGNIFICANCE STATEMENT Recent works in the rodent brain begin to link nucleosome remodeling-dependent epigenetic mechanism to memory consolidation. Here we show that BAF53b, an epigenetic factor involved in nucleosome remodeling, is induced in the lateral amygdala neurons at the late phase of consolidation after fear conditioning. Using specific gene knockdown or overexpression approaches, we identify the critical role of BAF53b in the lateral amygdala neurons for memory

  3. Rapid formation and flexible expressionof memories of subliminal word pairs

    Directory of Open Access Journals (Sweden)

    Thomas Peter Reber

    2011-11-01

    Full Text Available Our daily experiences are incidentally and rapidly encoded as episodic memories. Episodic memories consist of numerous associations (e.g., who gave what to whom where and when that can be expressed flexibly in new situations. Key features of episodic memory are speed of encoding, its associative nature, and its representational flexibility. Another defining feature of human episodic memory has been consciousness of encoding/retrieval. Here, we show that humans can rapidly form associations between subliminal words and minutes later retrieve these associations even if retrieval words were conceptually related to, but different from encoding words. Because encoding words were presented subliminally, associative encoding and retrieval were unconscious. Unconscious association formation and retrieval were dependent on a preceding understanding of task principles. We conclude that key computations underlying episodic memory – rapid encoding and flexible expression of associations - can operate outside consciousness.

  4. Gnosall Primary Care Memory Clinic: Eldercare facilitator role description and development.

    Science.gov (United States)

    Greaves, Ian; Greaves, Nicola; Walker, Elaine; Greening, Lesley; Benbow, Susan Mary; Jolley, David

    2015-07-01

    The Gnosall Primary Care Memory Clinic has been operating since 2006 and adds the skills of a specialist old age psychiatrist to the extensive skills and knowledge available in primary care. Key to the organisation and function of the clinic is the eldercare facilitator, a new role situated in primary care and linking with the specialist and a wide range of other agencies and people. In order to facilitate replication of the model elsewhere, the function, role and competencies of existing and previous eldercare facilitators in the clinic have been reviewed, clarified and related to a competency framework and to similar initiatives in the literature. The selection and training of people with the attributes and skills required to become an eldercare facilitator will determine whether extension of the model is successful elsewhere.

  5. Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation.

    Science.gov (United States)

    Johansen, Joshua P; Diaz-Mataix, Lorenzo; Hamanaka, Hiroki; Ozawa, Takaaki; Ycu, Edgar; Koivumaa, Jenny; Kumar, Ashwani; Hou, Mian; Deisseroth, Karl; Boyden, Edward S; LeDoux, Joseph E

    2014-12-23

    A long-standing hypothesis termed "Hebbian plasticity" suggests that memories are formed through strengthening of synaptic connections between neurons with correlated activity. In contrast, other theories propose that coactivation of Hebbian and neuromodulatory processes produce the synaptic strengthening that underlies memory formation. Using optogenetics we directly tested whether Hebbian plasticity alone is both necessary and sufficient to produce physiological changes mediating actual memory formation in behaving animals. Our previous work with this method suggested that Hebbian mechanisms are sufficient to produce aversive associative learning under artificial conditions involving strong, iterative training. Here we systematically tested whether Hebbian mechanisms are necessary and sufficient to produce associative learning under more moderate training conditions that are similar to those that occur in daily life. We measured neural plasticity in the lateral amygdala, a brain region important for associative memory storage about danger. Our findings provide evidence that Hebbian mechanisms are necessary to produce neural plasticity in the lateral amygdala and behavioral memory formation. However, under these conditions Hebbian mechanisms alone were not sufficient to produce these physiological and behavioral effects unless neuromodulatory systems were coactivated. These results provide insight into how aversive experiences trigger memories and suggest that combined Hebbian and neuromodulatory processes interact to engage associative aversive learning.

  6. Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation

    Science.gov (United States)

    Johansen, Joshua P.; Diaz-Mataix, Lorenzo; Hamanaka, Hiroki; Ozawa, Takaaki; Ycu, Edgar; Koivumaa, Jenny; Kumar, Ashwani; Hou, Mian; Deisseroth, Karl; Boyden, Edward S.; LeDoux, Joseph E.

    2014-01-01

    A long-standing hypothesis termed “Hebbian plasticity” suggests that memories are formed through strengthening of synaptic connections between neurons with correlated activity. In contrast, other theories propose that coactivation of Hebbian and neuromodulatory processes produce the synaptic strengthening that underlies memory formation. Using optogenetics we directly tested whether Hebbian plasticity alone is both necessary and sufficient to produce physiological changes mediating actual memory formation in behaving animals. Our previous work with this method suggested that Hebbian mechanisms are sufficient to produce aversive associative learning under artificial conditions involving strong, iterative training. Here we systematically tested whether Hebbian mechanisms are necessary and sufficient to produce associative learning under more moderate training conditions that are similar to those that occur in daily life. We measured neural plasticity in the lateral amygdala, a brain region important for associative memory storage about danger. Our findings provide evidence that Hebbian mechanisms are necessary to produce neural plasticity in the lateral amygdala and behavioral memory formation. However, under these conditions Hebbian mechanisms alone were not sufficient to produce these physiological and behavioral effects unless neuromodulatory systems were coactivated. These results provide insight into how aversive experiences trigger memories and suggest that combined Hebbian and neuromodulatory processes interact to engage associative aversive learning. PMID:25489081

  7. Stress facilitates consolidation of verbal memory for a film but does not affect retrieval.

    Science.gov (United States)

    Beckner, Victoria E; Tucker, David M; Delville, Yvon; Mohr, David C

    2006-06-01

    The effect of psychosocial stress on distinct memory processes was investigated in 157 college students using a brief film, which enabled comparison of verbal and visual memory by using a single complex stimulus. Participants were stressed either following stimuli presentation (consolidation) or before testing 48 hr later (retrieval) and were compared with no-stress controls. Salivary cortisol was measured before and 20 min after stress. The consolidation group significantly outperformed controls on total and verbal film scores. Stress did not impair retrieval relative to controls. Exploratory analyses revealed a significant correlation between cortisol and verbal scores across all groups (r = .18). Results provide the first evidence of a facilitative effect of a stressor on verbal memory, but failed to replicate retrieval findings.

  8. 8-OH-DPAT facilitated memory consolidation and increased hippocampal and cortical cAMP production.

    Science.gov (United States)

    Manuel-Apolinar, L; Meneses, A

    2004-01-05

    Animals were submitted to an associative learning task named Pavlovian/instrumental autoshaping (P/I-A) and treated with selective 5-HT1A and 5-HT7 receptor agonists and antagonists. Next, they were sacrificed, their brains removed, dissected and changes on cortical and hippocampal cyclic adenosine monophosphate (cAMP) production were determined. Results revealed that, the 8-OH-DPAT treatment facilitated memory consolidation of autoshaping and that effect was blocked completely by WAY100635 and partially by DR4004. WAY100635 or DR4004 alone had no effect on autoshaping. The cAMP results were complex and yielded no clear relationship to the memory results. Thus, cortical and hippocampal increased on cAMP production was observed following administration of the 5-HT(1A/7) agonist 8-OH-DPAT. The memory effect was, completely or partially, reversed by the selective antagonists WAY100635 (5-HT1A) or DR4004 (5-HT7), respectively.

  9. Intracerebroventricular histamine, but not 48/80, causes posttraining memory facilitation in the rat.

    Science.gov (United States)

    de Almeida, M A; Izquierdo, I

    1988-01-01

    The immediate posttraining intracerebroventricular injection of histamine (1 or 10 ng/rat) facilitated memory both of a stepdown inhibitory avoidance task, and of the habituation of rearing responses to an open field. As previously shown for the avoidance task, the combination of cimetidine (1,000 ng/rat) plus prometazine (1,000 ng/rat), but not each drug on its own, blocked the effect of histamine in the habituation task. The effect of histamine was not shared by the intracerebroventricular administration of the mast cell histamine releaser, 48/80 (0.1 to 100 micrograms/rat). The present findings indicate that the memory facilitatory action of histamine might be general across tasks, and that 48/80-releasable, presumably mast cell, endogenous histamine is probably not involved in memory regulation.

  10. HDAC7 Ubiquitination by the E3 Ligase CBX4 Is Involved in Contextual Fear Conditioning Memory Formation.

    Science.gov (United States)

    Jing, Xu; Sui, Wen-Hai; Wang, Shuai; Xu, Xu-Feng; Yuan, Rong-Rong; Chen, Xiao-Rong; Ma, Hui-Xian; Zhu, Ying-Xiao; Sun, Jin-Kai; Yi, Fan; Chen, Zhe-Yu; Wang, Yue

    2017-04-05

    Histone acetylation, an epigenetic modification, plays an important role in long-term memory formation. Recently, histone deacetylase (HDAC) inhibitors were demonstrated to promote memory formation, which raises the intriguing possibility that they may be used to rescue memory deficits. However, additional research is necessary to clarify the roles of individual HDACs in memory. In this study, we demonstrated that HDAC7, within the dorsal hippocampus of C57BL6J mice, had a late and persistent decrease after contextual fear conditioning (CFC) training (4-24 h), which was involved in long-term CFC memory formation. We also showed that HDAC7 decreased via ubiquitin-dependent degradation. CBX4 was one of the HDAC7 E3 ligases involved in this process. Nur77, as one of the target genes of HDAC7, increased 6-24 h after CFC training and, accordingly, modulated the formation of CFC memory. Finally, HDAC7 was involved in the formation of other hippocampal-dependent memories, including the Morris water maze and object location test. The current findings facilitate an understanding of the molecular and cellular mechanisms of HDAC7 in the regulation of hippocampal-dependent memory.SIGNIFICANCE STATEMENT The current findings demonstrated the effects of histone deacetylase 7 (HDAC7) on hippocampal-dependent memories. Moreover, we determined the mechanism of decreased HDAC7 in contextual fear conditioning (CFC) through ubiquitin-dependent protein degradation. We also verified that CBX4 was one of the HDAC7 E3 ligases. Finally, we demonstrated that Nur77, as one of the important targets for HDAC7, was involved in CFC memory formation. All of these proteins, including HDAC7, CBX4, and Nur77, could be potential therapeutic targets for preventing memory deficits in aging and neurological diseases. Copyright © 2017 the authors 0270-6474/17/373848-16$15.00/0.

  11. The Formation and Extinction of Fear Memory in Tree Shrews

    Directory of Open Access Journals (Sweden)

    Shujiang eShang

    2015-07-01

    Full Text Available Fear is an emotion that is well studied due to its importance for animal survival. Experimental animals, such as rats and mice, have been widely used to model fear. However, higher animals such as nonhuman primates have rarely been used to study fear due to ethical issues and high costs. Tree shrews are small mammals that are closely related to primates; they have been used to model human-related psychosocial conditions such as stress and alcohol tolerance. Here, we describe an experimental paradigm to study the formation and extinction of fear memory in tree shrews. We designed an experimental apparatus of a light/dark box with a voltage foot shock. We found that tree shrews preferred staying in the dark box in the daytime without stimulation and showed avoidance to voltage shocks applied to the footplate in a voltage-dependent manner. Foot shocks applied to the dark box for 5 days (10 minutes per day effectively reversed the light–dark preference of the tree shrews, and this memory lasted for more than 50 days without any sign of memory decay (extinction in the absence of further stimulation. However, this fear memory was reversed with 4 days of reverse training by applying the same stimulus to the light box. When reducing the stimulus intensity during the training period, a memory extinction and subsequently reinstatement effects were observed. Thus, our results describe an efficient method of monitoring fear memory formation and extinction in tree shrews.

  12. The formation and extinction of fear memory in tree shrews.

    Science.gov (United States)

    Shang, Shujiang; Wang, Cong; Guo, Chengbing; Huang, Xu; Wang, Liecheng; Zhang, Chen

    2015-01-01

    Fear is an emotion that is well-studied due to its importance for animal survival. Experimental animals, such as rats and mice, have been widely used to model fear. However, higher animals such as nonhuman primates have rarely been used to study fear due to ethical issues and high costs. Tree shrews are small mammals that are closely related to primates; they have been used to model human-related psychosocial conditions such as stress and alcohol tolerance. Here, we describe an experimental paradigm to study the formation and extinction of fear memory in tree shrews. We designed an experimental apparatus of a light/dark box with a voltage foot shock. We found that tree shrews preferred staying in the dark box in the daytime without stimulation and showed avoidance to voltage shocks applied to the footplate in a voltage-dependent manner. Foot shocks applied to the dark box for 5 days (10 min per day) effectively reversed the light-dark preference of the tree shrews, and this memory lasted for more than 50 days without any sign of memory decay (extinction) in the absence of further stimulation. However, this fear memory was reversed with 4 days of reverse training by applying the same stimulus to the light box. When reducing the stimulus intensity during the training period, a memory extinction and subsequently reinstatement effects were observed. Thus, our results describe an efficient method of monitoring fear memory formation and extinction in tree shrews.

  13. Mental representations of attachment figures facilitate recovery following upsetting autobiographical memory recall.

    Science.gov (United States)

    Selcuk, Emre; Zayas, Vivian; Günaydin, Gül; Hazan, Cindy; Kross, Ethan

    2012-08-01

    A growing literature shows that even the symbolic presence of an attachment figure facilitates the regulation of negative affect triggered by external stressors. Yet, in daily life, pernicious stressors are often internally generated--recalling an upsetting experience reliably increases negative affect, rumination, and susceptibility to physical and psychological health problems. The present research provides the first systematic examination of whether activating the mental representation of an attachment figure enhances the regulation of affect triggered by thinking about upsetting memories. Using 2 different techniques for priming attachment figure representations and 2 types of negative affect measures (explicit and implicit), activating the mental representation of an attachment figure (vs. an acquaintance or stranger) after recalling an upsetting memory enhanced recovery--eliminating the negative effects of the memory recall (Studies 1-3). In contrast, activating the mental representation of an attachment figure before recalling an upsetting memory had no such effect (Studies 1 and 2). Furthermore, activating the mental representation of an attachment figure after thinking about upsetting memories reduced negative thinking in a stream of consciousness task, and the magnitude of the attachment-induced affective recovery effects as assessed with explicit affect measures predicted mental and physical health in daily life (Study 3). Finally, a meta-analysis of the 3 studies (Study 4) showed that the regulatory benefits conferred by the mental representation of an attachment figure were weaker for individuals high on attachment avoidance. The implications of these findings for attachment, emotion regulation, and mental and physical health are discussed.

  14. Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation

    Directory of Open Access Journals (Sweden)

    Yan-Chu Chen

    2017-07-01

    Full Text Available Galectin-3, a member of the galectin protein family, has been found to regulate cell proliferation, inhibit apoptosis and promote inflammatory responses. Galectin-3 is also expressed in the adult rat hippocampus, but its role in learning and memory function is not known. Here, we found that contextual fear-conditioning training, spatial training or injection of NMDA into the rat CA1 area each dramatically decreased the level of endogenous galectin-3 expression. Overexpression of galectin-3 impaired fear memory, whereas galectin-3 knockout (KO enhanced fear retention, spatial memory and hippocampal long-term potentiation. Galectin-3 was further found to associate with integrin α3, an association that was decreased after fear-conditioning training. Transfection of the rat CA1 area with small interfering RNA against galectin-3 facilitated fear memory and increased phosphorylated focal adhesion kinase (FAK levels, effects that were blocked by co-transfection of the FAK phosphorylation-defective mutant Flag-FAKY397F. Notably, levels of serine-phosphorylated galectin-3 were decreased by fear conditioning training. In addition, blockade of galectin-3 phosphorylation at Ser-6 facilitated fear memory, whereas constitutive activation of galectin-3 at Ser-6 impaired fear memory. Interestingly galectin-1 plays a role in fear-memory formation similar to that of galectin-3. Collectively, our data provide the first demonstration that galectin-3 is a novel negative regulator of memory formation that exerts its effects through both extracellular and intracellular mechanisms.

  15. Wnt Signaling Is Required for Long-Term Memory Formation

    Directory of Open Access Journals (Sweden)

    Ying Tan

    2013-09-01

    Full Text Available Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNAi approach. Interfering with β-catenin expression in adult mushroom body neurons specifically impaired long-term memory (LTM without altering short-term memory. The impairment was reversible, being rescued by expression of a wild-type β-catenin transgene, and correlated with disruption of a cellular LTM trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt coreceptor, also impaired LTM. Wingless expression in wild-type flies was transiently elevated in the brain after LTM conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in adult mushroom bodies impairs LTM, indicating that this pathway mechanistically underlies this specific form of memory.

  16. The effect of Twitter exposure on false memory formation.

    Science.gov (United States)

    Fenn, Kimberly M; Griffin, Nicholas R; Uitvlugt, Mitchell G; Ravizza, Susan M

    2014-12-01

    Social media sites such as Facebook and Twitter have increased drastically in popularity. However, information on these sites is not verified and may contain inaccuracies. It is well-established that false information encountered after an event can lead to memory distortion. Therefore, social media may be particularly harmful for autobiographical memory. Here, we tested the effect of Twitter on false memory. We presented participants with a series of images that depicted a story and then presented false information about the images in a scrolling feed that bore either a low or high resemblance to a Twitter feed. Confidence for correct information was similar across the groups, but confidence for suggested information was significantly lower when false information was presented in a Twitter format. We propose that individuals take into account the medium of the message when integrating information into memory.

  17. Memory formation and memory alterations: 5-HT6 and 5-HT7 receptors, novel alternative.

    Science.gov (United States)

    Meneses, Alfredo

    2014-01-01

    Agonists and antagonists of the 5-hydroxytryptamine (serotonin) receptor6 (5-HT6) or receptor7 (5-HT7) might improve memory and/or reverse amnesia, although the mechanisms involved are poorly understood. Hence, the current work summarizes recent reviews and findings involving these receptors. Evidence indicates that diverse 5-HT6 receptor antagonists produce promnesic and/or antiamnesic effect in conditions, such as memory formation, age-related cognitive impairments and memory deficit in preclinical studies, as well as in diseases such as schizophrenia, Parkinson's, and Alzheimer's disease (AD). Memory, aging, and AD modify 5-HT6 receptors and signaling cascades; likewise, the modulation of 5-HT6 drugs on memory seems to be accompanied with neural changes. Moreover, 5-HT7 receptors are localized in brain areas mediating memory, including the cortex, hippocampus (e.g., Zola-Morgan and Squire, 1993) and raphe nuclei; however, the role of these receptors on memory has yet to be fully explored. Hence, findings and reviews are summarized in this work. Evidence suggests that both 5-HT7 receptor agonists and antagonists might have promnesic and anti-amnesic effects. These effects seem to be dependent on the basal level of performance, i.e., normal or impaired. Available evidence suggests that a potential utility of 5-HT6 and 5-HT7 receptor in mild-to-moderate AD patients and other memory dysfunctions as therapeutic targets.

  18. Multiple repressive mechanisms in the hippocampus during memory formation.

    Science.gov (United States)

    Cho, Jun; Yu, Nam-Kyung; Choi, Jun-Hyeok; Sim, Su-Eon; Kang, SukJae Joshua; Kwak, Chuljung; Lee, Seung-Woo; Kim, Ji-il; Choi, Dong Il; Kim, V Narry; Kaang, Bong-Kiun

    2015-10-02

    Memory stabilization after learning requires translational and transcriptional regulations in the brain, yet the temporal molecular changes that occur after learning have not been explored at the genomic scale. We used ribosome profiling and RNA sequencing to quantify the translational status and transcript levels in the mouse hippocampus after contextual fear conditioning. We revealed three types of repressive regulations: translational suppression of ribosomal protein-coding genes in the hippocampus, learning-induced early translational repression of specific genes, and late persistent suppression of a subset of genes via inhibition of estrogen receptor 1 (ESR1/ERα) signaling. In behavioral analyses, overexpressing Nrsn1, one of the newly identified genes undergoing rapid translational repression, or activating ESR1 in the hippocampus impaired memory formation. Collectively, this study unveils the yet-unappreciated importance of gene repression mechanisms for memory formation. Copyright © 2015, American Association for the Advancement of Science.

  19. How mood challenges emotional memory formation: an fMRI investigation.

    Science.gov (United States)

    Fitzgerald, Daniel A; Arnold, Jennifer F; Becker, Eni S; Speckens, Anne E M; Rinck, Mike; Rijpkema, Mark; Fernández, Guillén; Tendolkar, Indira

    2011-06-01

    Experimental mood manipulations and functional magnetic resonance imaging (fMRI) provide a unique opportunity for examining the neural correlates of mood-congruent memory formation. While prior studies in mood-disorder patients point to the medial temporal lobe in the genesis of mood-congruent memory (MCM) bias, the interaction between mood and emotional memory formation has not been investigated in healthy participants. In particular it remains unclear how regulatory structures in the pre-frontal cortex may be involved in mediating this phenomenon. In this study, event-related fMRI was performed on 20 healthy participants using a full-factorial, within-subjects repeated-measures design to examine how happy and sad moods impact memory for valenced stimuli (positive, negative and neutral words). Main effects of mood, stimulus valence and memory were examined as was activity related to successful memory formation during congruent and in-congruent moods. Behavioral results confirm an MCM bias while imaging results show amygdala and hippocampal engagement in a global mood and successful recall, respectively. MCM formation was characterized by increased activity during mood-congruent encoding of negative words in the orbito-frontal cortex (OFC) and for mood-incongruent processing of negative words in medial- and inferior-frontal gyri (MFG/IFG). These findings indicate that different pre-frontal regions facilitate mood-congruent and incongruent encoding of successfully recalled negative words at the time of learning, with OFC enhancing congruency and the left IFG and MFG helping overcome semantic incongruities between mood and stimulus valence.

  20. Regulation of Memory Formation by the Transcription Factor XBP1.

    Science.gov (United States)

    Martínez, Gabriela; Vidal, René L; Mardones, Pablo; Serrano, Felipe G; Ardiles, Alvaro O; Wirth, Craig; Valdés, Pamela; Thielen, Peter; Schneider, Bernard L; Kerr, Bredford; Valdés, Jose L; Palacios, Adrian G; Inestrosa, Nibaldo C; Glimcher, Laurie H; Hetz, Claudio

    2016-02-16

    Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer's disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR), mediating adaptation to endoplasmic reticulum (ER) stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP), whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF), a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Regulation of Memory Formation by the Transcription Factor XBP1

    Directory of Open Access Journals (Sweden)

    Gabriela Martínez

    2016-02-01

    Full Text Available Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer’s disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR, mediating adaptation to endoplasmic reticulum (ER stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP, whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF, a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress.

  2. Connected Classroom Technology Facilitates Multiple Components of Formative Assessment Practice

    Science.gov (United States)

    Shirley, Melissa L.; Irving, Karen E.

    2015-01-01

    Formative assessment has been demonstrated to result in increased student achievement across a variety of educational contexts. When using formative assessment strategies, teachers engage students in instructional tasks that allow the teacher to uncover levels of student understanding so that the teacher may change instruction accordingly. Tools…

  3. Facilitating participation in formative evaluation supported by effect map

    DEFF Research Database (Denmark)

    Granlien, Maren Sander

    2009-01-01

    designed effect map. The purpose of the effect map is twofold: a) To encourage user participation in the early activities of formative evaluation b) The effects specified can be used as formative evaluation measures and guidance in the process of improving the system. The evaluation approach and the effect...

  4. Induced Brain Plasticity after a Facilitation Programme for Autobiographical Memory in Multiple Sclerosis: A Preliminary Study

    Science.gov (United States)

    Ernst, Alexandra; Botzung, Anne; Gounot, Daniel; Sellal, François; Blanc, Frédéric; de Seze, Jerome; Manning, Liliann

    2012-01-01

    This preliminary study tackles the assessment and treatment of autobiographical memory (AbM) in relapsing-remitting multiple sclerosis (RR-MS) patients. Our aim was to investigate cerebral activation changes, following clinical improvement of AbM due to a cognitive training based on mental visual imagery (MVI). We assessed AbM using the Autobiographical Interview (AI) in eight patients and 15 controls. The latter subjects established normative data. The eight patients showed selective defective performance on the AI. Four patients were trained cognitively and underwent pre- and post-AI and fMRI. The remaining four patients took a second AI, at the same interval, but with no intervention in between. Results showed a significant improvement of AbM performance after the facilitation programme that could not be explained by learning effects since the AI scores remained stable between the two assessments in the second group of patients. As expected, AbM improvement was accompanied by an increased cerebral activity in posterior cerebral regions in post-facilitation fMRI examination. We interpret this activation changes in terms of reflecting the emphasis made on the role of MVI in memory retrieval through the facilitation programme. These preliminary significant clinical and neuroimaging changes suggest the beneficial effects of this technique to alleviate AbM retrieval deficit in MS patients. PMID:23125932

  5. Induced Brain Plasticity after a Facilitation Programme for Autobiographical Memory in Multiple Sclerosis: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Alexandra Ernst

    2012-01-01

    Full Text Available This preliminary study tackles the assessment and treatment of autobiographical memory (AbM in relapsing-remitting multiple sclerosis (RR-MS patients. Our aim was to investigate cerebral activation changes, following clinical improvement of AbM due to a cognitive training based on mental visual imagery (MVI. We assessed AbM using the Autobiographical Interview (AI in eight patients and 15 controls. The latter subjects established normative data. The eight patients showed selective defective performance on the AI. Four patients were trained cognitively and underwent pre- and post-AI and fMRI. The remaining four patients took a second AI, at the same interval, but with no intervention in between. Results showed a significant improvement of AbM performance after the facilitation programme that could not be explained by learning effects since the AI scores remained stable between the two assessments in the second group of patients. As expected, AbM improvement was accompanied by an increased cerebral activity in posterior cerebral regions in post-facilitation fMRI examination. We interpret this activation changes in terms of reflecting the emphasis made on the role of MVI in memory retrieval through the facilitation programme. These preliminary significant clinical and neuroimaging changes suggest the beneficial effects of this technique to alleviate AbM retrieval deficit in MS patients.

  6. Working Memory Capacity and Its Relation to Stroop Interference and Facilitation Effects in Individuals with Mild Cognitive Impairment

    Science.gov (United States)

    Sung, Jee Eun; Kim, Jin Hee; Jeong, Jee Hyang; Kang, Heejin

    2012-01-01

    Purpose: The purposes of the study were to investigate (a) the task-specific differences in short-term memory (STM) and working memory capacity (WMC) in individuals with mild cognitive impairment (MCI) and normal elderly adults (NEAs), (b) the Stroop interference and facilitation effects, and (c) the relationship of STM and WMC to the Stroop…

  7. Memory formation: from network structure to neural dynamics.

    Science.gov (United States)

    Feldt, Sarah; Wang, Jane X; Hetrick, Vaughn L; Berke, Joshua D; Zochowski, Michal

    2010-05-13

    Understanding the neural correlates of brain function is an extremely challenging task, since any cognitive process is distributed over a complex and evolving network of neurons that comprise the brain. In order to quantify observed changes in neuronal dynamics during hippocampal memory formation, we present metrics designed to detect directional interactions and the formation of functional neuronal ensembles. We apply these metrics to both experimental and model-derived data in an attempt to link anatomical network changes with observed changes in neuronal dynamics during hippocampal memory formation processes. We show that the developed model provides a consistent explanation of the anatomical network modifications that underlie the activity changes observed in the experimental data.

  8. 5-HT systems: emergent targets for memory formation and memory alterations.

    Science.gov (United States)

    Meneses, Alfredo

    2013-01-01

    Drugs acting through 5-hydroxytryptamine (serotonin or 5-HT) systems modulate memory and its alterations, although the mechanisms involved are poorly understood. 5-HT drugs may present promnesic and/or antiamnesic (or even being amnesic) effects. Key questions regarding 5-HT markers include whether receptors directly or indirectly participate and/or contribute to the physiological and pharmacological basis of memory and its pathogenesis; hence, the major aim of this article was to examine recent advances in emergent targets of the 5-HT systems for memory formation and memory alterations. Recent reviews and findings are summarized, mainly in the context of the growing notion of memory deficits in brain disorders (e.g., posttraumatic stress disorder, mild cognitive impairment, consumption of drugs, poststroke cognitive dysfunctions, schizophrenia, Parkinson disease, and infection-induced memory impairments). Mainly, mammalian and (some) human data were the focus. At least agonists and antagonists for 5-HT1A/1B, 5-HT2A/2B/2C, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors as well as serotonin uptake inhibitors seem to have a promnesic and/or antiamnesic effect in different conditions and 5-HT markers seem to be associated to neural changes. Available evidence offers clues about the possibilities, but the exact mechanisms remain unclear. For instance, 5-HT transporter expression seems to be a reliable neural marker related to memory mechanisms and its alterations.

  9. Increasing CRTC1 function in the dentate gyrus during memory formation or reactivation increases memory strength without compromising memory quality.

    Science.gov (United States)

    Sekeres, Melanie J; Mercaldo, Valentina; Richards, Blake; Sargin, Derya; Mahadevan, Vivek; Woodin, Melanie A; Frankland, Paul W; Josselyn, Sheena A

    2012-12-01

    Memory stabilization following encoding (synaptic consolidation) or memory reactivation (reconsolidation) requires gene expression and protein synthesis (Dudai and Eisenberg, 2004; Tronson and Taylor, 2007; Nader and Einarsson, 2010; Alberini, 2011). Although consolidation and reconsolidation may be mediated by distinct molecular mechanisms (Lee et al., 2004), disrupting the function of the transcription factor CREB impairs both processes (Kida et al., 2002; Mamiya et al., 2009). Phosphorylation of CREB at Ser133 recruits CREB binding protein (CBP)/p300 coactivators to activate transcription (Chrivia et al., 1993; Parker et al., 1996). In addition to this well known mechanism, CREB regulated transcription coactivators (CRTCs), previously called transducers of regulated CREB (TORC) activity, stimulate CREB-mediated transcription, even in the absence of CREB phosphorylation. Recently, CRTC1 has been shown to undergo activity-dependent trafficking from synapses and dendrites to the nucleus in excitatory hippocampal neurons (Ch'ng et al., 2012). Despite being a powerful and specific coactivator of CREB, the role of CRTC in memory is virtually unexplored. To examine the effects of increasing CRTC levels, we used viral vectors to locally and acutely increase CRTC1 in the dorsal hippocampus dentate gyrus region of mice before training or memory reactivation in context fear conditioning. Overexpressing CRTC1 enhanced both memory consolidation and reconsolidation; CRTC1-mediated memory facilitation was context specific (did not generalize to nontrained context) and long lasting (observed after virally expressed CRTC1 dissipated). CREB overexpression produced strikingly similar effects. Therefore, increasing CRTC1 or CREB function is sufficient to enhance the strength of new, as well as established reactivated, memories without compromising memory quality.

  10. PROSPECTION AND EMOTIONAL MEMORY: HOW EXPECTATION AFFECTS EMOTIONAL MEMORY FORMATION FOLLOWING SLEEP AND WAKE

    Directory of Open Access Journals (Sweden)

    Tony J Cunningham

    2014-08-01

    Full Text Available Successful prospective memory is necessarily driven by an expectation that encoded information will be relevant in the future, leading to its preferential placement in memory storage. Like expectation, emotional salience is another type of cue that benefits human memory formation. Although separate lines of research suggest that both emotional information and information explicitly expected to be important in the future benefit memory consolidation, it is unknown how expectation affects the processing of emotional information and whether sleep, which is known to maximize memory consolidation, plays a critical role. The purpose of this study was to investigate how expectation would impact the consolidation of emotionally salient content, and whether this impact would differ across delays of sleep and wake. Participants encoded scenes containing an emotionally charged negative or neutral foreground object placed on a plausible neutral background. After encoding, half of the participants were informed they would later be tested on the scenes (expected condition, while the other half received no information about the test (unexpected condition. At recognition, following a 12-hour delay of sleep or wakefulness, the scene components (objects and backgrounds were presented separately and one at a time, and participants were asked to determine if each component was old or new. Results revealed a greater disparity for memory of negative objects over their paired neutral backgrounds for both the sleep and wake groups when the memory test was expected compared to when it was unexpected, while neutral memory remained unchanged. Analyzing each group separately, the wake group showed a threefold increase in the magnitude of this object/background trade-off for emotional scenes when the memory test was expected compared to when it was unexpected, while those who slept performed similarly across conditions. These results suggest that emotional salience and

  11. Delayed onset of a daytime nap facilitates retention of declarative memory.

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    Sara E Alger

    Full Text Available BACKGROUND: Learning followed by a period of sleep, even as little as a nap, promotes memory consolidation. It is now generally recognized that sleep facilitates the stabilization of information acquired prior to sleep. However, the temporal nature of the effect of sleep on retention of declarative memory is yet to be understood. We examined the impact of a delayed nap onset on the recognition of neutral pictorial stimuli with an added spatial component. METHODOLOGY/PRINCIPAL FINDINGS: Participants completed an initial study session involving 150 neutral pictures of people, places, and objects. Immediately following the picture presentation, participants were asked to make recognition judgments on a subset of "old", previously seen, pictures versus intermixed "new" pictures. Participants were then divided into one of four groups who either took a 90-minute nap immediately, 2 hours, or 4 hours after learning, or remained awake for the duration of the experiment. 6 hours after initial learning, participants were again tested on the remaining "old" pictures, with "new" pictures intermixed. CONCLUSIONS/SIGNIFICANCE: Interestingly, we found a stabilizing benefit of sleep on the memory trace reflected as a significant negative correlation between the average time elapsed before napping and decline in performance from test to retest (p = .001. We found a significant interaction between the groups and their performance from test to retest (p = .010, with the 4-hour delay group performing significantly better than both those who slept immediately and those who remained awake (p = .044, p = .010, respectively. Analysis of sleep data revealed a significant positive correlation between amount of slow wave sleep (SWS achieved and length of the delay before sleep onset (p = .048. The findings add to the understanding of memory processing in humans, suggesting that factors such as waking processing and homeostatic increases in need for sleep over time modulate

  12. ERP evidence that auditory-visual speech facilitates working memory in younger and older adults.

    Science.gov (United States)

    Frtusova, Jana B; Winneke, Axel H; Phillips, Natalie A

    2013-06-01

    Auditory-visual (AV) speech enhances speech perception and facilitates auditory processing, as measured by event-related brain potentials (ERPs). Considering a perspective of shared resources between perceptual and cognitive processes, facilitated speech perception may render more resources available for higher-order functions. This study examined whether AV speech facilitation leads to better working memory (WM) performance in 23 younger and 20 older adults. Participants completed an n-back task (0- to 3-back) under visual-only (V-only), auditory-only (A-only), and AV conditions. The results showed faster responses across all memory loads and improved accuracy in the most demanding conditions (2- and 3-back) during AV compared with unisensory conditions. Older adults benefited from the AV presentation to the same extent as younger adults. WM performance of older adults during the AV presentation did not differ from that of younger adults in the A-only condition, suggesting that an AV presentation can help to counteract some of the age-related WM decline. The ERPs showed a decrease in the auditory N1 amplitude during the AV compared with A-only presentation in older adults, suggesting that the facilitation of perceptual processing becomes especially beneficial with aging. Additionally, the N1 occurred earlier in the AV than in the A-only condition for both age groups. These AV-induced modulations of auditory processing correlated with improvement in certain behavioral and ERP measures of WM. These results support an integrated model between perception and cognition, and suggest that processing speech under AV conditions enhances WM performance of both younger and older adults. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  13. Coexistence facilitates interspecific biofilm formation in complex microbial communities

    DEFF Research Database (Denmark)

    Madsen, Jonas Stenløkke; Røder, Henriette Lyng; Russel, Jakob

    2016-01-01

    , the underlying role of fundamental ecological factors, specifically coexistence and phylogenetic history, in biofilm formation remains unclear. This study examines how social interactions affect biofilm formation in multi-species co-cultures from five diverse environments. We found prevalence of increased......Social interactions in which bacteria respond to one another by modifying their phenotype are central determinants of microbial communities. It is known that interspecific interactions influence the biofilm phenotype of bacteria; a phenotype that is central to the fitness of bacteria. However...

  14. Facilitation of short-term social memory by ethanol in rats is mediated by dopaminergic receptors.

    Science.gov (United States)

    Prediger, Rui D S; Batista, Luciano C; Miyoshi, Edmar; Takahashi, Reinaldo N

    2004-08-12

    Ethanol is a drug that has apparently opposite effects on memory processes depending on when it is given relative to the task, as well as the nature of the task under study. Recently, we demonstrated that acute low doses of ethanol (0.5 and 1.0 g/kg, i.p.) improve the short-term social memory in rats in a specific and time-dependent manner, and that this action is, at least in part, related to opioid, but not to muscarinic receptors. In the present study, we evaluated whether this positive effect of ethanol on the short-term memory of rats is related to a reducing impact of interference during the task through two different procedures: the introduction of an unfamiliar juvenile rat or the placing of the adult rat in the open field during the inter-exposure interval. The actions of reserpine (0.4 and 0.8 mg/kg, s.c.), haloperidol (0.05 and 0.2 mg/kg, i.p.), the D2 receptor antagonist sulpiride (20.0 and 50.0 mg/kg, i.p.) and the D1 receptor antagonist SCH 23390 (0.01 and 0.03 mg/kg, s.c.) and their interaction with ethanol (1.0 g/kg, i.p.) in relation to short-term memory were also studied. The administration of ethanol (1.0 g/kg, i.p.), immediately after the end of the first presentation, did not reduce the effect on social memory of the introduction of an unfamiliar juvenile or placing the adult rat in the open field during the inter-exposure interval. The facilitatory effect of ethanol on social memory was inhibited by the pretreatment with reserpine and it was antagonized by the administration of haloperidol or sulpiride, but not by SCH 23390. These results indicate that the facilitation of short-term social memory by ethanol is not related to a reduction in the deleterious impact of interference and that this action of ethanol is mediated, at least in part, by D2 receptors, but not by D1 dopaminergic receptors.

  15. Prospection and emotional memory: how expectation affects emotional memory formation following sleep and wake.

    Science.gov (United States)

    Cunningham, Tony J; Chambers, Alexis M; Payne, Jessica D

    2014-01-01

    Successful prospective memory is necessarily driven by an expectation that encoded information will be relevant in the future, leading to its preferential placement in memory storage. Like expectation, emotional salience is another type of cue that benefits human memory formation. Although separate lines of research suggest that both emotional information and information explicitly expected to be important in the future benefit memory consolidation, it is unknown how expectation affects the processing of emotional information and whether sleep, which is known to maximize memory consolidation, plays a critical role. The purpose of this study was to investigate how expectation would impact the consolidation of emotionally salient content, and whether this impact would differ across delays of sleep and wake. Participants encoded scenes containing an emotionally charged negative or neutral foreground object placed on a plausible neutral background. After encoding, half of the participants were informed they would later be tested on the scenes (expected condition), while the other half received no information about the test (unexpected condition). At recognition, following a 12-h delay of sleep or wakefulness, the scene components (objects and backgrounds) were presented separately and one at a time, and participants were asked to determine if each component was old or new. Results revealed a greater disparity for memory of negative objects over their paired neutral backgrounds for both the sleep and wake groups when the memory test was expected compared to when it was unexpected, while neutral memory remained unchanged. Analyzing each group separately, the wake group showed a threefold increase in the magnitude of this object/background trade-off for emotional scenes when the memory test was expected compared to when it was unexpected, while those who slept performed similarly across conditions. These results suggest that emotional salience and expectation cues

  16. Distinct roles for the deacetylase domain of HDAC3 in the hippocampus and medial prefrontal cortex in the formation and extinction of memory.

    Science.gov (United States)

    Alaghband, Yasaman; Kwapis, Janine L; López, Alberto J; White, André O; Aimiuwu, Osasumwen V; Al-Kachak, Amni; Bodinayake, Kasuni K; Oparaugo, Nicole C; Dang, Richard; Astarabadi, Mariam; Matheos, Dina P; Wood, Marcelo A

    2017-09-07

    Histone deacetylases (HDACs) are chromatin modifying enzymes that have been implicated as powerful negative regulators of memory processes. HDAC3 has been shown to play a pivotal role in long-term memory for object location as well as the extinction of cocaine-associated memory, but it is unclear whether this function depends on the deacetylase domain of HDAC3. Here, we tested whether the deacetylase domain of HDAC3 has a role in object location memory formation as well as the formation and extinction of cocaine-associated memories. Using a deacetylase-dead point mutant of HDAC3, we found that selectively blocking HDAC3 deacetylase activity in the dorsal hippocampus enhanced long-term memory for object location, but had no effect on the formation of cocaine-associated memory. When this same point mutant virus of HDAC3 was infused into the prelimbic cortex, it failed to affect cocaine-associated memory formation. With regards to extinction, impairing the HDAC3 deacetylase domain in the infralimbic cortex had no effect on extinction, but a facilitated extinction effect was observed when the point mutant virus was delivered to the dorsal hippocampus. These results suggest that the deacetylase domain of HDAC3 plays a selective role in specific brain regions underlying long-term memory formation of object location as well as cocaine-associated memory formation and extinction. Copyright © 2017. Published by Elsevier Inc.

  17. Cognitive Processes Supporting Episodic Memory Formation in Childhood: The Role of Source Memory, Binding, and Executive Functioning

    Science.gov (United States)

    Raj, Vinaya; Bell, Martha Ann

    2010-01-01

    Episodic memories contain various forms of contextual detail (e.g., perceptual, emotional, cognitive details) that need to become integrated. Each of these contextual features can be used to attribute a memory episode to its source, or origin of information. Memory for source information is one critical component in the formation of episodic…

  18. Cognitive Processes Supporting Episodic Memory Formation in Childhood: The Role of Source Memory, Binding, and Executive Functioning

    Science.gov (United States)

    Raj, Vinaya; Bell, Martha Ann

    2010-01-01

    Episodic memories contain various forms of contextual detail (e.g., perceptual, emotional, cognitive details) that need to become integrated. Each of these contextual features can be used to attribute a memory episode to its source, or origin of information. Memory for source information is one critical component in the formation of episodic…

  19. Tracking down the path of memory: eye scanpaths facilitate retrieval of visuospatial information.

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    Bochynska, Agata; Laeng, Bruno

    2015-09-01

    Recent research points to a crucial role of eye fixations on the same spatial locations where an item appeared when learned, for the successful retrieval of stored information (e.g., Laeng et al. in Cognition 131:263-283, 2014. doi: 10.1016/j.cognition.2014.01.003 ). However, evidence about whether the specific temporal sequence (i.e., scanpath) of these eye fixations is also relevant for the accuracy of memory remains unclear. In the current study, eye fixations were recorded while looking at a checkerboard-like pattern. In a recognition session (48 h later), animations were shown where each square that formed the pattern was presented one by one, either according to the same, idiosyncratic, temporal sequence in which they were originally viewed by each participant or in a shuffled sequence although the squares were, in both conditions, always in their correct positions. Afterward, participants judged whether they had seen the same pattern before or not. Showing the elements serially according to the original scanpath's sequence yielded a significantly better recognition performance than the shuffled condition. In a forced fixation condition, where the gaze was maintained on the center of the screen, the advantage of memory accuracy for same versus shuffled scanpaths disappeared. Concluding, gaze scanpaths (i.e., the order of fixations and not simply their positions) are functional to visual memory and physical reenacting of the original, embodied, perception can facilitate retrieval.

  20. Intracerebellar vermis histamine facilitates memory consolidation in the elevated T maze model.

    Science.gov (United States)

    Silva-Marques, Bruna; Gianlorenço, Anna Carolyna Lepesteur; Mattioli, Rosana

    2016-05-01

    Experimental evidence suggests that the cerebellum plays a more complex role in learning than simply regulating the motor response. Rather, it is thought to play a significant role in the consolidation of emotional memory in mice. Due to the difficulty of interpreting fear and anxiety behaviors-the standard methodology for the study of the histaminergic system and emotional memory-in mice, we propose a behavioral assessment of mice subjected to the Elevated T-maze after histamine microinjection of the cerebellar vermis. Young male Swiss albino mice weighing 25-35g were used. In addition, locomotor activity was tested in an open field test. Our data suggest that histamine did not affect memory consolidation during escape or open field behavior at the doses used in this study. However, we observed a significant increase in inhibitory avoidance on the second day in animals receiving a dose of 6.8nmol/0.5μl, suggesting that histamine facilitates the consolidation of inhibitory avoidance in mice.

  1. [Inhibition of histone deacetylases in the chick brain modulates expression of c-Fos and ZENK transcription factors and facilitates establishment of long-term memory].

    Science.gov (United States)

    Toropova, K A; Anokhin, K V; Tiunova, A A

    2014-01-01

    The aim of the work was to examine the role of histone acetylation in memory consolidation in newborn chicks. We studied the effects of histone deacetylase inhibitor trichostatin A (TSA) on a "weak" memory for passive avoidance and on expression of two transcription factors c-Fos and ZENK known to play a role in neuronal plasticity in the chick brain. Intraventricular administration of trichostatin A prior to training produced a dose-dependent enhancement of memory when tested 24 hours after the training. It also increased neuronal expression of c-Fos and ZENK proteins: the density of ZENK immunopositive cells increased in the hippocampus and intermediate medial mesopallium and the density of c-Fos immunopositive cells increased in intermediate arcopallium and dorsocaudal nidopallium. Weak passive avoidance training did not produce further enhancement of c-Fos and ZENK expression in any of these brain areas. These data demonstrate possibility of facilitating long-term memory in day-old chicks by a histone deacetylases inhibitor, thus supporting the hypothesis on the role of histone acetylation in long-term memory formation. They also suggest that these effects might be mediated through modulation of transcriptional response in brain areas involved in consolidation of this form of memory.

  2. Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation.

    Science.gov (United States)

    Bieszczad, Kasia M; Bechay, Kiro; Rusche, James R; Jacques, Vincent; Kudugunti, Shashi; Miao, Wenyan; Weinberger, Norman M; McGaugh, James L; Wood, Marcelo A

    2015-09-23

    Research over the past decade indicates a novel role for epigenetic mechanisms in memory formation. Of particular interest is chromatin modification by histone deacetylases (HDACs), which, in general, negatively regulate transcription. HDAC deletion or inhibition facilitates transcription during memory consolidation and enhances long-lasting forms of synaptic plasticity and long-term memory. A key open question remains: How does blocking HDAC activity lead to memory enhancements? To address this question, we tested whether a normal function of HDACs is to gate information processing during memory formation. We used a class I HDAC inhibitor, RGFP966 (C21H19FN4O), to test the role of HDAC inhibition for information processing in an auditory memory model of learning-induced cortical plasticity. HDAC inhibition may act beyond memory enhancement per se to instead regulate information in ways that lead to encoding more vivid sensory details into memory. Indeed, we found that RGFP966 controls memory induction for acoustic details of sound-to-reward learning. Rats treated with RGFP966 while learning to associate sound with reward had stronger memory and additional information encoded into memory for highly specific features of sounds associated with reward. Moreover, behavioral effects occurred with unusually specific plasticity in primary auditory cortex (A1). Class I HDAC inhibition appears to engage A1 plasticity that enables additional acoustic features to become encoded in memory. Thus, epigenetic mechanisms act to regulate sensory cortical plasticity, which offers an information processing mechanism for gating what and how much is encoded to produce exceptionally persistent and vivid memories. Significance statement: Here we provide evidence of an epigenetic mechanism for information processing. The study reveals that a class I HDAC inhibitor (Malvaez et al., 2013; Rumbaugh et al., 2015; RGFP966, chemical formula C21H19FN4O) alters the formation of auditory memory by

  3. HSPB1 facilitates the formation of non-centrosomal microtubules.

    Directory of Open Access Journals (Sweden)

    Leonardo Almeida-Souza

    Full Text Available The remodeling capacity of microtubules (MT is essential for their proper function. In mammals, MTs are predominantly formed at the centrosome, but can also originate from non-centrosomal sites, a process that is still poorly understood. We here show that the small heat shock protein HSPB1 plays a role in the control of non-centrosomal MT formation. The HSPB1 expression level regulates the balance between centrosomal and non-centrosomal MTs. The HSPB1 protein can be detected specifically at sites of de novo forming non-centrosomal MTs, while it is absent from the centrosomes. In addition, we show that HSPB1 binds preferentially to the lattice of newly formed MTs in vitro, suggesting that its function occurs by stabilizing MT seeds. Our findings open new avenues for the understanding of the role of HSPB1 in the development, maintenance and protection of cells with specialized non-centrosomal MT arrays.

  4. Past, present, and future in hippocampal formation and memory research.

    Science.gov (United States)

    Muñoz-López, Mónica

    2015-06-01

    Over 100 years of research on the hippocampal formation has led us understand the consequences of lesions in humans, the functional networks, anatomical pathways, neuronal types and their local circuitry, receptors, molecules, intracellular cascades, and some of the physiological mechanisms underlying long-term spatial and episodic memory. In addition, complex computational models allow us to formulate sophisticated hypotheses; many of them testable with techniques recently developed unthinkable in the past. Although the neurobiology of the cognitive map is starting to be revealed today, we still face a future with many unresolved questions. The aim of this commentary is twofold. First is to point out some of the critical findings in hippocampal formation research and new challenges. Second, to briefly summarize what the anatomy of memory can tell us about how highly processed sensory information from distant cortical areas communicate with different subareas of the entorhinal cortex, dentate gyrus, and hippocampal subfields to integrate and consolidate unique episodic memory traces. © 2015 Wiley Periodicals, Inc.

  5. The Role of Long-Term Memory in a Test of Visual Working Memory: Proactive Facilitation but No Proactive Interference

    Science.gov (United States)

    Oberauer, Klaus; Awh, Edward; Sutterer, David W.

    2017-01-01

    We report 4 experiments examining whether associations in visual working memory are subject to proactive interference from long-term memory (LTM). Following a long-term learning phase in which participants learned the colors of 120 unique objects, a working memory (WM) test was administered in which participants recalled the precise colors of 3…

  6. The Role of Long-Term Memory in a Test of Visual Working Memory: Proactive Facilitation but No Proactive Interference

    Science.gov (United States)

    Oberauer, Klaus; Awh, Edward; Sutterer, David W.

    2017-01-01

    We report 4 experiments examining whether associations in visual working memory are subject to proactive interference from long-term memory (LTM). Following a long-term learning phase in which participants learned the colors of 120 unique objects, a working memory (WM) test was administered in which participants recalled the precise colors of 3…

  7. Small-conductance Ca2+-activated potassium type 2 channels regulate the formation of contextual fear memory.

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    Saravana R K Murthy

    Full Text Available Small-conductance, Ca2+ activated K+ channels (SK channels are expressed at high levels in brain regions responsible for learning and memory. In the current study we characterized the contribution of SK2 channels to synaptic plasticity and to different phases of hippocampal memory formation. Selective SK2 antisense-treatment facilitated basal synaptic transmission and theta-burst induced LTP in hippocampal brain slices. Using the selective SK2 antagonist Lei-Dab7 or SK2 antisense probes, we found that hippocampal SK2 channels are critical during two different time windows: 1 blockade of SK2 channels before the training impaired fear memory, whereas, 2 blockade of SK2 channels immediately after the training enhanced contextual fear memory. We provided the evidence that the post-training cleavage of the SK2 channels was responsible for the observed bidirectional effect of SK2 channel blockade on memory consolidation. Thus, Lei-Dab7-injection before training impaired the C-terminal cleavage of SK2 channels, while Lei-Dab7 given immediately after training facilitated the C-terminal cleavage. Application of the synthetic peptide comprising a leucine-zipper domain of the C-terminal fragment to Jurkat cells impaired SK2 channel-mediated currents, indicating that the endogenously cleaved fragment might exert its effects on memory formation by blocking SK2 channel-mediated currents. Our present findings suggest that SK2 channel proteins contribute to synaptic plasticity and memory not only as ion channels but also by additionally generating a SK2 C-terminal fragment, involved in both processes. The modulation of fear memory by down-regulating SK2 C-terminal cleavage might have applicability in the treatment of anxiety disorders in which fear conditioning is enhanced.

  8. Associations of unilateral whisker and olfactory signals induce synapse formation and memory cell recruitment in bilateral barrel cortices: cellular mechanism for unilateral training toward bilateral memory

    Directory of Open Access Journals (Sweden)

    Zilong Gao

    2016-12-01

    Full Text Available Somatosensory signals and operative skills learned by unilateral limbs can be retrieved bilaterally. In terms of cellular mechanism underlying this unilateral learning toward bilateral memory, we hypothesized that associative memory cells in bilateral cortices and synapse innervations between them were produced. In the examination of this hypothesis, we have observed that paired unilateral whisker and odor stimulations led to odorant-induced whisker motions in bilateral sides, which were attenuated by inhibiting the activity of barrel cortices. In the mice that showed bilateral cross-modal responses, the neurons in both sides of barrel cortices became to encode this new odor signal alongside the innate whisker signal. Axon projections and synapse formations from the barrel cortex, which was co-activated with the piriform cortex, toward its contralateral barrel cortex were upregulated. Glutamatergic synaptic transmission in bilateral barrel cortices was upregulated and GABAergic synaptic transmission was downregulated. The associative activations of the sensory cortices facilitate new axon projection, glutamatergic synapse formation and GABAergic synapse downregulation, which drive the neurons to be recruited as associative memory cells in the bilateral cortices. Our data reveals the productions of associative memory cells and synapse innervations in bilateral sensory cortices for unilateral training toward bilateral memory.

  9. Associations of Unilateral Whisker and Olfactory Signals Induce Synapse Formation and Memory Cell Recruitment in Bilateral Barrel Cortices: Cellular Mechanism for Unilateral Training Toward Bilateral Memory

    Science.gov (United States)

    Gao, Zilong; Chen, Lei; Fan, Ruicheng; Lu, Wei; Wang, Dangui; Cui, Shan; Huang, Li; Zhao, Shidi; Guan, Sudong; Zhu, Yan; Wang, Jin-Hui

    2016-01-01

    Somatosensory signals and operative skills learned by unilateral limbs can be retrieved bilaterally. In terms of cellular mechanism underlying this unilateral learning toward bilateral memory, we hypothesized that associative memory cells in bilateral cortices and synapse innervations between them were produced. In the examination of this hypothesis, we have observed that paired unilateral whisker and odor stimulations led to odorant-induced whisker motions in bilateral sides, which were attenuated by inhibiting the activity of barrel cortices. In the mice that showed bilateral cross-modal responses, the neurons in both sides of barrel cortices became to encode this new odor signal alongside the innate whisker signal. Axon projections and synapse formations from the barrel cortex, which was co-activated with the piriform cortex, toward its contralateral barrel cortex (CBC) were upregulated. Glutamatergic synaptic transmission in bilateral barrel cortices was upregulated and GABAergic synaptic transmission was downregulated. The associative activations of the sensory cortices facilitate new axon projection, glutamatergic synapse formation and GABAergic synapse downregulation, which drive the neurons to be recruited as associative memory cells in the bilateral cortices. Our data reveal the productions of associative memory cells and synapse innervations in bilateral sensory cortices for unilateral training toward bilateral memory. PMID:28018178

  10. Visual working memory simultaneously guides facilitation and inhibition during visual search.

    Science.gov (United States)

    Dube, Blaire; Basciano, April; Emrich, Stephen M; Al-Aidroos, Naseem

    2016-07-01

    During visual search, visual working memory (VWM) supports the guidance of attention in two ways: It stores the identity of the search target, facilitating the selection of matching stimuli in the search array, and it maintains a record of the distractors processed during search so that they can be inhibited. In two experiments, we investigated whether the full contents of VWM can be used to support both of these abilities simultaneously. In Experiment 1, participants completed a preview search task in which (a) a subset of search distractors appeared before the remainder of the search items, affording participants the opportunity to inhibit them, and (b) the search target varied from trial to trial, requiring the search target template to be maintained in VWM. We observed the established signature of VWM-based inhibition-reduced ability to ignore previewed distractors when the number of distractors exceeds VWM's capacity-suggesting that VWM can serve this role while also representing the target template. In Experiment 2, we replicated Experiment 1, but added to the search displays a singleton distractor that sometimes matched the color (a task-irrelevant feature) of the search target, to evaluate capture. We again observed the signature of VWM-based preview inhibition along with attentional capture by (and, thus, facilitation of) singletons matching the target template. These findings indicate that more than one VWM representation can bias attention at a time, and that these representations can separately affect selection through either facilitation or inhibition, placing constraints on existing models of the VWM-based guidance of attention.

  11. Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain

    Directory of Open Access Journals (Sweden)

    Prendergast Julie

    2009-11-01

    Full Text Available Abstract Background Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1 engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.. An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS was used to measure metabolite levels in seven voxels of interest (VOIs (including hippocampus before and after learning. Results Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA/(Cr+Cho ratio. Conclusion Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training.

  12. Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain.

    LENUS (Irish Health Repository)

    Roche, Richard Ap

    2009-01-01

    BACKGROUND: Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1) engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.). An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to measure metabolite levels in seven voxels of interest (VOIs) (including hippocampus) before and after learning. RESULTS: Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal\\/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA\\/(Cr+Cho) ratio. CONCLUSION: Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training.

  13. Facilitation of memory encoding in primate hippocampus by a neuroprosthesis that promotes task-specific neural firing

    Science.gov (United States)

    Hampson, Robert E.; Song, Dong; Opris, Ioan; Santos, Lucas M.; Shin, Dae C.; Gerhardt, Greg A.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Sam A.

    2013-12-01

    Objective. Memory accuracy is a major problem in human disease and is the primary factor that defines Alzheimer’s, ageing and dementia resulting from impaired hippocampal function in the medial temporal lobe. Development of a hippocampal memory neuroprosthesis that facilitates normal memory encoding in nonhuman primates (NHPs) could provide the basis for improving memory in human disease states. Approach. NHPs trained to perform a short-term delayed match-to-sample (DMS) memory task were examined with multi-neuron recordings from synaptically connected hippocampal cell fields, CA1 and CA3. Recordings were analyzed utilizing a previously developed nonlinear multi-input multi-output (MIMO) neuroprosthetic model, capable of extracting CA3-to-CA1 spatiotemporal firing patterns during DMS performance. Main results. The MIMO model verified that specific CA3-to-CA1 firing patterns were critical for the successful encoding of sample phase information on more difficult DMS trials. This was validated by the delivery of successful MIMO-derived encoding patterns via electrical stimulation to the same CA1 recording locations during the sample phase which facilitated task performance in the subsequent, delayed match phase, on difficult trials that required more precise encoding of sample information. Significance. These findings provide the first successful application of a neuroprosthesis designed to enhance and/or repair memory encoding in primate brain.

  14. Inhibiting corticosterone synthesis during fear memory formation exacerbates cued fear extinction memory deficits within the single prolonged stress model.

    Science.gov (United States)

    Keller, Samantha M; Schreiber, William B; Stanfield, Briana R; Knox, Dayan

    2015-01-01

    Using the single prolonged stress (SPS) animal model of post-traumatic stress disorder (PTSD), previous studies suggest that enhanced glucocorticoid receptor (GR) expression leads to cued fear extinction retention deficits. However, it is unknown how the endogenous ligand of GRs, corticosterone (CORT), may contribute to extinction retention deficits in the SPS model. Given that CORT synthesis during fear learning is critical for fear memory consolidation and SPS enhances GR expression, CORT synthesis during fear memory formation could strengthen fear memory in SPS rats by enhancing GR activation during fear learning. In turn, this could lead to cued fear extinction retention deficits. We tested the hypothesis that CORT synthesis during fear learning leads to cued fear extinction retention deficits in SPS rats by administering the CORT synthesis inhibitor metyrapone to SPS and control rats prior to fear conditioning, and observed the effect this had on extinction memory. Inhibiting CORT synthesis during fear memory formation in control rats tended to decrease cued freezing, though this effect never reached statistical significance. Contrary to our hypothesis, inhibiting CORT synthesis during fear memory formation disrupted extinction retention in SPS rats. This finding suggests that even though SPS exposure leads to cued fear extinction memory deficits, CORT synthesis during fear memory formation enhances extinction retention in SPS rats. This suggests that stress-induced CORT synthesis in previously stressed rats can be beneficial.

  15. Molecular Mechanisms Underlying Formation of Long-Term Reward Memories and Extinction Memories in the Honeybee ("Apis Mellifera")

    Science.gov (United States)

    Eisenhardt, Dorothea

    2014-01-01

    The honeybee ("Apis mellifera") has long served as an invertebrate model organism for reward learning and memory research. Its capacity for learning and memory formation is rooted in the ecological need to efficiently collect nectar and pollen during summer to ensure survival of the hive during winter. Foraging bees learn to associate a…

  16. Working memory binding and episodic memory formation in aging, mild cognitive impairment, and Alzheimer’s dementia

    NARCIS (Netherlands)

    Geldorp, B. van; Heringa, S.M.; Berg, E. van den; Olde Rikkert, M.G.M.; Biessels, G.J.; Kessels, R.P.C.

    2015-01-01

    Introduction: Recent studies indicate that in both normal and pathological aging working memory (WM) performance deteriorates, especially when associations have to be maintained. However, most studies typically do not assess the relationship between WM and episodic memory formation. In the present

  17. Early and late stages of working-memory maintenance contribute differentially to long-term memory formation

    NARCIS (Netherlands)

    Bergmann, H.C.; Kiemeneij, A.; Fernandez, G.S.E.; Kessels, R.P.C.

    2013-01-01

    The present paper investigated the role of early and late stages of working-memory maintenance, which have been suggested to differentially contribute to long-term memory formation. In experiment 1, we administered a delayed-match-to-sample task, requiring participants to remember line drawings of n

  18. Molecular Mechanisms Underlying Formation of Long-Term Reward Memories and Extinction Memories in the Honeybee ("Apis Mellifera")

    Science.gov (United States)

    Eisenhardt, Dorothea

    2014-01-01

    The honeybee ("Apis mellifera") has long served as an invertebrate model organism for reward learning and memory research. Its capacity for learning and memory formation is rooted in the ecological need to efficiently collect nectar and pollen during summer to ensure survival of the hive during winter. Foraging bees learn to associate a…

  19. Hippocampal metaplasticity is required for the formation of temporal associative memories.

    Science.gov (United States)

    Xu, Jian; Antion, Marcia D; Nomura, Toshihiro; Kraniotis, Stephen; Zhu, Yongling; Contractor, Anis

    2014-12-10

    Metaplasticity regulates the threshold for modification of synaptic strength and is an important regulator of learning rules; however, it is not known whether these cellular mechanisms for homeostatic regulation of synapses contribute to particular forms of learning. Conditional ablation of mGluR5 in CA1 pyramidal neurons resulted in the inability of low-frequency trains of afferent activation to prime synapses for subsequent theta burst potentiation. Priming-induced metaplasticity requires mGluR5-mediated mobilization of endocannabinoids during the priming train to induce long-term depression of inhibition (I-LTD). Mice lacking priming-induced plasticity had no deficit in spatial reference memory tasks, but were impaired in an associative task with a temporal component. Conversely, enhancing endocannabinoid signaling facilitated temporal associative memory acquisition and, after training animals in these tasks, ex vivo I-LTD was partially occluded and theta burst LTP was enhanced. Together, these results suggest a link between metaplasticity mechanisms in the hippocampus and the formation of temporal associative memories.

  20. [Spatial Cognition and Episodic Memory Formation in the Limbic Cortex].

    Science.gov (United States)

    Kobayashi, Yasushi

    2017-04-01

    The limbic lobe defined by Broca is a cortical region with highly diverse structure and functions, and comprises the paleo-, archi-, and neocortices as well as their transitional zones. In the limbic lobe, Brodmann designated areas 27, 28, 34, 35, and 36 adjacent to the hippocampus, and areas 23, 24, 25, 26, 29, 30, 31, 32, and 33 around the corpus callosum. In the current literature, areas 27 and 28 correspond to the presubiculum and entorhinal cortex, respectively. Area 34 represents the cortico-medial part of the amygdaloid complex. Areas 35 and 36 roughly cover the perirhinal and parahippocampal cortices. Areas 24, 25, 32, and 33 belong to the anterior cingulate gyrus, while areas 23, 26, 29, 30, and 31 to the posterior cingulate gyrus. Areas 25, 32, and the anteroinferior portion of area 24 are deeply involved in emotional responses, particularly in their autonomic functions, through reciprocal connections with the amygdaloid complex, anterior thalamus and projections to the brainstem and spinal visceral centers. Areas 29 and 30 have dense reciprocal connections with areas 23 and 31, the dorsolateral prefrontal areas, and the regions related to the hippocampus. They play pivotal roles in mediating spatial cognition, working memory processing, and episodic memory formation.

  1. Level of Processing Modulates the Neural Correlates of Emotional Memory Formation

    Science.gov (United States)

    Ritchey, Maureen; LaBar, Kevin S.; Cabeza, Roberto

    2011-01-01

    Emotion is known to influence multiple aspects of memory formation, including the initial encoding of the memory trace and its consolidation over time. However, the neural mechanisms whereby emotion impacts memory encoding remain largely unexplored. The present study used a levels-of-processing manipulation to characterize the impact of emotion on…

  2. Friend or foe? Decoding the facilitative and disruptive effects of emotion on working memory in younger and older adults

    Directory of Open Access Journals (Sweden)

    Linda eTruong

    2014-02-01

    Full Text Available A growing body of work on emotion-cognition interactions has revealed both facilitative and disruptive effects of emotion on working memory in younger adults. These differing effects may vary by the goal relevancy of emotion within a task. Additionally, it is possible that these emotional effects would be larger for older adults, considering findings of preserved emotional processing with age. To test these hypotheses, the current study examined the effects of emotional content and aging on working memory for target information in the presence of distraction. Thirty-six younger (ages 18-29 and 36 older adults (ages 65-87 completed a delayed-response working memory task. Participants viewed two target words intermixed with two distracter words, and then judged whether a subsequently presented probe word was one of the target words. The emotional content (valence and arousal of targets and distracters was systematically manipulated. Results indicated that emotional targets facilitated working memory in both age groups. In contrast, emotional distracters disrupted performance. Negative distracters were particularly disruptive for older adults, but younger adults did not show an emotional interference effect. These findings help clarify discrepancies in the literature and contribute to the sparse research on emotional working memory in older adults.

  3. Amygdala’s involvement in facilitating associative learning-induced plasticity: a promiscuous role for the amygdala in memory acquisition

    Directory of Open Access Journals (Sweden)

    Lily S Chau

    2012-10-01

    Full Text Available It is widely accepted that the amygdala plays a critical role in acquisition and consolidation of fear-related memories. Some of the more widely employed behavioral paradigms that have assisted in solidifying the amygdala’s role in fear-related memories are associative learning paradigms. With most associative learning tasks, a neutral conditioned stimulus (CS is paired with a salient unconditioned stimulus (US that elicits an unconditioned response (UR. After multiple CS-US pairings, the subject learns that the CS predicts the onset or delivery of the US, and thus elicits a learned conditioned response (CR. Most fear-related associative paradigms have suggested that an aspect of the fear association is stored in the amygdala; however, some fear-motivated associative paradigms suggest that the amygdala is not a site of storage, but rather facilitates consolidation in other brain regions. Based upon various learning theories, one of the most likely sites for storage of long-term memories is the neocortex. In support of these theories, findings from our laboratory, and others, have demonstrated that trace-conditioning, an associative paradigm where there is a separation in time between the CS and US, induces learning-specific neocortical plasticity. The following review will discuss the amygdala’s involvement, either as a site of storage or facilitating storage in other brain regions such as the neocortex, in fear- and non-fear-motivated associative paradigms. In this review, we will discuss recent findings suggesting a broader role for the amygdala in increasing the saliency of behaviorally relevant information, thus facilitating acquisition for all forms of memory, both fear- and non-fear-related. This proposed promiscuous role of the amygdala in facilitating acquisition for all memories further suggests a potential role of the amygdala in general learning disabilities.

  4. Amygdala's involvement in facilitating associative learning-induced plasticity: a promiscuous role for the amygdala in memory acquisition.

    Science.gov (United States)

    Chau, Lily S; Galvez, Roberto

    2012-01-01

    It is widely accepted that the amygdala plays a critical role in acquisition and consolidation of fear-related memories. Some of the more widely employed behavioral paradigms that have assisted in solidifying the amygdala's role in fear-related memories are associative learning paradigms. With most associative learning tasks, a neutral conditioned stimulus (CS) is paired with a salient unconditioned stimulus (US) that elicits an unconditioned response (UR). After multiple CS-US pairings, the subject learns that the CS predicts the onset or delivery of the US, and thus elicits a learned conditioned response (CR). Most fear-related associative paradigms have suggested that an aspect of the fear association is stored in the amygdala; however, some fear-motivated associative paradigms suggest that the amygdala is not a site of storage, but rather facilitates consolidation in other brain regions. Based upon various learning theories, one of the most likely sites for storage of long-term memories is the neocortex. In support of these theories, findings from our laboratory, and others, have demonstrated that trace-conditioning, an associative paradigm where there is a separation in time between the CS and US, induces learning-specific neocortical plasticity. The following review will discuss the amygdala's involvement, either as a site of storage or facilitating storage in other brain regions such as the neocortex, in fear- and non-fear-motivated associative paradigms. In this review, we will discuss recent findings suggesting a broader role for the amygdala in increasing the saliency of behaviorally relevant information, thus facilitating acquisition for all forms of memory, both fear- and non-fear-related. This proposed promiscuous role of the amygdala in facilitating acquisition for all memories further suggests a potential role of the amygdala in general learning disabilities.

  5. Shp2 in forebrain neurons regulates synaptic plasticity, locomotion, and memory formation in mice.

    Science.gov (United States)

    Kusakari, Shinya; Saitow, Fumihito; Ago, Yukio; Shibasaki, Koji; Sato-Hashimoto, Miho; Matsuzaki, Yasunori; Kotani, Takenori; Murata, Yoji; Hirai, Hirokazu; Matsuda, Toshio; Suzuki, Hidenori; Matozaki, Takashi; Ohnishi, Hiroshi

    2015-05-01

    Shp2 (Src homology 2 domain-containing protein tyrosine phosphatase 2) regulates neural cell differentiation. It is also expressed in postmitotic neurons, however, and mutations of Shp2 are associated with clinical syndromes characterized by mental retardation. Here we show that conditional-knockout (cKO) mice lacking Shp2 specifically in postmitotic forebrain neurons manifest abnormal behavior, including hyperactivity. Novelty-induced expression of immediate-early genes and activation of extracellular-signal-regulated kinase (Erk) were attenuated in the cerebral cortex and hippocampus of Shp2 cKO mice, suggestive of reduced neuronal activity. In contrast, ablation of Shp2 enhanced high-K(+)-induced Erk activation in both cultured cortical neurons and synaptosomes, whereas it inhibited that induced by brain-derived growth factor in cultured neurons. Posttetanic potentiation and paired-pulse facilitation were attenuated and enhanced, respectively, in hippocampal slices from Shp2 cKO mice. The mutant mice also manifested transient impairment of memory formation in the Morris water maze. Our data suggest that Shp2 contributes to regulation of Erk activation and synaptic plasticity in postmitotic forebrain neurons and thereby controls locomotor activity and memory formation.

  6. Rhinal-hippocampal theta coherence during declarative memory formation: interaction with gamma synchronization?

    NARCIS (Netherlands)

    Fell, J.; Klaver, P.; Elfadil, H.; Schaller, C.; Elger, C.E.; Fernandez, G.S.E.

    2003-01-01

    The hippocampus and the rhinal cortex, two substructures of the medial temporal lobe, together play a crucial role in human declarative memory formation. To investigate in detail the mechanism connecting these two structures transiently during memory formation we recorded depth EEG in epilepsy

  7. Dissociation between Complete Hippocampal Context Memory Formation and Context Fear Acquisition

    Science.gov (United States)

    Leake, Jessica; Zinn, Raphael; Corbit, Laura; Vissel, Bryce

    2017-01-01

    Rodents require a minimal time period to explore a context prior to footshock to display plateau-level context fear at test. To investigate whether this rapid fear plateau reflects complete memory formation within that short time-frame, we used the immediate-early gene product Arc as an indicator of hippocampal context memory formation-related…

  8. Ant workers exhibit specialization and memory during raft formation

    Science.gov (United States)

    Avril, Amaury; Purcell, Jessica; Chapuisat, Michel

    2016-06-01

    By working together, social insects achieve tasks that are beyond the reach of single individuals. A striking example of collective behaviour is self-assembly, a process in which individuals link their bodies together to form structures such as chains, ladders, walls or rafts. To get insight into how individual behavioural variation affects the formation of self-assemblages, we investigated the presence of task specialization and the role of past experience in the construction of ant rafts. We subjected groups of Formica selysi workers to two consecutive floods and monitored the position of individuals in rafts. Workers showed specialization in their positions when rafting, with the same individuals consistently occupying the top, middle, base or side position in the raft. The presence of brood modified workers' position and raft shape. Surprisingly, workers' experience in the first rafting trial with brood influenced their behaviour and raft shape in the subsequent trial without brood. Overall, this study sheds light on the importance of workers' specialization and memory in the formation of self-assemblages.

  9. The role of reconsolidation and the dynamic process of long-term memory formation and storage

    Directory of Open Access Journals (Sweden)

    Cristina M Alberini

    2011-03-01

    Full Text Available It is becoming increasingly clear that the processes of memory formation and storage are exquisitely dynamic. Elucidating the nature and temporal evolution of the biological changes that accompany encoding, storage and retrieval is key to understand memory formation. For explicit or medial temporal lobe-dependent memories that form after a discrete event and are stored for a long time, the physical changes underlying the encoding and processing of the information (memory trace or engram remain in a fragile state for some time. However, over time, the new memory becomes increasingly resistant to disruption until it is consolidated. Retrieval or reactivation of an apparently consolidated memory can render the memory labile again, and reconsolidation is the process that occurs to mediate its restabilization. Reconsolidation also evolves with the age of the memory: Young memories are sensitive to postreactivation disruption, but older memories are more resistant. Why does a memory become labile again if it is retrieved or reactivated? Here I suggest that the main function of reconsolidation is to contribute to the lingering consolidation process and mediate memory strengthening. I also discuss the literature and results regarding the influence of the passage of time on the reconsolidation of memory. These points have important implications for the use of reconsolidation in therapeutic settings.

  10. Anodal transcranial direct current stimulation over the supramarginal gyrus facilitates pitch memory.

    Science.gov (United States)

    Schaal, Nora K; Williamson, Victoria J; Banissy, Michael J

    2013-11-01

    Functional neuroimaging studies have shown activation of the supramarginal gyrus during pitch memory tasks. A previous transcranial direct current stimulation study using cathodal stimulation over the left supramarginal gyrus reported a detrimental effect on short-term pitch memory performance, indicating an important role of the supramarginal gyrus in pitch memory. The current study aimed to determine whether pitch memory could be improved following anodal stimulation of the left supramarginal gyrus. The performances of non-musicians on two pitch memory tasks (pitch recognition and recall) and a visual memory control task following anodal or sham transcranial direct current stimulation were compared. The results show that, post-stimulation, the anodal group but not the control group performed significantly better on both pitch memory tasks; performance did not differ on the face memory task. These findings provide strong support for the causal involvement of the left supramarginal gyrus in the pitch memory process, and highlight the potential efficacy of transcranial direct current stimulation as a tool to improve pitch memory. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. Role of 5-HT6 receptors in memory formation.

    Science.gov (United States)

    Meneses, A

    2001-09-01

    Mice lacking the 5-HT(6) receptor presented neither gross anatomical or behavioral abnormalities nor obvious changes in microscopic brain morphology, and their performance in rotarod, open field and novel object testing paradigms revealed no differences compared with wild-type animals. Nevertheless, an association between the 5-HT(6) receptor polymorphism C267T and Alzheimer's disease has been reported. Interestingly, the 5-HT(6) antisense oligonucleotide decreased 5-HT(6) gene expression and enhanced spatial learning acquisition in the water maze. Similarly, injection of the 5-HT(6) receptor antagonist Ro-04-6790 improved learning consolidation in an autoshaping task, while mCPP, scopolamine and dizocilpine decreased performance. The effect induced by scopolamine or dizocilpine, but not that induced by mCPP, was completely or partially reversed by Ro-04-6790. Ro-04-6790 did not modify the 8-OH-DPAT facilitatory effects on learning consolidation. Since Ro-04-6790 facilitatory effect was unaffected by 5-HT(1A), 5-HT(2A/2B/2C), 5-HT(3), 5-HT(4) or 5-HT(7) receptor blockade, the facilitatory effect induced by Ro-04-6790 involved specifically 5-HT6 receptors. Similarly, the 5-HT(6) receptor antagonist SB-271046 improved retention in the water maze and produced a significant performance improvement in aged rats in an operant-delayed alternation task. A series of Ro-04-6790 analogues that penetrate the brain and specifically bind to 5-HT(6) receptors reversed scopolamine-induced retention deficit in a passive avoidance learning test. Collectively, these data provide further support to the notion that 5-HT systems, via 5-HT(6) receptors, also play a significant role in memory formation under normal and dysfunctional memory conditions.

  12. Social Isolation During Adolescence Strengthens Retention of Fear Memories and Facilitates Induction of Late-Phase Long-Term Potentiation.

    Science.gov (United States)

    Liu, Ji-Hong; You, Qiang-Long; Wei, Mei-Dan; Wang, Qian; Luo, Zheng-Yi; Lin, Song; Huang, Lang; Li, Shu-Ji; Li, Xiao-Wen; Gao, Tian-Ming

    2015-12-01

    Social isolation during the vulnerable period of adolescence produces emotional dysregulation that often manifests as abnormal behavior in adulthood. The enduring consequence of isolation might be caused by a weakened ability to forget unpleasant memories. However, it remains unclear whether isolation affects unpleasant memories. To address this, we used a model of associative learning to induce the fear memories and evaluated the influence of isolation mice during adolescence on the subsequent retention of fear memories and its underlying cellular mechanisms. Following adolescent social isolation, we found that mice decreased their social interaction time and had an increase in anxiety-related behavior. Interestingly, when we assessed memory retention, we found that isolated mice were unable to forget aversive memories when tested 4 weeks after the original event. Consistent with this, we observed that a single train of high-frequency stimulation (HFS) enabled a late-phase long-term potentiation (L-LTP) in the hippocampal CA1 region of isolated mice, whereas only an early-phase LTP was observed with the same stimulation in the control mice. Social isolation during adolescence also increased brain-derived neurotrophic factor (BDNF) expression in the hippocampus, and application of a tropomyosin-related kinase B (TrkB) receptor inhibitor ameliorated the facilitated L-LTP seen after isolation. Together, our results suggest that adolescent isolation may result in mental disorders during adulthood and that this may stem from an inability to forget the unpleasant memories via BDNF-mediated synaptic plasticity. These findings may give us a new strategy to prevent mental disorders caused by persistent unpleasant memories.

  13. The neurobiological bases of memory formation: from physiological conditions to psychopathology.

    Science.gov (United States)

    Bisaz, Reto; Travaglia, Alessio; Alberini, Cristina M

    2014-01-01

    The formation of long-term memories is a function necessary for an adaptive survival. In the last two decades, great progress has been made in the understanding of the biological bases of memory formation. The identification of mechanisms necessary for memory consolidation and reconsolidation, the processes by which the posttraining and postretrieval fragile memory traces become stronger and insensitive to disruption, has indicated new approaches for investigating and treating psychopathologies. In this review, we will discuss some key biological mechanisms found to be critical for memory consolidation and strengthening, the role/s and mechanisms of memory reconsolidation, and how the interference with consolidation and/or reconsolidation can modulate the retention and/or storage of memories that are linked to psychopathologies.

  14. Critical Role of the Circadian Clock in Memory Formation: Lessons from Aplysia

    Directory of Open Access Journals (Sweden)

    Lisa Carlson Lyons

    2011-12-01

    Full Text Available Unraveling the complexities of learning and the formation of memory requires identification of the cellular and molecular processes through which neural plasticity arises as well as recognition of the conditions or factors through which those processes are modulated. With its relatively simple nervous system, the marine mollusk Aplysia californica has proven an outstanding model system for studies of memory formation and identification of the molecular mechanisms underlying learned behaviors, including classical and operant associative learning paradigms and non-associative behaviors. In vivo behavioral studies in Aplysia have significantly furthered our understanding of how the endogenous circadian clock modulates memory formation. Sensitization of the tail-siphon withdrawal reflex represents a defensive non-associative learned behavior for which the circadian clock strongly modulates intermediate and long-term memory formation. Likewise, Aplysia exhibit circadian rhythms in long-term memory, but not short-term memory, for an operant associative learning paradigm. This review focuses on circadian modulation of intermediate and long-term memory and the putative mechanisms through which this modulation occurs. Additionally, potential functions and the adaptive advantages of time of day pressure on memory formation are considered. The influence of the circadian clock on learning and memory crosses distant phylogeny highlighting the evolutionary importance of the circadian clock on metabolic, physiological and behavioral processes. Thus, studies in a simple invertebrate model system have and will continue to provide critical mechanistic insights to complementary processes in higher organisms.

  15. Facilitative Effects of Forgetting from Short-Term Memory on Growth of Long-Term Memory in Retardates

    Science.gov (United States)

    Sperber, Richard D.

    1976-01-01

    Competing explanations of the beneficial effect of spacing in retardate discrimination learning were tested. Results are inconsistent with consolidation and rehearsal theories but support the prediction of the Geber, Greenfield, and House spacing model that forgetting from short-term memory facilities retardate learning. (Author/SB)

  16. Working memory cells' behavior may be explained by cross-regional networks with synaptic facilitation.

    Directory of Open Access Journals (Sweden)

    Sergio Verduzco-Flores

    Full Text Available Neurons in the cortex exhibit a number of patterns that correlate with working memory. Specifically, averaged across trials of working memory tasks, neurons exhibit different firing rate patterns during the delay of those tasks. These patterns include: 1 persistent fixed-frequency elevated rates above baseline, 2 elevated rates that decay throughout the tasks memory period, 3 rates that accelerate throughout the delay, and 4 patterns of inhibited firing (below baseline analogous to each of the preceding excitatory patterns. Persistent elevated rate patterns are believed to be the neural correlate of working memory retention and preparation for execution of behavioral/motor responses as required in working memory tasks. Models have proposed that such activity corresponds to stable attractors in cortical neural networks with fixed synaptic weights. However, the variability in patterned behavior and the firing statistics of real neurons across the entire range of those behaviors across and within trials of working memory tasks are typical not reproduced. Here we examine the effect of dynamic synapses and network architectures with multiple cortical areas on the states and dynamics of working memory networks. The analysis indicates that the multiple pattern types exhibited by cells in working memory networks are inherent in networks with dynamic synapses, and that the variability and firing statistics in such networks with distributed architectures agree with that observed in the cortex.

  17. Concurrent Working Memory Load Can Facilitate Selective Attention: Evidence for Specialized Load

    Science.gov (United States)

    Park, Soojin; Kim, Min-Shik; Chun, Marvin M.

    2007-01-01

    Load theory predicts that concurrent working memory load impairs selective attention and increases distractor interference (N. Lavie, A. Hirst, J. W. de Fockert, & E. Viding, see record 2004-17825-003). Here, the authors present new evidence that the type of concurrent working memory load determines whether load impairs selective attention or not.…

  18. The timing of associative memory formation: frontal lobe and anterior medial temporal lobe activity at associative binding predicts memory.

    Science.gov (United States)

    Hales, J B; Brewer, J B

    2011-04-01

    The process of associating items encountered over time and across variable time delays is fundamental for creating memories in daily life, such as for stories and episodes. Forming associative memory for temporally discontiguous items involves medial temporal lobe structures and additional neocortical processing regions, including prefrontal cortex, parietal lobe, and lateral occipital regions. However, most prior memory studies, using concurrently presented stimuli, have failed to examine the temporal aspect of successful associative memory formation to identify when activity in these brain regions is predictive of associative memory formation. In the current study, functional MRI data were acquired while subjects were shown pairs of sequentially presented visual images with a fixed interitem delay within pairs. This design allowed the entire time course of the trial to be analyzed, starting from onset of the first item, across the 5.5-s delay period, and through offset of the second item. Subjects then completed a postscan recognition test for the items and associations they encoded during the scan and their confidence for each. After controlling for item-memory strength, we isolated brain regions selectively involved in associative encoding. Consistent with prior findings, increased regional activity predicting subsequent associative memory success was found in anterior medial temporal lobe regions of left perirhinal and entorhinal cortices and in left prefrontal cortex and lateral occipital regions. The temporal separation within each pair, however, allowed extension of these findings by isolating the timing of regional involvement, showing that increased response in these regions occurs during binding but not during maintenance.

  19. Involuntary conscious memory facilitates cued recall performance: further evidence that chaining occurs during voluntary recall.

    Science.gov (United States)

    Mace, John H

    2009-01-01

    Recent studies have shown that conscious recollection of the past occurs spontaneously when subjects voluntarily recall their own past experiences or a list of previously studied words. Naturalistic diary studies and laboratory studies of this phenomenon, often called involuntary conscious memory (ICM), show that it occurs in 2 ways. One is direct ICM retrieval, which occurs when a cue spontaneously triggers a conscious memory; the other is chained ICM retrieval, which occurs when a retrieved conscious memory spontaneously triggers another. Laboratory studies investigating ICM show that chained ICM retrieval occurs on voluntary autobiographical memory tasks. The present results show that chained ICM retrieval also occurs on a voluntary word list memory task (cued recall). These results are among a handful suggesting that ICM retrieval routinely occurs during voluntary recall.

  20. Detection of impaired IgG antibody formation facilitates the decision on early immunoglobulin replacement in hypogammaglobulinemic patients

    Directory of Open Access Journals (Sweden)

    Hermann Maximilian Wolf

    2015-02-01

    Full Text Available Hypogammaglobulinemia (serum IgG lower than 2SD below the age-matched mean and clinical symptoms such as increased susceptibility to infection, autoimmune manifestations, granulomatous disease, unexplained polyclonal lymphoproliferation are considered to be diagnostic hallmarks in patients with common variable immunodeficiency (CVID, the most frequent clinically severe primary immunodeficiency syndrome. In the present study we investigated patients with hypogammaglobulinemia and no clinical or immunological signs of defective cell-mediated immunity and differentiated two groups on the basis of their IgG antibody formation capacity against a variety of different antigens (bacterial toxins, polysaccharide antigens, viral antigens. Patients with hypogammaglobulinemia and intact antibody production (HIAP displayed no or only mild susceptibility to infections, while CVID patients showed marked susceptibility to bacterial infections that normalized following initiation of IVIG or SCIG replacement therapy. There was a substantial overlap in IgG serum levels between the asymptomatic HIAP group and the CVID patients examined before immunoglobulin treatment. HIAP patients showed normal levels of switched B memory cells (CD19+CD27+IgD-, while both decreased and normal levels of switched B memory cells could be found in CVID patients. IgG antibody response to a primary antigen, tick borne encephalitis virus (TBEV, was defective in CVID patients, thus confirming their substantial defect in IgG antibody production. Defective IgG antibody production against multiple antigens could also be demonstrated in an adult patient with recurrent infections but normal IgG levels. To facilitate early treatment before recurrent infections may lead to organ damage the antibody formation capacity should be examined in hypogammaglobulinemic patients and the decision to treat should be based on the finding of impaired IgG antibody production.

  1. Early and late stages of working-memory maintenance contribute differentially to long-term memory formation.

    Science.gov (United States)

    Bergmann, Heiko C; Kiemeneij, Anne; Fernández, Guillén; Kessels, Roy P C

    2013-06-01

    The present paper investigated the role of early and late stages of working-memory maintenance, which have been suggested to differentially contribute to long-term memory formation. In experiment 1, we administered a delayed-match-to-sample task, requiring participants to remember line drawings of non-sense three-dimensional stimuli. In the delay phase, participants were either presented with a fixation cross (for 2 or 9s) or with one of two different interference tasks, varying in visual overlap with the target. The interference task was presented 1.5, 4.5 or 7.5s after target offset. Early interfering and early probing disproportionately affected performance on an unexpected subsequent recognition-memory task compared to later interference or probing. This was not modulated by the type of interference task. In Experiment 2, we examined whether the formation of a holistic internal code of the target may be a gradual process. An analogous delayed-match-to-sample task was administered, with interference after 0.5, 2.5 or 4.5s after target offset. The early and middle interference condition similarly disproportionately affected performance compared to later interference. Hence, the present results support the view of a functional dissociation between early and late stages of working-memory maintenance and that early working-memory processes contribute particularly to long-term memory formation.

  2. Sex differences in stress effects on response and spatial memory formation.

    Science.gov (United States)

    Guenzel, Friederike M; Wolf, Oliver T; Schwabe, Lars

    2014-03-01

    Stress and stress hormones are known to affect learning and memory processes. However, although effects of stress on hippocampus-dependent declarative learning and memory are well-documented, relatively little attention has been paid to the impact of stress on striatum-dependent stimulus-response (S-R) learning and memory. Recent evidence indicates that glucocorticoid stress hormones shortly after learning enhance S-R memory consolidation, whereas stress prior to retention testing impairs S-R memory retrieval. Whether stress affects also the acquisition of S-R memories in humans remains unclear. For this reason, we examined here the effects of acute stress on S-R memory formation and contrasted these stress effects with those on hippocampus-dependent spatial memory. Healthy men and women underwent a stressor (socially evaluated cold pressor test, SECPT) or a control manipulation before they completed an S-R task and two spatial learning tasks. Memory was assessed one week later. Our data showed that stress impaired S-R memory performance in men but not in women. Conversely, spatial memory was impaired by stress in women but not in men. These findings provide further evidence that stress may alter learning and memory processes beyond the hippocampus. Moreover, our data underline that participants' sex may play a critical role in the impact of stress on multiple memory systems.

  3. Inter-individual differences in trait negative affect moderate cortisol's effects on memory formation: preliminary findings from two studies.

    Science.gov (United States)

    Abercrombie, Heather C; Wirth, Michelle M; Hoks, Roxanne M

    2012-05-01

    Acute emotional arousal moderates the effects of cortisol on memory. However, it is currently unknown how stable inter-individual differences (i.e., traits) moderate cortisol's effects on memory. In two studies using within-subjects designs - 31 healthy males in Study 1 and 42 healthy subjects (22 female) in Study 2 - we measured trait negative affect (NA) and presented emotional and neutral pictures. In Study 1, we manipulated endogenous cortisol levels using a speech stressor following encoding. In Study 2, using a randomized placebo-controlled design, we pharmacologically manipulated cortisol levels prior to encoding (0.1mg/kg hydrocortisone vs. saline infused over 30min). Free recall for pictures was subsequently assessed. Trait NA repeatedly moderated the relationship between cortisol and memory formation. Findings suggested the speculative conclusion that the direction of effects may vary by sex. In males, cortisol was related to memory facilitation in subjects with lower Trait NA. Conversely, females with higher Trait NA showed greater cortisol-related increases in memory. Trait NA may be a stable inter-individual difference predicting neurocognitive effects of cortisol during stressors.

  4. Studies Shed Light on Cross-modal Memory Facilitation of Fruit Flies

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ As a result of their threeyear studies in Drosophilae (fruit flies),CAS scientists reveal that the memory and learning in the insect could be enhanced by stimuli combining olfactory (or smell) and visual signals.

  5. Natural variation in long-term memory formation among Nasonia parasitic wasp species.

    Science.gov (United States)

    Hoedjes, Katja M; Smid, Hans M

    2014-06-01

    Closely related species of parasitic wasps can differ substantially in memory dynamics. In this study we demonstrate differences in the number of conditioning trials required to form long-term memory between the closely related parasitic wasp species Nasonia vitripennis and Nasonia giraulti (Hymenoptera: Pteromalidae). A single conditioning trial, in which a female wasp associates an odour with the reward of finding a host, results in the formation of transcription-dependent long-term memory in N. vitripennis, whereas N. giraulti requires spaced training to do so. Memory formation does not depend on the type of reward: oviposition, which was hypothesized to be a 'larger' reward results in similar memory retention as host feeding in both Nasonia species. There are several genetic and genomic tools available for Nasonia species to identify genetic mechanisms that underlie the observed variation in the number of trials required to form long-term memory. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. From working memory to epilepsy: Dynamics of facilitation and inhibition in a cortical network

    Science.gov (United States)

    Verduzco-Flores, Sergio; Ermentrout, Bard; Bodner, Mark

    2009-03-01

    Persistent states are believed to be the correlate for short-term or working memory. Using a previously derived model for working memory, we show that disruption of the lateral inhibition can lead to a variety of pathological states. These states are analogs of reflex or pattern-sensitive epilepsy. Simulations, numerical bifurcation analysis, and fast-slow decomposition are used to explore the dynamics of this network.

  7. X-Eye: A reference format for eye tracking data to facilitate analyses across databases

    Science.gov (United States)

    Winkler, Stefan; Savoy, Florian M.; Subramanian, Ramanathan

    2014-02-01

    Datasets of images annotated with eye tracking data constitute important ground truth for the development of saliency models, which have applications in many areas of electronic imaging. While comparisons and reviews of saliency models abound, similar comparisons among the eye tracking databases themselves are rare. In an earlier paper, we reviewed the content and purpose of over two dozen databases available in the public domain and discussed their commonalities and differences. A major issue is that the formats of the various datasets vary a lot owing to the nature of tools used for eye movement recordings, and often specialized code is required to use the data for further analysis. In this paper, we therefore propose a common reference format for eye tracking data, together with conversion routines for 16 existing image eye tracking databases to that format. Furthermore, we conduct a few analyses on these datasets as examples of what X-Eye facilitates.

  8. Chitosan facilitates structure formation of the salivary gland by regulating the basement membrane components.

    Science.gov (United States)

    Yang, Tsung-Lin; Hsiao, Ya-Chuan

    2015-10-01

    Tissue structure is important for inherent physiological function and should be recapitulated during tissue engineering for regenerative purposes. The salivary gland is a branched organ that is responsible for saliva secretion and regulation. The salivary glands develop from epithelial-mesenchymal interactions, and depend on the support of the basement membrane (BM). Chitosan-based biomaterials have been demonstrated to be competent in facilitating the formation of salivary gland tissue structure. However, the underlying mechanisms have remained elusive. In the developing submandibular gland (SMG), the chitosan effect was found to diminish when collagen and laminin were removed from cultured SMG explants. Chitosan increased the expression of BM components including collagen, laminin, and heparan sulfate proteoglycan, and also facilitated BM components and the corresponding receptors to be expressed in tissue-specific patterns beneficial for SMG branching. The chitosan effect decreased when either laminin components or receptors were inhibited, as well when the downstream signaling was blocked. Our results revealed that chitosan promotes salivary glands branching through the BM. By regulating BM components and receptors, chitosan efficiently stimulated downstream signaling to facilitate salivary gland branching. The present study revealed the underlying mechanism of the chitosan effect in engineering SMG structure formation.

  9. Prenatal complex rhythmic music sound stimulation facilitates postnatal spatial learning but transiently impairs memory in the domestic chick.

    Science.gov (United States)

    Kauser, H; Roy, S; Pal, A; Sreenivas, V; Mathur, R; Wadhwa, S; Jain, S

    2011-01-01

    Early experience has a profound influence on brain development, and the modulation of prenatal perceptual learning by external environmental stimuli has been shown in birds, rodents and mammals. In the present study, the effect of prenatal complex rhythmic music sound stimulation on postnatal spatial learning, memory and isolation stress was observed. Auditory stimulation with either music or species-specific sounds or no stimulation (control) was provided to separate sets of fertilized eggs from day 10 of incubation. Following hatching, the chicks at age 24, 72 and 120 h were tested on a T-maze for spatial learning and the memory of the learnt task was assessed 24 h after training. In the posthatch chicks at all ages, the plasma corticosterone levels were estimated following 10 min of isolation. The chicks of all ages in the three groups took less (p memory after 24 h of training, only the music-stimulated chicks at posthatch age 24 h took a significantly longer (p music sounds facilitates spatial learning, though the music stimulation transiently impairs postnatal memory. 2011 S. Karger AG, Basel.

  10. Activation of Midbrain Structures by Associative Novelty and the Formation of Explicit Memory in Humans

    Science.gov (United States)

    Schott, Bjorn H.; Sellner, Daniela B.; Lauer, Corinna-J.; Habib, Reza; Frey, Julietta U.; Guderian, Sebastian; Heinze, Hans-Jochen; Duzel, Emrah

    2004-01-01

    Recent evidence suggests a close functional relationship between memory formation in the hippocampus and dopaminergic neuromodulation originating in the ventral tegmental area and medial substantia nigra of the midbrain. Here we report midbrain activation in two functional MRI studies of visual memory in healthy young adults. In the first study,…

  11. System Consolidation During Sleep - A Common Principle Underlying Psychological and Immunological Memory Formation

    NARCIS (Netherlands)

    Westermann, Jürgen; Lange, Tanja; Textor, Johannes; Born, Jan

    2015-01-01

    Sleep benefits the consolidation of psychological memory, and there are hints that sleep likewise supports immunological memory formation. Comparing psychological and immunological domains, we make the case for active system consolidation that is similarly established in both domains and partly conv

  12. System consolidation during sleep - a common principle underlying psychological and immunological memory formation

    NARCIS (Netherlands)

    Westermann, J.; Lange, T.; Textor, J.C.; Born, J. van den

    2015-01-01

    Sleep benefits the consolidation of psychological memory, and there are hints that sleep likewise supports immunological memory formation. Comparing psychological and immunological domains, we make the case for active system consolidation that is similarly established in both domains and partly conv

  13. Dissecting medial temporal lobe contributions to item and associative memory formation.

    NARCIS (Netherlands)

    Qin, S.; Rijpkema, M.J.P.; Tendolkar, I.; Piekema, C.; Hermans, E.J.; Binder, M.; Petersson, K.M.; Luo, J.; Fernandez, G.S.E.

    2009-01-01

    A fundamental and intensively discussed question is whether medial temporal lobe (MTL) processes that lead to non-associative item memories differ in their anatomical substrate from processes underlying associative memory formation. Using event-related functional magnetic resonance imaging, we imple

  14. Activation of Midbrain Structures by Associative Novelty and the Formation of Explicit Memory in Humans

    Science.gov (United States)

    Schott, Bjorn H.; Sellner, Daniela B.; Lauer, Corinna-J.; Habib, Reza; Frey, Julietta U.; Guderian, Sebastian; Heinze, Hans-Jochen; Duzel, Emrah

    2004-01-01

    Recent evidence suggests a close functional relationship between memory formation in the hippocampus and dopaminergic neuromodulation originating in the ventral tegmental area and medial substantia nigra of the midbrain. Here we report midbrain activation in two functional MRI studies of visual memory in healthy young adults. In the first study,…

  15. Processes Underlying Developmental Reversals in False-Memory Formation: Comment on Brainerd, Reyna, and Ceci (2008)

    Science.gov (United States)

    Ghetti, Simona

    2008-01-01

    C. J. Brainerd, V. F. Reyna, and S. J. Ceci (2008) reviewed compelling evidence of developmental reversals in false-memory formation (i.e., younger children exhibit lower false-memory rates than do older children and adults) and proposed that this phenomenon depends on the development of gist processing (i.e., the ability to identify and process…

  16. Co-learning facilitates memory in mice: a new avenue in social neuroscience.

    Science.gov (United States)

    Lipina, Tatiana V; Roder, John C

    2013-01-01

    Social context affects brain function but our understanding of its neurobiology is at an early stage. The mere presence of one individual can alter the cognitive capacities of another and social learning has been demonstrated in many species, including the mouse. We asked several questions: 1. How can active engagement of two familiar mice in the same learning activity (co-learning) alter their memory? 2. Under which environmental conditions (aversive vs non-aversive) can we expect the memory to be enhanced, impaired, or not affected? 3. Can a genetic factor modify the co-learning effect on memory? More specifically, can co-learning correct memory deficits in autistic-like BTBR inbred mice with deficient sociability? We demonstrated that pairs of familiar inbred mice of the same or different genotypes (C57BL/6J and BTBR) that were habituated to new objects and their spatial location, had enhanced episodic memory in the spatial object recognition test, whereas individually-trained animals failed to solve this task. Notably, the co-learning effect was genotype-dependent. BTBR mice paired with BTBR cage-mates in the habituation session modestly ameliorated their performance in the object recognition test but co-learning with a familiar C57BL/6J mouse completely normalized episodic memory deficit. Next, we explored the co-learning effect on fear memory in these inbred strains. Interestingly, mice of both genotypes displayed significantly enhanced contextual fear memory once they had been conditioned together with BTBR animals. The same influence of BTBR presence was observed on cued fear memory in C57BL/6J mice, whereas a modest co-learning effect was found on cued fear conditioning in the BTBR strain. Taken together, we demonstrated for the first time the co-learning effect on cognitive capacities in mice, which can be modified by genetic background and environmental conditions. The possible implications of this methodological approach in social neuroscience are

  17. Syntactic Recursion Facilitates and Working Memory Predicts Recursive Theory of Mind

    Science.gov (United States)

    Arslan, Burcu; Hohenberger, Annette; Verbrugge, Rineke

    2017-01-01

    In this study, we focus on the possible roles of second-order syntactic recursion and working memory in terms of simple and complex span tasks in the development of second-order false belief reasoning. We tested 89 Turkish children in two age groups, one younger (4;6–6;5 years) and one older (6;7–8;10 years). Although second-order syntactic recursion is significantly correlated with the second-order false belief task, results of ordinal logistic regressions revealed that the main predictor of second-order false belief reasoning is complex working memory span. Unlike simple working memory and second-order syntactic recursion tasks, the complex working memory task required processing information serially with additional reasoning demands that require complex working memory strategies. Based on our results, we propose that children’s second-order theory of mind develops when they have efficient reasoning rules to process embedded beliefs serially, thus overcoming a possible serial processing bottleneck. PMID:28072823

  18. Narrative organisation at encoding facilitated children's long-term episodic memory.

    Science.gov (United States)

    Wang, Qi; Bui, Van-Kim; Song, Qingfang

    2015-01-01

    This study examined the effect of narrative organisation at encoding on long-term episodic memory in a sample of five- to seven-year-old children (N = 113). At an initial interview, children were asked to narrate a story from a picture book. Six months later, they were interviewed again and asked to recall the story and answer a series of direct questions about the story. Children who initially encoded more information in narrative and produced more complete, complex, cohesive and coherent narratives remembered the story in greater detail and accuracy following the six-month interval, independent of age and verbal skills. The relation between narrative organisation and memory was consistent across culture and gender. These findings provide new insight into the critical role of narrative in episodic memory.

  19. Multiple repressive mechanisms in the hippocampus during memory formation

    National Research Council Canada - National Science Library

    Cho, Jun; Yu, Nam-Kyung; Choi, Jun-Hyeok; Sim, Su-Eon; Kang, SukJae Joshua; Kwak, Chuljung; Lee, Seung-Woo; Kim, Ji-il; Choi, Dong Il; Kim, V Narry; Kaang, Bong-Kiun

    2015-01-01

    Memory stabilization after learning requires translational and transcriptional regulations in the brain, yet the temporal molecular changes that occur after learning have not been explored at the genomic scale...

  20. Hippocampal-neocortical interactions in memory formation, consolidation, and reconsolidation.

    Science.gov (United States)

    Wang, Szu-Han; Morris, Richard G M

    2010-01-01

    This review, focusing on work using animals, updates a theoretical approach whose aim is to translate neuropsychological ideas about the psychological and anatomical organization of memory into the neurobiological domain. It is suggested that episodic-like memory consists of both automatic and controlled components, with the medial temporal mediation of memory encoding including neurobiological mechanisms that are primarily automatic or incidental. These ideas, in the cognitive and behavioral domain, are linked to neurophysiological ideas about cellular consolidation concerning synaptic potentiation, particularly the relationship between protein synthesis-dependent long-term changes and shorter-lasting post-translational mechanisms. Ideas from psychology about mental schemas are considered in relation to the phenomenon of systems consolidation and, specifically, about how prior knowledge can alter the rate at which consolidation occurs. Finally, the hippocampal-neocortical interactions theory is updated in relation to reconsolidation, a process that enables updating of stored memory traces in response to novelty.

  1. Novelty processing and memory formation in Parkinson's disease

    NARCIS (Netherlands)

    Schomaker, J; Berendse, H W; Foncke, E M J; van der Werf, Y D; van den Heuvel, O A; Theeuwes, J; Meeter, M

    BACKGROUND: Parkinson's disease (PD) is characterized by a degeneration of nigrostriatal dopaminergic cells, resulting in dopamine depletion. This depletion is counteracted through dopamine replacement therapy (DRT). Dopamine has been suggested to affect novelty processing and memory, which suggests

  2. Autoradiographic study of serotonin transporter during memory formation.

    Science.gov (United States)

    Tellez, Ruth; Rocha, Luisa; Castillo, Carlos; Meneses, Alfredo

    2010-09-01

    Serotonin transporter (SERT) has been associated with drugs of abuse like d-methamphetamine (METH). METH is well known to produce effects on the monoamine systems but it is unclear how METH affects SERT and memory. Here the effects of METH and the serotonin reuptake inhibitor fluoxetine (FLX) on autoshaping and novel object recognition (NOR) were investigated. Notably, both memory tasks recruit different behavioral, neural and cognitive demand. In autoshaping task a dose-response curve for METH was determined. METH (1.0mg/kg) impaired short-term memory (STM; lasting less of 90min) in NOR and impaired both STM and long-term memory (LTM; lasting 24 and 48h) in autoshaping, indicating that METH had long-lasting effects in the latter task. A comparative autoradiography study of the relationship between the binding pattern of SERT in autoshaping new untrained vs. trained treated (METH, FLX, or both) animals was made. Considering that hemispheric dominance is important for LTM, hence right vs. left hemisphere of the brain was compared. Results showed that trained animals decreased cortical SERT binding relative to untrained ones. In untrained and trained treated animals with the amnesic dose (1.0mg/kg) of METH SERT binding in several areas including hippocampus and cortex decreased, more remarkably in the trained animals. In contrast, FLX improved memory, increased SERT binding, prevented the METH amnesic effect and re-established the SERT binding. In general, memory and amnesia seemed to make SERT more vulnerable to drugs effects.

  3. Change in the relative contributions of habit and working memory facilitates serial reversal learning expertise in rhesus monkeys.

    Science.gov (United States)

    Hassett, Thomas C; Hampton, Robert R

    2017-02-09

    Functionally distinct memory systems likely evolved in response to incompatible demands placed on learning by distinct environmental conditions. Working memory appears adapted, in part, for conditions that change frequently, making rapid acquisition and brief retention of information appropriate. In contrast, habits form gradually over many experiences, adapting organisms to contingencies of reinforcement that are stable over relatively long intervals. Serial reversal learning provides an opportunity to simultaneously examine the processes involved in adapting to rapidly changing and relatively stable contingencies. In serial reversal learning, selecting one of the two simultaneously presented stimuli is positively reinforced, while selection of the other is not. After a preference for the positive stimulus develops, the contingencies of reinforcement reverse. Naïve subjects adapt to such reversals gradually, perseverating in selection of the previously rewarded stimulus. Experts reverse rapidly according to a win-stay, lose-shift response pattern. We assessed whether a change in the relative control of choice by habit and working memory accounts for the development of serial reversal learning expertise. Across three experiments, we applied manipulations intended to attenuate the contribution of working memory but leave the contribution of habit intact. We contrasted performance following long and short intervals in Experiments 1 and 2, and we interposed a competing cognitive load between trials in Experiment 3. These manipulations slowed the acquisition of reversals in expert subjects, but not naïve subjects, indicating that serial reversal learning expertise is facilitated by a shift in the control of choice from passively acquired habit to actively maintained working memory.

  4. NT-3 Facilitates Hippocampal Plasticity and Learning and Memory by Regulating Neurogenesis

    Science.gov (United States)

    Sakata, Kazuko; Akbarian, Schahram; Bates, Brian; Jaenisch, Rudolf; Lu, Bai; Shimazu, Kazuhiro; Zhao, Mingrui

    2006-01-01

    In the adult brain, the expression of NT-3 is largely confined to the hippocampal dentate gyrus (DG), an area exhibiting significant neurogenesis. Using a conditional mutant line in which the "NT-3" gene is deleted in the brain, we investigated the role of NT-3 in adult neurogenesis, hippocampal plasticity, and memory. Bromodeoxyuridine…

  5. Modality-specific alpha modulations facilitate long-term memory encoding in the presence of distracters

    NARCIS (Netherlands)

    Jiang, H.; Gerven, M.A.J. van; Jensen, O.

    2014-01-01

    It has been proposed that long-term memory encoding is not only dependent on engaging task-relevant regions but also on disengaging task-irrelevant regions. In particular, oscillatory alpha activity has been shown to be involved in shaping the functional architecture of the working brain because it

  6. Modality-specific Alpha Modulations Facilitate Long-term Memory Encoding in the Presence of Distracters

    NARCIS (Netherlands)

    Jiang, H.; Gerven, M.A.J. van; Jensen, O.

    2015-01-01

    It has been proposed that long-term memory encoding is not only dependent on engaging task-relevant regions but also on disengaging task-irrelevant regions. In particular, oscillatory alpha activity has been shown to be involved in shaping the functional architecture of the working brain because it

  7. Facilitation of Memory for Extinction of Drug-Induced Conditioned Reward: Role of Amygdala and Acetylcholine

    Science.gov (United States)

    Schroeder, Jason P.; Packard, Mark G.

    2004-01-01

    eThese experiments examined the effects of posttrial peripheral and intra-amygdala injections of the cholinergic muscarinic receptor agonist oxotremorine on memory consolidation underlying extinction of amphetamine conditioned place preference (CPP) behavior. Male Long-Evans rats were initially trained and tested for an amphetamine (2 mg/kg) CPP.…

  8. Does stress remove the HDAC brakes for the formation and persistence of long-term memory?

    Science.gov (United States)

    White, André O; Wood, Marcelo A

    2014-07-01

    It has been known for numerous decades that gene expression is required for long-lasting forms of memory. In the past decade, the study of epigenetic mechanisms in memory processes has revealed yet another layer of complexity in the regulation of gene expression. Epigenetic mechanisms do not only provide complexity in the protein regulatory complexes that control coordinate transcription for specific cell function, but the epigenome encodes critical information that integrates experience and cellular history for specific cell functions as well. Thus, epigenetic mechanisms provide a unique mechanism of gene expression regulation for memory processes. This may be why critical negative regulators of gene expression, such as histone deacetylases (HDACs), have powerful effects on the formation and persistence of memory. For example, HDAC inhibition has been shown to transform a subthreshold learning event into robust long-term memory and also generate a form of long-term memory that persists beyond the point at which normal long-term memory fails. A key question that is explored in this review, from a learning and memory perspective, is whether stress-dependent signaling drives the formation and persistence of long-term memory via HDAC-dependent mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Does stress remove the HDAC brakes for the formation and persistence of long-term memory?

    Science.gov (United States)

    White, André O.; Wood, Marcelo A.

    2013-01-01

    It has been known for numerous decades that gene expression is required for long-lasting forms of memory. In the past decade, the study of epigenetic mechanisms in memory processes has revealed yet another layer of complexity in the regulation of gene expression. Epigenetic mechanisms do not only provide complexity in the protein regulatory complexes that control coordinate transcription for specific cell function, but the epigenome encodes critical information that integrates experience and cellular history for specific cell functions as well. Thus, epigenetic mechanisms provide a unique mechanism of gene expression regulation for memory processes. This may be why critical negative regulators of gene expression, such as histone deacetylases (HDACs), have powerful effects on the formation and persistence of memory. For example, HDAC inhibition has been shown to transform a subthreshold learning event into robust long-term memory and also generate a form of long-term memory that persists beyond the point at which normal long-term memory fails. A key question that is explored in this review, from a learning and memory perspective, is whether stress-dependent signaling drives the formation and persistence of long-term memory via HDAC-dependent mechanisms. PMID:24149059

  10. The interaction of working memory performance and episodic memory formation in patients with Korsakoff's amnesia

    NARCIS (Netherlands)

    Geldorp, B. van; Bergmann, H.; Robertson, J.; Wester, A.J.; Kessels, R.P.C.

    2012-01-01

    Both neuroimaging work and studies investigating amnesic patients have shown involvement of the medial temporal lobe during working memory tasks, especially when multiple items or features have to be associated. However, so far no study has examined the relationship between working memory and subseq

  11. The interaction of working memory performance and episodic memory formation in patients with Korsakoff's amnesia.

    NARCIS (Netherlands)

    Geldorp, B. van; Bergmann, H.C.; Robertson, J.; Wester, A.J.; Kessels, R.P.C.

    2012-01-01

    Both neuroimaging work and studies investigating amnesic patients have shown involvement of the medial temporal lobe during working memory tasks, especially when multiple items or features have to be associated. However, so far no study has examined the relationship between working memory and

  12. The interaction of working memory performance and episodic memory formation in patients with Korsakoff's amnesia

    NARCIS (Netherlands)

    Geldorp, B. van; Bergmann, H.; Robertson, J.; Wester, A.J.; Kessels, R.P.C.

    2012-01-01

    Both neuroimaging work and studies investigating amnesic patients have shown involvement of the medial temporal lobe during working memory tasks, especially when multiple items or features have to be associated. However, so far no study has examined the relationship between working memory and

  13. The interaction of working memory performance and episodic memory formation in patients with Korsakoff's amnesia.

    NARCIS (Netherlands)

    Geldorp, B. van; Bergmann, H.C.; Robertson, J.; Wester, A.J.; Kessels, R.P.C.

    2012-01-01

    Both neuroimaging work and studies investigating amnesic patients have shown involvement of the medial temporal lobe during working memory tasks, especially when multiple items or features have to be associated. However, so far no study has examined the relationship between working memory and subseq

  14. Facilitating memory for novel characters by reducing neural repetition suppression in the left fusiform cortex.

    Directory of Open Access Journals (Sweden)

    Gui Xue

    Full Text Available BACKGROUND: The left midfusiform and adjacent regions have been implicated in processing and memorizing familiar words, yet its role in memorizing novel characters has not been well understood. METHODOLOGY/PRINCIPAL FINDINGS: Using functional MRI, the present study examined the hypothesis that the left midfusiform is also involved in memorizing novel characters and spaced learning could enhance the memory by enhancing the left midfusiform activity during learning. Nineteen native Chinese readers were scanned while memorizing the visual form of 120 Korean characters that were novel to the subjects. Each character was repeated four times during learning. Repetition suppression was manipulated by using two different repetition schedules: massed learning and spaced learning, pseudo-randomly mixed within the same scanning session. Under the massed learning condition, the four repetitions were consecutive (with a jittered inter-repetition interval to improve the design efficiency. Under the spaced learning condition, the four repetitions were interleaved with a minimal inter-repetition lag of 6 stimuli. Spaced learning significantly improved participants' performance during the recognition memory test administered one hour after the scan. Stronger left midfusiform and inferior temporal gyrus activities during learning (summed across four repetitions were associated with better memory of the characters, based on both within- and cross-subjects analyses. Compared to massed learning, spaced learning significantly reduced neural repetition suppression and increased the overall activities in these regions, which were associated with better memory for novel characters. CONCLUSIONS/SIGNIFICANCE: These results demonstrated a strong link between cortical activity in the left midfusiform and memory for novel characters, and thus challenge the visual word form area (VWFA hypothesis. Our results also shed light on the neural mechanisms of the spacing effect in

  15. [The effect of impression formation on memory of trait words: relation between coding and retrieval process].

    Science.gov (United States)

    Takaoka, M

    2000-08-01

    Three experiments investigated the effect of impression formation of a person on the recall and recognition of trait words. The subjects were assigned to one of four groups: Impression, Memory, Impression-Memory, and Incidental groups. Each subject performed an orienting task followed by free recall and recognition tests. In a recall test, false recall of antonyms of targets occurred more often in the Memory group than in the Impression group. There was no difference in the correct recall. In a multiple choice recognition test and a yes-no recognition test, false recognition to antonyms of targets occurred more often in the Memory group than in the Impression group. Hit to targets occurred more often in the Impression group than in the Memory group. These results were interpreted as showing that formation of an impression for a person had different effects for recall and recognition tests. The results were discussed in terms of a relation between encoding and retrieval processes.

  16. HCF-1 self-association via an interdigitated Fn3 structure facilitates transcriptional regulatory complex formation.

    Science.gov (United States)

    Park, Jihye; Lammers, Fabienne; Herr, Winship; Song, Ji-Joon

    2012-10-23

    Host-cell factor 1 (HCF-1) is an unusual transcriptional regulator that undergoes a process of proteolytic maturation to generate N- (HCF-1(N)) and C- (HCF-1(C)) terminal subunits noncovalently associated via self-association sequence elements. Here, we present the crystal structure of the self-association sequence 1 (SAS1) including the adjacent C-terminal HCF-1 nuclear localization signal (NLS). SAS1 elements from each of the HCF-1(N) and HCF-1(C) subunits form an interdigitated fibronectin type 3 (Fn3) tandem repeat structure. We show that the C-terminal NLS recruited by the interdigitated SAS1 structure is required for effective formation of a transcriptional regulatory complex: the herpes simplex virus VP16-induced complex. Thus, HCF-1(N)-HCF-1(C) association via an integrated Fn3 structure permits an NLS to facilitate formation of a transcriptional regulatory complex.

  17. Stress in the zoo: Tracking the impact of stress on memory formation over time.

    Science.gov (United States)

    Vogel, Susanne; Schwabe, Lars

    2016-09-01

    Although stress is well known to modulate human memory, precisely how memory formation is altered by a stressful encounter remains unclear. Stress effects on cognition are mainly mediated by the rapidly acting sympathetic nervous system, resulting in the release of catecholamines, and the slower acting hypothalamus-pituitary-adrenal axis secreting cortisol, which induces its effects on cognition through fast, non-genomic actions and delayed, genomic actions. Importantly, these different waves of the physiological stress response are thought to dynamically alter neural processing in brain regions important for memory such as the amygdala and the hippocampus. However, the precise time course of stress effects on memory formation is still unclear. To track the development of stress effects on memory over time, we tested individuals who underwent a stressful experience or a control procedure before a 2-h walk through a zoo, while an automatic camera continuously photographed the events they encoded. In a recognition memory test one week later, participants were presented with target photographs of their own zoo tour and lure photographs from an alternate tour. Stressed participants showed better memory for the experimental treatment than control participants, and this memory enhancement for the stressful encounter itself was directly linked to the sympathetic stress response. Moreover, stress enhanced memory for events encoded 41-65min after stressor onset, which was associated with the cortisol stress response, most likely arising from non-genomic cortisol actions. However, memory for events encoded long after the stressor, when genomic cortisol actions had most likely developed, remained unchanged. Our findings provide novel insights into how stress effects on memory formation develop over time, depending on the activity of major physiological stress response systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Temporal effects of dehydroepiandrosterone sulfate on memory formation in day-old chicks.

    Science.gov (United States)

    Sujkovic, E; Mileusnic, R; Fry, J P; Rose, S P R

    2007-08-24

    Dehydroepiandrosterone sulfate (DHEAS) has been shown to enhance memory retention in different animal models and in various learning paradigms. In the present study, we investigated the effect of peripherally administered DHEAS on the acquisition, consolidation and retention of memory using a weak version of the one-trial passive avoidance task in day-old chicks. Intraperitoneally administered DHEAS (20 mg/kg) either 30 min before or 30 min and 4.5 h after training on the weakly aversive stimulus, enhanced recall at 24 h following training, suggesting a potentiation of not only the acquisition but also the early and late phases of memory consolidation. In contrast, when DHEAS was administered at 30 min prior to the 24 h retention test there was no memory enhancement, indicating a lack of effect on memory retrieval. Memory recall was unaltered when DHEAS was administered at 30 min before training in a control group trained on a strongly aversive stimulus, confirming memory-specific effects. Interestingly, the memory enhancement appeared to be sex-specific as male chicks showed higher recall than females. These findings provide further evidence that DHEAS enhances memory and may be involved in the temporal cascade of long-term memory formation.

  19. Spatial memory deficits and motor coordination facilitation in cGMP-dependent protein kinase type II-deficient mice.

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    Wincott, Charlotte M; Kim, Seonil; Titcombe, Roseann F; Tukey, David S; Girma, Hiwot K; Pick, Joseph E; Devito, Loren M; Hofmann, Franz; Hoeffer, Charles; Ziff, Edward B

    2013-01-01

    Activity-dependent trafficking of AMPA receptors to synapses regulates synaptic strength. Activation of the NMDA receptor induces several second messenger pathways that contribute to receptor trafficking-dependent plasticity, including the NO pathway, which elevates cGMP. In turn, cGMP activates the cGMP-dependent protein kinase type II (cGKII), which phosphorylates the AMPA receptor subunit GluA1 at serine 845, a critical step facilitating synaptic delivery in the mechanism of activity-dependent synaptic potentiation. Since cGKII is expressed in the striatum, amygdala, cerebral cortex, and hippocampus, it has been proposed that mice lacking cGKII may present phenotypic differences compared to their wild-type littermates in emotion-dependent tasks, learning and memory, and drug reward salience. Previous studies have shown that cGKII KO mice ingest higher amounts of ethanol as well as exhibit elevated anxiety levels compared to wild-type (WT) littermates. Here, we show that cGKII KO mice are significantly deficient in spatial learning while exhibiting facilitated motor coordination, demonstrating a clear dependence of memory-based tasks on cGKII. We also show diminished GluA1 phosphorylation in the postsynaptic density (PSD) of cGKII KO prefrontal cortex while in hippocampal PSD fractions, phosphorylation was not significantly altered. These data suggest that the role of cGKII may be more robust in particular brain regions, thereby impacting complex behaviors dependent on these regions differently.

  20. Microtubule Dynamicity Is More Important than Stability in Memory Formation: an In Vivo Study.

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    Atarod, Deyhim; Eskandari-Sedighi, Ghazaleh; Pazhoohi, Farid; Karimian, Seyed Morteza; Khajeloo, Mojtaba; Riazi, Gholam Hossein

    2015-06-01

    It has been shown that microtubule (MT) activity and dynamics can have huge impacts on synaptic plasticity and memory formation. This is mainly due to various functions of MTs in neurons; MTs are involved in dendritic spine formation, axonal transportation, neuronal polarity, and receptor trafficking. Recent studies from our group and other labs have suggested the possible role of brain MT dynamicity and activity in memory; however, there is a need for more detailed studies regarding this aspect. In this study, we have tried to evaluate the importance of microtubule dynamicity rather than stability in memory formation in vivo. In order to investigate the role of MT stability in memory formation, we treated mice with paclitaxel-a classic microtubule-stabilizing agent. We then studied the behavior of treated animals using Morris water maze (MWM) test. To measure the effect of injected paclitaxel on MT polymerization kinetics, we conducted polymerization assays on brain extracts of the same paclitaxel-treated animals. Our results show that paclitaxel treatment affects animals' memory in a negative way and treated animals behave poorly in MWM compared to control group. In addition, our kinetics studies show that MT stability is significantly increased in brain extracts from paclitaxel-treated mice, but MT dynamics is reduced. Thus, we suggest that dynamicity is a very important feature of MT protein structures, and regarding memory formation, dynamicity is more important than stability and high activity.

  1. CREB binding protein is required for both short-term and long-term memory formation.

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    Chen, Guiquan; Zou, Xiaoyan; Watanabe, Hirotaka; van Deursen, Jan M; Shen, Jie

    2010-09-29

    CREB binding protein (CBP) is a transcriptional coactivator with histone acetyltransferase activity. Our prior study suggested that CBP might be a key target of presenilins in the regulation of memory formation and neuronal survival. To elucidate the role of CBP in the adult brain, we generated conditional knock-out (cKO) mice in which CBP is completely inactivated in excitatory neurons of the postnatal forebrain. Histological analysis revealed normal neuronal morphology and absence of age-dependent neuronal degeneration in the CBP cKO cerebral cortex. CBP cKO mice exhibited robust impairment in the formation of spatial, associative, and object-recognition memory. In addition to impaired long-term memory, CBP cKO mice also displayed deficits in short-term associative and object-recognition memory. Administration of a histone deacetylase inhibitor, trichostatin A, rescued the reduction of acetylated histones in the CBP cKO cortex but failed to rescue either short- or long-term memory deficits, suggesting that the memory impairment may not be caused by general reduction of histone acetyltransferase activity in CBP cKO mice. Further microarray and Western analysis showed decreased expression of calcium-calmodulin-dependent kinase isoforms and NMDA and AMPA receptor subunits in the cerebral cortex of CBP cKO mice. Collectively, these findings suggest a crucial role for CBP in the formation of both short- and long-term memory.

  2. Protooncogenes subserve memory formation in the adult CNS.

    Science.gov (United States)

    Sweatt, J D

    2001-09-13

    Studies of the signal transduction mechanisms underlying learning and memory have provided many new insights into the molecular mechanisms underlying associative conditioning in mammals. In this issue of Neuron, Gean and colleagues report the discovery that the PI-3 kinase/AKT(PKB) pathway contributes to LTP and the consolidation of amygdala-dependent cued fear conditioning in rats.

  3. Oxytocin selectively facilitates learning with social feedback and increases activity and functional connectivity in emotional memory and reward processing regions.

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    Hu, Jiehui; Qi, Song; Becker, Benjamin; Luo, Lizhu; Gao, Shan; Gong, Qiyong; Hurlemann, René; Kendrick, Keith M

    2015-06-01

    In male Caucasian subjects, learning is facilitated by receipt of social compared with non-social feedback, and the neuropeptide oxytocin (OXT) facilitates this effect. In this study, we have first shown a cultural difference in that male Chinese subjects actually perform significantly worse in the same reinforcement associated learning task with social (emotional faces) compared with non-social feedback. Nevertheless, in two independent double-blind placebo (PLC) controlled between-subject design experiments we found OXT still selectively facilitated learning with social feedback. Similar to Caucasian subjects this OXT effect was strongest with feedback using female rather than male faces. One experiment performed in conjunction with functional magnetic resonance imaging showed that during the response, but not feedback phase of the task, OXT selectively increased activity in the amygdala, hippocampus, parahippocampal gyrus and putamen during the social feedback condition, and functional connectivity between the amygdala and insula and caudate. Therefore, OXT may be increasing the salience and reward value of anticipated social feedback. In the PLC group, response times and state anxiety scores during social feedback were associated with signal changes in these same regions but not in the OXT group. OXT may therefore have also facilitated learning by reducing anxiety in the social feedback condition. Overall our results provide the first evidence for cultural differences in social facilitation of learning per se, but a similar selective enhancement of learning with social feedback under OXT. This effect of OXT may be associated with enhanced responses and functional connectivity in emotional memory and reward processing regions.

  4. GABA, glutamate, dopamine and serotonin transporters expression on memory formation and amnesia.

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    Tellez, Ruth; Gómez-Víquez, Leticia; Meneses, Alfredo

    2012-02-01

    Notwithstanding several neurotransmission systems are frequently related to memory formation, amnesia and/or therapeutic targets for memory alterations, the role of transporters γ-aminobutyric acid (GABA, GAT1), glutamate (neuronal glutamate transporter excitatory amino acid carrier; EACC1), dopamine (DAT) and serotonin (SERT) is poorly understood. Hence, in this paper Western-blot analysis was used to evaluate expression changes on them during memory formation in trained and untrained rats treated with the selective serotonin transporter inhibitor fluoxetine, the amnesic drug d-methamphetamine (METH) and fluoxetine plus METH. Transporters expression was evaluated in the hippocampus, prefrontal cortex and striatum. Data indicated that in addition of memory performance other behavioral parameters (e.g., explorative behavior, food-intake, etc.) that memory formation was recorded. Thus, memory formation in a Pavlovian/instrumental autoshaping was associated to up-regulation of prefrontal cortex GAT1 and EAAC1, striatal SERT, DAT and EACC1; while, hippocampal EACC1, GAT1 and SERT were down-regulated. METH impaired short (STM) and long-term memory (LTM), at 24 or 48h. The METH-induced amnesia down-regulated SERT, DAT, EACC1 and GAT1 in hippocampus and the GAT1 in striatum; no-changes were observed in prefrontal cortex. Post-training administration of fluoxetine improved LTM (48h), which was associated to DAT, GAT1 (prefrontal cortex) up-regulation, but GAT1 (striatum) and SERT (hippocampus) down-regulation. Fluoxetine plus METH administration was able to prevent amnesia, which was associated to DAT, EACC1 and GAT1 (prefrontal cortex), SERT and DAT (hippocampus) and EACC1 or DAT (striatal) up-regulation. Together these data show that memory formation, amnesia and anti-amnesic effects are associated to specific patters of transporters expression.

  5. Neural substrates of successful working memory and long-term memory formation in a relational spatial memory task.

    Science.gov (United States)

    Bergmann, Heiko C; Daselaar, Sander M; Fernández, Guillén; Kessels, Roy P C

    2016-11-01

    Working memory (WM) tasks may involve brain activation actually implicated in long-term memory (LTM). In order to disentangle these two memory systems, we employed a combined WM/LTM task, using a spatial relational (object-location) memory paradigm and analyzed which brain areas were associated with successful performance for either task using fMRI. Critically, we corrected for the performance on the respective memory task when analyzing subsequent memory effects. The WM task consisted of a delayed-match-to-sample task assessed in an MRI scanner. Each trial consisted of an indoor or outdoor scene in which the exact configuration of four objects had to be remembered. After a short delay (7-13 s), the scene was presented from a different angle and spatial recognition for two objects was tested. After scanning, participants received an unexpected subsequent recognition memory (LTM) task, where the two previously unprobed objects were tested. Brain activity during encoding, delay phase and probe phase was analyzed based on WM and LTM performance. Results showed that successful WM performance, when corrected for LTM performance, was associated with greater activation in the inferior frontal gyrus and left fusiform gyrus during the early stage of the maintenance phase. A correct decision during the WM probe was accompanied by greater activation in a wide network, including bilateral hippocampus, right superior parietal gyrus and bilateral insula. No voxels exhibited supra-threshold activity during the encoding phase, and we did not find any differential activity for correct versus incorrect trials in the WM task when comparing LTM correct versus LTM incorrect trials.

  6. Hippocampal long-term depression is facilitated by the acquisition and updating of memory of spatial auditory content and requires mGlu5 activation.

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    Dietz, Birte; Manahan-Vaughan, Denise

    2017-03-15

    Long-term potentiation (LTP) and long-term depression (LTD) are key cellular processes that support memory formation. Whereas increases of synaptic strength by means of LTP may support the creation of a spatial memory 'engram', LTD appears to play an important role in refining and optimising experience-dependent encoding. A differentiation in the role of hippocampal subfields is apparent. For example, LTD in the dentate gyrus (DG) is enabled by novel learning about large visuospatial features, whereas in area CA1, it is enabled by learning about discrete aspects of spatial content, whereby, both discrete visuospatial and olfactospatial cues trigger LTD in CA1. Here, we explored to what extent local audiospatial cues facilitate information encoding in the form of LTD in these subfields. Coupling of low frequency afferent stimulation (LFS) with discretely localised, novel auditory tones in the sonic hearing, or ultrasonic range, facilitated short-term depression (STD) into LTD (>24 h) in CA1, but not DG. Re-exposure to the now familiar audiospatial configuration ca. 1 week later failed to enhance STD. Reconfiguration of the same audiospatial cues resulted anew in LTD when ultrasound, but not non-ultrasound cues were used. LTD facilitation that was triggered by novel exposure to spatially arranged tones, or to spatial reconfiguration of the same tones were both prevented by an antagonism of the metabotropic glutamate receptor, mGlu5. These data indicate that, if behaviourally salient enough, the hippocampus can use audiospatial cues to facilitate LTD that contributes to the encoding and updating of spatial representations. Effects are subfield-specific, and require mGlu5 activation, as is the case for visuospatial information processing. These data reinforce the likelihood that LTD supports the encoding of spatial features, and that this occurs in a qualitative and subfield-specific manner. They also support that mGlu5 is essential for synaptic encoding of spatial

  7. The differential role of cortical protein synthesis in taste memory formation and persistence

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    Levitan, David; Gal-Ben-Ari, Shunit; Heise, Christopher; Rosenberg, Tali; Elkobi, Alina; Inberg, Sharon; Sala, Carlo; Rosenblum, Kobi

    2016-05-01

    The current dogma suggests that the formation of long-term memory (LTM) is dependent on protein synthesis but persistence of the memory trace is not. However, many of the studies examining the effect of protein synthesis inhibitors (PSIs) on LTM persistence were performed in the hippocampus, which is known to have a time-dependent role in memory storage, rather than the cortex, which is considered to be the main structure to store long-term memories. Here we studied the effect of PSIs on LTM formation and persistence in male Wistar Hola (n⩾5) rats by infusing the protein synthesis inhibitor, anisomycin (100 μg, 1 μl), into the gustatory cortex (GC) during LTM formation and persistence in conditioned taste aversion (CTA). We found that local anisomycin infusion to the GC before memory acquisition impaired LTM formation (P=8.9E-5), but had no effect on LTM persistence when infused 3 days post acquisition (P=0.94). However, when we extended the time interval between treatment with anisomycin and testing from 3 days to 14 days, LTM persistence was enhanced (P=0.01). The enhancement was on the background of stable and non-declining memory, and was not recapitulated by another amnesic agent, APV (10 μg, 1 μl), an N-methyl-D-aspartate receptor antagonist (P=0.54). In conclusion, CTA LTM remains sensitive to the action of PSIs in the GC even 3 days following memory acquisition. This sensitivity is differentially expressed between the formation and persistence of LTM, suggesting that increased cortical protein synthesis promotes LTM formation, whereas decreased protein synthesis promotes LTM persistence.

  8. The differential role of cortical protein synthesis in taste memory formation and persistence

    Science.gov (United States)

    Levitan, David; Gal-Ben-Ari, Shunit; Heise, Christopher; Rosenberg, Tali; Elkobi, Alina; Inberg, Sharon; Sala, Carlo; Rosenblum, Kobi

    2016-01-01

    The current dogma suggests that the formation of long-term memory (LTM) is dependent on protein synthesis but persistence of the memory trace is not. However, many of the studies examining the effect of protein synthesis inhibitors (PSIs) on LTM persistence were performed in the hippocampus, which is known to have a time-dependent role in memory storage, rather than the cortex, which is considered to be the main structure to store long-term memories. Here we studied the effect of PSIs on LTM formation and persistence in male Wistar Hola (n ≥ 5) rats by infusing the protein synthesis inhibitor, anisomycin (100 μg, 1 μl), into the gustatory cortex (GC) during LTM formation and persistence in conditioned taste aversion (CTA). We found that local anisomycin infusion to the GC before memory acquisition impaired LTM formation (P = 8.9E − 5), but had no effect on LTM persistence when infused 3 days post acquisition (P = 0.94). However, when we extended the time interval between treatment with anisomycin and testing from 3 days to 14 days, LTM persistence was enhanced (P = 0.01). The enhancement was on the background of stable and non-declining memory, and was not recapitulated by another amnesic agent, APV (10 μg, 1 μl), an N-methyl-d-aspartate receptor antagonist (P = 0.54). In conclusion, CTA LTM remains sensitive to the action of PSIs in the GC even 3 days following memory acquisition. This sensitivity is differentially expressed between the formation and persistence of LTM, suggesting that increased cortical protein synthesis promotes LTM formation, whereas decreased protein synthesis promotes LTM persistence. PMID:27721985

  9. Synaptic scaling enables dynamically distinct short- and long-term memory formation.

    Directory of Open Access Journals (Sweden)

    Christian Tetzlaff

    2013-10-01

    Full Text Available Memory storage in the brain relies on mechanisms acting on time scales from minutes, for long-term synaptic potentiation, to days, for memory consolidation. During such processes, neural circuits distinguish synapses relevant for forming a long-term storage, which are consolidated, from synapses of short-term storage, which fade. How time scale integration and synaptic differentiation is simultaneously achieved remains unclear. Here we show that synaptic scaling - a slow process usually associated with the maintenance of activity homeostasis - combined with synaptic plasticity may simultaneously achieve both, thereby providing a natural separation of short- from long-term storage. The interaction between plasticity and scaling provides also an explanation for an established paradox where memory consolidation critically depends on the exact order of learning and recall. These results indicate that scaling may be fundamental for stabilizing memories, providing a dynamic link between early and late memory formation processes.

  10. Synaptic scaling enables dynamically distinct short- and long-term memory formation.

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    Tetzlaff, Christian; Kolodziejski, Christoph; Timme, Marc; Tsodyks, Misha; Wörgötter, Florentin

    2013-10-01

    Memory storage in the brain relies on mechanisms acting on time scales from minutes, for long-term synaptic potentiation, to days, for memory consolidation. During such processes, neural circuits distinguish synapses relevant for forming a long-term storage, which are consolidated, from synapses of short-term storage, which fade. How time scale integration and synaptic differentiation is simultaneously achieved remains unclear. Here we show that synaptic scaling - a slow process usually associated with the maintenance of activity homeostasis - combined with synaptic plasticity may simultaneously achieve both, thereby providing a natural separation of short- from long-term storage. The interaction between plasticity and scaling provides also an explanation for an established paradox where memory consolidation critically depends on the exact order of learning and recall. These results indicate that scaling may be fundamental for stabilizing memories, providing a dynamic link between early and late memory formation processes.

  11. DHX36 enhances RIG-I signaling by facilitating PKR-mediated antiviral stress granule formation.

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    Ji-Seung Yoo

    2014-03-01

    Full Text Available RIG-I is a DExD/H-box RNA helicase and functions as a critical cytoplasmic sensor for RNA viruses to initiate antiviral interferon (IFN responses. Here we demonstrate that another DExD/H-box RNA helicase DHX36 is a key molecule for RIG-I signaling by regulating double-stranded RNA (dsRNA-dependent protein kinase (PKR activation, which has been shown to be essential for the formation of antiviral stress granule (avSG. We found that DHX36 and PKR form a complex in a dsRNA-dependent manner. By forming this complex, DHX36 facilitates dsRNA binding and phosphorylation of PKR through its ATPase/helicase activity. Using DHX36 KO-inducible MEF cells, we demonstrated that DHX36 deficient cells showed defect in IFN production and higher susceptibility in RNA virus infection, indicating the physiological importance of this complex in host defense. In summary, we identify a novel function of DHX36 as a critical regulator of PKR-dependent avSG to facilitate viral RNA recognition by RIG-I-like receptor (RLR.

  12. DHX36 enhances RIG-I signaling by facilitating PKR-mediated antiviral stress granule formation.

    Science.gov (United States)

    Yoo, Ji-Seung; Takahasi, Kiyohiro; Ng, Chen Seng; Ouda, Ryota; Onomoto, Koji; Yoneyama, Mitsutoshi; Lai, Janice Ching; Lattmann, Simon; Nagamine, Yoshikuni; Matsui, Tadashi; Iwabuchi, Kuniyoshi; Kato, Hiroki; Fujita, Takashi

    2014-03-01

    RIG-I is a DExD/H-box RNA helicase and functions as a critical cytoplasmic sensor for RNA viruses to initiate antiviral interferon (IFN) responses. Here we demonstrate that another DExD/H-box RNA helicase DHX36 is a key molecule for RIG-I signaling by regulating double-stranded RNA (dsRNA)-dependent protein kinase (PKR) activation, which has been shown to be essential for the formation of antiviral stress granule (avSG). We found that DHX36 and PKR form a complex in a dsRNA-dependent manner. By forming this complex, DHX36 facilitates dsRNA binding and phosphorylation of PKR through its ATPase/helicase activity. Using DHX36 KO-inducible MEF cells, we demonstrated that DHX36 deficient cells showed defect in IFN production and higher susceptibility in RNA virus infection, indicating the physiological importance of this complex in host defense. In summary, we identify a novel function of DHX36 as a critical regulator of PKR-dependent avSG to facilitate viral RNA recognition by RIG-I-like receptor (RLR).

  13. Early calcium increase triggers the formation of olfactory long-term memory in honeybees

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    Matsumoto Yukihisa

    2009-06-01

    Full Text Available Abstract Background Synaptic plasticity associated with an important wave of gene transcription and protein synthesis underlies long-term memory processes. Calcium (Ca2+ plays an important role in a variety of neuronal functions and indirect evidence suggests that it may be involved in synaptic plasticity and in the regulation of gene expression correlated to long-term memory formation. The aim of this study was to determine whether Ca2+ is necessary and sufficient for inducing long-term memory formation. A suitable model to address this question is the Pavlovian appetitive conditioning of the proboscis extension reflex in the honeybee Apis mellifera, in which animals learn to associate an odor with a sucrose reward. Results By modulating the intracellular Ca2+ concentration ([Ca2+]i in the brain, we show that: (i blocking [Ca2+]i increase during multiple-trial conditioning selectively impairs long-term memory performance; (ii conversely, increasing [Ca2+]i during single-trial conditioning triggers long-term memory formation; and finally, (iii as was the case for long-term memory produced by multiple-trial conditioning, enhancement of long-term memory performance induced by a [Ca2+]i increase depends on de novo protein synthesis. Conclusion Altogether our data suggest that during olfactory conditioning Ca2+ is both a necessary and a sufficient signal for the formation of protein-dependent long-term memory. Ca2+ therefore appears to act as a switch between short- and long-term storage of learned information.

  14. The relationship between trait empathy and memory formation for social vs. non-social information.

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    Wagner, Ullrich; Handke, Lisa; Walter, Henrik

    2015-01-01

    To navigate successfully through their complex social environment, humans need both empathic and mnemonic skills. Little is known on how these two types of psychological abilities relate to each other in humans. Although initial clinical findings suggest a positive association, systematic investigations in healthy subject samples have not yet been performed. Differentiating cognitive and affective aspects of empathy, we assumed that cognitive empathy would be positively associated with general memory performance, while affective empathy, due to enhanced other-related emotional reactions, would be related to a relative memory advantage for information of social as compared to non-social relevance. We investigated in young healthy participants the relationship between dispositional cognitive and affective empathy, as measured by Davis' Interpersonal Reactivity Index (Journal of Personality and Social Psychology, 44, 113-126, 1983), and memory formation for stimuli (numbers presented in a lottery choice task) that could be encoded in either a social (other-related) or a non-social (self-related) way within the task. Cognitive empathy, specifically perspective taking, correlated with overall memory performance (regardless of encoding condition), while affective empathy, specifically empathic personal distress, predicted differential memory for socially vs. non-socially encoded information. Both cognitive and affective empathy are associated with memory formation, but in different ways, depending on the social nature of the memory content. These results open new and so far widely neglected avenues of psychological research on the relationship between social and cognitive skills.

  15. Terms of the debate on the format and structure of visual memory.

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    Suchow, Jordan W; Fougnie, Daryl; Brady, Timothy F; Alvarez, George A

    2014-10-01

    Our ability to actively maintain information in visual memory is strikingly limited. There is considerable debate about why this is so. As with many questions in psychology, the debate is framed dichotomously: Is visual working memory limited because it is supported by only a small handful of discrete "slots" into which visual representations are placed, or is it because there is an insufficient supply of a "resource" that is flexibly shared among visual representations? Here, we argue that this dichotomous framing obscures a set of at least eight underlying questions. Separately considering each question reveals a rich hypothesis space that will be useful for building a comprehensive model of visual working memory. The questions regard (1) an upper limit on the number of represented items, (2) the quantization of the memory commodity, (3) the relationship between how many items are stored and how well they are stored, (4) whether the number of stored items completely determines the fidelity of a representation (vs. fidelity being stochastic or variable), (5) the flexibility with which the memory commodity can be assigned or reassigned to items, (6) the format of the memory representation, (7) how working memories are formed, and (8) how memory representations are used to make responses in behavioral tasks. We reframe the debate in terms of these eight underlying questions, placing slot and resource models as poles in a more expansive theoretical space.

  16. Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis

    Science.gov (United States)

    Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

    2015-01-01

    Metabolic homeostasis is regulated by the brain, whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipids levels. Importantly, this function of metabolic learning requires not only the mushroom body but the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis. PMID:25848677

  17. Homologue of Protein Kinase Mζ Maintains Context Aversive Memory and Underlying Long-Term Facilitation in Terrestrial Snail Helix.

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    Pavel M. Balaban

    2015-06-01

    Full Text Available It has been shown that a variety of long-term memories in different regions of the brain and in different species are quickly erased by local inhibition of PKMζ. Using antibodies to mammalian PKMζ, we describe in the present study the localization of immunoreactive molecules in the nervous system of the terrestrial snail Helix lucorum. Presence of a homologue of PKMζ was confirmed with transcriptomics. We have demonstrated in behavioral experiments that contextual fear memory disappeared under a blockade of PKMζ with a selective peptide blocker of PKMζ (ZIP, but not with scrambled ZIP. If ZIP was combined with a reminder (20 min in noxious context, no impairment of the long-term contextual memory was observed. In electrophysiological experiments we investigated whether PKMζ takes part in the maintenance of long-term facilitation (LTF in the neural circuit mediating tentacle withdrawal. LTF of excitatory synaptic inputs to premotor interneurons was induced by high-frequency nerve stimulation combined with serotonin bath applications and lasted at least four hours. We found that bath application of 2x10-6 M ZIP at the 90th min after the tetanization reduced the EPSP amplitude to the non-tetanized EPSP values. Applications of the scrambled ZIP peptide at a similar time and concentration didn't affect the EPSP amplitudes. In order to test whether effects of ZIP are specific to the synapses, we performed experiments with LTF of somatic membrane responses to local glutamate applications. It was shown earlier that serotonin application in such an artificial synapse condition elicits LTF of responses to glutamate. It was found that ZIP had no effect on LTF in these conditions, which may be explained by the very low concentration of PKMζ molecules in somata of these identified neurons, as evidenced by immunochemistry. Obtained results suggest that the Helix homologue of PKMζ might be involved in post-induction maintenance of long-term changes in

  18. Effects of acute methamphetamine on emotional memory formation in humans: encoding vs consolidation.

    Science.gov (United States)

    Ballard, Michael E; Weafer, Jessica; Gallo, David A; de Wit, Harriet

    2015-01-01

    Understanding how stimulant drugs affect memory is important for understanding their addictive potential. Here we examined the effects of acute d-methamphetamine (METH), administered either before (encoding phase) or immediately after (consolidation phase) study on memory for emotional and neutral images in healthy humans. Young adult volunteers (N = 60) were randomly assigned to either an encoding group (N = 29) or a consolidation group (N = 31). Across three experimental sessions, they received placebo and two doses of METH (10, 20 mg) either 45 min before (encoding) or immediately after (consolidation) viewing pictures of emotionally positive, neutral, and negative scenes. Memory for the pictures was tested two days later, under drug-free conditions. Half of the sample reported sleep disturbances following the high dose of METH, which affected their memory performance. Therefore, participants were classified as poor sleepers (less than 6 hours; n = 29) or adequate sleepers (6 or more hours; n = 31) prior to analyses. For adequate sleepers, METH (20 mg) administered before encoding significantly improved memory accuracy relative to placebo, especially for emotional (positive and negative), compared to neutral, stimuli. For poor sleepers in the encoding group, METH impaired memory. METH did not affect memory in the consolidation group regardless of sleep quality. These results extend previous findings showing that METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation. METH does not appear to facilitate consolidation if administered after encoding. The study also demonstrates the important role of sleep in memory studies.

  19. Effects of acute methamphetamine on emotional memory formation in humans: encoding vs consolidation.

    Directory of Open Access Journals (Sweden)

    Michael E Ballard

    Full Text Available Understanding how stimulant drugs affect memory is important for understanding their addictive potential. Here we examined the effects of acute d-methamphetamine (METH, administered either before (encoding phase or immediately after (consolidation phase study on memory for emotional and neutral images in healthy humans. Young adult volunteers (N = 60 were randomly assigned to either an encoding group (N = 29 or a consolidation group (N = 31. Across three experimental sessions, they received placebo and two doses of METH (10, 20 mg either 45 min before (encoding or immediately after (consolidation viewing pictures of emotionally positive, neutral, and negative scenes. Memory for the pictures was tested two days later, under drug-free conditions. Half of the sample reported sleep disturbances following the high dose of METH, which affected their memory performance. Therefore, participants were classified as poor sleepers (less than 6 hours; n = 29 or adequate sleepers (6 or more hours; n = 31 prior to analyses. For adequate sleepers, METH (20 mg administered before encoding significantly improved memory accuracy relative to placebo, especially for emotional (positive and negative, compared to neutral, stimuli. For poor sleepers in the encoding group, METH impaired memory. METH did not affect memory in the consolidation group regardless of sleep quality. These results extend previous findings showing that METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation. METH does not appear to facilitate consolidation if administered after encoding. The study also demonstrates the important role of sleep in memory studies.

  20. Hippocampal signaling pathways are involved in stress-induced impairment of memory formation in rats.

    Science.gov (United States)

    Sardari, Maryam; Rezayof, Ameneh; Khodagholi, Fariba

    2015-11-02

    Stress is a potent modulator of hippocampal-dependent memory formation. The aim of the present study was to assess the role of hippocampal signaling pathways in stress-induced memory impairment in male Wistar rats. The animals were exposed to acute elevated platform (EP) stress and memory formation was measured by a step-through type passive avoidance task. The results indicated that post-training or pre-test exposure to EP stress impaired memory consolidation or retrieval respectively. Using western blot analysis, it was found that memory retrieval was associated with the increase in the levels of phosphorylated cAMP-responsive element binding protein (P-CREB), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and its downstream targets in the hippocampus. In contrast, the stress exposure decreased the hippocampal levels of these proteins. In addition, stress-induced impairment of memory consolidation or retrieval was associated with the decrease in the P-CREB/CREB ratio and the PGC-1α level in the hippocampus. On the other hand, the hippocampal level of nuclear factor E2-related factor 2 (Nrf2) and gamma-glutamylcysteine synthetase (γ-GCS) which are the master regulators of defense system were decreased by the stress exposure. The increased hippocampal levels of Nrf2 and it׳s downstream was observed during memory retrieval, while stress-induced impairment of memory consolidation or retrieval inhibited this hippocampal signaling pathway. Overall, these findings suggest that down-regulation of CREB/PGC-1α signaling cascade and Nrf2 antioxidant pathways in the hippocampus may be associated with memory impairment induced by stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Identification of transmitter systems and learning tag molecules involved in behavioral tagging during memory formation

    OpenAIRE

    Moncada, Diego; Ballarini, Fabricio; Martinez, María Cecilia; Frey, Julietta U.; Viola, Haydee

    2011-01-01

    Long-term memory (LTM) consolidation requires the synthesis of plasticity-related proteins (PRPs). In addition, we have shown recently that LTM formation also requires the setting of a “learning tag” able to capture those PRPs. Weak training, which results only in short-term memory, can set a tag to use PRPs derived from a temporal-spatial closely related event to promote LTM formation. Here, we studied the involvement of glutamatergic, dopaminergic, and noradrenergic inputs on the setting of...

  2. Automata Networks Model of Memory Loss Effects on the Formation of Linguistic Conventions

    CERN Document Server

    Vera, Javier

    2015-01-01

    This paper proposes an Automata Networks approach to address the influence of memory loss on the formation of shared conventions. We focus our analysis on a numerical description of the dynamics over one and two dimensional periodic lattices, through an energy function that measures the local agreement between the individuals. For the two dimensional case, it exhibits a sharp transition on the relation between the energy and the parameter defined to measure the amount of memory loss. Finally, we briefly discuss the implications for the formation of language.

  3. Language facilitates event memory in early childhood: Child comprehension, adult-provided linguistic support and delayed recall at 16 months.

    Science.gov (United States)

    Lukowski, Angela F; Phung, Janice N; Milojevich, Helen M

    2015-01-01

    Adult-provided supportive language facilitates memory for the past in preverbal and verbal children. Work conducted with 18-month-olds indicates that children benefit from supportive adult language when tested after a 4-week delay but not when tested immediately after sequence demonstration; moreover, findings reveal that supportive language provided only at test may be more facilitative of recall after a delay relative to supportive language provided only at encoding. In the present study, we examined whether child language comprehension abilities moderated the extent to which preverbal children benefitted from supportive language provided at encoding and test. The findings indicated that child language comprehension and supportive language provided at encoding were unassociated with performance at baseline or immediate imitation; however, the moderating effect of child language comprehension on adult-provided supportive language at encoding and test was observed after a 1-week delay. Correlations revealed continuous associations between general comprehension scores and recall performance after the 1-week delay on sequences presented in the most supportive condition at encoding. Taken together, the presented findings reveal that the complex interplay between language and cognition is established in early childhood, with foundational relations emerging before children are capable of verbally reporting on the past.

  4. Neuroticism and conscientiousness respectively constrain and facilitate short-term plasticity within the working memory neural network.

    Science.gov (United States)

    Dima, Danai; Friston, Karl J; Stephan, Klaas E; Frangou, Sophia

    2015-10-01

    Individual differences in cognitive efficiency, particularly in relation to working memory (WM), have been associated both with personality dimensions that reflect enduring regularities in brain configuration, and with short-term neural plasticity, that reflects task-related changes in brain connectivity. To elucidate the relationship of these two divergent mechanisms, we tested the hypothesis that personality dimensions, which reflect enduring aspects of brain configuration, inform about the neurobiological framework within which short-term, task-related plasticity, as measured by effective connectivity, can be facilitated or constrained. As WM consistently engages the dorsolateral prefrontal (DLPFC), parietal (PAR), and anterior cingulate cortex (ACC), we specified a WM network model with bidirectional, ipsilateral, and contralateral connections between these regions from a functional magnetic resonance imaging dataset obtained from 40 healthy adults while performing the 3-back WM task. Task-related effective connectivity changes within this network were estimated using Dynamic Causal Modelling. Personality was evaluated along the major dimensions of Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. Only two dimensions were relevant to task-dependent effective connectivity. Neuroticism and Conscientiousness respectively constrained and facilitated neuroplastic responses within the WM network. These results suggest individual differences in cognitive efficiency arise from the interplay between enduring and short-term plasticity in brain configuration.

  5. Self-regulation of frontal-midline theta facilitates memory updating and mental set shifting

    Directory of Open Access Journals (Sweden)

    Stefanie eEnriquez-Geppert

    2014-12-01

    Full Text Available Frontal-midline (fm theta oscillations as measured via the electroencephalogram (EEG have been suggested as neural working language of executive functioning. Their power has been shown to increase when cognitive processing or task performance is enhanced. Thus, the question arises whether learning to increase fm-theta amplitudes would functionally impact the behavioral performance in tasks probing executive functions (EFs. Here, the effects of neurofeedback, a learning method to self-up-regulate fm-theta over frontal-midline electrodes, on the four most representative EFs, memory updating, set shifting, conflict monitoring, and motor inhibition are presented. Before beginning and after completing an individualized, eight-session gap-spaced neurofeedback intervention, the three-back, letter/number task-switching, Stroop, and stop-signal tasks were tested while measuring the EEG. Self-determined up-regulation of fm-theta and its putative role for executive functioning were compared to an active control group, the so-called pseudo-neurofeedback group. Task-related fm-theta activity after training differed significantly between groups. More importantly, though, after neurofeedback significantly enhanced behavioral performance was observed. The training group showed higher accuracy scores in the three-back task and reduced mixing and shifting costs in letter/number task-switching. However, this specific protocol type did not affect performance in tasks probing conflict monitoring and motor inhibition. Thus, our results suggest a modulation of proactive but not reactive mechanisms of cognitive control. In sum, the modulation of fm-theta via neurofeedback may serve as potent treatment approach for executive dysfunctions.

  6. Unraveling the complexities of circadian and sleep interactions with memory formation through invertebrate research

    Directory of Open Access Journals (Sweden)

    Maximilian eMichel

    2014-08-01

    Full Text Available Across phylogeny, the endogenous biological clock has been recognized as providing adaptive advantages to organisms through coordination of physiological and behavioral processes. Recent research has emphasized the role of circadian modulation of memory in generating peaks and troughs in cognitive performance. The circadian clock along with homeostatic processes also regulates sleep, which itself impacts the formation and consolidation of memory. Thus, the circadian clock, sleep and memory form a triad with ongoing dynamic interactions. With technological advances and the development of a global 24/7 society, understanding the mechanisms underlying these connections becomes pivotal for development of therapeutic treatments for memory disorders and to address issues in cognitive performance arising from non-traditional work schedules. Invertebrate models, such as Drosophila melanogaster and the mollusks Aplysia and Lymnaea, have proven invaluable tools for identification of highly conserved molecular processes in memory. Recent research from invertebrate systems has outlined the influence of sleep and the circadian clock upon synaptic plasticity. In this review, we discuss the effects of the circadian clock and sleep on memory formation in invertebrates drawing attention to the potential of in vivo and in vitro approaches that harness the power of simple invertebrate systems to correlate individual cellular processes with complex behaviors. In conclusion, this review highlights how studies in invertebrates with relatively simple nervous systems can provide mechanistic insights into corresponding behaviors in higher organisms and can be used to outline possible therapeutic options to guide further targeted inquiry.

  7. Unraveling the complexities of circadian and sleep interactions with memory formation through invertebrate research.

    Science.gov (United States)

    Michel, Maximilian; Lyons, Lisa C

    2014-01-01

    Across phylogeny, the endogenous biological clock has been recognized as providing adaptive advantages to organisms through coordination of physiological and behavioral processes. Recent research has emphasized the role of circadian modulation of memory in generating peaks and troughs in cognitive performance. The circadian clock along with homeostatic processes also regulates sleep, which itself impacts the formation and consolidation of memory. Thus, the circadian clock, sleep and memory form a triad with ongoing dynamic interactions. With technological advances and the development of a global 24/7 society, understanding the mechanisms underlying these connections becomes pivotal for development of therapeutic treatments for memory disorders and to address issues in cognitive performance arising from non-traditional work schedules. Invertebrate models, such as Drosophila melanogaster and the mollusks Aplysia and Lymnaea, have proven invaluable tools for identification of highly conserved molecular processes in memory. Recent research from invertebrate systems has outlined the influence of sleep and the circadian clock upon synaptic plasticity. In this review, we discuss the effects of the circadian clock and sleep on memory formation in invertebrates drawing attention to the potential of in vivo and in vitro approaches that harness the power of simple invertebrate systems to correlate individual cellular processes with complex behaviors. In conclusion, this review highlights how studies in invertebrates with relatively simple nervous systems can provide mechanistic insights into corresponding behaviors in higher organisms and can be used to outline possible therapeutic options to guide further targeted inquiry.

  8. Septo-Hippocampo-Septal Loop and Memory Formation

    Directory of Open Access Journals (Sweden)

    Fatemeh Khakpai

    2013-01-01

    Full Text Available   Cholinergic and GABAergic fibers in the medial septal/diagonal band of Broca (MS/DB area project to the hippocampus and constitute the septo-hippocampal pathway, which has been proven in learning and memory. In addition, the hippocampus has bidirectional connections with the septum, which use this relation for self-regulation of cholinergic input.   The activity of septal and hippocampal neurons is modulated by several neurotransmitters including glutamatergic neurons from the entorhinal cortex, serotonergic fibers from the raphe nucleus, dopaminergic neurons from the ventral tegmental area (VTA, histaminergic cells from the tuberomammillary nucleus and adrenergic fibers from the locus coeruleus (LC. Thus, changes in the glutamatergic, serotonergic and etc. mediated transmission in the MS/DB may influence cholinergic or GABAergic transmission in the hippocampus.

  9. Septo-Hippocampo-Septal Loop and Memory Formation

    Directory of Open Access Journals (Sweden)

    Fatemeh Khakpai

    2012-12-01

    Full Text Available Cholinergic and GABAergic fibers in the medial septal/diagonal band of Broca (MS/DB area project to the hippocampus and constitute the septo-hippocampal pathway, which has been proven in learning and memory. In addition, the hippocampus has bidirectional connections with the septum, which use this relation for self-regulation of cholinergic input. The activity of septal and hippocampal neurons is modulated by several neurotransmitters including glutamatergic neurons from the entorhinal cortex, serotonergic fibers from the raphe nucleus, dopaminergic neurons from the ventral tegmental area (VTA, histaminergic cells from the tuberomammillary nucleus and adrenergic fibers from the locus coeruleus (LC. Thus, changes in the glutamatergic, serotonergic and etc. mediated transmission in the MS/DB may influence cholinergic or GABAergic transmission in the hippocampus.

  10. The Drosophila cell adhesion molecule klingon is required for long-term memory formation and is regulated by Notch.

    Science.gov (United States)

    Matsuno, Motomi; Horiuchi, Junjiro; Tully, Tim; Saitoe, Minoru

    2009-01-06

    The ruslan (rus) mutant was previously identified in a behavioral screen for mutants defective in long-lasting memory, which consists of two consolidated memory types, anesthesia-resistant memory, and protein synthesis-dependent long-term memory (LTM). We demonstrate here that rus is a new allele of klingon (klg), which encodes a homophilic cell adhesion molecule. Klg is acutely required for LTM but not anesthesia-resistant memory formation, and Klg expression increases upon LTM induction. LTM formation also requires activity of the Notch cell-surface receptor. Although defects in Notch have been implicated in memory loss because of Alzheimer's disease, downstream signaling linking Notch to memory have not been determined. Strikingly, we found that Notch activity increases upon LTM induction and regulates Klg expression. Furthermore, Notch-induced enhancement of LTM is disrupted by a klg mutation. We propose that Klg is a downstream effector of Notch signaling that links Notch activity to memory.

  11. Neuroepigenetics of memory formation and impairment: the role of microRNAs.

    Science.gov (United States)

    Saab, Bechara J; Mansuy, Isabelle M

    2014-05-01

    MicroRNAs (miRNAs) are a class of short non-coding RNAs that primarily regulate protein synthesis through reversible translational repression or mRNA degradation. MiRNAs can act by translational control of transcription factors or via direct action on the chromatin, and thereby contribute to the non-genetic control of gene-environment interactions. MiRNAs that regulate components of pathways required for learning and memory further modulate the influence of epigenetics on cognition in the normal and diseased brain. This review summarizes recent data exemplifying the known roles of miRNAs in memory formation in different model organisms, and describes how neuronal plasticity regulates miRNA biogenesis, activity and degradation. It also examines the relevance of miRNAs for memory impairment in human, using recent clinical observations related to neurodevelopmental and neurodegenerative diseases, and discusses the potential mechanisms by which these miRNAs may contribute to memory disorders.

  12. Memory

    Science.gov (United States)

    ... it has to decide what is worth remembering. Memory is the process of storing and then remembering this information. There are different types of memory. Short-term memory stores information for a few ...

  13. Tianeptine: 5-HT uptake sites and 5-HT(1-7) receptors modulate memory formation in an autoshaping Pavlovian/instrumental task.

    Science.gov (United States)

    Meneses, Alfredo

    2002-05-01

    Recent studies using invertebrate and mammal species have revealed that, endogenous serotonin (5-hydroxytryptamine, 5-HT) modulates cognitive processes, particularly learning and memory, though, at present, it is unclear the manner, where, and how long 5-HT systems are involved. Hence in this work, an attempt was made to study the effects of 5-HT endogenous on memory formation, using a 5-HT uptake facilitator (tianeptine) and, selective 5-HT(1-7) receptor antagonists to determine whether 5-HT uptake sites and which 5-HT receptors are involved, respectively. Results showed that post-training tianeptine injection enhanced memory consolidation in an autoshaping Pavlovian/instrumental learning task, which has been useful to detect changes on memory formation elicited by drugs or aging. On interaction experiments, ketanserin (5-HT(1D/2A/2C) antagonist) slightly enhanced tianeptine effects, while WAY 100635 (5-HT(1A) antagonist), SB-224289 (5-HT(1B) inverse agonist), SB-200646 (5-HT(2B/2C) antagonist), ondansetron (5-HT(3) antagonist), GR 127487 (5-HT(4) antagonist), Ro 04-6790 (5-HT(6) antagonist), DR 4004 (5-HT(7) antagonist), or fluoxetine (an inhibitor of 5-HT reuptake) blocked the facilitatory tianeptine effect. Notably, together tianeptine and Ro 04-6790 impaired learning consolidation. Moreover, 5-HT depletion completely reversed the tianeptine effect. Tianeptine also normalized an impaired memory elicited by scopolamine (an antimuscarinic) or dizocilpine (non-competitive glutamatergic antagonist), while partially reversed that induced by TFMPP (5-HT(1B/1D/2A-2C/7) agonist/antagonist). Finally, tianeptine-fluoxetine coadministration had no effect on learning consolidation; nevertheless, administration of an acetylcholinesterase inhibitor, phenserine, potentiated subeffective tianeptine or fluoxetine doses. Collectively, these data confirmed that endogenously 5-HT modulates, via uptake sites and 5-HT(1-7) receptors, memory consolidation, and are consistent with the

  14. Overexpression of Protein Kinase Mζ in the Prelimbic Cortex Enhances the Formation of Long-Term Fear Memory.

    Science.gov (United States)

    Xue, Yan-Xue; Zhu, Zhen-Zhen; Han, Hai-Bin; Liu, Jian-Feng; Meng, Shi-Qiu; Chen, Chen; Yang, Jian-Li; Wu, Ping; Lu, Lin

    2015-08-01

    Neuroplasticity in the prefrontal cortex (PFC) after fear conditioning has been suggested to regulate the formation and expression of fear memory. Protein kinase Mζ (PKMζ), an isoform of protein kinase C with persistent activity, is involved in the formation and maintenance of memory. However, less is known about the role of PKMζ in the PFC in the formation of fear memory. We investigated whether the overexpression of PKMζ enhances the formation of auditory fear memory in rats. We found that microinfusion of lentiviral vector-expressing PKMζ into the prelimbic cortex (PrL) selectively enhanced the expression of PKMζ without influencing the expression of other isoforms of PKC. The overexpression of PKMζ in the PrL enhanced the formation of long-term fear memory without affecting short-term fear memory, whereas the overexpression of PKMζ in the infralimbic cortex had no effect on either short-term or long-term fear memory. The overexpression of PKMζ in the PrL had no effect on anxiety-like behavior or locomotor activity. We also found that PKMζ overexpression potentiated the fear conditioning-induced increase in the membrane levels of glutamate subunit 2 of AMPA receptors in the PrL. These results demonstrate that the overexpression of PKMζ in the PrL but not infralimbic cortex selectively enhanced the formation of long-term fear memory, and PKMζ in the PrL may be involved in the formation of fear memory.

  15. HDAC3 Is a Critical Negative Regulator of Long-Term Memory Formation

    Science.gov (United States)

    McQuown, Susan C.; Barrett, Ruth M.; Matheos, Dina P.; Post, Rebecca J.; Rogge, George A.; Alenghat, Theresa; Mullican, Shannon E.; Jones, Steven; Rusche, James R.; Lazar, Mitchell A.; Wood, Marcelo A.

    2011-01-01

    Gene expression is dynamically regulated by chromatin modifications on histone tails, such as acetylation. In general, histone acetylation promotes transcription, whereas histone deacetylation negatively regulates transcription. The interplay between histone acetyl-transerases and histone deacetylases (HDACs) is pivotal for the regulation of gene expression required for long-term memory processes. Currently, very little is known about the role of individual HDACs in learning and memory. We examined the role of HDAC3 in long-term memory using a combined genetic and pharmacologic approach. We used HDAC3–FLOX genetically modified mice in combination with adeno-associated virus-expressing Cre recombinase to generate focal homozygous deletions of Hdac3 in area CA1 of the dorsal hippocampus. To complement this approach, we also used a selective inhibitor of HDAC3, RGFP136 [N-(6-(2-amino-4-fluorophenylamino)-6-oxohexyl)-4-methylbenzamide]. Immunohistochemistry showed that focal deletion or intrahippocampal delivery of RGFP136 resulted in increased histone acetylation. Both the focal deletion of HDAC3 as well as HDAC3 inhibition via RGFP136 significantly enhanced long-term memory in a persistent manner. Next we examined expression of genes implicated in long-term memory from dorsal hippocampal punches using quantitative reverse transcription-PCR. Expression of nuclear receptor subfamily 4 group A, member 2 (Nr4a2) and c-fos was significantly increased in the hippocampus of HDAC3–FLOX mice compared with wild-type controls. Memory enhancements observed in HDAC3–FLOX mice were abolished by intrahippocampal delivery of Nr4a2 small interfering RNA, suggesting a mechanism by which HDAC3 negatively regulates memory formation. Together, these findings demonstrate a critical role for HDAC3 in the molecular mechanisms underlying long-term memory formation. PMID:21228185

  16. Inferential Costs of Trait Centrality in Impression Formation: Organization in Memory and Misremembering.

    Science.gov (United States)

    Nunes, Ludmila D; Garcia-Marques, Leonel; Ferreira, Mário B; Ramos, Tânia

    2017-01-01

    An extension of the DRM paradigm was used to study the impact of central traits (Asch, 1946) in impression formation. Traits corresponding to the four clusters of the implicit theory of personality-intellectual, positive and negative; and social, positive and negative (Rosenberg et al., 1968)-were used to develop lists containing several traits of one cluster and one central trait prototypical of the opposite cluster. Participants engaging in impression formation relative to participants engaging in memorization not only produced higher levels of false memories corresponding to the same cluster of the list traits but, under response time pressure at retrieval, also produced more false memories of the cluster corresponding to the central trait. We argue that the importance of central traits stems from their ability to activate their corresponding semantic space within a specialized associative memory structure underlying the implicit theory of personality.

  17. Inferential Costs of Trait Centrality in Impression Formation: Organization in Memory and Misremembering

    Science.gov (United States)

    Nunes, Ludmila D.; Garcia-Marques, Leonel; Ferreira, Mário B.; Ramos, Tânia

    2017-01-01

    An extension of the DRM paradigm was used to study the impact of central traits (Asch, 1946) in impression formation. Traits corresponding to the four clusters of the implicit theory of personality—intellectual, positive and negative; and social, positive and negative (Rosenberg et al., 1968)—were used to develop lists containing several traits of one cluster and one central trait prototypical of the opposite cluster. Participants engaging in impression formation relative to participants engaging in memorization not only produced higher levels of false memories corresponding to the same cluster of the list traits but, under response time pressure at retrieval, also produced more false memories of the cluster corresponding to the central trait. We argue that the importance of central traits stems from their ability to activate their corresponding semantic space within a specialized associative memory structure underlying the implicit theory of personality. PMID:28878708

  18. Lactate release from astrocytes to neurons contributes to cocaine memory formation

    KAUST Repository

    Boury-Jamot, Benjamin

    2016-10-12

    The identification of neural substrates underlying the long lasting debilitating impact of drug cues is critical for developing novel therapeutic tools. Metabolic coupling has long been considered a key mechanism through which astrocytes and neurons actively interact in response of neuronal activity, but recent findings suggested that disrupting metabolic coupling may represent an innovative approach to prevent memory formation, in particular drug-related memories. Here, we review converging evidence illustrating how memory and addiction share neural circuitry and molecular mechanisms implicating lactate-mediated metabolic coupling between astrocytes and neurons. With several aspects of addiction depending on mnemonic processes elicited by drug experience, disrupting lactate transport involved in the formation of a pathological learning, linking the incentive, and motivational effects of drugs with drug-conditioned stimuli represent a promising approach to encourage abstinence.

  19. Genome-wide chromatin and gene expression profiling during memory formation and maintenance in adult mice.

    Science.gov (United States)

    Centeno, Tonatiuh Pena; Shomroni, Orr; Hennion, Magali; Halder, Rashi; Vidal, Ramon; Rahman, Raza-Ur; Bonn, Stefan

    2016-10-11

    Recent evidence suggests that the formation and maintenance of memory requires epigenetic changes. In an effort to understand the spatio-temporal extent of learning and memory-related epigenetic changes we have charted genome-wide histone and DNA methylation profiles, in two different brain regions, two cell types, and three time-points, before and after learning. In this data descriptor we provide detailed information on data generation, give insights into the rationale of experiments, highlight necessary steps to assess data quality, offer guidelines for future use of the data and supply ready-to-use code to replicate the analysis results. The data provides a blueprint of the gene regulatory network underlying short- and long-term memory formation and maintenance. This 'healthy' gene regulatory network of learning can now be compared to changes in neurological or psychiatric diseases, providing mechanistic insights into brain disorders and highlighting potential therapeutic avenues.

  20. Inferential Costs of Trait Centrality in Impression Formation: Organization in Memory and Misremembering

    Directory of Open Access Journals (Sweden)

    Ludmila D. Nunes

    2017-08-01

    Full Text Available An extension of the DRM paradigm was used to study the impact of central traits (Asch, 1946 in impression formation. Traits corresponding to the four clusters of the implicit theory of personality—intellectual, positive and negative; and social, positive and negative (Rosenberg et al., 1968—were used to develop lists containing several traits of one cluster and one central trait prototypical of the opposite cluster. Participants engaging in impression formation relative to participants engaging in memorization not only produced higher levels of false memories corresponding to the same cluster of the list traits but, under response time pressure at retrieval, also produced more false memories of the cluster corresponding to the central trait. We argue that the importance of central traits stems from their ability to activate their corresponding semantic space within a specialized associative memory structure underlying the implicit theory of personality.

  1. Ostryopsis davidiana seedlings inoculated with ectomycorrhizal fungi facilitate formation of mycorrhizae on Pinus tabulaeformis seedlings.

    Science.gov (United States)

    Bai, Shu-Lan; Li, Guo-Lei; Liu, Yong; Kasten Dumroese, R; Lv, Rui-Heng

    2009-08-01

    Reforestation in China is important for reversing anthropogenic activities that degrade the environment. Pinus tabulaeformis is desired for these activities, but survival and growth of seedlings can be hampered by lack of ectomycorrhizae. When outplanted in association with Ostryopsis davidiana plants on reforestation sites, P. tabulaeformis seedlings become mycorrhizal and survival and growth are enhanced; without O. davidiana, pines often remain without mycorrhizae and performance is poorer. To better understand this relationship, we initiated an experiment using rhizoboxes that restricted root and tested the hypothesis that O. davidiana seedlings facilitated ectomycorrhizae formation on P. tabulaeformis seedlings through hyphal contact. We found that without O. davidiana seedlings, inocula of five indigenous ectomycorrhizal fungi were unable to grow and associate with P. tabulaeformis seedlings. Inocula placed alongside O. davidiana seedlings, however, resulted in enhanced growth and nutritional status of O. davidiana and P. tabulaeformis seedlings, and also altered rhizosphere pH and phosphatase activity. We speculate that these species form a common mycorrhizal network and this association enhances outplanting performance of P. tabulaeformis seedlings used for forest restoration.

  2. Interaction of DDP with bovine serum albumin facilitates formation of the protein dimers

    Science.gov (United States)

    Belaya, I.; Chikhirzhina, E.; Polyanichko, A.

    2017-07-01

    Interaction of bovine serum albumin (BSA) with cis- and trans- isomers of diamminedichloroplatinum(II) (DDP) was studied using electrophoretic analysis and Fourier transformed infrared spectroscopy (FTIR). The application of FTIR spectroscopy allowed us to study the DDP/BSA complexes in D2O solutions using protein concentrations close to the physiological level (30 mg/ml) with platinum to BSA molar ratios in the range of 1:1 to 150:1. Under these conditions we have observed formation of relatively weak non-covalent intermolecular protein complexes, which dominated over the BSA-Pt-BSA crosslinks. Analysis of the IR spectra in the region of amide I‧ band revealed that the fraction of the α-helical regions in the protein decreases from ∼65% to approximately 55% and 48% in the complexes with cis- and trans-DDP respectively, while the amount of extended β-structures increases from ∼15 to 20% in BSA to 20-30% in its complexes with cis-DDP and up to 35-40% in trans-DDP/BSA complexes. Based on the data obtained we conclude that multiple intermolecular interactions take place in the solution facilitated by the changes in the BSA secondary structure, induced by DDP binding.

  3. Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation

    Science.gov (United States)

    Li, Jasmine; Hardy, Kristine; Phetsouphanh, Chan; Tu, Wen Juan; Sutcliffe, Elissa L.; McCuaig, Robert; Sutton, Christopher R.; Zafar, Anjum; Munier, C. Mee Ling; Zaunders, John J.; Xu, Yin; Theodoratos, Angelo; Tan, Abel; Lim, Pek Siew; Knaute, Tobias; Masch, Antonia; Zerweck, Johannes; Brezar, Vedran; Milburn, Peter J.; Dunn, Jenny; Casarotto, Marco G.; Turner, Stephen J.; Seddiki, Nabila; Kelleher, Anthony D.

    2016-01-01

    ABSTRACT Memory T cells are characterized by their rapid transcriptional programs upon re-stimulation. This transcriptional memory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4+ T cells, here, we show that the signaling enzyme, protein kinase C theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to transcriptional-memory-responsive genes to induce transcriptional activation. Flanked by permissive histone modifications, these PKC-enriched regions are significantly enriched with NF-κB motifs in ex vivo bulk and vaccinia-responsive human memory CD4+ T cells. Within the nucleus, PKC-θ catalytic activity maintains the Ser536 phosphorylation on the p65 subunit of NF-κB (also known as RelA) and can directly influence chromatin accessibility at transcriptional memory genes by regulating H2B deposition through Ser32 phosphorylation. Furthermore, using a cytoplasm-restricted PKC-θ mutant, we highlight that chromatin-anchored PKC-θ integrates activating signals at the chromatin template to elicit transcriptional memory responses in human memory T cells. PMID:27149922

  4. Protein degradation and protein synthesis in long-term memory formation

    Directory of Open Access Journals (Sweden)

    Timothy J Jarome

    2014-06-01

    Full Text Available Long-term memory (LTM formation requires transient changes in the activity of intracellular signaling cascades that are thought to regulate new gene transcription and de novo protein synthesis in the brain. Consistent with this, protein synthesis inhibitors impair LTM for a variety of behavioral tasks when infused into the brain around the time of training or following memory retrieval, suggesting that protein synthesis is a critical step in LTM storage in the brain. However, evidence suggests that protein degradation mediated by the ubiquitin-proteasome system may also be a critical regulator of LTM formation and stability following retrieval. This requirement for increased protein degradation has been shown in the same brain regions in which protein synthesis is required for LTM storage. Additionally, increases in the phosphorylation of proteins involved in translational control parallel increases in protein polyubiquitination and the increased demand for protein degradation is regulated by intracellular signaling molecules thought to regulate protein synthesis during LTM formation. In some cases inhibiting proteasome activity can rescue memory impairments that result from pharmacological blockade of protein synthesis, suggesting that protein degradation may control the requirement for protein synthesis during the memory storage process. Results such as these suggest that protein degradation and synthesis are both critical for LTM formation and may interact to properly consolidate and store memories in the brain. Here, we review the evidence implicating protein synthesis and degradation in LTM storage and highlight the areas of overlap between these two opposing processes. We also discuss evidence suggesting these two processes may interact to properly form and store memories. LTM storage likely requires a coordinated regulation between protein degradation and synthesis at multiple sites in the mammalian brain.

  5. Natural amyloid-β oligomers acutely impair the formation of a contextual fear memory in mice.

    Directory of Open Access Journals (Sweden)

    Kara A Kittelberger

    Full Text Available Memory loss is one of the hallmark symptoms of Alzheimer's disease (AD. It has been proposed that soluble amyloid-beta (Abeta oligomers acutely impair neuronal function and thereby memory. We here report that natural Abeta oligomers acutely impair contextual fear memory in mice. A natural Abeta oligomer solution containing Abeta monomers, dimers, trimers, and tetramers was derived from the conditioned medium of 7PA2 cells, a cell line that expresses human amyloid precursor protein containing the Val717Phe familial AD mutation. As a control we used 7PA2 conditioned medium from which Abeta oligomers were removed through immunodepletion. Separate groups of mice were injected with Abeta and control solutions through a cannula into the lateral brain ventricle, and subjected to fear conditioning using two tone-shock pairings. One day after fear conditioning, mice were tested for contextual fear memory and tone fear memory in separate retrieval trials. Three experiments were performed. For experiment 1, mice were injected three times: 1 hour before and 3 hours after fear conditioning, and 1 hour before context retrieval. For experiments 2 and 3, mice were injected a single time at 1 hour and 2 hours before fear conditioning respectively. In all three experiments there was no effect on tone fear memory. Injection of Abeta 1 hour before fear conditioning, but not 2 hours before fear conditioning, impaired the formation of a contextual fear memory. In future studies, the acute effect of natural Abeta oligomers on contextual fear memory can be used to identify potential mechanisms and treatments of AD associated memory loss.

  6. Formation and adaptation of memory : Neurobiological mechanisms underlying learning and reversal learning

    NARCIS (Netherlands)

    Havekes, Robbert

    2008-01-01

    The hippocampus is a brain region that plays a critical role in memory formation. In addition, it has been suggested that this brain region is important for ‘updating’ information that is incorrect or outdated. The main goal of this thesis project was to investigate which neurobiological processes

  7. How mood challenges emotional memory formation: An fMRI investigation

    NARCIS (Netherlands)

    Fitzgerald, D.A.; Arnold, J.F.; Becker, E.S.; Speckens, A.E.M.; Rinck, M.; Rijpkema, M.J.P.; Fernandez, G.S.E.; Tendolkar, I.

    2011-01-01

    Experimental mood manipulations and functional magnetic resonance imaging (fMRI) provide a unique opportunity for examining the neural correlates of mood-congruent memory formation. While prior studies in mood-disorder patients point to the medial temporal lobe in the genesis of mood-congruent memor

  8. How mood challenges emotional memory formation: an fMRI investigation

    NARCIS (Netherlands)

    Fitzgerald, D.A.; Arnold, J.F.; Becker, E.S.; Speckens, A.E.M.; Rinck, M.; Rijpkema, M.J.P.; Fernandez, G.S.E.; Tendolkar, I.

    2011-01-01

    Experimental mood manipulations and functional magnetic resonance imaging (fMRI) provide a unique opportunity for examining the neural correlates of mood-congruent memory formation. While prior studies in mood-disorder patients point to the medial temporal lobe in the genesis of mood-congruent memor

  9. The Impact of Testing on the Formation of Children's and Adults' False Memories

    NARCIS (Netherlands)

    Brackmann, Nathalie; Otgaar, Henry; Sauerland, Melanie; Howe, Mark L

    2016-01-01

    Witnesses are frequently questioned immediately following a crime. The effects of such testing on false recall are inconclusive: Testing may inoculate against subsequent misinformation or enhance false memory formation. We examined whether different types of processing can account for these discrepa

  10. CREB binding protein is required for both short-term and long-term memory formation

    NARCIS (Netherlands)

    Chen, G.; Zou, X.; Watanabe, H.; Deursen, J.M.A. van; Shen, J.

    2010-01-01

    CREB binding protein (CBP) is a transcriptional coactivator with histone acetyltransferase activity. Our prior study suggested that CBP might be a key target of presenilins in the regulation of memory formation and neuronal survival. To elucidate the role of CBP in the adult brain, we generated cond

  11. CREB binding protein is required for both short-term and long-term memory formation

    NARCIS (Netherlands)

    Chen, G.; Zou, X.; Watanabe, H.; Deursen, J.M.A. van; Shen, J.

    2010-01-01

    CREB binding protein (CBP) is a transcriptional coactivator with histone acetyltransferase activity. Our prior study suggested that CBP might be a key target of presenilins in the regulation of memory formation and neuronal survival. To elucidate the role of CBP in the adult brain, we generated

  12. Cognitive Association Formation in Episodic Memory: Evidence from Event-Related Potentials

    Science.gov (United States)

    Kim, Alice S. N.; Vallesi, Antonino; Picton, Terence W.; Tulving, Endel

    2009-01-01

    The present study focused on the processes underlying cognitive association formation by investigating subsequent memory effects. Event-related potentials were recorded as participants studied pairs of words, presented one word at a time, for later recall. The findings showed that a frontal-positive late wave (LW), which occurred 1-1.6 s after the…

  13. Formation and adaptation of memory : Neurobiological mechanisms underlying learning and reversal learning

    NARCIS (Netherlands)

    Havekes, Robbert

    2008-01-01

    The hippocampus is a brain region that plays a critical role in memory formation. In addition, it has been suggested that this brain region is important for ‘updating’ information that is incorrect or outdated. The main goal of this thesis project was to investigate which neurobiological processes u

  14. Probing the neural correlates of associative memory formation : a parametrically analyzed event-related functional MRI study

    NARCIS (Netherlands)

    Tendolkar, I.; Arnold, J.F.; Petersson, K.M.; Weis, S.; Eijndhoven, P. van; Buitelaar, J.K.; Fernandez, G.

    2007-01-01

    The medial temporal lobe (MTL) is crucial for declarative memory formation, but the function of its subcomponents in associative memory formation remains controversial. Most functional imaging studies on this topic are based on a stepwise approach comparing a condition with and one without

  15. The Cambridge Car Memory Test: a task matched in format to the Cambridge Face Memory Test, with norms, reliability, sex differences, dissociations from face memory, and expertise effects.

    Science.gov (United States)

    Dennett, Hugh W; McKone, Elinor; Tavashmi, Raka; Hall, Ashleigh; Pidcock, Madeleine; Edwards, Mark; Duchaine, Bradley

    2012-06-01

    Many research questions require a within-class object recognition task matched for general cognitive requirements with a face recognition task. If the object task also has high internal reliability, it can improve accuracy and power in group analyses (e.g., mean inversion effects for faces vs. objects), individual-difference studies (e.g., correlations between certain perceptual abilities and face/object recognition), and case studies in neuropsychology (e.g., whether a prosopagnosic shows a face-specific or object-general deficit). Here, we present such a task. Our Cambridge Car Memory Test (CCMT) was matched in format to the established Cambridge Face Memory Test, requiring recognition of exemplars across view and lighting change. We tested 153 young adults (93 female). Results showed high reliability (Cronbach's alpha = .84) and a range of scores suitable both for normal-range individual-difference studies and, potentially, for diagnosis of impairment. The mean for males was much higher than the mean for females. We demonstrate independence between face memory and car memory (dissociation based on sex, plus a modest correlation between the two), including where participants have high relative expertise with cars. We also show that expertise with real car makes and models of the era used in the test significantly predicts CCMT performance. Surprisingly, however, regression analyses imply that there is an effect of sex per se on the CCMT that is not attributable to a stereotypical male advantage in car expertise.

  16. Promoter-Specific Effects of DREADD Modulation on Hippocampal Synaptic Plasticity and Memory Formation.

    Science.gov (United States)

    López, Alberto J; Kramár, Enikö; Matheos, Dina P; White, André O; Kwapis, Janine; Vogel-Ciernia, Annie; Sakata, Keith; Espinoza, Monica; Wood, Marcelo A

    2016-03-23

    Designer receptors exclusively activated by designer drug (DREADDs) are a novel tool with the potential to bidirectionally drive cellular, circuit, and ultimately, behavioral changes. We used DREADDs to evaluate memory formation in a hippocampus-dependent task in mice and effects on synaptic physiology in the dorsal hippocampus. We expressed neuron-specific (hSyn promoter) DREADDs that were either excitatory (HM3D) or inhibitory (HM4D) in the dorsal hippocampus. As predicted, hSyn-HM3D was able to transform a subthreshold learning event into long-term memory (LTM), and hSyn-HM4D completely impaired LTM formation. Surprisingly, the opposite was observed during experiments examining the effects on hippocampal long-term potentiation (LTP). hSyn-HM3D impaired LTP and hSyn-HM4D facilitated LTP. Follow-up experiments indicated that the hSyn-HM3D-mediated depression of fEPSP appears to be driven by presynaptic activation of inhibitory currents, whereas the hSyn-HM4D-mediated increase of fEPSP is induced by a reduction in GABAA receptor function. To determine whether these observations were promoter specific, we next examined the effects of using the CaMKIIα promoter that limits expression to forebrain excitatory neurons. CaMKIIα-HM3D in the dorsal hippocampus led to the transformation of a subthreshold learning event into LTM, whereas CaMKIIα-HM4D blocked LTM formation. Consistent with these findings, baseline synaptic transmission and LTP was increased in CaMKIIα-HM3D hippocampal slices, whereas slices from CaMKIIα-HM4D mice produced expected decreases in baseline synaptic transmission and LTP. Together, these experiments further demonstrate DREADDs as being a robust and reliable means of modulating neuronal function to manipulate long-term changes in behavior, while providing evidence for specific dissociations between LTM and LTP. This study evaluates the efficacy of designer receptors exclusively activated by designer drug (DREADDs) as a means of bidirectionally

  17. Nitric oxide is necessary for long-term facilitation of synaptic responses and for development of context memory in terrestrial snails.

    Science.gov (United States)

    Korshunova, T A; Balaban, P M

    2014-04-25

    Correlated electrophysiological and behavioral experiments in the snail Helix lucorum were conducted to investigate the contribution of nitric oxide (NO) to synaptic plasticity during withdrawal reflex and aversive context memory development. Time, stimulation frequency and number of tetani/electrical shocks were determined in vitro and in vivo. In isolated brain preparations, nerve tetanization accompanied by bath application of serotonin induced long-term facilitation (LTF) of the excitatory postsynaptic potential (EPSP) in withdrawal interneurons. Bathing with either the NO-synthase inhibitor N-omega-nitro-L-arginin (L-NNA) or the NO-scavenger 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl 3-oxide (PTIO) before the tetanization prevented tetanus-induced long-term increase of EPSP. Withdrawal interneurons are key elements in the network underlying aversive behavior, with LTF considered the basis for aversive learning. We hypothesized that L-NNA injections in free-behaving snails could influence aversive learning. Snails were trained for 1 or 5days to remember the context in which they were shocked. In one-day training experiments, the snails received 5 electrical shocks in one context. Different groups of snails were sham-injected or L-NNA-injected before or after training. After training, the sham-injected groups demonstrated a significant increase in behavioral responses compared to the L-NNA-injected groups. On the following day, only sham-injected snails demonstrated altered behavioral responses, but no associative context differences were observed. These results correlated with the electrophysiological results. In another series of experiments, the snails received electrical shocks for 5days. Testing on the second day after training demonstrated that the sham-injected group maintained selective aversive context memory, whereas the L-NNA-injected snails were not different between the two contexts. Together these results demonstrated that inhibition of NO

  18. Hallucinatory experience as aberrant event memory formation: Implications for the pathophysiology of schizophrenia.

    Science.gov (United States)

    Behrendt, Ralf-Peter

    2016-11-03

    If hallucinations are not fundamentally different from normal wakeful experiences, then the neural basis of hallucinations has to be essentially that of consciousness in general. The additional insight that consciousness reflects the formation (as opposed to consolidation) of event (episodic) memories links the pathophysiology of hallucinations to the hippocampus. Perceptions and misperceptions, insofar as they are consciously experienced, constitute contextualized and unitary phenomena (which are embedded as discrete events in the stream of consciousness); they are experiential manifestations of activity patters that recurrently emerge in the CA3 network of the hippocampus (and that are secondarily consolidated into retrievable and declarable memories). The hippocampus, forming allocentric representations of objects in their world context (event memories), is a point of convergence of neocortical sensory processing streams. Moreover, being extensively modulated by the organism's physiological state, the hippocampus embeds such representations in an emotional context and, through its output to the medial prefrontal cortex, guides decision-making and goal-selection processes. Although sensory and associative processing in the neocortex makes an important contribution to the formation of behaviourally adaptive representations in the hippocampus, it is becoming clearer that pattern formation in the hippocampus is in itself the neural correlate of consciousness and that disruptions in relational memory processing in the hippocampus can give rise to hallucinations. Neurobiological and neuroimaging findings in schizophrenia research can be integrated within the proposed conceptual framework.

  19. Notch-inducible hyperphosphorylated CREB and its ultradian oscillation in long-term memory formation.

    Science.gov (United States)

    Zhang, Jiabin; Little, Christopher J; Tremmel, Daniel M; Yin, Jerry C P; Wesley, Cedric S

    2013-07-31

    Notch is a cell surface receptor that is known to regulate developmental processes by establishing physical contact between neighboring cells. Many recent studies show that it also plays an important role in the formation of long-term memory (LTM) in adults, implying that memory formation requires regulation at the level of cell-cell contacts among brain cells. Neither the target of Notch activity in LTM formation nor the underlying mechanism of regulation is known. We report here results of our studies in adult Drosophila melanogaster showing that Notch regulates dCrebB-17A, the CREB protein. CREB is a transcriptional factor that is pivotal for intrinsic and synaptic plasticity involved in LTM formation. Notch in conjunction with PKC activity upregulates the level of a hyperphosphorylated form of CREB (hyper-PO4 CREB) and triggers its ultradian oscillation, both of which are linked to LTM formation. One of the sites that is phosphorylated in hyper-PO4 CREB is serine 231, which is the functional equivalent of mammalian CREB serine 133, the phosphorylation of which is an important regulator of CREB functions. Our data suggest the model that Notch and PKC activities generate a cyclical accumulation of cytoplasmic hyper-PO4 CREB that is a precursor for generating the nuclear CREB isoforms. Cyclical accumulation of CREB might be important for repetitive aspects of LTM formation, such as memory consolidation. Because Notch, PKC, and CREB have been implicated in many neurodegenerative diseases (e.g., Alzheimer's disease), our data might also shed some light on memory loss and dementia.

  20. Oscillatory activity in the monkey hippocampus during visual exploration and memory formation.

    Science.gov (United States)

    Jutras, Michael J; Fries, Pascal; Buffalo, Elizabeth A

    2013-08-06

    Primates explore the visual world through the use of saccadic eye movements. Neuronal activity in the hippocampus, a structure known to be essential for memory, is modulated by this saccadic activity, but the relationship between visual exploration through saccades and memory formation is not well understood. Here, we identify a link between theta-band (3-12 Hz) oscillatory activity in the hippocampus and saccadic activity in monkeys performing a recognition memory task. As monkeys freely explored novel images, saccades produced a theta-band phase reset, and the reliability of this phase reset was predictive of subsequent recognition. In addition, enhanced theta-band power before stimulus onset predicted stronger stimulus encoding. Together, these data suggest that hippocampal theta-band oscillations act in concert with active exploration in the primate and possibly serve to establish the optimal conditions for stimulus encoding.

  1. Formation and nonvolatile memory characteristics of W nanocrystals by in-situ steam generation oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shih-Cheng [Department of Electrical Engineering and Institute of Electronic Engineering, National Tsing Hua University, Taiwan (China); Chang, Ting-Chang, E-mail: tcchang@mail.phys.nsysu.edu.t [Department of Physics and Center for Nanoscience and Nanotechnology, National Sun Yat-Sen University Taiwan (China); Hsieh, Chieh-Ming [Institute of Electronics, National Chiao Tung University, Taiwan, HsinChu, 300 Taiwan (China); Li, Hung-Wei [Department of Photonics and Institute of Electro-Optical Engineering, National Chiao Tung University, Hsinchu, Taiwan (China); Sze, S.M. [Institute of Electronics, National Chiao Tung University, Taiwan, HsinChu, 300 Taiwan (China); Nien, Wen-Ping; Chan, Chia-Wei [ProMOS Technologies, No. 19 Li Hsin Rd., Science-Based Industrial Park, Hsinchu, 300 Taiwan (China); Yeh, Fon-Shan [Department of Electrical Engineering and Institute of Electronic Engineering, National Tsing Hua University, Taiwan (China); Tai, Ya-Hsiang [Department of Photonics and Display Institute, National Chiao Tung University, Hsinchu, Taiwan (China)

    2010-12-30

    The authors provide the formation and memory effects of W nanocrystals nonvolatile memory in this study. The charge trapping layer of stacked a-Si and WSi{sub 2} was deposited by low pressure chemical vapor deposition (LPCVD) and was oxidized by in-situ steam generation system to form uniform W nanocrystals embedded in SiO{sub 2}. Transmission electron microscopy analyses revealed the microstructure in the thin film and X-ray photon-emission spectra indicated the variation of chemical composition under different oxidizing conditions. Electrical measurement analyses showed the different charge storage effects because the different oxidizing conditions influence composition of trapping layer and surrounding oxide quality. Moreover, the data retention and endurance characteristics of the formed W nanocrystal memory devices were compared and studied. The results show that the reliability of the structure with 2% hydrogen and 98% oxygen at 950 {sup o}C oxidizing condition has the best performance among the samples.

  2. The Effect of Sex and Menstrual Phase on Memory Formation during Nap.

    Science.gov (United States)

    Mednick, Sara C; Sattari, Negin; McDevitt, Elizabeth A; Panas, Dagmara; Niknazar, Mohammad; Ahmadi, Maryam; Naji, Mohsen; Baker, Fiona

    2017-09-16

    Memory formation can be influenced by sleep and sex hormones in both men and women, and by the menstrual cycle in women. Though many studies have shown that sleep benefits the consolidation of memories, it is not clear whether this effect differs between men and women in general or according to menstrual phase in women. The present study investigated the effect of sex and menstrual cycle on memory consolidation of face-name associations (FNA) following a daytime nap. Recognition memory was tested using a face-name paired associates task with a polysomnographic nap between morning and evening testing. Seventeen healthy women (age: 20.75 (1.98) years) were studied at two time points of their menstrual cycles, defined from self-report and separated by 2 weeks (perimenses: -5 days to + 6 days from the start of menses, and non-perimenses: outside of the perimenses phase) and compared with eighteen healthy men (age: 22.01 (2.91) years). Regardless of menstrual phase, women had better pre-nap performance than men. Further, menstrual phase affected post-nap memory consolidation, with women showing greater forgetting in their perimenses phase compared with their non-perimenses phase, and men. Interestingly, post-nap performance correlated with electrophysiological events during sleep (slow oscillations, spindles, and temporal coupling between the two), however, these correlations differed according to menstrual phase and sex. Men's performance improvement was associated with the temporal coupling of spindles and slow oscillations (i.e., spindle/SO coincidence) as well as spindles. Women, however, showed an association with slow oscillations during non-perimenses, whereas when they were in their perimenses phase of their cycle, women appeared to show an association only with sleep spindle events for consolidation. These findings add to the growing literature demonstrating sex and menstrual phase effects on memory formation during sleep. Copyright © 2017. Published by

  3. Neural state and trait bases of mood-incongruent memory formation and retrieval in first-episode major depression.

    Science.gov (United States)

    van Wingen, Guido A; van Eijndhoven, Philip; Cremers, Henk R; Tendolkar, Indira; Verkes, Robbert Jan; Buitelaar, Jan K; Fernández, Guillén

    2010-06-01

    Mood-congruent cognitive biases constitute critical factors for the vulnerability to depression and its maintenance. One important aspect is impaired memory for positive information during depression and after recovery. To elucidate its state (during depression only) and trait (during depression and recovery) related neural bases, we investigated medication free depressed, recovered, and healthy individuals with functional MRI while they memorized and recognized happy and neutral face stimuli. The imaging results revealed group differences in mood-incongruent successful memory encoding and retrieval activity already in the absence of significant memory performance differences. State effects were observed in the amygdala and posterior cingulate cortex. Whereas the amygdala was generally involved in memory formation, its activity predicted subsequent forgetting of neutral faces in depressed patients. Furthermore, the amygdala and posterior cingulate cortex were involved in memory retrieval of happy faces in depressed patients only. Trait effects were observed in the fusiform gyrus and prefrontal cortex. The fusiform gyrus was involved in memory formation and retrieval of happy faces in both patient groups, whereas it was involved in memory formation and retrieval of neutral faces in healthy individuals. Similar trait effects were observed during memory retrieval in the orbitofrontal cortex and left inferior frontal gyrus. Thus, while memory processing of positive information in the amygdala and posterior cingulate cortex is biased during depression only, memory processing in the fusiform gyrus and prefrontal cortex is biased also after recovery. These distinct neural mechanisms may respectively constitute symptom maintenance and cognitive vulnerability factors for depression.

  4. Role of gonadal hormones in anxiety and fear memory formation and inhibition in male mice.

    Science.gov (United States)

    McDermott, Carmel M; Liu, Dana; Schrader, Laura A

    2012-03-20

    Recent research investigating Pavlovian fear conditioning and fear extinction has elucidated the neurocircuitry involved in acquisition and inhibition of fear responses. Modulatory factors that may underlie individual differences in fear acquisition and inhibition, however, are not well understood. Testosterone is known to affect anxiety-like behavior and cognitive processing. In this study, we hypothesized that castration would increase anxiety and reduce memory for contextual fear conditioning in an age-dependent manner. In addition, castration would reduce the rate of extinction to context, as high levels of testosterone correlate with reduced PTSD-like symptoms. We compared behaviors in male mice that were castrated at one of two different time points, either before puberty (at 4 weeks) or after puberty (at 10 weeks) to sham-operated control mice. The behaviors investigated included: anxiety, cued and contextual fear conditioning, and extinction of the fear memory. An interaction of hormone status and age and a significant effect of age were measured in the elevated plus maze, a measure of anxiety. Castration caused a significant reduction of contextual fear memory, but no effect on cued fear memory. There was no significant effect of castration on extinction. Interestingly, a significant effect of age of the mouse at the time of testing was observed on extinction. These results suggest that endogenous androgens during puberty are important for anxiety and fear memory formation. In addition, these results define a late post-adolescent developmental time point for changes in anxiety and fear extinction.

  5. The influence of self-awareness on emotional memory formation: an fMRI study.

    Science.gov (United States)

    Pais-Vieira, Carla; Wing, Erik A; Cabeza, Roberto

    2016-04-01

    Evidence from functional neuroimaging studies of emotional perception shows that when attention is focused on external features of emotional stimuli (external perceptual orienting--EPO), the amygdala is primarily engaged, but when attention is turned inwards towards one's own emotional state (interoceptive self-orienting--ISO), regions of the salience network, such as the anterior insula (AI) and the dorsal anterior cingulate cortex (dACC), also play a major role. Yet, it is unknown if ISO boosts the contributions of AI and dACC not only to emotional 'perception' but also to emotional 'memory'. To investigate this issue, participants were scanned with functional magnetic resonance imaging (fMRI) while viewing emotional and neutral pictures under ISO or EPO, and memory was tested several days later. The study yielded three main findings: (i) emotion boosted perception-related activity in the amygdala during both ISO and EPO and in the right AI exclusively during ISO; (ii) emotion augmented activity predicting subsequent memory in AI and dACC during ISO but not during EPO and (iii) high confidence memory was associated with increased amygdala-dACC connectivity, selectively for ISO encoding. These findings show, for the first time, that ISO promotes emotional memory formation via regions associated with interoceptive awareness of emotional experience, such as AI and dACC.

  6. Development of deactivation of the default-mode network during episodic memory formation

    Science.gov (United States)

    Chai, Xiaoqian J.; Ofen, Noa; Gabrieli, John D. E.; Whitfield-Gabrieli, Susan

    2014-01-01

    Task-induced deactivation of the default-mode network (DMN) has been associated in adults with successful episodic memory formation, possibly as a mechanism to focus allocation of mental resources for successful encoding of external stimuli. We investigated developmental changes of deactivation of the DMN (posterior cingulate, medial prefrontal, and bilateral lateral parietal cortices) during episodic memory formation in children, adolescents, and young adults (ages 8–24), who studied scenes during functional magnetic resonance imaging (fMRI). Recognition memory improved with age. We defined DMN regions of interest from a different sample of participants with the same age range, using resting-state fMRI. In adults, there was greater deactivation of the DMN for scenes that were later remembered than scenes that were later forgotten. In children, deactivation of the default-network did not differ reliably between scenes that were later remembered or forgotten. Adolescents exhibited a pattern of activation intermediate to that of children and adults. The hippocampal region, often considered part of the DMN, showed a functional dissociation with the rest of the DMN by exhibiting increased activation for later remembered than later forgotten scene that was similar across age groups. These findings suggest that development of memory ability from childhood through adulthood may involve increased deactivation of the neocortical DMN during learning. PMID:24064072

  7. Putting names to faces: successful encoding of associative memories activates the anterior hippocampal formation.

    Science.gov (United States)

    Sperling, Reisa; Chua, Elizabeth; Cocchiarella, Andrew; Rand-Giovannetti, Erin; Poldrack, Russell; Schacter, Daniel L; Albert, Marilyn

    2003-10-01

    The ability to form associations between previously unrelated items of information, such as names and faces, is an essential aspect of episodic memory function. The neural substrate that determines success vs. failure in learning these associations remains to be elucidated. Using event-related functional MRI during the encoding of novel face-name associations, we found that successfully remembered face-name pairs showed significantly greater activation in the anterior hippocampal formation bilaterally and left inferior prefrontal cortex, compared to pairs that were forgotten. Functional connectivity analyses revealed significant correlated activity between the right and left hippocampus and neocortical regions during successful, but not attempted, encoding. These findings suggest that anterior regions of the hippocampal formation, in particular, are crucial for successful associative encoding and that the degree of coordination between hippocampal and neocortical activity may predict the likelihood of subsequent memory.

  8. Search strategy selection in the Morris water maze indicates allocentric map formation during learning that underpins spatial memory formation.

    Science.gov (United States)

    Rogers, Jake; Churilov, Leonid; Hannan, Anthony J; Renoir, Thibault

    2017-03-01

    Using a Matlab classification algorithm, we demonstrate that a highly salient distal cue array is required for significantly increased likelihoods of spatial search strategy selection during Morris water maze spatial learning. We hypothesized that increased spatial search strategy selection during spatial learning would be the key measure demonstrating the formation of an allocentric map to the escape location. Spatial memory, as indicated by quadrant preference for the area of the pool formally containing the hidden platform, was assessed as the main measure that this allocentric map had formed during spatial learning. Our C57BL/6J wild-type (WT) mice exhibit quadrant preference in the highly salient cue paradigm but not the low, corresponding with a 120% increase in the odds of a spatial search strategy selection during learning. In contrast, quadrant preference remains absent in serotonin 1A receptor (5-HT1AR) knockout (KO) mice, who exhibit impaired search strategy selection during spatial learning. Additionally, we also aimed to assess the impact of the quality of the distal cue array on the spatial learning curves of both latency to platform and path length using mixed-effect regression models and found no significant associations or interactions. In contrast, we demonstrated that the spatial learning curve for search strategy selection was absent during training in the low saliency paradigm. Therefore, we propose that allocentric search strategy selection during spatial learning is the learning parameter in mice that robustly indicates the formation of a cognitive map for the escape goal location. These results also suggest that both latency to platform and path length spatial learning curves do not discriminate between allocentric and egocentric spatial learning and do not reliably predict spatial memory formation. We also show that spatial memory, as indicated by the absolute time in the quadrant formerly containing the hidden platform alone (without

  9. Comment on "Multiple repressive mechanisms in the hippocampus during memory formation".

    Science.gov (United States)

    Mathew, Rebecca S; Mullan, Hillary; Blusztajn, Jan Krzysztof; Lehtinen, Maria K

    2016-07-29

    Cho et al. (Reports, 2 October 2015, p. 82) report that gene repression after contextual fear conditioning regulates hippocampal memory formation. We observe low levels of expression for many of the top candidate genes in the hippocampus and robust expression in the choroid plexus, as well as repression at 4 hours after contextual fear conditioning, suggesting the inclusion of choroid plexus messenger RNAs in Cho et al. hippocampal samples.

  10. Hardware format pattern banks for the Associative memory boards in the ATLAS Fast Tracker Trigger System

    CERN Document Server

    Grewcoe, Clay James

    2014-01-01

    The aim of this project is to streamline and update the process of encoding the pattern bank to hardware format in the Associative memory board (AM) of the Fast Tracker (FTK) for the ATLAS detector. The encoding is also adapted to Gray code to eliminate possible misreadings in high frequency devices such as this one, ROOT files are used to store the pattern banks because of the compression utilized in ROOT.

  11. Framing memories: How the retrieval query format shapes the neural bases of remembering.

    Science.gov (United States)

    Raposo, Ana; Frade, Sofia; Alves, Mara

    2016-08-01

    The way memory questions are framed influences the information that is searched, retrieved, and monitored during remembering. This fMRI study aimed at clarifying how the format of the retrieval query shapes the neural basis of source recollection. During encoding, participants made semantic (pleasantness) or perceptual (number of letters) judgments about words. Subsequently, in a source memory test, the retrieval query was manipulated such that for half of the items from each encoding task, the retrieval query emphasized the semantic source (i.e., semantic query format: "Is this word from the pleasantness task?"), whereas for the other half the retrieval query emphasized the alternate, perceptual source (i.e., perceptual query format: "Is this word from the letter task?"). The results showed that the semantic query format was associated with higher source recognition than the perceptual query format. This behavioral advantage was accompanied by increased activation in several regions associated to controlled semantic elaboration and monitoring of internally-generated features about the past event. In particular, for items semantically encoded, the semantic query, relative to the perceptual query, induced activation in medial prefrontal cortex (PFC), hippocampal, parahippocampal and middle temporal cortex. Conversely, for items perceptually encoded, the semantic query recruited the lateral PFC and occipital-fusiform areas. Interestingly, the semantic format also influenced the processing of new items, eliciting greater L lateral and medial PFC activation. In contrast, the perceptual query format (versus the semantic format) only prompted greater activation in R orbitofrontal cortex and the R inferior parietal lobe, for items encoded in a perceptual manner and for new items, respectively. The results highlight the role of the retrieval query format in source remembering, showing that the retrieval query that emphasizes the semantic source promotes the use of semantic

  12. Direct observation of conductive filament formation in Alq3 based organic resistive memories

    Energy Technology Data Exchange (ETDEWEB)

    Busby, Y., E-mail: yan.busby@unamur.be; Pireaux, J.-J. [Research Center in the Physics of Matter and Radiation (PMR), Laboratoire Interdisciplinaire de Spectroscopie Electronique (LISE), University of Namur, B-5000 Namur (Belgium); Nau, S.; Sax, S. [NanoTecCenter Weiz Forschungsgesellschaft mbH, Franz-Pichler Straße 32, A-8160 Weiz (Austria); List-Kratochvil, E. J. W. [NanoTecCenter Weiz Forschungsgesellschaft mbH, Franz-Pichler Straße 32, A-8160 Weiz (Austria); Institute of Solid State Physics, Graz University of Technology, A-8010 Graz (Austria); Novak, J.; Banerjee, R.; Schreiber, F. [Institute of Applied Physics, Eberhard-Karls-Universität Tübingen, D-72076 Tübingen (Germany)

    2015-08-21

    This work explores resistive switching mechanisms in non-volatile organic memory devices based on tris(8-hydroxyquinolie)aluminum (Alq{sub 3}). Advanced characterization tools are applied to investigate metal diffusion in ITO/Alq{sub 3}/Ag memory device stacks leading to conductive filament formation. The morphology of Alq{sub 3}/Ag layers as a function of the metal evaporation conditions is studied by X-ray reflectivity, while depth profile analysis with X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry is applied to characterize operational memory elements displaying reliable bistable current-voltage characteristics. 3D images of the distribution of silver inside the organic layer clearly point towards the existence of conductive filaments and allow for the identification of the initial filament formation and inactivation mechanisms during switching of the device. Initial filament formation is suggested to be driven by field assisted diffusion of silver from abundant structures formed during the top electrode evaporation, whereas thermochemical effects lead to local filament inactivation.

  13. Notch Intracellular Domain (NICD) Suppresses Long-Term Memory Formation in Adult Drosophila Flies.

    Science.gov (United States)

    Zhang, Jiabin; Yin, Jerry C P; Wesley, Cedric S

    2015-08-01

    Notch receptor signaling is evolutionarily conserved and well known for its roles in animal development. Many studies in Drosophila have shown that Notch also performs important functions in memory formation in adult flies. An intriguing observation is that increased expression of the full-length Notch receptor (Nfull) triggers long-term memory (LTM) formation even after very weak training (single training). Canonical Notch signaling is mediated by Notch intracellular domain (NICD), but it is not known whether increased expression of NICD recapitulates the LTM enhancement induced by increased Nfull expression. Here, we report that increased NICD expression either has no impact on LTM formation or suppresses it. Furthermore, it either has no impact or decreases both the levels and activity of cAMP response element binding protein, a key factor supporting LTM. These results indicate that NICD signaling is not sufficient to explain Nfull-induced LTM enhancement. Our findings may also shed light on the molecular mechanisms of memory loss in neurological diseases associated with increased NICD expression and canonical Notch signaling.

  14. Sex-Dependent Up-Regulation of Two Splicing Factors, Psf and Srp20, during Hippocampal Memory Formation

    Science.gov (United States)

    Antunes-Martins, Ana; Mizuno, Keiko; Irvine, Elaine E.; Lepicard, Eve M.; Giese, K. Peter

    2007-01-01

    Gene transcription is required for long-term memory (LTM) formation. LTM formation is impaired in a male-specific manner in mice lacking either of the two Ca[superscript 2+] / calmodulin-dependent kinase kinase ("Camkk") genes. Since altered transcription was suggested to cause these impairments in LTM formation, we used microarrays to screen for…

  15. Facilitation of peptide fibre formation by arginine-phosphate/carboxylate interactions

    Indian Academy of Sciences (India)

    K Krishna Prasad; Sandeep Verma

    2008-01-01

    This study describes peptide fibre formation in a hexapeptide, derived from the V3 loop of HIV-1, mediated by the interactions between arginine residues and phosphate/carboxylate anions. This charge neutralization approach was further confirmed when the deletion of arginine residue from the hexapeptide sequence resulted in fibre formation, which was studied by a combination of microscopic techniques.

  16. Dynamic O-GlcNAc modification regulates CREB-mediated gene expression and memory formation.

    Science.gov (United States)

    Rexach, Jessica E; Clark, Peter M; Mason, Daniel E; Neve, Rachael L; Peters, Eric C; Hsieh-Wilson, Linda C

    2012-01-22

    The transcription factor cyclic AMP-response element binding protein (CREB) is a key regulator of many neuronal processes, including brain development, circadian rhythm and long-term memory. Studies of CREB have focused on its phosphorylation, although the diversity of CREB functions in the brain suggests additional forms of regulation. Here we expand on a chemoenzymatic strategy for quantifying glycosylation stoichiometries to characterize the functional roles of CREB glycosylation in neurons. We show that CREB is dynamically modified with an O-linked β-N-acetyl-D-glucosamine sugar in response to neuronal activity and that glycosylation represses CREB-dependent transcription by impairing its association with CREB-regulated transcription coactivator (CRTC; also known as transducer of regulated CREB activity). Blocking glycosylation of CREB alters cellular function and behavioral plasticity, enhancing both axonal and dendritic growth and long-term memory consolidation. Our findings demonstrate a new role for O-glycosylation in memory formation and provide a mechanistic understanding of how glycosylation contributes to critical neuronal functions. Moreover, we identify a previously unknown mechanism for the regulation of activity-dependent gene expression, neural development and memory.

  17. Low-power resistive random access memory by confining the formation of conducting filaments

    Science.gov (United States)

    Huang, Yi-Jen; Shen, Tzu-Hsien; Lee, Lan-Hsuan; Wen, Cheng-Yen; Lee, Si-Chen

    2016-06-01

    Owing to their small physical size and low power consumption, resistive random access memory (RRAM) devices are potential for future memory and logic applications in microelectronics. In this study, a new resistive switching material structure, TiOx/silver nanoparticles/TiOx/AlTiOx, fabricated between the fluorine-doped tin oxide bottom electrode and the indium tin oxide top electrode is demonstrated. The device exhibits excellent memory performances, such as low operation voltage (<±1 V), low operation power, small variation in resistance, reliable data retention, and a large memory window. The current-voltage measurement shows that the conducting mechanism in the device at the high resistance state is via electron hopping between oxygen vacancies in the resistive switching material. When the device is switched to the low resistance state, conducting filaments are formed in the resistive switching material as a result of accumulation of oxygen vacancies. The bottom AlTiOx layer in the device structure limits the formation of conducting filaments; therefore, the current and power consumption of device operation are significantly reduced.

  18. Low-power resistive random access memory by confining the formation of conducting filaments

    Directory of Open Access Journals (Sweden)

    Yi-Jen Huang

    2016-06-01

    Full Text Available Owing to their small physical size and low power consumption, resistive random access memory (RRAM devices are potential for future memory and logic applications in microelectronics. In this study, a new resistive switching material structure, TiOx/silver nanoparticles/TiOx/AlTiOx, fabricated between the fluorine-doped tin oxide bottom electrode and the indium tin oxide top electrode is demonstrated. The device exhibits excellent memory performances, such as low operation voltage (<±1 V, low operation power, small variation in resistance, reliable data retention, and a large memory window. The current-voltage measurement shows that the conducting mechanism in the device at the high resistance state is via electron hopping between oxygen vacancies in the resistive switching material. When the device is switched to the low resistance state, conducting filaments are formed in the resistive switching material as a result of accumulation of oxygen vacancies. The bottom AlTiOx layer in the device structure limits the formation of conducting filaments; therefore, the current and power consumption of device operation are significantly reduced.

  19. Exchange Protein Activated by cAMP Enhances Long-Term Memory Formation Independent of Protein Kinase A

    Science.gov (United States)

    Ma, Nan; Abel, Ted; Hernandez, Pepe J.

    2009-01-01

    It is well established that cAMP signaling within neurons plays a major role in the formation of long-term memories--signaling thought to proceed through protein kinase A (PKA). However, here we show that exchange protein activated by cAMP (Epac) is able to enhance the formation of long-term memory in the hippocampus and appears to do so…

  20. A novel melatonin agonist Neu-P11 facilitates memory performance and improves cognitive impairment in a rat model of Alzheimer' disease.

    Science.gov (United States)

    He, Pingping; Ouyang, Xinping; Zhou, Shouhong; Yin, Weidong; Tang, Chaoke; Laudon, Moshe; Tian, Shaowen

    2013-06-01

    Previous studies have shown that melatonin is implicated in modulating learning and memory processing. Melatonin also exerts neuroprotective activities against Aβ-induced injury in vitro and in vivo. Neu-P11 (piromelatine, N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-oxo-4H-pyran-2-carboxamide) is a novel melatonin (MT1/MT2) receptor agonist and a serotonin 5-HT1A/1D receptor agonist recently developed for the treatment of insomnia. In the present study we firstly investigated whether Neu-P11 and melatonin enhance memory performance in the novel object recognition (NOR) task in rats, and then assessed whether Neu-P11 and melatonin improve neuronal and cognitive impairment in a rat model of Alzheimer' disease (AD) induced by intrahippocampal Aβ(1-42) injection. The results showed that a single morning or afternoon administration of Neu-P11 enhanced object recognition memory measured at 4 or 24h after training. Melatonin was effective in the memory facilitating effects only when administered in the afternoon. Further results showed that intrahippocampal Aβ(1-42) injection resulted in hippocampal cellular loss, as well as decreased learning ability and memory in the Y maze and NOR tasks in rats. Neu-P11 but not melatonin attenuated cellular loss and cognitive impairment in the rat AD model. The current data suggest that Neu-P11 may serve as a novel agent for the treatment of AD.

  1. Protease-activated receptor-1 modulates hippocampal memory formation and synaptic plasticity.

    Science.gov (United States)

    Almonte, Antoine G; Qadri, Laura H; Sultan, Faraz A; Watson, Jennifer A; Mount, Daniel J; Rumbaugh, Gavin; Sweatt, J David

    2013-01-01

    Protease-activated receptor-1 (PAR1) is an unusual G-protein coupled receptor (GPCR) that is activated through proteolytic cleavage by extracellular serine proteases. Although previous work has shown that inhibiting PAR1 activation is neuroprotective in models of ischemia, traumatic injury, and neurotoxicity, surprisingly little is known about PAR1's contribution to normal brain function. Here, we used PAR1-/- mice to investigate the contribution of PAR1 function to memory formation and synaptic function. We demonstrate that PAR1-/- mice have deficits in hippocampus-dependent memory. We also show that while PAR1-/- mice have normal baseline synaptic transmission at Schaffer collateral-CA1 synapses, they exhibit severe deficits in N-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP). Mounting evidence indicates that activation of PAR1 leads to potentiation of NMDAR-mediated responses in CA1 pyramidal cells. Taken together, this evidence and our data suggest an important role for PAR1 function in NMDAR-dependent processes subserving memory formation and synaptic plasticity. © 2012 International Society for Neurochemistry.

  2. Microinjection of valproic acid into the ventrolateral orbital cortex enhances stress-related memory formation.

    Directory of Open Access Journals (Sweden)

    Yan Zhao

    Full Text Available There is collecting evidence suggesting that the process of chromatin remodeling such as changes in histone acetylation contribute to the formation of stress-related memory. Recently, the ventrolateral orbital cortex (VLO, a major subdivision of orbitofrontal cortex (OFC, was shown to be involved in antidepressant-like actions through epigenetic mechanisms. Here, we further investigated the effects of the histone deacetylase inhibitor (HDACi valproic acid (VPA on stress-related memory formation and the underlying molecular mechanisms by using the traditional two-day forced swimming test (FST. The results showed that VPA significantly increased the immobility time on day 2 when infused into the VLO before the initial forced swim stress on day 1. The learned immobility response to the stress was associated with increased phosphorylation of extracellular signal-regulated kinase (ERK in VLO and hippocampus on the first day. The levels of phosphorylated ERK (phospho-ERK in VLO and hippocampus were significantly decreased when retested 24 h later. The pretreatment with intra-VLO VPA infusion further reduced the activation of ERK on day 2 and day 7 compared with the saline controls. Moreover, the VPA infusion pretreatment also induced a significantly decreased BDNF level in the VLO on day 2, whereas no change was detected in the hippocampus. These findings suggest that VPA enhance the memories of emotionally stressful events and the ERK activity is implicated in stimulating adaptive and mnemonic processes in case the event would recur.

  3. Extracellular DNA facilitates the formation of functional amyloids in Staphylococcus aureus biofilms.

    Science.gov (United States)

    Schwartz, Kelly; Ganesan, Mahesh; Payne, David E; Solomon, Michael J; Boles, Blaise R

    2016-01-01

    Persistent staphylococcal infections often involve surface-associated communities called biofilms. Staphylococcus aureus biofilm development is mediated by the co-ordinated production of the biofilm matrix, which can be composed of polysaccharides, extracellular DNA (eDNA) and proteins including amyloid fibers. The nature of the interactions between matrix components, and how these interactions contribute to the formation of matrix, remain unclear. Here we show that the presence of eDNA in S. aureus biofilms promotes the formation of amyloid fibers. Conditions or mutants that do not generate eDNA result in lack of amyloids during biofilm growth despite the amyloidogeneic subunits, phenol soluble modulin peptides, being produced. In vitro studies revealed that the presence of DNA promotes amyloid formation by PSM peptides. Thus, this work exposes a previously unacknowledged interaction between biofilm matrix components that furthers our understanding of functional amyloid formation and S. aureus biofilm biology.

  4. Effects of systemic administration of histone deacetylase inhibitor on memory formation and immediate early gene expression in chick brain.

    Science.gov (United States)

    Tiunova, A A; Toropova, K A; Konovalova, E V; Anokhin, K V

    2012-09-01

    We studied the effects of histone deacetylase inhibitor that stimulates transcriptional activity via histone hyperacetylation on memory formation. Sodium butyrate and sodium valproate enhanced memory in chicks following "weak" training with memory transfer into long-term state. Quantitative analysis of c-Fos and ZENK transcriptional factor gene expression in six structures of chick brain revealed induction of these genes in the structures involved in this type of learning. Sodium valproate administration did not increase this induction, but even reduced it. These findings suggest that sodium butyrate and sodium valproate exert cognitive stimulating action in the "weak" memory formation paradigm, and that this effect is not mediated via enhanced expression of transcriptional factors, which are traditionally considered as "molecular switcher" for memory transfer into long-term state.

  5. Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice.

    Science.gov (United States)

    Cui, Yihui; Jin, Jing; Zhang, Xuliang; Xu, Hao; Yang, Liguo; Du, Dan; Zeng, Qingwen; Tsien, Joe Z; Yu, Huiting; Cao, Xiaohua

    2011-01-01

    Prefrontal cortex plays an important role in working memory, attention regulation and behavioral inhibition. Its functions are associated with NMDA receptors. However, there is little information regarding the roles of NMDA receptor NR2B subunit in prefrontal cortical synaptic plasticity and prefrontal cortex-related working memory. Whether the up-regulation of NR2B subunit influences prefrontal cortical synaptic plasticity and working memory is not yet clear. In the present study, we measured prefrontal cortical synaptic plasticity and working memory function in NR2B overexpressing transgenic mice. In vitro electrophysiological data showed that overexpression of NR2B specifically in the forebrain region resulted in enhancement of prefrontal cortical long-term potentiation (LTP) but did not alter long-term depression (LTD). The enhanced LTP was completely abolished by a NR2B subunit selective antagonist, Ro25-6981, indicating that overexpression of NR2B subunit is responsible for enhanced LTP. In addition, NR2B transgenic mice exhibited better performance in a set of working memory paradigms including delay no-match-to-place T-maze, working memory version of water maze and odor span task. Our study provides evidence that NR2B subunit of NMDA receptor in prefrontal cortex is critical for prefrontal cortex LTP and prefrontal cortex-related working memory.

  6. Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice.

    Directory of Open Access Journals (Sweden)

    Yihui Cui

    Full Text Available Prefrontal cortex plays an important role in working memory, attention regulation and behavioral inhibition. Its functions are associated with NMDA receptors. However, there is little information regarding the roles of NMDA receptor NR2B subunit in prefrontal cortical synaptic plasticity and prefrontal cortex-related working memory. Whether the up-regulation of NR2B subunit influences prefrontal cortical synaptic plasticity and working memory is not yet clear. In the present study, we measured prefrontal cortical synaptic plasticity and working memory function in NR2B overexpressing transgenic mice. In vitro electrophysiological data showed that overexpression of NR2B specifically in the forebrain region resulted in enhancement of prefrontal cortical long-term potentiation (LTP but did not alter long-term depression (LTD. The enhanced LTP was completely abolished by a NR2B subunit selective antagonist, Ro25-6981, indicating that overexpression of NR2B subunit is responsible for enhanced LTP. In addition, NR2B transgenic mice exhibited better performance in a set of working memory paradigms including delay no-match-to-place T-maze, working memory version of water maze and odor span task. Our study provides evidence that NR2B subunit of NMDA receptor in prefrontal cortex is critical for prefrontal cortex LTP and prefrontal cortex-related working memory.

  7. Distribution of glutamine synthetase in the chick forebrain: implications for passive avoidance memory formation.

    Science.gov (United States)

    O'Dowd, B S; Ng, K T; Robinson, S R

    1997-01-01

    The glial enzyme glutamine synthetase (GS) converts glutamate to glutamine; the latter is used by neurons for the resynthesis of glutamate and GABA. We have used a monoclonal antibody to GS to examine the regional distribution of this enzyme in the forebrains of day-old chicks. GS was detected in glia throughout the rostral and caudal regions of the forebrain and was particularly intense in the hippocampus, area parahippocampus and parts of the hyperstriatal and paleostriatal complex, regions widely considered to be involved in memory formation. Thus, our data provide an anatomical framework for the conclusion that neurons require the support of glia in order to restock their glutamate and/or GABA transmitter supplies during memory processing.

  8. Activity dependent protein degradation is critical for the formation and stability of fear memory in the amygdala.

    Directory of Open Access Journals (Sweden)

    Timothy J Jarome

    Full Text Available Protein degradation through the ubiquitin-proteasome system [UPS] plays a critical role in some forms of synaptic plasticity. However, its role in memory formation in the amygdala, a site critical for the formation of fear memories, currently remains unknown. Here we provide the first evidence that protein degradation through the UPS is critically engaged at amygdala synapses during memory formation and retrieval. Fear conditioning results in NMDA-dependent increases in degradation-specific polyubiquitination in the amygdala, targeting proteins involved in translational control and synaptic structure and blocking the degradation of these proteins significantly impairs long-term memory. Furthermore, retrieval of fear memory results in a second wave of NMDA-dependent polyubiquitination that targets proteins involved in translational silencing and synaptic structure and is critical for memory updating following recall. These results indicate that UPS-mediated protein degradation is a major regulator of synaptic plasticity necessary for the formation and stability of long-term memories at amygdala synapses.

  9. Roles of aminergic neurons in formation and recall of associative memory in crickets

    Directory of Open Access Journals (Sweden)

    Makoto Mizunami

    2010-11-01

    Full Text Available We review recent progress in the study of roles of octopaminergic (OA-ergic and dopaminergic (DA-ergic signaling in insect classical conditioning, focusing on our studies on crickets. Studies on olfactory learning in honey bees and fruit-flies have suggested that OA-ergic and DA-ergic neurons convey reinforcing signals of appetitive unconditioned stimulus (US and aversive US, respectively. Our work suggested that this is applicable to olfactory, visual pattern and color learning in crickets, indicating that this feature is ubiquitous in learning of various sensory stimuli. We also showed that aversive memory decayed much faster than did appetitive memory, and we proposed that this feature is common in insects and humans. Our study also suggested that activation of OA- or DA-ergic neurons is needed for appetitive or aversive memory recall, respectively. To account for this finding, we proposed a model in which it is assumed that two types of synaptic connections are strengthened by conditioning and are activated during memory recall, one type being connections from neurons representing conditioned stimulus (CS to neurons inducing conditioned response and the other being connections from neurons representing CS to OA- or DA-ergic neurons representing appetitive or aversive US, respectively. The former is called stimulus-response (S-R connection and the latter is called stimulus-stimulus (S-S connection by theorists studying classical conditioning in vertebrates. Results of our studies using a second-order conditioning procedure supported our model. We propose that insect classical conditioning involves the formation of S-S connection and its activation for memory recall, which are often called cognitive processes.

  10. The Role of Cannabinoid Transmission in Emotional Memory Formation: Implications for Addiction and Schizophrenia

    Directory of Open Access Journals (Sweden)

    Huibing eTan

    2014-06-01

    Full Text Available Emerging evidence from both basic and clinical research demonstrates an important role for endocannabinoid (ECB signaling in the processing of emotionally salient information, learning and memory. Cannabinoid transmission within neural circuits involved in emotional processing has been shown to modulate the acquisition, recall and extinction of emotionally salient memories and importantly, can strongly modulate the emotional salience of incoming sensory information. Two neural regions in particular, the medial prefrontal cortex (PFC and the basolateral nucleus of the amygdala (BLA, play important roles in emotional regulation and contain high levels of cannabinoid receptors. Furthermore, both regions show profound abnormalities in neuropsychiatric disorders such as addiction and schizophrenia. Considerable evidence has demonstrated that cannabinoid transmission functionally interacts with dopamine (DA, a neurotransmitter system that is of exceptional importance for both addictive behaviours and the neuropsychopathology of disorders like schizophrenia. Research in our laboratory has focused on how cannabinoid transmission both within and extrinsic to the mesolimbic DA system, including the BLAmPFC circuitry, can modulate both rewarding and aversive emotional information. In this review, we will summarize clinical and basic neuroscience research demonstrating the importance of cannabinoid signaling within this neural circuitry. In particular, evidence will be reviewed emphasizing the importance of cannabinoid signaling within the BLAmPFC circuitry in the context of emotional salience processing, memory formation and memory-related plasticity. We propose that aberrant states of hyper or hypoactive ECB signaling within the amygdala-prefrontal cortical circuit may lead to dysregulation of mesocorticolimbic DA transmission controlling the processing of emotionally salient information. These disturbances may in turn lead to emotional processing

  11. Antibodies mediate formation of neutrophil extracellular traps in the middle ear and facilitate secondary pneumococcal otitis media.

    Science.gov (United States)

    Short, Kirsty R; von Köckritz-Blickwede, Maren; Langereis, Jeroen D; Chew, Keng Yih; Job, Emma R; Armitage, Charles W; Hatcher, Brandon; Fujihashi, Kohtaro; Reading, Patrick C; Hermans, Peter W; Wijburg, Odilia L; Diavatopoulos, Dimitri A

    2014-01-01

    Otitis media (OM) (a middle ear infection) is a common childhood illness that can leave some children with permanent hearing loss. OM can arise following infection with a variety of different pathogens, including a coinfection with influenza A virus (IAV) and Streptococcus pneumoniae (the pneumococcus). We and others have demonstrated that coinfection with IAV facilitates the replication of pneumococci in the middle ear. Specifically, we used a mouse model of OM to show that IAV facilitates the outgrowth of S. pneumoniae in the middle ear by inducing middle ear inflammation. Here, we seek to understand how the host inflammatory response facilitates bacterial outgrowth in the middle ear. Using B cell-deficient infant mice, we show that antibodies play a crucial role in facilitating pneumococcal replication. We subsequently show that this is due to antibody-dependent neutrophil extracellular trap (NET) formation in the middle ear, which, instead of clearing the infection, allows the bacteria to replicate. We further demonstrate the importance of these NETs as a potential therapeutic target through the transtympanic administration of a DNase, which effectively reduces the bacterial load in the middle ear. Taken together, these data provide novel insight into how pneumococci are able to replicate in the middle ear cavity and induce disease.

  12. Reactive microglia and macrophage facilitate the formation of Müller glia-derived retinal progenitors.

    Science.gov (United States)

    Fischer, Andy J; Zelinka, Christopher; Gallina, Donika; Scott, Melissa A; Todd, Levi

    2014-10-01

    In retinas where Müller glia have been stimulated to become progenitor cells, reactive microglia are always present. Thus, we investigated how the activation or ablation of microglia/macrophage influences the formation of Müller glia-derived progenitor cells (MGPCs) in the retina in vivo. Intraocular injections of the Interleukin-6 (IL6) stimulated the reactivity of microglia/macrophage, whereas other types of retinal glia appear largely unaffected. In acutely damaged retinas where all of the retinal microglia/macrophage were ablated, the formation of proliferating MGPCs was greatly diminished. With the microglia ablated in damaged retinas, levels of Notch and related genes were unchanged or increased, whereas levels of ascl1a, TNFα, IL1β, complement component 3 (C3) and C3a receptor were significantly reduced. In the absence of retinal damage, the combination of insulin and Fibroblast growth factor 2 (FGF2) failed to stimulate the formation of MGPCs when the microglia/macrophage were ablated. In addition, intraocular injections of IL6 and FGF2 stimulated the formation of MGPCs in the absence of retinal damage, and this generation of MGPCs was blocked when the microglia/macrophage were absent. We conclude that the activation of microglia and/or infiltrating macrophage contributes to the formation of proliferating MGPCs, and these effects may be mediated by components of the complement system and inflammatory cytokines.

  13. Facilitation of tactile working memory by top-down suppression from prefrontal to primary somatosensory cortex during sensory interference.

    Science.gov (United States)

    Savolainen, Petri; Carlson, Synnöve; Boldt, Robert; Neuvonen, Tuomas; Hannula, Henri; Hiltunen, Jaana; Salonen, Oili; Ma, Yuan-Ye; Pertovaara, Antti

    2011-06-01

    Tactile working memory (WM) is improved by increasing top-down suppression of interfering sensory processing in S1 via a link from the middle frontal gyrus (MFG) to S1. Here we studied in healthy subjects whether the efficacy of top-down suppression varies with submodality of sensory interference. Navigated stimulation of the MFG-S1 link significantly improved tactile WM performance when accompanied by tactile but not visual interference of memory maintenance.

  14. Identification of transmitter systems and learning tag molecules involved in behavioral tagging during memory formation.

    Science.gov (United States)

    Moncada, Diego; Ballarini, Fabricio; Martinez, María Cecilia; Frey, Julietta U; Viola, Haydee

    2011-08-02

    Long-term memory (LTM) consolidation requires the synthesis of plasticity-related proteins (PRPs). In addition, we have shown recently that LTM formation also requires the setting of a "learning tag" able to capture those PRPs. Weak training, which results only in short-term memory, can set a tag to use PRPs derived from a temporal-spatial closely related event to promote LTM formation. Here, we studied the involvement of glutamatergic, dopaminergic, and noradrenergic inputs on the setting of an inhibitory avoidance (IA) learning tag and the synthesis of PRPs. Rats explored an open field (PRP donor) followed by weak (tag inducer) or strong (tag inducer plus PRP donor) IA training. Throughout pharmacological interventions around open-field and/or IA sessions, we found that hippocampal dopamine D1/D5- and β-adrenergic receptors are specifically required to induce PRP synthesis. Moreover, activation of the glutamatergic NMDA receptors is required for setting the learning tags, and this machinery further required α-Ca(2+)/calmodulin-dependent protein kinase II and PKA but not ERK1/2 activity. Together, the present findings emphasize an essential role of the induction of PRPs and learning tags for LTM formation. The existence of only the PRP or the tag was insufficient for stabilization of the mnemonic trace.

  15. Identification of transmitter systems and learning tag molecules involved in behavioral tagging during memory formation

    Science.gov (United States)

    Moncada, Diego; Ballarini, Fabricio; Martinez, María Cecilia; Frey, Julietta U.; Viola, Haydee

    2011-01-01

    Long-term memory (LTM) consolidation requires the synthesis of plasticity-related proteins (PRPs). In addition, we have shown recently that LTM formation also requires the setting of a “learning tag” able to capture those PRPs. Weak training, which results only in short-term memory, can set a tag to use PRPs derived from a temporal-spatial closely related event to promote LTM formation. Here, we studied the involvement of glutamatergic, dopaminergic, and noradrenergic inputs on the setting of an inhibitory avoidance (IA) learning tag and the synthesis of PRPs. Rats explored an open field (PRP donor) followed by weak (tag inducer) or strong (tag inducer plus PRP donor) IA training. Throughout pharmacological interventions around open-field and/or IA sessions, we found that hippocampal dopamine D1/D5- and β-adrenergic receptors are specifically required to induce PRP synthesis. Moreover, activation of the glutamatergic NMDA receptors is required for setting the learning tags, and this machinery further required α-Ca2+/calmodulin-dependent protein kinase II and PKA but not ERK1/2 activity. Together, the present findings emphasize an essential role of the induction of PRPs and learning tags for LTM formation. The existence of only the PRP or the tag was insufficient for stabilization of the mnemonic trace. PMID:21768371

  16. Circadian clock proteins control adaptation to novel environment and memory formation

    Science.gov (United States)

    A.Kondratova, Anna; V.Dubrovsky, Yuliya; Antoch, Marina P.; Kondratov, Roman V.

    2010-01-01

    Deficiency of the transcription factor BMAL1, a core component of the circadian clock, results in an accelerated aging phenotype in mice. The circadian clock regulates many physiological processes and was recently implicated in control of brain-based activities, such as memory formation and the regulation of emotions. Aging is accompanied by the decline in brain physiology, particularly decline in the response and adaptation to novelty. We investigated the role of the circadian clock in exploratory behavior and habituation to novelty using the open field paradigm. We found that mice with a deficiency of the circadian transcription factor BMAL1 display hyperactivity in novel environments and impaired intra- and intersession habituation, indicative of defects in short- and long-term memory formation. In contrast, mice double-deficient for the circadian proteins CRY1 and CRY2 (repressors of the BMAL1-mediated transcription) demonstrate reduced activity and accelerated habituation when compared to wild type mice. Mice with mutation in theClock gene (encoding the BMAL1 transcription partner) show normal locomotion, but increased rearing activity and impaired intersession habituation. BMAL1 is highly expressed in the neurons of the hippocampus - a brain region associated with spatial memory formation; BMAL1 deficiency disrupts circadian oscillation in gene expression and reactive oxygen species homeostasis in the brain, which may be among the possible mechanisms involved. Thus, we suggest that the BMAL1:CLOCK activity is critical for the proper exploratory and habituation behavior, and that the circadian clock prepares organism for a new round of everyday activities through optimization of behavioral learning. PMID:20519775

  17. Model Building to Facilitate Understanding of Holliday Junction and Heteroduplex Formation, and Holliday Junction Resolution

    Science.gov (United States)

    Selvarajah, Geeta; Selvarajah, Susila

    2016-01-01

    Students frequently expressed difficulty in understanding the molecular mechanisms involved in chromosomal recombination. Therefore, we explored alternative methods for presenting the two concepts of the double-strand break model: Holliday junction and heteroduplex formation, and Holliday junction resolution. In addition to a lecture and…

  18. Promoter-Specific Effects of DREADD Modulation on Hippocampal Synaptic Plasticity and Memory Formation

    OpenAIRE

    Lopez, AJ; Kramar, E; Matheos, DP; White, AO; Kwapis, J; Vogel-Ciernia, A; Sakata, K.; Espinoza, M; Wood, MA

    2016-01-01

    Designer receptors exclusively activated by designer drug (DREADDs) are a novel tool with the potential to bidirectionally drive cellular, circuit, and ultimately, behavioral changes. We used DREADDs to evaluate memory formation in a hippocampus-dependent task in mice and effects on synaptic physiology in the dorsal hippocampus. We expressed neuron-specific (hSyn promoter) DREADDs that were either excitatory (HM3D) or inhibitory (HM4D) in the dorsal hippocampus. As predicted, hSyn–HM3D was ab...

  19. A Memory/Immunology-Based Control Approach with Applications to Multiple Spacecraft Formation Flying

    Directory of Open Access Journals (Sweden)

    Liguo Weng

    2013-01-01

    Full Text Available This paper addresses the problem of formation control for multiple spacecrafts in Planetary Orbital Environment (POE. Due to the presence of diverse interferences and uncertainties in the outer space, such as the changing spacecraft mass, unavailable space parameters, and varying gravity forces, traditional control methods encounter great difficulties in this area. A new control approach inspired by human memory and immune system is proposed, and this approach is shown to be capable of learning from past control experience and current behavior to improve its performance. It demands much less system dynamic information as compared with traditional controls. Both theoretic analysis and computer simulation verify its effectiveness.

  20. Bax Activation Initiates the Assembly of a Multimeric Catalyst that Facilitates Bax Pore Formation in Mitochondrial Outer Membranes

    Science.gov (United States)

    Kushnareva, Yulia; Andreyev, Alexander Y.; Kuwana, Tomomi; Newmeyer, Donald D.

    2012-01-01

    Bax/Bak-mediated mitochondrial outer membrane permeabilization (MOMP) is essential for “intrinsic” apoptotic cell death. Published studies used synthetic liposomes to reveal an intrinsic pore-forming activity of Bax, but it is unclear how other mitochondrial outer membrane (MOM) proteins might facilitate this function. We carefully analyzed the kinetics of Bax-mediated pore formation in isolated MOMs, with some unexpected results. Native MOMs were more sensitive than liposomes to added Bax, and MOMs displayed a lag phase not observed with liposomes. Heat-labile MOM proteins were required for this enhanced response. A two-tiered mathematical model closely fit the kinetic data: first, Bax activation promotes the assembly of a multimeric complex, which then catalyzes the second reaction, Bax-dependent pore formation. Bax insertion occurred immediately upon Bax addition, prior to the end of the lag phase. Permeabilization kinetics were affected in a reciprocal manner by [cBid] and [Bax], confirming the “hit-and-run” hypothesis of cBid-induced direct Bax activation. Surprisingly, MOMP rate constants were linearly related to [Bax], implying that Bax acts non-cooperatively. Thus, the oligomeric catalyst is distinct from Bax. Moreover, contrary to common assumption, pore formation kinetics depend on Bax monomers, not oligomers. Catalyst formation exhibited a sharp transition in activation energy at ∼28°C, suggesting a role for membrane lipid packing. Furthermore, catalyst formation was strongly inhibited by chemical antagonists of the yeast mitochondrial fission protein, Dnm1. However, the mammalian ortholog, Drp1, was undetectable in mitochondrial outer membranes. Moreover, ATP and GTP were dispensable for MOMP. Thus, the data argue that oligomerization of a catalyst protein, distinct from Bax and Drp1, facilitates MOMP, possibly through a membrane-remodeling event. PMID:23049480

  1. Muscarinic receptors activity in the perirhinal cortex and hippocampus has differential involvement in the formation of recognition memory.

    Science.gov (United States)

    Balderas, Israela; Morin, Jean-Pascal; Rodriguez-Ortiz, Carlos J; Bermudez-Rattoni, Federico

    2012-05-01

    In this work we probed the effects of post-trial infusions of the muscarinic receptor antagonist scopolamine on object recognition memory formation. Scopolamine was infused bilaterally immediately after the sample phase in the perirhinal cortex or dorsal hippocampus and animals were tested for short-term (90 min) or long-term (24 h) memory. Results showed that scopolamine impaired short-term memory when injected in either the perirhinal cortex or hippocampus. Nevertheless, scopolamine disrupted long-term memory when administrated in the perirhinal cortex but not when applied in the hippocampus. Long-term memory was unaffected when scopolamine was infused 160 min after the sample phase or 90 min before test phase. Our data indicate that short-term recognition memory requires muscarinic receptors signaling in both the perirhinal cortex and hippocampus, whereas long-term recognition memory depends on muscarinic receptors in the perirhinal cortex but not hippocampus. These results support a differential involvement of muscarinic activity in these two medial temporal lobe structures in the formation of recognition memory. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Early memory formation disrupted by atypical PKC inhibitor ZIP in the medial prefrontal cortex but not hippocampus.

    Science.gov (United States)

    Evuarherhe, Obaro; Barker, Gareth R I; Savalli, Giorgia; Warburton, Elizabeth C; Brown, Malcolm W

    2014-08-01

    Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesized to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluA2 subunit. A myristoylated PKMζ pseudosubstrate peptide (ZIP) blocks PKMζ activity. We examined the actions of ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition memory in rats during early memory formation and memory maintenance. ZIP infusion in either hippocampus or mPFC impaired memory maintenance. However, early memory formation was impaired by ZIP in mPFC but not hippocampus; and blocking GluA2-dependent removal of AMPA receptors did not affect this impairment caused by ZIP in the mPFC. The findings indicate: (i) a difference in the actions of ZIP in hippocampus and medial prefrontal cortex, and (ii) a GluA2-independent target of ZIP (possibly PKCλ) in the mPFC during early memory formation. © 2014 Wiley Periodicals, Inc.

  3. Reward signal in a recurrent circuit drives appetitive long-term memory formation.

    Science.gov (United States)

    Ichinose, Toshiharu; Aso, Yoshinori; Yamagata, Nobuhiro; Abe, Ayako; Rubin, Gerald M; Tanimoto, Hiromu

    2015-11-17

    Dopamine signals reward in animal brains. A single presentation of a sugar reward to Drosophila activates distinct subsets of dopamine neurons that independently induce short- and long-term olfactory memories (STM and LTM, respectively). In this study, we show that a recurrent reward circuit underlies the formation and consolidation of LTM. This feedback circuit is composed of a single class of reward-signaling dopamine neurons (PAM-α1) projecting to a restricted region of the mushroom body (MB), and a specific MB output cell type, MBON-α1, whose dendrites arborize that same MB compartment. Both MBON-α1 and PAM-α1 neurons are required during the acquisition and consolidation of appetitive LTM. MBON-α1 additionally mediates the retrieval of LTM, which is dependent on the dopamine receptor signaling in the MB α/β neurons. Our results suggest that a reward signal transforms a nascent memory trace into a stable LTM using a feedback circuit at the cost of memory specificity.

  4. MstX and a putative potassium channel facilitate biofilm formation in Bacillus subtilis.

    Directory of Open Access Journals (Sweden)

    Matthew E Lundberg

    Full Text Available Biofilms constitute the predominant form of microbial life and a potent reservoir for innate antibiotic resistance in systemic infections. In the spore-forming bacterium Bacillus subtilis, the transition from a planktonic to sessile state is mediated by mutually exclusive regulatory pathways controlling the expression of genes required for flagellum or biofilm formation. Here, we identify mstX and yugO as novel regulators of biofilm formation in B. subtilis. We show that expression of mstX and the downstream putative K+ efflux channel, yugO, is necessary for biofilm development in B. subtilis, and that overexpression of mstX induces biofilm assembly. Transcription of the mstX-yugO operon is under the negative regulation of SinR, a transcription factor that governs the switch between planktonic and sessile states. Furthermore, mstX regulates the activity of Spo0A through a positive autoregulatory loop involving KinC, a histidine kinase that is activated by potassium leakage. The addition of potassium abrogated mstX-mediated biofilm formation. Our findings expand the role of Spo0A and potassium homeostasis in the regulation of bacterial development.

  5. Effect of Laser Welding Parameters on Formation of NiTi Shape Memory Alloy Welds

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    Wei Wang

    2014-01-01

    Full Text Available In this work experimental trials of welding of NiTi flat plates with 2.0 mm thickness were conducted using a 4.5 kW continuous wave (CW Nd:YAG laser. The influences of laser output power, welding speed, defocus amount and side-blow shielding gas flow rate on the morphology, welding depth and width, and quality of the welded seam were investigated. Meanwhile, the effects of heat input on the mechanical and functional properties of welded joints were studied. The results show that laser welding can take better formation in NiTi alloys. The matching curves with laser power and welding speed affecting different formation of welds were experimentally acquired, which can provide references for laser welding and engineering application of NiTi alloy. The heat input has obvious effects on the ultimate tensile strength (UTS and shape memory behavior of the welded joints.

  6. Encoding-related EEG oscillations during memory formation are modulated by mood state.

    Science.gov (United States)

    Gärtner, Matti; Bajbouj, Malek

    2014-12-01

    Mood states have a strong impact on how we process incoming information. It has been proposed that positive mood facilitates elaborative, relational encoding, whereas negative mood promotes a more careful, stimulus-driven encoding style. Previous electrophysiological studies have linked successful information encoding to power increases in slow (30 Hz) gamma oscillations, as well as to power decreases in midrange (8-30 Hz) alpha/beta oscillations. Whether different mood states modulate encoding-related oscillations has not been investigated yet. In order to address this question, we used an experimental mood induction procedure and recorded electroencephalograms from 20 healthy participants while they performed a free recall memory task after positive and negative mood induction. We found distinct oscillatory patterns in positive and negative mood. Successful encoding in positive mood was accompanied by widespread power increases in the delta band, whereas encoding success in negative mood was specifically accompanied by frontal power decreases in the beta band. On the behavioral level, memory performance was enhanced in positive mood. Our findings show that mood differentially modulates the neural correlates of successful information encoding and thus contribute to an understanding of how mood shapes different processing styles.

  7. Effectiveness of an intervention to facilitate prompt referral to memory clinics in the United Kingdom: Cluster randomised controlled trial.

    Directory of Open Access Journals (Sweden)

    Gill Livingston

    2017-03-01

    Full Text Available Most people with dementia do not receive timely diagnosis, preventing them from making informed plans about their future and accessing services. Many countries have a policy to increase timely diagnosis, but trials aimed at changing general practitioner (GP practice have been unsuccessful. We aimed to assess whether a GP's personal letter, with an evidence-based leaflet about overcoming barriers to accessing help for memory problems-aimed at empowering patients and families-increases timely dementia diagnosis and patient presentation to general practice.Multicentre, cluster-randomised controlled trial with raters masked to an online computer-generated randomisation system assessing 1 y outcome. We recruited 22 general practices (August 2013-September 2014 and 13 corresponding secondary care memory services in London, Hertfordshire, and Essex, United Kingdom. Eligible patients were aged ≥70 y, without a known diagnosis of dementia, living in their own homes. There were 6,387 such patients in 11 intervention practices and 8,171 in the control practices. The primary outcome was cognitive severity on Mini Mental State Examination (MMSE. Main secondary outcomes were proportion of patients consulting their GP with suspected memory disorders and proportion of those referred to memory clinics. There was no between-group difference in cognitive severity at diagnosis (99 intervention, mean MMSE = 22.04, 95% confidence intervals (CIs = 20.95 to 23.13; 124 control, mean MMSE = 22.59, 95% CI = 21.58 to 23.6; p = 0.48. GP consultations with patients with suspected memory disorders increased in intervention versus control group (odds ratio = 1.41; 95% CI = 1.28, 1.54. There was no between-group difference in the proportions of patients referred to memory clinics (166, 2.5%; 220, 2.7%; p = .077 respectively. The study was limited as we do not know whether the additional patients presenting to GPs had objective as well as subjective memory problems and

  8. Flavonoid Hesperidin Induces Synapse Formation and Improves Memory Performance through the Astrocytic TGF-β1

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    Isadora Matias

    2017-06-01

    Full Text Available Synapse formation and function are critical events for the brain function and cognition. Astrocytes are active participants in the control of synapses during development and adulthood, but the mechanisms underlying astrocyte synaptogenic potential only began to be better understood recently. Currently, new drugs and molecules, including the flavonoids, have been studied as therapeutic alternatives for modulation of cognitive processes in physiological and pathological conditions. However, the cellular targets and mechanisms of actions of flavonoids remain poorly elucidated. In the present study, we investigated the effects of hesperidin on memory and its cellular and molecular targets in vivo and in vitro, by using a short-term protocol of treatment. The novel object recognition test (NOR was used to evaluate memory performance of mice intraperitoneally treated with hesperidin 30 min before the training and again before the test phase. The direct effects of hesperidin on synapses and astrocytes were also investigated using in vitro approaches. Here, we described hesperidin as a new drug able to improve memory in healthy adult mice by two main mechanisms: directly, by inducing synapse formation and function between hippocampal and cortical neurons; and indirectly, by enhancing the synaptogenic ability of cortical astrocytes mainly due to increased secretion of transforming growth factor beta-1 (TGF-β1 by these cells. Our data reinforces the known neuroprotective effect of hesperidin and, by the first time, characterizes its synaptogenic action on the central nervous system (CNS, pointing astrocytes and TGF-β1 signaling as new cellular and molecular targets of hesperidin. Our work provides not only new data regarding flavonoid’s actions on the CNS but also shed light on possible new therapeutic alternative based on astrocyte biology.

  9. Neural Correlates of Auditory Processing, Learning and Memory Formation in Songbirds

    Science.gov (United States)

    Pinaud, R.; Terleph, T. A.; Wynne, R. D.; Tremere, L. A.

    Songbirds have emerged as powerful experimental models for the study of auditory processing of complex natural communication signals. Intact hearing is necessary for several behaviors in developing and adult animals including vocal learning, territorial defense, mate selection and individual recognition. These behaviors are thought to require the processing, discrimination and memorization of songs. Although much is known about the brain circuits that participate in sensorimotor (auditory-vocal) integration, especially the ``song-control" system, less is known about the anatomical and functional organization of central auditory pathways. Here we discuss findings associated with a telencephalic auditory area known as the caudomedial nidopallium (NCM). NCM has attracted significant interest as it exhibits functional properties that may support higher order auditory functions such as stimulus discrimination and the formation of auditory memories. NCM neurons are vigorously dr iven by auditory stimuli. Interestingly, these responses are selective to conspecific, relative to heterospecific songs and artificial stimuli. In addition, forms of experience-dependent plasticity occur in NCM and are song-specific. Finally, recent experiments employing high-throughput quantitative proteomics suggest that complex protein regulatory pathways are engaged in NCM as a result of auditory experience. These molecular cascades are likely central to experience-associated plasticity of NCM circuitry and may be part of a network of calcium-driven molecular events that support the formation of auditory memory traces.

  10. Microstructural changes in memory and reticular formation neural pathway after simple concussion

    Institute of Scientific and Technical Information of China (English)

    Lin Ouyang; Rongyue Shi; Yuhui Xiao; Jiarong Meng; Yihe Guo; Guangming Lu

    2012-01-01

    Patients with concussion often present with temporary disturbance of consciousness.The microstructural and functional changes in the brain associated with concussion,as well as the relationship with transient cognitive disorders,are currently unclear.In the present study,a rabbit model of simple concussion was established.Magnetic resonance-diffusion tensor imaging results revealed that the corona radiata and midbrain exhibited significantly decreased fractional anisotropy values in the neural pathways associated with memory and the reticular formation.In addition,the apparent diffusion coefficient values were significantly increased following injury compared with those before injury.Following a 1-hour period of quiet rest,the fractional anisotropy values significantly increased,and apparent diffusion coefficient values significantly decreased,returning to normal pre-injury levels.In contrast,the fractional anisotropy values and apparent diffusion coefficient values in the corpus callosum,thalamus and hippocampus showed no statistical significant alterations following injury.These findings indicate that the neural pathways associated with memory and the reticular formation pathway exhibit reversible microstructural white matter changes when concussion occurs,and these changes are exhibited to a different extent in different regions.

  11. Rapid formation and selective stabilization of synapses for enduring motor memories.

    Science.gov (United States)

    Xu, Tonghui; Yu, Xinzhu; Perlik, Andrew J; Tobin, Willie F; Zweig, Jonathan A; Tennant, Kelly; Jones, Theresa; Zuo, Yi

    2009-12-17

    Novel motor skills are learned through repetitive practice and, once acquired, persist long after training stops. Earlier studies have shown that such learning induces an increase in the efficacy of synapses in the primary motor cortex, the persistence of which is associated with retention of the task. However, how motor learning affects neuronal circuitry at the level of individual synapses and how long-lasting memory is structurally encoded in the intact brain remain unknown. Here we show that synaptic connections in the living mouse brain rapidly respond to motor-skill learning and permanently rewire. Training in a forelimb reaching task leads to rapid (within an hour) formation of postsynaptic dendritic spines on the output pyramidal neurons in the contralateral motor cortex. Although selective elimination of spines that existed before training gradually returns the overall spine density back to the original level, the new spines induced during learning are preferentially stabilized during subsequent training and endure long after training stops. Furthermore, we show that different motor skills are encoded by different sets of synapses. Practice of novel, but not previously learned, tasks further promotes dendritic spine formation in adulthood. Our findings reveal that rapid, but long-lasting, synaptic reorganization is closely associated with motor learning. The data also suggest that stabilized neuronal connections are the foundation of durable motor memory.

  12. Formation and composition of titanium oxinitride nanocrystals synthesized via nitridizing titanium oxide for nonvolatile memory applications

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Li-Wei; Chang, Chun-Yen [Department of Electronics Engineering, National Chiao Tung University, Hsinchu, 300, Taiwan (China); Institute of Electronics, National Chiao Tung University, Hsinchu, 300, Taiwan (China); Chang, Ting-Chang, E-mail: tcchang@mail.phys.nsysu.edu.tw [Department of Physics, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan (China); Center for Nanoscience and Nanotechnology, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan (China); Tu, Chun-Hao; Wang, Pai-Syuan [Department of Electronics Engineering, National Chiao Tung University, Hsinchu, 300, Taiwan (China); Institute of Electronics, National Chiao Tung University, Hsinchu, 300, Taiwan (China); Lin, Chao-Cheng [Green Energy and Environment Research Laboratories, Industrial Technology Research Institute, Hsinchu, 310, Taiwan (China); Chen, Min-Chen [Department of Physics, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan (China); Huang, Hui-Chun; Gan, Der-Shin; Ho, New-Jin [Institute of Materials Science and Engineering, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan (China); Chen, Shih-Ching [Department of Physics, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan (China); Chen, Shih-Cheng [Department of Electrical Engineering, National Tsing Hua University, Hsinchu, 310, Taiwan, ROC (China); Institute of Electronic Engineering, National Tsing Hua University, Hsinchu, 310, Taiwan (China)

    2011-09-01

    Formation and composition analyses of titanium oxinitride nanocrystals (NCs) fabricated via treating a magnetron co-sputtered thin film of titanium and silicon dioxide with a rapid thermal annealing in nitrogen ambient were demonstrated for nonvolatile memory applications. Phase separation characteristics with different annealing conditions were examined by transmission electron microscopy and chemical bonding characteristics were confirmed by X-ray photon emission spectra. It was observed that a blanket layer composed mainly of titanium oxide was still present as annealing temperature was increased to 700 deg. C, associated with the thermodynamically stable phase of titanium oxide. Furthermore, a higher thermal treatment of 900 deg. C induced formation of a well-separated NC structure and caused simultaneously partial nitridation of the titanium oxide, thereby forming titanium oxinitride NCs. A significant capacitance-voltage hysteresis in threshold voltage shift at 1 V was easily achieved under a small sweeping voltage range of + 2 V/-2 V, and a memory window retention of 2.2 V was obtained after 10{sup 7} s by extrapolation under a 1 s initial-program/erase condition of + 5 V/-5 V, respectively.

  13. Formation of Phobos and Deimos in a giant collision scenario facilitated by a large transient moon

    Science.gov (United States)

    Rosenblatt, Pascal; Charnoz, Sébastien; Dunseath, Kevin; Terao-Dunseath, Mariko; Trinh, Antony; Hyodo, Ryuki; Genda, Hidenori; Toupin, Steven

    2016-10-01

    Mars has two natural satellites, Phobos and Deimos, similar to asteroids but whose current orbital parameters are not consistent with those of captured objects. We present an alternative scenario, backed by numerical simulations, in which Phobos and Deimos are formed in situ from a disc of debris resulting from a giant impact which gave Mars its spin and its north-south dichotomy. In this, a small number of large inner moons spawn at the Roche limit of the inner disc and then migrate outwards. Smaller debris in the outer, less dense part of the disc tend to accumulate at mean motion orbital resonances generated by these moons, hence facilitating their accretion. Our numerical simulations robustly reproduce the current Martian system of one more massive satellite lying just below the synchronous orbit and one less massive satellite above it. The large inner moons eventually fall back onto Mars as the inner disc itself empties, leaving the two small satellites to evolve under tidal dissipation to their current orbits. Our scenario offers an explanation for why Mars did not end up with one single large Moon like Earth, nor with numerous small moons like the giant planets. It also implies that Phobos and Deimos may be composed of material from both Mars and the impactor.

  14. Employing Computer Assisted Assessment (CAA to facilitate formative assessment in the State Secondary School: a case study

    Directory of Open Access Journals (Sweden)

    Effimia Karagianni

    2012-02-01

    Full Text Available Based on theories of assessment as well as on the pedagogical and administrative advantages Computer Assisted Assessment (CAA has to offer in foreign language learning, the study presented in this paper examines how computers can facilitate the formative assessment of EFL learners and enhance their feeling of responsibility towards monitoring their progress. The subjects of the study were twenty five 14-year-old students attending the third class of a State Gymnasium in Greece. The instruments utilized were questionnaires on motivation and learning styles, three quizzes designed with the software Hot Potatoes, a self–assessment questionnaire and an evaluation questionnaire showing the subjects’ attitudes towards the experience of using computers for assessing purposes. After reviewing formative assessment, CAA and how these two can be combined, the paper focuses on the description of the three class quizzes used in the study. Ιnformation from the questionnaires filled in by students combined with the results of the quizzes, shows how computers can be used to provide continuous ongoing measurement of students’ progress needed for formative assessment. The results are also used to show how students and teachers can benefit from formative CAA and the extent to which such kind of assessment could be applicable in the Greek state school reality.

  15. Aging and memory improvement through semantic clustering: The role of list-presentation format.

    Science.gov (United States)

    Kuhlmann, Beatrice G; Touron, Dayna R

    2016-11-01

    The present study examined how the presentation format of the study list influences younger and older adults' semantic clustering. Spontaneous clustering did not differ between age groups or between an individual-words (presentation of individual study words in consecution) and a whole-list (presentation of the whole study list at once for the same total duration) presentation format in 132 younger (18-30 years, M = 19.7) and 120 older (60-84 years, M = 69.5) adults. However, after instructions to use semantic clustering (second list) age-related differences in recall magnified, indicating a utilization deficiency, and both age groups achieved higher recall in the whole-list than in the individual-words format. While this whole-list benefit was comparable across age groups, it is notable that older adults were only able to improve their average recall performance after clustering instructions in the whole-list but not in the individual-words format. In both formats, instructed clustering was correlated with processing resources (processing speed and, especially, working memory capacity), particularly in older adults. Spontaneous clustering, however, was not related to processing resources but to metacognitive beliefs about the efficacy and difficulty of semantic clustering, neither of which indicated awareness of the benefits of the whole-list presentation format in either age group. Taken together, the findings demonstrate that presentation format has a nontrivial influence on the utilization of semantic clustering in adults. The analyses further highlight important differences between output-based and list-based clustering measures. (PsycINFO Database Record

  16. Estradiol replacement enhances fear memory formation, impairs extinction and reduces COMT expression levels in the hippocampus of ovariectomized female mice.

    Science.gov (United States)

    McDermott, Carmel M; Liu, Dan; Ade, Catherine; Schrader, Laura A

    2015-02-01

    Females experience depression, posttraumatic stress disorder (PTSD), and anxiety disorders at approximately twice the rate of males, but the mechanisms underlying this difference remain undefined. The effect of sex hormones on neural substrates presents a possible mechanism. We investigated the effect of ovariectomy at two ages, before puberty and in adulthood, and 17β-estradiol (E2) replacement administered chronically in drinking water on anxiety level, fear memory formation, and extinction. Based on previous studies, we hypothesized that estradiol replacement would impair fear memory formation and enhance extinction rate. Females, age 4 weeks and 10 weeks, were divided randomly into 4 groups; sham surgery, OVX, OVX+low E2 (200nM), and OVX+high E2 (1000nM). Chronic treatment with high levels of E2 significantly increased anxiety levels measured in the elevated plus maze. In both age groups, high levels of E2 significantly increased contextual fear memory but had no effect on cued fear memory. In addition, high E2 decreased the rate of extinction in both ages. Finally, catechol-O-methyltransferase (COMT) is important for regulation of catecholamine levels, which play a role in fear memory formation and extinction. COMT expression in the hippocampus was significantly reduced by high E2 replacement, implying increased catecholamine levels in the hippocampus of high E2 mice. These results suggest that estradiol enhanced fear memory formation, and inhibited fear memory extinction, possibly stabilizing the fear memory in female mice. This study has implications for a neurobiological mechanism for PTSD and anxiety disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Low-dose nicotine facilitates spatial memory in ApoE-knockout mice in the radial arm maze.

    Science.gov (United States)

    Sultana, Ruby; Ameno, Kiyoshi; Jamal, Mostofa; Miki, Takanori; Tanaka, Naoko; Ono, Junichiro; Kinoshita, Hiroshi; Nakamura, Yu

    2013-06-01

    Here, we investigated the effects of nicotine on spatial memory in ApoE-knockout (ApoE-KO) and wild-type (WT) mice in a radial arm maze. Training occurred on three consecutive days and the test was performed on day 4, with one trial per day. Then on day 4, animals were administered nicotine (0.1, 0.25, 0.5, and 1.0 mg/kg) or the antagonist of nicotinic receptors (nAChRs) mecamylamine (MEC 2 mg/kg) alone or together with 0.1 mg/kg nicotine. The number of errors in the first eight choices was recorded. The results were that 0.1 mg/kg nicotine decreased errors in ApoE-KO mice, while 0.1 and 0.25 mg/kg nicotine reduced errors in WT mice, indicating that lower doses of nicotine elicit a memory improvement. In contrast, 1.0 mg/kg nicotine increased errors in WT mice, but not in ApoE-KO mice. MEC alone had no noticeable effect on errors in either strain of mice. However, co-administration of 0.1 mg/kg nicotine and MEC increased errors and reduced the effects of nicotine in WT mice, but not in ApoE-KO mice. Our study found a biphasic effect of nicotine in WT mice: it improves spatial memory at lower doses and impairs it at a higher dose. In ApoE-KO mice, nicotine improves memory at a low dose and has no effect at a higher dose, suggesting that the ApoE deficiency may influence the efficacy of nicotine. Moreover, a reversal of nicotinic effects with MEC was seen in WT mice, indicating the likelihood of the involvement of nAChRs in the spatial-memory response to nicotine.

  18. Teachers and the religious socialization of adolescents: facilitation of meaningful religious identity formation processes.

    Science.gov (United States)

    Cohen-Malayev, Maya; Schachter, Elli P; Rich, Yisrael

    2014-02-01

    This study investigated the effects of religious education on student religious identity over and above parent religiosity by examining student perceptions of two aspects of teacher functioning: teacher caring and teacher as role-model. We posited that effects of these variables on students' religious identity are mediated by student perceptions that the school provides a non-alienating religious atmosphere and meaningful religious studies. Participants were 2691 male and female students (grades 9-12) in 152 classes of 25 schools from the Jewish public-religious sector in Israel. Results indicate that in addition to their parents' religiosity, adolescents' perceptions of their teachers as role models and their religious studies as meaningful are important variables affecting their religious identity. Moreover, this research suggests that religious identity formation processes flourish in an educational environment which students perceive as accommodating religious exploration. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  19. Emotional face expression modulates occipital-frontal effective connectivity during memory formation in a bottom-up fashion.

    Science.gov (United States)

    Xiu, Daiming; Geiger, Maximilian J; Klaver, Peter

    2015-01-01

    This study investigated the role of bottom-up and top-down neural mechanisms in the processing of emotional face expression during memory formation. Functional brain imaging data was acquired during incidental learning of positive ("happy"), neutral and negative ("angry" or "fearful") faces. Dynamic Causal Modeling (DCM) was applied on the functional magnetic resonance imaging (fMRI) data to characterize effective connectivity within a brain network involving face perception (inferior occipital gyrus and fusiform gyrus) and successful memory formation related areas (hippocampus, superior parietal lobule, amygdala, and orbitofrontal cortex). The bottom-up models assumed processing of emotional face expression along feed forward pathways to the orbitofrontal cortex. The top-down models assumed that the orbitofrontal cortex processed emotional valence and mediated connections to the hippocampus. A subsequent recognition memory test showed an effect of negative emotion on the response bias, but not on memory performance. Our DCM findings showed that the bottom-up model family of effective connectivity best explained the data across all subjects and specified that emotion affected most bottom-up connections to the orbitofrontal cortex, especially from the occipital visual cortex and superior parietal lobule. Of those pathways to the orbitofrontal cortex the connection from the inferior occipital gyrus correlated with memory performance independently of valence. We suggest that bottom-up neural mechanisms support effects of emotional face expression and memory formation in a parallel and partially overlapping fashion.

  20. Emotional face expression modulates occipital-frontal effective connectivity during memory formation in a bottom-up fashion

    Directory of Open Access Journals (Sweden)

    Daiming eXiu

    2015-04-01

    Full Text Available This study investigated the role of bottom-up and top-down neural mechanisms in the processing of emotional face expression during memory formation. Functional brain imaging data was acquired during incidental learning of positive (‘happy’, neutral and negative (‘angry’ or ‘fearful’ faces. Dynamic Causal Modeling (DCM was applied on the fMRI data to characterize effective connectivity within a brain network involving face perception (inferior occipital gyrus and fusiform gyrus and successful memory formation related areas (hippocampus, superior parietal lobule, amygdala and orbitofrontal cortex. The bottom-up models assumed processing of emotional face expression along feed forward pathways to the orbitofrontal cortex. The top-down models assumed that the orbitofrontal cortex processed emotional valence and mediated connections to the hippocampus. A subsequent recognition memory test showed an effect of negative emotion on the response bias, but not on memory performance. Our DCM findings showed that the bottom-up model family of effective connectivity best explained the data across all subjects and specified that emotion affected most bottom-up connections to the orbitofrontal cortex, especially from the occipital visual cortex and superior parietal lobule. Of those pathways to the orbitofrontal cortex the connection from the inferior occipital gyrus correlated with memory performance independently of valence. We suggest that bottom-up neural mechanisms support effects of emotional face expression and memory formation in a parallel and partially overlapping fashion.

  1. Histaminergic modulation of cholinergic release from the nucleus basalis magnocellularis into insular cortex during taste aversive memory formation.

    Directory of Open Access Journals (Sweden)

    Liliana Purón-Sierra

    Full Text Available The ability of acetylcholine (ACh to alter specific functional properties of the cortex endows the cholinergic system with an important modulatory role in memory formation. For example, an increase in ACh release occurs during novel stimulus processing, indicating that ACh activity is critical during early stages of memory processing. During novel taste presentation, there is an increase in ACh release in the insular cortex (IC, a major structure for taste memory recognition. There is extensive evidence implicating the cholinergic efferents of the nucleus basalis magnocellularis (NBM in cortical activity changes during learning processes, and new evidence suggests that the histaminergic system may interact with the cholinergic system in important ways. However, there is little information as to whether changes in cholinergic activity in the IC are modulated during taste memory formation. Therefore, in the present study, we evaluated the influence of two histamine receptor subtypes, H1 in the NBM and H3 in the IC, on ACh release in the IC during conditioned taste aversion (CTA. Injection of the H3 receptor agonist R-α-methylhistamine (RAMH into the IC or of the H1 receptor antagonist pyrilamine into the NBM during CTA training impaired subsequent CTA memory, and simultaneously resulted in a reduction of ACh release in the IC. This study demonstrated that basal and cortical cholinergic pathways are finely tuned by histaminergic activity during CTA, since dual actions of histamine receptor subtypes on ACh modulation release each have a significant impact during taste memory formation.

  2. Role of the hippocampus in memory formation: restorative encoding memory integration neural device as a cognitive neural prosthesis.

    Science.gov (United States)

    Berger, Theodore; Song, Dong; Chan, Rosa; Shin, Dae; Marmarelis, Vasilis; Hampson, Robert; Sweatt, Andrew; Heck, Christi; Liu, Charles; Wills, Jack; Lacoss, Jeff; Granacki, John; Gerhardt, Greg; Deadwyler, Sam

    2012-01-01

    Remind, which stands for "restorative encoding memory integration neural device," is a Defense Advanced Research Projects Agency (DARPA)-sponsored program to construct the first-ever cognitive prosthesis to replace lost memory function and enhance the existing memory capacity in animals and, ultimately, in humans. Reaching this goal involves understanding something fundamental about the brain that has not been understood previously: how the brain internally codes memories. In developing a hippocampal prosthesis for the rat, we have been able to demonstrate a multiple-input, multiple- output (MIMO) nonlinear model that predicts in real time the spatiotemporal codes for specific memories required for correct performance on a standard learning/memory task, i.e., delayed-nonmatch-to-sample (DNMS) memory. The MIMO model has been tested successfully in a number of contexts; most notably, in animals with a pharmacologically disabled hippocampus, we were able to reinstate long-term memories necessary for correct DNMS behavior by substituting a MIMO model-predicted code, delivered by electrical stimulation to the hippocampus through an array of electrodes, resulting in spatiotemporal hippocampal activity that is normally generated endogenously. We also have shown that delivering the same model-predicted code to electrode-implanted control animals with a normally functioning hippocampus substantially enhances animals memory capacity above control levels. These results in rodents have formed the basis for extending the MIMO model to nonhuman primates; this is now underway as the last step of the REMIND program before developing a MIMO-based cognitive prosthesis for humans.

  3. Facilitating the use of implicit memory and learning in the physical therapy management of individuals with Alzheimer disease: a case series.

    Science.gov (United States)

    White, Laura; Ford, Matthew P; Brown, Cynthia J; Peel, Claire; Triebel, Kristen L

    2014-01-01

    Physical rehabilitation of individuals with Alzheimer disease (AD) is often complicated by impairments in explicit memory and learning. Rehabilitation strategies that facilitate the use of the preserved implicit memory system may be effective in treating patients with AD. The purpose of this case series is to describe the application of these strategies, including high-repetition practice, errorless learning (EL), and spaced retrieval, to the physical therapy management of individuals with moderate AD. Three women aged 89 to 95 years with moderate AD who resided in an assisted living facility participated in physical therapy to address their mobility limitations. Twelve physical therapy sessions were scheduled over a period of 4 weeks. Interventions were individually designed to address the mobility needs of each patient, and rehabilitation strategies based on implicit learning principles were integrated into the interventions. All patients participated in at least 10 of the 12 physical therapy sessions. Improvements in performance of objective measures of balance were observed in all patients, although only 1 patient's balance score exceeded the minimal detectable change. No significant clinical change was observed in any patients on the Timed Up and Go Test or self-selected gait speed. Principles of implicit learning were integrated into the interventions for these patients with moderate AD. However, the feasibility of applying the EL paradigm was limited. Further research on the effectiveness of EL, spaced retrieval, and other rehabilitation strategies that facilitate implicit learning of mobility skills in patients with AD is needed to promote optimal physical therapy outcomes in this patient population.

  4. Modulation of neuronal signal transduction and memory formation by synaptic zinc

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    Carlos eSindreu

    2011-11-01

    Full Text Available The physiological role of synaptic zinc has remained largely enigmatic since its initial detection in hippocampal mossy fibers over fifty years ago. The past few years have witnessed a number of studies highlighting the ability of zinc ions to regulate ion channels and intracellular signaling pathways implicated in neuroplasticity, and others that shed some light on the elusive role of synaptic zinc in learning and memory. Recent behavioral studies using knock out mice for the synapse-specific zinc transporter ZnT-3 indicate that vesicular zinc is required for the formation of memories dependent on the hippocampus and the amygdala, two brain centers that are prominently innervated by zinc-rich fibers. A common theme emerging from this research is the activity-dependent regulation of the Erk1/2 mitogen-activated-protein kinase pathway by synaptic zinc through diverse mechanisms in neurons. Here we discuss current knowledge on how synaptic zinc may play a role in cognition through its impact on neuronal signaling.

  5. Modulation of neuronal signal transduction and memory formation by synaptic zinc.

    Science.gov (United States)

    Sindreu, Carlos; Storm, Daniel R

    2011-01-01

    The physiological role of synaptic zinc has remained largely enigmatic since its initial detection in hippocampal mossy fibers over 50 years ago. The past few years have witnessed a number of studies highlighting the ability of zinc ions to regulate ion channels and intracellular signaling pathways implicated in neuroplasticity, and others that shed some light on the elusive role of synaptic zinc in learning and memory. Recent behavioral studies using knock-out mice for the synapse-specific zinc transporter ZnT-3 indicate that vesicular zinc is required for the formation of memories dependent on the hippocampus and the amygdala, two brain centers that are prominently innervated by zinc-rich fibers. A common theme emerging from this research is the activity-dependent regulation of the Erk1/2 mitogen-activated-protein kinase pathway by synaptic zinc through diverse mechanisms in neurons. Here we discuss current knowledge on how synaptic zinc may play a role in cognition through its impact on neuronal signaling.

  6. Memory formation and retention are affected in adult miR-132/212 knockout mice.

    Science.gov (United States)

    Hernandez-Rapp, Julia; Smith, Pascal Y; Filali, Mohammed; Goupil, Claudia; Planel, Emmanuel; Magill, Stephen T; Goodman, Richard H; Hébert, Sébastien S

    2015-01-01

    The miR-132/212 family is thought to play an important role in neural function and plasticity, while its misregulation has been observed in various neurodegenerative disorders. In this study, we analyzed 6-month-old miR-132/212 knockout mice in a battery of cognitive and non-cognitive behavioral tests. No significant changes were observed in reflexes and basic sensorimotor functions as determined by the SHIRPA primary screen. Accordingly, miR-132/212 knockout mice did not differ from wild-type controls in general locomotor activity in an open-field test. Furthermore, no significant changes of anxiety were measured in an elevated plus maze task. However, the mutant mice showed retention phase defects in a novel object recognition test and in the T-water maze. Moreover, the learning and probe phases in the Barnes maze were clearly altered in knockout mice when compared to controls. Finally, changes in BDNF, CREB, and MeCP2 were identified in the miR-132/212-deficient mice, providing a potential mechanism for promoting memory loss. Taken together, these results further strengthen the role of miR-132/212 in memory formation and retention, and shed light on the potential consequences of its deregulation in neurodegenerative diseases.

  7. Response to Comment on "Multiple repressive mechanisms in the hippocampus during memory formation".

    Science.gov (United States)

    Cho, Jun; Yu, Nam-Kyung; Kim, V Narry; Kaang, Bong-Kiun

    2016-07-29

    Mathew et al. propose that many candidate genes identified in our study may reflect the events in the choroid plexus (ChP) potentially included in hippocampal samples. We reanalyze our data and find that the ChP inclusion is unlikely to affect our major conclusions regarding the basal suppression of translational machinery or the early translational repression (at 5 to 10 minutes). As Mathew et al. examined for a subset of genes at 4 hours, we agree that the late suppression may partly reflect the events in the ChP. Although the precise contribution of anatomical sources remains to be clarified, our behavioral analyses indicate that the late-phase suppression of these genes may contribute to memory formation.

  8. Reaction mechanism between "memory effect" and induction time of gas hydrate formation

    Institute of Scientific and Technical Information of China (English)

    SUN Deng-lin; WU Qiang; ZHANG Bao-yong

    2008-01-01

    Using visual experimental apparatus,one system(T40,1×10-3 mol/L,nonadded with coal)and another system(T40,2×10-3 mol/L,added with coal)were experimented with for three times and two times.respectively.Five groups of P-T experimental parameters were obtained using the data logger system and analyzed combined with the video information of the experiments.Maior conclustions show that the induction time is shortened by 10-20 times in the experimental system containing residual pentahedral ring structures;"memory effect"can accelerate the dynamic progress and improve the thermodynamic conditions of gas hydrate formation.

  9. Lactobacillus casei-01 facilitates the ameliorative effects of proanthocyanidins extracted from lotus seedpod on learning and memory impairment in scopolamine-induced amnesia mice.

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    Juan Xiao

    Full Text Available Learning and memory abilities are associated with alterations in gut function. The two-way proanthocyanidins-microbiota interaction in vivo enhances the physiological activities of proanthocyanidins and promotes the regulation of gut function. Proanthocyanidins extracted from lotus seedpod (LSPC have shown the memory-enhancing ability. However, there has been no literature about whether Lactobacillus casei-01 (LC enhances the ameliorative effects of LSPC on learning and memory abilities. In this study, learning and memory abilities of scopolamine-induced amnesia mice were evaluated by Y-maze test after 20-day administration of LC (10(9 cfu/kg body weight (BW, LSPC (low dose was 60 mg/kg BW (L-LSPC and high dose was 90 mg/kg BW (H-LSPC, or LSPC and LC combinations (L-LSPC+LC and H-LSPC+LC. Alterations in antioxidant defense ability and oxidative damage of brain, serum and colon, and brain cholinergic system were investigated as the possible mechanisms. As a result, the error times of H-LSPC+LC group were reduced by 41.59% and 68.75% relative to those of H-LSPC and LC groups respectively. LSPC and LC combinations ameliorated scopolamine-induced memory impairment by improving total antioxidant capacity (TAOC level, glutathione peroxidase (GSH-Px and total superoxide dismutase (T-SOD activities of brain, serum and colon, suppressing malondialdehyde (MDA level of brain, serum and colon, and inhibiting brain acetylcholinesterase (AchE, myeloperoxidase, total nitric oxide synthase and neural nitric oxide synthase (nNOS activities, and nNOS mRNA level. Moreover, LC facilitated the ameliorative effects of H-LSPC on GSH-Px activity of colon, TAOC level, GSH-Px activity and ratio of T-SOD to MDA of brain and serum, and the inhibitory effects of H-LSPC on serum MDA level, brain nNOS mRNA level and AchE activity. These results indicated that LC promoted the memory-enhancing effect of LSPC in scopolamine-induced amnesia mice.

  10. Transcriptional profiling reveals regulated genes in the hippocampus during memory formation

    Science.gov (United States)

    Donahue, Christine P.; Jensen, Roderick V.; Ochiishi, Tomoyo; Eisenstein, Ingrid; Zhao, Mingrui; Shors, Tracey; Kosik, Kenneth S.

    2002-01-01

    Transcriptional profiling (TP) offers a powerful approach to identify genes activated during memory formation and, by inference, the molecular pathways involved. Trace eyeblink conditioning is well suited for the study of regional gene expression because it requires the hippocampus, whereas the highly parallel task, delay conditioning, does not. First, we determined when gene expression was most regulated during trace conditioning. Rats were exposed to 200 trials per day of paired and unpaired stimuli each day for 4 days. Changes in gene expression were most apparent 24 h after exposure to 200 trials. Therefore, we profiled gene expression in the hippocampus 24 h after 200 trials of trace eyeblink conditioning, on multiple arrays using additional animals. Of 1,186 genes on the filter array, seven genes met the statistical criteria and were also validated by real-time polymerase chain reaction. These genes were growth hormone (GH), c-kit receptor tyrosine kinase (c-kit), glutamate receptor, metabotropic 5 (mGluR5), nerve growth factor-beta (NGF-beta), Jun oncogene (c-Jun), transmembrane receptor Unc5H1 (UNC5H1), and transmembrane receptor Unc5H2 (UNC5H2). All these genes, except for GH, were downregulated in response to trace conditioning. GH was upregulated; therefore, we also validated the downregulation of the GH inhibitor, somatostatin (SST), even though it just failed to meet criteria on the arrays. By during situ hybridization, GH was expressed throughout the cell layers of the hippocampus in response to trace conditioning. None of the genes regulated in trace eyeblink conditioning were similarly affected by delay conditioning, a task that does not require the hippocampus. These findings demonstrate that transcriptional profiling can exhibit a repertoire of genes sensitive to the formation of hippocampal-dependent associative memories.

  11. Transcriptional profiling reveals regulated genes in the hippocampus during memory formation

    Science.gov (United States)

    Donahue, Christine P.; Jensen, Roderick V.; Ochiishi, Tomoyo; Eisenstein, Ingrid; Zhao, Mingrui; Shors, Tracey; Kosik, Kenneth S.

    2002-01-01

    Transcriptional profiling (TP) offers a powerful approach to identify genes activated during memory formation and, by inference, the molecular pathways involved. Trace eyeblink conditioning is well suited for the study of regional gene expression because it requires the hippocampus, whereas the highly parallel task, delay conditioning, does not. First, we determined when gene expression was most regulated during trace conditioning. Rats were exposed to 200 trials per day of paired and unpaired stimuli each day for 4 days. Changes in gene expression were most apparent 24 h after exposure to 200 trials. Therefore, we profiled gene expression in the hippocampus 24 h after 200 trials of trace eyeblink conditioning, on multiple arrays using additional animals. Of 1,186 genes on the filter array, seven genes met the statistical criteria and were also validated by real-time polymerase chain reaction. These genes were growth hormone (GH), c-kit receptor tyrosine kinase (c-kit), glutamate receptor, metabotropic 5 (mGluR5), nerve growth factor-beta (NGF-beta), Jun oncogene (c-Jun), transmembrane receptor Unc5H1 (UNC5H1), and transmembrane receptor Unc5H2 (UNC5H2). All these genes, except for GH, were downregulated in response to trace conditioning. GH was upregulated; therefore, we also validated the downregulation of the GH inhibitor, somatostatin (SST), even though it just failed to meet criteria on the arrays. By during situ hybridization, GH was expressed throughout the cell layers of the hippocampus in response to trace conditioning. None of the genes regulated in trace eyeblink conditioning were similarly affected by delay conditioning, a task that does not require the hippocampus. These findings demonstrate that transcriptional profiling can exhibit a repertoire of genes sensitive to the formation of hippocampal-dependent associative memories.

  12. BDNF activates mTOR to regulate GluR1 expression required for memory formation.

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    Leandro Slipczuk

    Full Text Available BACKGROUND: The mammalian target of Rapamycin (mTOR kinase plays a key role in translational control of a subset of mRNAs through regulation of its initiation step. In neurons, mTOR is present at the synaptic region, where it modulates the activity-dependent expression of locally-translated proteins independently of mRNA synthesis. Indeed, mTOR is necessary for different forms of synaptic plasticity and long-term memory (LTM formation. However, little is known about the time course of mTOR activation and the extracellular signals governing this process or the identity of the proteins whose translation is regulated by this kinase, during mnemonic processing. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that consolidation of inhibitory avoidance (IA LTM entails mTOR activation in the dorsal hippocampus at the moment of and 3 h after training and is associated with a rapid and rapamycin-sensitive increase in AMPA receptor GluR1 subunit expression, which was also blocked by intra-hippocampal delivery of GluR1 antisense oligonucleotides (ASO. In addition, we found that pre- or post-training administration of function-blocking anti-BDNF antibodies into dorsal CA1 hampered IA LTM retention, abolished the learning-induced biphasic activation of mTOR and its readout, p70S6K and blocked GluR1 expression, indicating that BDNF is an upstream factor controlling mTOR signaling during fear-memory consolidation. Interestingly, BDNF ASO hindered LTM retention only when given into dorsal CA1 1 h after but not 2 h before training, suggesting that BDNF controls the biphasic requirement of mTOR during LTM consolidation through different mechanisms: an early one involving BDNF already available at the moment of training, and a late one, happening around 3 h post-training that needs de novo synthesis of this neurotrophin. CONCLUSIONS/SIGNIFICANCE: IN CONCLUSION, OUR FINDINGS DEMONSTRATE THAT: 1 mTOR-mediated mRNA translation is required for memory consolidation during

  13. An Exploration of Teachers' Narratives: What Are the Facilitators and Constraints Which Promote or Inhibit "Good" Formative Assessment Practices in Schools?

    Science.gov (United States)

    Sach, Elizabeth

    2015-01-01

    This paper set out to explore teachers' narratives in order to understand some of the facilitators and constraints which promote or inhibit good formative assessment practices in schools. A "responsive interview" approach was used to probe a small sample of lower and middle school teachers' perceptions of formative assessment.…

  14. The formation of recent and remote memory is associated with time-dependent formation of dendritic spines in the hippocampus and anterior cingulate cortex.

    Science.gov (United States)

    Restivo, Leonardo; Vetere, Gisella; Bontempi, Bruno; Ammassari-Teule, Martine

    2009-06-24

    Although hippocampal-cortical interactions are crucial for the formation of enduring declarative memories, synaptic events that govern long-term memory storage remain mostly unclear. We present evidence that neuronal structural changes, i.e., dendritic spine growth, develop sequentially in the hippocampus and anterior cingulate cortex (aCC) during the formation of recent and remote contextual fear memory. We found that mice placed in a conditioning chamber for one 7 min conditioning session and exposed to five footshocks (duration, 2 s; intensity, 0.7 mA; interstimulus interval, 60 s) delivered through the grid floor exhibited robust fear response when returned to the experimental context 24 h or 36 d after the conditioning. We then observed that their fear response at the recent, but not the remote, time point was associated with an increase in spine density on hippocampal neurons, whereas an inverse temporal pattern of spine density changes occurred on aCC neurons. At each time point, hippocampal or aCC structural alterations were achieved even in the absence of recent or remote memory tests, thus suggesting that they were not driven by retrieval processes. Furthermore, ibotenic lesions of the hippocampus impaired remote memory and prevented dendritic spine growth on aCC neurons when they were performed immediately after the conditioning, whereas they were ineffective when performed 24 d later. These findings reveal that gradual structural changes modifying connectivity in hippocampal-cortical networks underlie the formation and expression of remote memory, and that the hippocampus plays a crucial but time-limited role in driving structural plasticity in the cortex.

  15. Molecular and Neuronal Plasticity Mechanisms in the Amygdala-Prefrontal Cortical Circuit: Implications for Opiate Addiction Memory Formation

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    Laura G Rosen

    2015-11-01

    Full Text Available The persistence of associative memories linked to the rewarding properties of drugs of abuse is a core underlying feature of the addiction process. Opiate class drugs in particular, possess potent euphorigenic effects which, when linked to environmental cues, can produce drug-related ‘trigger’ memories that may persist for lengthy periods of time, even during abstinence, in both humans and other animals. Furthermore, the transitional switch from the drug-naïve, non-dependent state to states of dependence and withdrawal, represents a critical boundary between distinct neuronal and molecular substrates associated with opiate-reward memory formation. Identifying the functional molecular and neuronal mechanisms related to the acquisition, consolidation, recall and extinction phases of opiate-related reward memories is critical for understanding, and potentially reversing, addiction-related memory plasticity characteristic of compulsive drug-seeking behaviors. The mammalian prefrontal cortex (PFC and basolateral nucleus of the amygdala (BLA share important functional and anatomical connections that are involved importantly in the processing of associative memories linked to drug reward. In addition, both regions share interconnections with the mesolimbic pathway’s ventral tegmental area (VTA and nucleus accumbens (NAc and can modulate dopamine (DA transmission and neuronal activity associated with drug-related DAergic signaling dynamics. In this review, we will summarize research from both human and animal modelling studies highlighting the importance of neuronal and molecular plasticity mechanisms within this circuitry during critical phases of opiate addiction-related learning and memory processing. Specifically, we will focus on two molecular signaling pathways known to be involved in both drug-related neuroadaptations and in memory-related plasticity mechanisms; the extracellular-signal-regulated kinase system (ERK and the Ca2+/calmodulin

  16. Molecular and neuronal plasticity mechanisms in the amygdala-prefrontal cortical circuit: implications for opiate addiction memory formation.

    Science.gov (United States)

    Rosen, Laura G; Sun, Ninglei; Rushlow, Walter; Laviolette, Steven R

    2015-01-01

    The persistence of associative memories linked to the rewarding properties of drugs of abuse is a core underlying feature of the addiction process. Opiate class drugs in particular, possess potent euphorigenic effects which, when linked to environmental cues, can produce drug-related "trigger" memories that may persist for lengthy periods of time, even during abstinence, in both humans, and other animals. Furthermore, the transitional switch from the drug-naïve, non-dependent state to states of dependence and withdrawal, represents a critical boundary between distinct neuronal and molecular substrates associated with opiate-reward memory formation. Identifying the functional molecular and neuronal mechanisms related to the acquisition, consolidation, recall, and extinction phases of opiate-related reward memories is critical for understanding, and potentially reversing, addiction-related memory plasticity characteristic of compulsive drug-seeking behaviors. The mammalian prefrontal cortex (PFC) and basolateral nucleus of the amygdala (BLA) share important functional and anatomical connections that are involved importantly in the processing of associative memories linked to drug reward. In addition, both regions share interconnections with the mesolimbic pathway's ventral tegmental area (VTA) and nucleus accumbens (NAc) and can modulate dopamine (DA) transmission and neuronal activity associated with drug-related DAergic signaling dynamics. In this review, we will summarize research from both human and animal modeling studies highlighting the importance of neuronal and molecular plasticity mechanisms within this circuitry during critical phases of opiate addiction-related learning and memory processing. Specifically, we will focus on two molecular signaling pathways known to be involved in both drug-related neuroadaptations and in memory-related plasticity mechanisms; the extracellular-signal-regulated kinase system (ERK) and the Ca(2+)/calmodulin-dependent protein

  17. The participation of NMDA receptors, PKC, and MAPK in the formation of memory following operant conditioning in Lymnaea

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    Rosenegger David

    2010-08-01

    Full Text Available Abstract Background Memory is the ability to store, retain, and later retrieve information that has been learned. Intermediate term memory (ITM that persists for up to 3 h requires new protein synthesis. Long term memory (LTM that persists for at least 24 h requires: DNA transcription, RNA translation, and the trafficking of newly synthesized proteins. It has been shown in a number of different model systems that NMDA receptors, protein kinase C (PKC and mitogen activated protein kinase (MAPK are all involved in the memory formation process. Results Here we show that snails trained in control conditions are capable of forming, depending on the training procedure used, either ITM or LTM. However, blockage of NMDA receptors (MK 801, inhibition of PKC (GF109203X hydrochloride and MAPK activity (UO126 prevent the formation of both ITM and LTM. Conclusions The injection of either U0126 or GF109203X, which inhibit MAPK and PKC activity respectively, 1 hour prior to training results in the inhibition of both ITM and LTM formation. We further found that NMDA receptor activity was necessary in order for both ITM and LTM formation.

  18. The Calmodulin-Binding Transcription Activator CAMTA1 Is Required for Long-Term Memory Formation in Mice

    Science.gov (United States)

    Bas-Orth, Carlos; Tan, Yan-Wei; Oliveira, Ana M. M.; Bengtson, C. Peter; Bading, Hilmar

    2016-01-01

    The formation of long-term memory requires signaling from the synapse to the nucleus to mediate neuronal activity-dependent gene transcription. Synapse-to-nucleus communication is initiated by influx of calcium ions through synaptic NMDA receptors and/or L-type voltage-gated calcium channels and involves the activation of transcription factors by…

  19. NMDA Receptor- and ERK-Dependent Histone Methylation Changes in the Lateral Amygdala Bidirectionally Regulate Fear Memory Formation

    Science.gov (United States)

    Gupta-Agarwal, Swati; Jarome, Timothy J.; Fernandez, Jordan; Lubin, Farah D.

    2014-01-01

    It is well established that fear memory formation requires de novo gene transcription in the amygdala. We provide evidence that epigenetic mechanisms in the form of histone lysine methylation in the lateral amygdala (LA) are regulated by NMDA receptor (NMDAR) signaling and involved in gene transcription changes necessary for fear memory…

  20. Inhibition of Different Histone Acetyltransferases (HATs) Uncovers Transcription-Dependent and -Independent Acetylation-Mediated Mechanisms in Memory Formation

    Science.gov (United States)

    Merschbaecher, Katja; Hatko, Lucyna; Folz, Jennifer; Mueller, Uli

    2016-01-01

    Acetylation of histones changes the efficiency of the transcription processes and thus contributes to the formation of long-term memory (LTM). In our comparative study, we used two inhibitors to characterize the contribution of different histone acetyl transferases (HATs) to appetitive associative learning in the honeybee. For one we applied…

  1. The Ubiquitin-Specific Protease 14 (USP14) Is a Critical Regulator of Long-Term Memory Formation

    Science.gov (United States)

    Jarome, Timothy J.; Kwapis, Janine L.; Hallengren, Jada J.; Wilson, Scott M.; Helmstetter, Fred J.

    2014-01-01

    Numerous studies have suggested a role for ubiquitin-proteasome-mediated protein degradation in learning-dependent synaptic plasticity; however, very little is known about how protein degradation is regulated at the level of the proteasome during memory formation. The ubiquitin-specific protease 14 (USP14) is a proteasomal deubiquitinating enzyme…

  2. The Ubiquitin-Specific Protease 14 (USP14) Is a Critical Regulator of Long-Term Memory Formation

    Science.gov (United States)

    Jarome, Timothy J.; Kwapis, Janine L.; Hallengren, Jada J.; Wilson, Scott M.; Helmstetter, Fred J.

    2014-01-01

    Numerous studies have suggested a role for ubiquitin-proteasome-mediated protein degradation in learning-dependent synaptic plasticity; however, very little is known about how protein degradation is regulated at the level of the proteasome during memory formation. The ubiquitin-specific protease 14 (USP14) is a proteasomal deubiquitinating enzyme…

  3. The Calmodulin-Binding Transcription Activator CAMTA1 Is Required for Long-Term Memory Formation in Mice

    Science.gov (United States)

    Bas-Orth, Carlos; Tan, Yan-Wei; Oliveira, Ana M. M.; Bengtson, C. Peter; Bading, Hilmar

    2016-01-01

    The formation of long-term memory requires signaling from the synapse to the nucleus to mediate neuronal activity-dependent gene transcription. Synapse-to-nucleus communication is initiated by influx of calcium ions through synaptic NMDA receptors and/or L-type voltage-gated calcium channels and involves the activation of transcription factors by…

  4. Effect of Associative Learning on Memory Spine Formation in Mouse Barrel Cortex

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    Malgorzata Jasinska

    2016-01-01

    Full Text Available Associative fear learning, in which stimulation of whiskers is paired with mild electric shock to the tail, modifies the barrel cortex, the functional representation of sensory receptors involved in the conditioning, by inducing formation of new inhibitory synapses on single-synapse spines of the cognate barrel hollows and thus producing double-synapse spines. In the barrel cortex of conditioned, pseudoconditioned, and untreated mice, we analyzed the number and morphological features of dendritic spines at various maturation and stability levels: sER-free spines, spines containing smooth endoplasmic reticulum (sER, and spines containing spine apparatus. Using stereological analysis of serial sections examined by transmission electron microscopy, we found that the density of double-synapse spines containing spine apparatus was significantly increased in the conditioned mice. Learning also induced enhancement of the postsynaptic density area of inhibitory synapses as well as increase in the number of polyribosomes in such spines. In single-synapse spines, the effects of conditioning were less pronounced and included increase in the number of polyribosomes in sER-free spines. The results suggest that fear learning differentially affects single- and double-synapse spines in the barrel cortex: it promotes maturation and stabilization of double-synapse spines, which might possibly contribute to permanent memory formation, and upregulates protein synthesis in single-synapse spines.

  5. The formation and stability of recognition memory: what happens upon recall?

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    Sabrina eDavis

    2010-11-01

    Full Text Available The idea that an already consolidated memory can become destabilised after recall and requires a process of reconsolidation to maintain it for subsequent use has gained much credence over the past decade. Experimental studies in rodents have shown pharmacological, genetic or injurious manipulation at the time of memory reactivation can disrupt the already consolidated memory. Despite the force of experimental data showing this phenomenon, a number of questions have remained unanswered and no consensus has emerged as to the conditions under which a memory can be disrupted following reactivation. To date most rodent studies of reconsolidation are based on negatively reinforced memories, in particular fear-associated memories, while the storage and stability of forms of memory that do not rely on explicit reinforcement have been less often studied. In this review, we focus on recognition memory, a paradigm widely used in humans to probe declarative memory. We briefly outline recent advances in our understanding of the processes and brain circuits involved in recognition memory and review the evidence that recognition memory can undergo reconsolidation upon reactivation. We also review recent findings suggesting that some molecular mechanisms underlying consolidation of recognition memory are similarly recruited after recall to ensure memory stability, while others are more specifically engaged in consolidation or reconsolidation. Finally, we provide novel data on the role of Rsk2, a mental retardation gene, and of the transcription factor zif268/egr1 in reconsolidation of object-location memory, and offer suggestions as to how assessing the activation of certain molecular mechanisms following recall in recognition memory may help understand the relative importance of different aspects of remodelling or updating long-lasting memories.

  6. Implications of psychosocial stress on memory formation in a typical male versus female student sample.

    NARCIS (Netherlands)

    Cornelisse, S.; van Stegeren, A.H.; Joëls, M.

    2011-01-01

    Stress is known to differentially modulate memory function. Memory can be impaired or strengthened by stress, depending on e.g. the memory type and phase under study, the emotional value of the learned information and the sex of the subjects. Here, we addressed the latter and investigated the impact

  7. Implications of psychosocial stress on memory formation in a typical male versus female student sample.

    NARCIS (Netherlands)

    Cornelisse, S.; van Stegeren, A.H.; Joëls, M.

    2011-01-01

    Stress is known to differentially modulate memory function. Memory can be impaired or strengthened by stress, depending on e.g. the memory type and phase under study, the emotional value of the learned information and the sex of the subjects. Here, we addressed the latter and investigated the impact

  8. Short-term memory formation and long-term memory consolidation are enhanced by cellular prion association to stress-inducible protein 1.

    Science.gov (United States)

    Coitinho, Adriana S; Lopes, Marilene H; Hajj, Glaucia N M; Rossato, Janine I; Freitas, Adriana R; Castro, Cibele C; Cammarota, Martin; Brentani, Ricardo R; Izquierdo, Ivan; Martins, Vilma R

    2007-04-01

    Cellular prion protein (PrP(C)) is a cell surface glycoprotein that interacts with several ligands such as laminin, NCAM (Neural-Cell Adhesion Molecule) and the stress-inducible protein 1 (STI1). PrP(C) association with these proteins in neurons mediates adhesion, differentiation and protection against programmed cell death. Herein, we used an aversively motivated learning paradigm in rats to investigate whether STI1 interaction with PrP(C) affects short-term memory (STM) formation and long-term memory (LTM) consolidation. Blockage of PrP(C)-STI1 interaction with intra-hippocampal infusion of antibodies against PrP(C) or STI1 immediately after training impaired both STM and LTM. Furthermore, infusion of PrP(C) peptide 106-126, which competes for PrP(C)-STI1 interaction, also inhibited both forms of memory. Remarkably, STI1 peptide 230-245, which includes the PrP(C) binding site, had a potent enhancing effect on memory performance, which could be blocked by co-treatment with the competitive PrP(C) peptide 106-126. Taken together, these results demonstrate that PrP(C)-STI1 interaction modulates both STM and LTM and suggests a potential use of ST11 peptide 230-245 as a pharmacological agent.

  9. Temporal dynamics of Arc gene induction in hippocampus: relationship to context memory formation.

    Science.gov (United States)

    Pevzner, Aleksandr; Miyashita, Teiko; Schiffman, Aaron J; Guzowski, John F

    2012-03-01

    Past studies have proposed a role for the hippocampus in the rapid encoding of context memories. Despite this, there is little data regarding the molecular processes underlying the stable formation of a context representation that occurs in the time window established through such behavioral studies. One task that is useful for investigating the rapid encoding of context is contextual fear conditioning (CFC). Behavioral studies demonstrate that animals require approximately 30 s of exploration prior to a footshock to form a contextual representation supporting CFC. Thus, any potential molecular process required for the stabilization of the cellular representation for context must be activated within this narrow and behaviorally defined time window. Detection of the immediate-early gene Arc presents an ideal method to assess the activation of specific neuronal ensembles, given past studies showing the context specific expression of Arc in CA3 and CA1 subfields and the role of Arc in hippocampal long-term synaptic plasticity. Therefore, we examined the temporal dynamics of Arc induction within the hippocampus after brief context exposure to determine whether experience-dependent Arc expression could be involved in the rapid encoding of incidental context memories. We found that the duration of context exposure differentially activated Arc expression in hippocampal subfields, with CA3 showing rapid engagement within as little as 3 s of exposure. By contrast, Arc induction in CA1 required 30 s of context exposure to reach maximal levels. A parallel behavioral experiment revealed that 30 s, but not 3 s, exposure to a context resulted in strong conditioned freezing 24 h later, consistent with past studies from other laboratories. The current study is the first to examine the rapid temporal dynamics of Arc induction in hippocampus in a well-defined context memory paradigm. These studies demonstrate within 30 s of context exposure Arc is fully activated in CA3 and CA1

  10. Cytomegalovirus upregulates expression of CCR5 in central memory cord blood mononuclear cells, which may facilitate in utero HIV type 1 transmission.

    Science.gov (United States)

    Johnson, Erica L; Howard, Chanie L; Thurman, Joy; Pontiff, Kyle; Johnson, Elan S; Chakraborty, Rana

    2015-01-15

    Administration of combination antiretroviral therapy to human immunodeficiency virus type 1 (HIV-1)-infected pregnant women significantly reduces vertical transmission. In contrast, maternal co-opportunistic infection with primary or reactivated cytomegalovirus (CMV) or other pathogens may facilitate in utero transmission of HIV-1 by activation of cord blood mononuclear cells (CBMCs). Here we examine the targets and mechanisms that affect fetal susceptibility to HIV-1 in utero. Using flow cytometry, we demonstrate that the fraction of CD4(+)CD45RO(+) and CD4(+)CCR5(+) CBMCs is minimal, which may account for the low level of in utero HIV-1 transmission. Unstimulated CD4(+) CBMCs that lack CCR5/CD45RO showed reduced levels of HIV-1 infection. However, upon in vitro stimulation with CMV, CBMCs undergo increased proliferation to upregulate the fraction of T central memory cells and expression of CCR5, which enhances susceptibility to HIV-1 infection in vitro. These data suggest that activation induced by CMV in vivo may alter CCR5 expression in CD4(+) T central memory cells to promote in utero transmission of HIV-1.

  11. Inhibition of different histone acetyltransferases (HATs) uncovers transcription-dependent and -independent acetylation-mediated mechanisms in memory formation.

    Science.gov (United States)

    Merschbaecher, Katja; Hatko, Lucyna; Folz, Jennifer; Mueller, Uli

    2016-02-01

    Acetylation of histones changes the efficiency of the transcription processes and thus contributes to the formation of long-term memory (LTM). In our comparative study, we used two inhibitors to characterize the contribution of different histone acetyl transferases (HATs) to appetitive associative learning in the honeybee. For one we applied garcinol, an inhibitor of the HATs of the p300 (EP300 binding protein)/CBP (CREB-binding protein) family, and the HATs of the PCAF (p300/CBP-associated factor) family. As comparative agent we applied C646, a specific inhibitor that selectively blocks HATS of the p300/CBP family. Immunochemical analysis reveals differences in histone H3 acetylation in the honeybee brain, in response to the injection of either C646 or garcinol. Behavioral assessment reveals that the two drugs cause memory impairment of different nature when injected after associative conditioning: processes disturbed by garcinol are annihilated by the established transcription blocker actinomycin D and thus seem to require transcription processes. Actions of C646 are unaltered by actinomycin D, and thus seem to be independent of transcription. The outcome of our different approaches as summarized suggests that distinct HATs contribute to different acetylation-mediated processes in memory formation. We further deduce that the acetylation-mediated processes in memory formation comprise transcription-dependent and transcription-independent mechanisms.

  12. Differentially expressed genes linked to natural variation in long-term memory formation in Cotesia parasitic wasps

    Directory of Open Access Journals (Sweden)

    Joke J. F. A. Van Vugt

    2015-09-01

    Full Text Available Even though learning and memory are universal traits in the Animal Kingdom, closely related species reveal substantial variation in learning rate and memory dynamics. To determine the genetic background of this natural variation, we studied two congeneric parasitic wasp species, Cotesia glomerata and C. rubecula, which lay their eggs in caterpillars of the large and small cabbage white butterfly. A successful egg laying event serves as an unconditioned stimulus in a classical conditioning paradigm, where plant odors become associated to the encounter of a suitable host caterpillar. Depending on the host species, the number of conditioning trials and the parasitic wasp species, three different types of transcription-dependent long-term memory (LTM and one type of transcription-independent, anesthesia-resistant memory (ARM can be distinguished. To identify transcripts underlying these differences in memory formation, we isolated mRNA from parasitic wasp heads at three different time points between induction and consolidation of each of the four memory types, and for each sample three biological replicates, where after strand-specific paired-end 100 bp deep sequencing. Transcriptomes were assembled de novo and differential expression was determined for each memory type and time point after conditioning, compared to unconditioned wasps. Most differentially expressed (DE genes and antisense transcripts were only DE in one of the LTM types. Among the DE genes that were DE in two or more LTM types, were many protein kinases and phosphatases, small GTPases, receptors and ion channels. Some genes were DE in opposing directions between any of the LTM memory types and ARM, suggesting that ARM in Cotesia requires the transcription of genes inhibiting LTM or vice versa. We discuss our findings in the context of neuronal functioning, including RNA splicing and transport, epigenetic regulation, neurotransmitter/peptide synthesis and antisense transcription. In

  13. Vegetation pattern formation in semiarid systems induced by long-range competition in the absence of facilitation mechanisms.

    Science.gov (United States)

    Martinez-Garcia, Ricardo; Calabrese, Justin M.; Hernandez-Garcia, Emilio; Lopez, Cristobal

    2014-05-01

    and its range. When the finite range of the competitive interaction is considered used kernel functions with a finite range, whose Fourier transform may have negative values, patterns emerge in the system. This is a rather general condition if we consider the finite length of the roots responsible of long-range competition for water in plant ecosystems.Therefore, our findings support the notion that, under fairly broad conditions, only competition is required for patterns to occur and suggest that the role of short-range facilitation mechanisms may not be as fundamental to pattern formation as has previously been thought. REFERENCES: C.A. Klausmeier, Science, 284, 1826-1828 (1999). F. Borgogno, P. D'Odorico, F. Laio and L. Ridolfi, Reviews of Geophysics, 4, RG1005 (2009). R. Martinez-Garcia, J.M. Calabrese, and C. Lopez, Journal of Theoretical Biology, 333, 156-165 (2013). R. Martinez-Garcia, J. M. Calabrese, E. Hernandez-Garcia, and C. Lopez, Geophysical Research Letters, 40, 6143-6147,(2013).

  14. Semantic processes leading to true and false memory formation in schizophrenia.

    Science.gov (United States)

    Paz-Alonso, Pedro M; Ghetti, Simona; Ramsay, Ian; Solomon, Marjorie; Yoon, Jong; Carter, Cameron S; Ragland, J Daniel

    2013-07-01

    Encoding semantic relationships between items on word lists (semantic processing) enhances true memories, but also increases memory distortions. Episodic memory impairments in schizophrenia (SZ) are strongly driven by failures to process semantic relations, but the exact nature of these relational semantic processing deficits is not well understood. Here, we used a false memory paradigm to investigate the impact of implicit and explicit semantic processing manipulations on episodic memory in SZ. Thirty SZ and 30 demographically matched healthy controls (HC) studied Deese/Roediger-McDermott (DRM) lists of semantically associated words. Half of the lists had strong implicit semantic associations and the remainder had low strength associations. Similarly, half of the lists were presented under "standard" instructions and the other half under explicit "relational processing" instructions. After study, participants performed recall and old/new recognition tests composed of targets, critical lures, and unrelated lures. HC exhibited higher true memories and better discriminability between true and false memory compared to SZ. High, versus low, associative strength increased false memory rates in both groups. However, explicit "relational processing" instructions positively improved true memory rates only in HC. Finally, true and false memory rates were associated with severity of disorganized and negative symptoms in SZ. These results suggest that reduced processing of semantic relationships during encoding in SZ may stem from an inability to implement explicit relational processing strategies rather than a fundamental deficit in the implicit activation and retrieval of word meanings from patients' semantic lexicon.

  15. Implications of psychosocial stress on memory formation in a typical male versus female student sample.

    Science.gov (United States)

    Cornelisse, Sandra; van Stegeren, Anda H; Joëls, Marian

    2011-05-01

    Stress is known to differentially modulate memory function. Memory can be impaired or strengthened by stress, depending on e.g. the memory type and phase under study, the emotional value of the learned information and the sex of the subjects. Here, we addressed the latter and investigated the impact of psychosocial stress on long-term memory for neutral and emotional pictures and working memory in typical samples of male versus female students. In total, 77 subjects (54 women of which 39 used oral contraceptives) were exposed to either the Trier Social Stress Test (TSST) or a control condition, and then engaged in a long-term memory task (emotionally arousing and neutral pictures; surprise recall after one week) and a working memory (n-back) task. During the experiment salivary cortisol and alpha-amylase levels as well as subjective affect state were assessed. As expected, stress hormone concentrations as well as subjective negative affect states increased significantly in response to the stress task. Men reacted more to the stressor in terms of cortisol responses than women, probably due to oral contraceptive use of the latter. Results show that, in male as well as in female students, memory for emotional arousing information was better than for neutral information, in both the stress and control condition. Stress enhanced recognition memory for emotional versus neutral pictures only in male subjects. Moreover, stress enhanced working memory, particularly in males, during the first block of a 2-back task. The lack of stress effects on memory in women might be explained by oral contraceptive use, leading to blunted HPA-axis responses and secondary to reduced stress effects on memory. The results emphasize that stress affects both long-term and working memory differentially in male versus female students.

  16. Protein degradation by ubiquitin–proteasome system in formation and labilization of contextual conditioning memory

    Science.gov (United States)

    Sol Fustiñana, María; de la Fuente, Verónica; Federman, Noel; Freudenthal, Ramiro

    2014-01-01

    The ubiquitin–proteasome system (UPS) of protein degradation has been evaluated in different forms of neural plasticity and memory. The role of UPS in such processes is controversial. Several results support the idea that the activation of this system in memory consolidation is necessary to overcome negative constrains for plasticity. In this case, the inhibition of the UPS during consolidation impairs memory. Similar results were reported for memory reconsolidation. However, in other cases, the inhibition of UPS had no effect on memory consolidation and reconsolidation but impedes the amnesic action of protein synthesis inhibition after retrieval. The last finding suggests a specific action of the UPS inhibitor on memory labilization. However, another interpretation is possible in terms of the synthesis/degradation balance of positive and negative elements in neural plasticity, as was found in the case of long-term potentiation. To evaluate these alternative interpretations, other reconsolidation-interfering drugs than translation inhibitors should be tested. Here we analyzed initially the UPS inhibitor effect in contextual conditioning in crabs. We found that UPS inhibition during consolidation impaired long-term memory. In contrast, UPS inhibition did not affect memory reconsolidation after contextual retrieval but, in fact, impeded memory labilization, blocking the action of drugs that does not affect directly the protein synthesis. To extend these finding to vertebrates, we performed similar experiments in contextual fear memory in mice. We found that the UPS inhibitor in hippocampus affected memory consolidation and blocked memory labilization after retrieval. These findings exclude alternative interpretations to the requirement of UPS in memory labilization and give evidence of this mechanism in both vertebrates and invertebrates. PMID:25135196

  17. 人类外显记忆脑机制研究进展%The Neural Mechanisms of Human Explicit Memory Formation

    Institute of Scientific and Technical Information of China (English)

    程灶火; 王力

    2002-01-01

    The fMRI and ERPs have played important role s in understanding neura l mechanisms of human memory. Recent studies have revealed that distinct regions in medial temporal and prefrontal areas exhibit more neural activity during suc cessful than unsuccessful memory formation. The results from different studies s uggest that relational and non-relational memories are mediated by distinct sub- regions in medial temporal and prefrontal cortex and there are extensive interac tions between them in a parallel and bi-directional fashions. Emotionally arousi ng events enhance neural activity in amygdala, which in turn may modulate proces sing in other brain regions responsible for declarative memory formation.

  18. A songbird forebrain area potentially involved in auditory discrimination and memory formation

    Indian Academy of Sciences (India)

    Raphael Pinaud; Thomas A Terleph

    2008-03-01

    Songbirds rely on auditory processing of natural communication signals for a number of social behaviors, including mate selection, individual recognition and the rare behavior of vocal learning – the ability to learn vocalizations through imitation of an adult model, rather than by instinct. Like mammals, songbirds possess a set of interconnected ascending and descending auditory brain pathways that process acoustic information and that are presumably involved in the perceptual processing of vocal communication signals. Most auditory areas studied to date are located in the caudomedial forebrain of the songbird and include the thalamo-recipient field L (subfields L1, L2 and L3), the caudomedial and caudolateral mesopallium (CMM and CLM, respectively) and the caudomedial nidopallium (NCM). This review focuses on NCM, an auditory area previously proposed to be analogous to parts of the primary auditory cortex in mammals. Stimulation of songbirds with auditory stimuli drives vigorous electrophysiological responses and the expression of several activity-regulated genes in NCM. Interestingly, NCM neurons are tuned to species-specific songs and undergo some forms of experience-dependent plasticity in-vivo. These activity-dependent changes may underlie long-term modifications in the functional performance of NCM and constitute a potential neural substrate for auditory discrimination. We end this review by discussing evidence that suggests that NCM may be a site of auditory memory formation and/or storage.

  19. Individual language experience modulates rapid formation of cortical memory circuits for novel words

    Science.gov (United States)

    Kimppa, Lilli; Kujala, Teija; Shtyrov, Yury

    2016-01-01

    Mastering multiple languages is an increasingly important ability in the modern world; furthermore, multilingualism may affect human learning abilities. Here, we test how the brain’s capacity to rapidly form new representations for spoken words is affected by prior individual experience in non-native language acquisition. Formation of new word memory traces is reflected in a neurophysiological response increase during a short exposure to novel lexicon. Therefore, we recorded changes in electrophysiological responses to phonologically native and non-native novel word-forms during a perceptual learning session, in which novel stimuli were repetitively presented to healthy adults in either ignore or attend conditions. We found that larger number of previously acquired languages and earlier average age of acquisition (AoA) predicted greater response increase to novel non-native word-forms. This suggests that early and extensive language experience is associated with greater neural flexibility for acquiring novel words with unfamiliar phonology. Conversely, later AoA was associated with a stronger response increase for phonologically native novel word-forms, indicating better tuning of neural linguistic circuits to native phonology. The results suggest that individual language experience has a strong effect on the neural mechanisms of word learning, and that it interacts with the phonological familiarity of the novel lexicon. PMID:27444206

  20. Proteolysis of proBDNF is a key regulator in the formation of memory.

    Directory of Open Access Journals (Sweden)

    Philip Barnes

    Full Text Available It is essential to understand the molecular processes underlying long-term memory to provide therapeutic targets of aberrant memory that produce pathological behaviour in humans. Under conditions of recall, fully-consolidated memories can undergo reconsolidation or extinction. These retrieval-mediated memory processes may rely on distinct molecular processes. The cellular mechanisms initiating the signature molecular events are not known. Using infusions of protein synthesis inhibitors, antisense oligonucleotide targeting brain-derived neurotrophic factor (BDNF mRNA or tPA-STOP (an inhibitor of the proteolysis of BDNF protein into the hippocampus of the awake rat, we show that acquisition and extinction of contextual fear memory depended on the increased and decreased proteolysis of proBDNF (precursor BDNF in the hippocampus, respectively. Conditions of retrieval that are known to initiate the reconsolidation of contextual fear memory, a BDNF-independent memory process, were not correlated with altered proBDNF cleavage. Thus, the processing of BDNF was associated with the acquisition of new information and the updating of information about a salient stimulus. Furthermore, the differential requirement for the processing of proBDNF by tPA in distinct memory processes suggest that the molecular events actively engaged to support the storage and/or the successful retrieval of memory depends on the integration of ongoing experience with past learning.

  1. Involvement of 5-HT(2A/2B/2C) receptors on memory formation: simple agonism, antagonism, or inverse agonism?

    Science.gov (United States)

    Meneses, Alfredo

    2002-12-01

    1. The 5-HT2 receptors subdivision into the 5-HT(2A/2B/2C) subtypes along with the advent of the selective antagonists has allowed a more detailed investigation on the role and therapeutic significance of these subtypes in cognitive functions. The present study further analyzed the 5-HT2 receptors role on memory consolidation. 2. The SB-200646 (a selective 5-HT(2B/2C) receptor antagonist) and LY215840 (a nonselective 5-HT(2/7) receptor antagonist) posttraining administration had no effect on an autoshaped memory consolidation. However, both drugs significantly and differentially antagonized the memory impairments induced by 1-(3-chlorophenyl)piperazine (mCPP), 1-naphtyl-piperazine (1-NP), mesulergine, or N-(3-trifluoromethylphenyl) piperazine (TFMPP). 3. In contrast, SB-200646 failed to modify the facilitatory procognitive effect produced by (+/-)-2.5-dimethoxy-4-iodoamphetamine (DOI) or ketanserin, which were sensitive to MDL100907 (a selective 5-HT2A receptor antagonist) and to a LY215840 high dose. 4. Finally, SB-200646 reversed the learning deficit induced by dizocilpine, but not that by scopolamine: while SB-200646 and MDL100907 coadministration reversed memory deficits induced by both drugs. 5. It is suggested that 5-HT(2B/2C) receptors might be involved on memory formation probably mediating a suppressive or constraining action. Whether the drug-induced memory impairments in this study are explained by simple agonism, antagonism, or inverse agonism at 5-HT2 receptors remains unclear at this time. 6. Notably, the 5-HT2 receptor subtypes blockade may provide some benefit to reverse poor memory consolidation conditions associated with decreasedcholinergic, glutamatergic, and/or serotonergic neurotransmission.

  2. Detection of central circuits implicated in the formation of novel pain memories

    Directory of Open Access Journals (Sweden)

    Upadhyay J

    2016-09-01

    Full Text Available Jaymin Upadhyay,1 Julia Granitzka,1 Thomas Bauermann,2 Ulf Baumgärtner,3 Markus Breimhorst,1 Rolf-Detlef Treede,3 Frank Birklein1 1Department of Neurology, 2Department of Neuroradiology, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, 3Department of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim (CBTM, Heidelberg University, Mannheim, Germany Abstract: Being able to remember physically and emotionally painful events in one’s own past may shape behavior, and can create an aversion to a variety of situations. Pain imagination is a related process that may include recall of past experiences, in addition to production of sensory and emotional percepts without external stimuli. This study aimed to understand 1 the central nervous system processes that underlie pain imagination, 2 the retrieval of pain memories, and 3 to compare the latter with visual object memory. These goals were achieved by longitudinally investigating brain function with functional magnetic resonance imaging in a unique group of healthy volunteers who had never experienced tooth pain. In these subjects, we compared brain responses elicited during three experimental conditions in the following order: imagination of tooth pain (pain imagination, remembering one’s own house (object memory, and remembrance of tooth pain following an episode of induced acute tooth pain (pain memory. Key observations stemming from group-level conjunction analyses revealed common activation in the posterior parietal cortex for both pain imagination and pain memory, while object and pain memory each had strong activation predominantly within the middle frontal gyrus. When contrasting pain imagination and memory, significant activation differences were observed in subcortical structures (ie, parahippocampus – pain imagination > pain memory; midbrain – pain memory > pain imagination. Importantly, these findings were observed in the presence of

  3. Modeling for Formation of Conducting Path in Cu/SiO2/Pt Memory Devices: Based on Soft Breakdown Mechanism

    Science.gov (United States)

    Luo, J. M.

    2013-09-01

    The forming process before resistive switching in Cu/ SiO2/Pt memory devices, corresponding to the formation of conducting path, can be regarded as the dielectric soft breakdown. Based on the analysis of breakdown mechanism, a dynamic model combining the transition of Cu ions with the space-charge effect has been proposed, and demonstrates that the forming voltage depends on the thickness of oxide, the sweep rate of voltage and temperature. The predictions of the model are consistent with the experiment data reported in the literature and it is believed that the transition of Cu ions across the oxide and the accumulation of Cu ions at the SiO2/Pt interface could be responsible for the conductive path formation in Cu/SiO2/Pt memory devices.

  4. Irrelevant features of a stimulus can either facilitate or disrupt performance in a working memory task: the role of fluid intelligence.

    Directory of Open Access Journals (Sweden)

    Bernardo Perfetti

    Full Text Available It has been shown that fluid intelligence (gf is fundamental to overcome interference due to information of a previously encoded item along a task-relevant domain. However, the biasing effect of task-irrelevant dimensions is still unclear as well as its relation with gf. The present study aimed at clarifying these issues. Gf was assessed in 60 healthy subjects. In a different session, the same subjects performed two versions (letter-detection and spatial of a three-back working memory task with a set of physically identical stimuli (letters presented at different locations on the screen. In the letter-detection task, volunteers were asked to match stimuli on the basis of their identity whereas, in the spatial task, they were required to match items on their locations. Cross-domain bias was manipulated by pseudorandomly inserting a match between the current and the three back items on the irrelevant domain. Our findings showed that a task-irrelevant feature of a salient stimulus can actually bias the ongoing performance. We revealed that, at trials in which the current and the three-back items matched on the irrelevant domain, group accuracy was lower (interference. On the other hand, at trials in which the two items matched on both the relevant and irrelevant domains, the group showed an enhancement of the performance (facilitation. Furthermore, we demonstrated that individual differences in fluid intelligence covaries with the ability to override cross-domain interference in that higher gf subjects showed better performance at interference trials than low gf subjects. Altogether, our findings suggest that stimulus features irrelevant to the task can affect cognitive performance along the relevant domain and that gf plays an important role in protecting relevant memory contents from the hampering effect of such a bias.

  5. Irrelevant features of a stimulus can either facilitate or disrupt performance in a working memory task: the role of fluid intelligence.

    Science.gov (United States)

    Perfetti, Bernardo; Tesse, Marcello; Varanese, Sara; Saggino, Aristide; Onofrj, Marco

    2011-01-01

    It has been shown that fluid intelligence (gf) is fundamental to overcome interference due to information of a previously encoded item along a task-relevant domain. However, the biasing effect of task-irrelevant dimensions is still unclear as well as its relation with gf. The present study aimed at clarifying these issues. Gf was assessed in 60 healthy subjects. In a different session, the same subjects performed two versions (letter-detection and spatial) of a three-back working memory task with a set of physically identical stimuli (letters) presented at different locations on the screen. In the letter-detection task, volunteers were asked to match stimuli on the basis of their identity whereas, in the spatial task, they were required to match items on their locations. Cross-domain bias was manipulated by pseudorandomly inserting a match between the current and the three back items on the irrelevant domain. Our findings showed that a task-irrelevant feature of a salient stimulus can actually bias the ongoing performance. We revealed that, at trials in which the current and the three-back items matched on the irrelevant domain, group accuracy was lower (interference). On the other hand, at trials in which the two items matched on both the relevant and irrelevant domains, the group showed an enhancement of the performance (facilitation). Furthermore, we demonstrated that individual differences in fluid intelligence covaries with the ability to override cross-domain interference in that higher gf subjects showed better performance at interference trials than low gf subjects. Altogether, our findings suggest that stimulus features irrelevant to the task can affect cognitive performance along the relevant domain and that gf plays an important role in protecting relevant memory contents from the hampering effect of such a bias.

  6. Motor Skills Enhance Procedural Memory Formation and Protect against Age-Related Decline

    NARCIS (Netherlands)

    Muller, N.C.; Genzel, L.K.E.; Konrad, B.N; Pawlowski, M.; Neville, D.; Fernandez, G.; Steiger, A.; Dresler, M.

    2016-01-01

    The ability to consolidate procedural memories declines with increasing age. Prior knowledge enhances learning and memory consolidation of novel but related information in various domains. Here, we present evidence that prior motor experience-in our case piano skills-increases procedural learning

  7. Cognitive Backward Masking: A Window Into the Formation of a Short-Term Memory Trace

    NARCIS (Netherlands)

    Nieuwenstein, Mark; Wyble, Brad

    2012-01-01

    Working memory consolidation denotes the process that enables sensory information to be stored in short-term memory. What is currently unclear is how long this process takes and whether it continues after a stimulus has been masked. Here, we address these matters by examining whether the consolidati

  8. Endogenous BDNF Is Required for Long-Term Memory Formation in the Rat Parietal Cortex

    Science.gov (United States)

    Alonso, Mariana; Bekinschtein, Pedro, Cammarota, Martin; Vianna, Monica R. M.; Izquierdo, Ivan; Medina, Jorge H.

    2005-01-01

    Information storage in the brain is a temporally graded process involving different memory phases as well as different structures in the mammalian brain. Cortical plasticity seems to be essential to store stable long-term memories, although little information is available at the moment regarding molecular and cellular events supporting memory…

  9. Effects of Aging on True and False Memory Formation: An fMRI Study

    Science.gov (United States)

    Dennis, Nancy A.; Kim, Hongkeun; Cabeza, Roberto

    2007-01-01

    Compared to young, older adults are more likely to forget events that occurred in the past as well as remember events that never happened. Previous studies examining false memories and aging have shown that these memories are more likely to occur when new items share perceptual or semantic similarities with those presented during encoding. It is…

  10. Natural variation in long-term memory formation among Nasonia parasitic wasp species

    NARCIS (Netherlands)

    Hoedjes, K.M.; Smid, H.M.

    2014-01-01

    Closely related species of parasitic wasps can differ substantially in memory dynamics. In this study we demonstrate differences in the number of conditioning trials required to form long-term memory between the closely related parasitic wasp species Nasonia vitripennis and Nasonia giraulti

  11. Cognitive Backward Masking: A Window Into the Formation of a Short-Term Memory Trace

    NARCIS (Netherlands)

    Nieuwenstein, Mark; Wyble, Brad

    2012-01-01

    Working memory consolidation denotes the process that enables sensory information to be stored in short-term memory. What is currently unclear is how long this process takes and whether it continues after a stimulus has been masked. Here, we address these matters by examining whether the

  12. Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation

    Directory of Open Access Journals (Sweden)

    Inoue Naoko

    2009-03-01

    Full Text Available Abstract Background The formation of long-term memory (LTM and the late phase of long-term potentiation (L-LTP depend on macromolecule synthesis, translation, and transcription in neurons. vesl-1S (VASP/Ena-related gene upregulated during seizure and LTP, also known as homer-1a is an LTP-induced immediate early gene. The short form of Vesl (Vesl-1S is an alternatively spliced isoform of the vesl-1 gene, which also encodes the long form of the Vesl protein (Vesl-1L. Vesl-1L is a postsynaptic scaffolding protein that binds to and modulates the metabotropic glutamate receptor 1/5 (mGluR1/5, the IP3 receptor, and the ryanodine receptor. Vesl-1 null mutant mice show abnormal behavior, which includes anxiety- and depression-related behaviors, and an increase in cocaine-induced locomotion; however, the function of the short form of Vesl in behavior is poorly understood because of the lack of short-form-specific knockout mice. Results In this study, we generated short-form-specific gene targeting (KO mice by knocking in part of vesl-1L/homer-1c cDNA. Homozygous KO mice exhibited normal spine number and morphology. Using the contextual fear conditioning test, we demonstrated that memory acquisition and short-term memory were normal in homozygous KO mice. In contrast, these mice showed impairment in fear memory consolidation. Furthermore, the process from recent to remote memory was affected in homozygous KO mice. Interestingly, reactivation of previously consolidated fear memory attenuated the conditioning-induced freezing response in homozygous KO mice, which suggests that the short form plays a role in fear memory reconsolidation. General activity, emotional performance, and sensitivity to electrofootshock were normal in homozygous KO mice. Conclusion These results indicate that the short form of the Vesl family of proteins plays a role in multiple steps of long-term, but not short-term, fear memory formation.

  13. DNA methylation changes in plasticity genes accompany the formation and maintenance of memory.

    Science.gov (United States)

    Halder, Rashi; Hennion, Magali; Vidal, Ramon O; Shomroni, Orr; Rahman, Raza-Ur; Rajput, Ashish; Centeno, Tonatiuh Pena; van Bebber, Frauke; Capece, Vincenzo; Garcia Vizcaino, Julio C; Schuetz, Anna-Lena; Burkhardt, Susanne; Benito, Eva; Navarro Sala, Magdalena; Javan, Sanaz Bahari; Haass, Christian; Schmid, Bettina; Fischer, Andre; Bonn, Stefan

    2016-01-01

    The ability to form memories is a prerequisite for an organism's behavioral adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell types and three time points before and after contextual learning. We found that histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression. Although long-lasting changes were almost exclusive to neurons, learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provide evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring.

  14. Serotonin mediation of early memory formation via 5-HT2B receptor-induced glycogenolysis in the day-old chick

    OpenAIRE

    Marie Elizabeth Gibbs; Leif eHertz

    2014-01-01

    Investigation of the effects of serotonin on memory formation in the chick revealed an action on at least two 5-HT receptors. Serotonin injected intracerebrally produced a biphasic effect on memory consolidation with enhancement at low doses and inhibition at higher doses. The non-selective 5-HT receptor antagonist methiothepin and the selective 5-HT2B/C receptor antagonist SB221284 both inhibited memory, suggesting actions of serotonin on at least two different receptor subtypes. The 5-HT2B/...

  15. Cortisol's effects on hippocampal activation in depressed patients are related to alterations in memory formation.

    Science.gov (United States)

    Abercrombie, Heather C; Jahn, Allison L; Davidson, Richard J; Kern, Simone; Kirschbaum, Clemens; Halverson, Jerry

    2011-01-01

    Many investigators have hypothesized that brain response to cortisol is altered in depression. However, neural activation in response to exogenously manipulated cortisol elevations has not yet been directly examined in depressed humans. Animal research shows that glucocorticoids have robust effects on hippocampal function, and can either enhance or suppress neuroplastic events in the hippocampus depending on a number of factors. We hypothesized that depressed individuals would show 1) altered hippocampal response to exogenous administration of cortisol, and 2) altered effects of cortisol on learning. In a repeated-measures design, 19 unmedicated depressed and 41 healthy individuals completed two fMRI scans. Fifteen mg oral hydrocortisone (i.e., cortisol) or placebo (order randomized and double-blind) was administered 1 h prior to encoding of emotional and neutral words during fMRI scans. Data analysis examined the effects of cortisol administration on 1) brain activation during encoding, and 2) subsequent free recall for words. Cortisol affected subsequent recall performance in depressed but not healthy individuals. We found alterations in hippocampal response to cortisol in depressed women, but not in depressed men (who showed altered response to cortisol in other regions, including subgenual prefrontal cortex). In both depressed men and women, cortisol's effects on hippocampal function were positively correlated with its effects on recall performance assessed days later. Our data provide evidence that in depressed compared to healthy women, cortisol's effects on hippocampal function are altered. Our data also show that in both depressed men and women, cortisol's effects on emotional memory formation and hippocampal function are related.

  16. Age Differences in the Contribution of Recollection and Familiarity to False-Memory Formation: A New Paradigm to Examine Developmental Reversals

    Science.gov (United States)

    Lyons, Kristen E.; Ghetti, Simona; Cornoldi, Cesare

    2010-01-01

    Using a new method for studying the development of false-memory formation, we examined developmental differences in the rates at which 6-, 7-, 9-, 10-, and 18-year-olds made two types of memory errors: backward causal-inference errors (i.e. falsely remembering having viewed the non-viewed cause of a previously viewed effect), and gap-filling…

  17. System consolidation of memory during sleep.

    Science.gov (United States)

    Born, Jan; Wilhelm, Ines

    2012-03-01

    Over the past two decades, research has accumulated compelling evidence that sleep supports the formation of long-term memory. The standard two-stage memory model that has been originally elaborated for declarative memory assumes that new memories are transiently encoded into a temporary store (represented by the hippocampus in the declarative memory system) before they are gradually transferred into a long-term store (mainly represented by the neocortex), or are forgotten. Based on this model, we propose that sleep, as an offline mode of brain processing, serves the 'active system consolidation' of memory, i.e. the process in which newly encoded memory representations become redistributed to other neuron networks serving as long-term store. System consolidation takes place during slow-wave sleep (SWS) rather than rapid eye movement (REM) sleep. The concept of active system consolidation during sleep implicates that (a) memories are reactivated during sleep to be consolidated, (b) the consolidation process during sleep is selective inasmuch as it does not enhance every memory, and (c) memories, when transferred to the long-term store undergo qualitative changes. Experimental evidence for these three central implications is provided: It has been shown that reactivation of memories during SWS plays a causal role for consolidation, that sleep and specifically SWS consolidates preferentially memories with relevance for future plans, and that sleep produces qualitative changes in memory representations such that the extraction of explicit and conscious knowledge from implicitly learned materials is facilitated.

  18. WRP/srGAP3 facilitates the initiation of spine development by an inverse F-BAR domain, and its loss impairs long-term memory.

    Science.gov (United States)

    Carlson, Benjamin R; Lloyd, Krissey E; Kruszewski, Allison; Kim, Il-Hwan; Rodriguiz, Ramona M; Heindel, Clifford; Faytell, Marika; Dudek, Serena M; Wetsel, William C; Soderling, Scott H

    2011-02-16

    The WAVE-associated Rac GAP, WRP, is thought to regulate key aspects of synapse development and function and may be linked to mental retardation in humans. WRP contains a newly described inverse F-BAR (IF-BAR) domain of unknown function. Our studies show that this domain senses/facilitates outward protrusions analogous to filopodia and that the molecular basis for this is likely explained by a convex lipid-binding surface on the WRP IF-BAR domain. In dendrites the IF-BAR domain of WRP forms a bud on the shaft from which precursors to spines emerge. Loss of WRP in vivo and in vitro results in reduced density of spines. In vivo this is primarily a loss of mushroom-shaped spines. Developmentally, WRP function is critical at the onset of spinogenesis, when dendritic filopodia are prevalent. Finally, because WRP is implicated in mental retardation, behaviors of WRP heterozygous and null mice have been evaluated. Results from these studies confirm that loss of WRP is linked to impaired learning and memory.

  19. VGF and Its C-Terminal Peptide TLQP-62 Regulate Memory Formation in Hippocampus via a BDNF-TrkB-Dependent Mechanism

    National Research Council Canada - National Science Library

    Lin, Wei-Jye; Jiang, Cheng; Sadahiro, Masato; Bozdagi, Ozlem; Vulchanova, Lucy; Alberini, Cristina M; Salton, Stephen R

    2015-01-01

    .... In this study, we show in the adult mouse hippocampus that expression of the granin family gene Vgf and secretion of its C-terminal VGF-derived peptide TLQP-62 are required for fear memory formation...

  20. A robust method of measuring other-race and other-ethnicity effects: the Cambridge Face Memory Test format.

    Directory of Open Access Journals (Sweden)

    Elinor McKone

    Full Text Available Other-race and other-ethnicity effects on face memory have remained a topic of consistent research interest over several decades, across fields including face perception, social psychology, and forensic psychology (eyewitness testimony. Here we demonstrate that the Cambridge Face Memory Test format provides a robust method for measuring these effects. Testing the Cambridge Face Memory Test original version (CFMT-original; European-ancestry faces from Boston USA and a new Cambridge Face Memory Test Chinese (CFMT-Chinese, with European and Asian observers, we report a race-of-face by race-of-observer interaction that was highly significant despite modest sample size and despite observers who had quite high exposure to the other race. We attribute this to high statistical power arising from the very high internal reliability of the tasks. This power also allows us to demonstrate a much smaller within-race other ethnicity effect, based on differences in European physiognomy between Boston faces/observers and Australian faces/observers (using the CFMT-Australian.

  1. A robust method of measuring other-race and other-ethnicity effects: the Cambridge Face Memory Test format.

    Science.gov (United States)

    McKone, Elinor; Stokes, Sacha; Liu, Jia; Cohan, Sarah; Fiorentini, Chiara; Pidcock, Madeleine; Yovel, Galit; Broughton, Mary; Pelleg, Michel

    2012-01-01

    Other-race and other-ethnicity effects on face memory have remained a topic of consistent research interest over several decades, across fields including face perception, social psychology, and forensic psychology (eyewitness testimony). Here we demonstrate that the Cambridge Face Memory Test format provides a robust method for measuring these effects. Testing the Cambridge Face Memory Test original version (CFMT-original; European-ancestry faces from Boston USA) and a new Cambridge Face Memory Test Chinese (CFMT-Chinese), with European and Asian observers, we report a race-of-face by race-of-observer interaction that was highly significant despite modest sample size and despite observers who had quite high exposure to the other race. We attribute this to high statistical power arising from the very high internal reliability of the tasks. This power also allows us to demonstrate a much smaller within-race other ethnicity effect, based on differences in European physiognomy between Boston faces/observers and Australian faces/observers (using the CFMT-Australian).

  2. VGF and Its C-Terminal Peptide TLQP-62 Regulate Memory Formation in Hippocampus via a BDNF-TrkB-Dependent Mechanism.

    Science.gov (United States)

    Lin, Wei-Jye; Jiang, Cheng; Sadahiro, Masato; Bozdagi, Ozlem; Vulchanova, Lucy; Alberini, Cristina M; Salton, Stephen R

    2015-07-15

    Regulated expression and secretion of BDNF, which activates TrkB receptor signaling, is known to play a critical role in cognition. Identification of additional modulators of cognitive behavior that regulate activity-dependent BDNF secretion and/or potentiate TrkB receptor signaling would therefore be of considerable interest. In this study, we show in the adult mouse hippocampus that expression of the granin family gene Vgf and secretion of its C-terminal VGF-derived peptide TLQP-62 are required for fear memory formation. We found that hippocampal VGF expression and TLQP-62 levels were transiently induced after fear memory training and that sequestering secreted TLQP-62 peptide in the hippocampus immediately after training impaired memory formation. Reduced VGF expression was found to impair learning-evoked Rac1 induction and phosphorylation of the synaptic plasticity markers cofilin and synapsin in the adult mouse hippocampus. Moreover, TLQP-62 induced acute, transient activation of the TrkB receptor and subsequent CREB phosphorylation in hippocampal slice preparations and its administration immediately after training enhanced long-term memory formation. A critical role of BDNF-TrkB signaling as a downstream effector in VGF/TLQP-62-mediated memory consolidation was further revealed by posttraining activation of BDNF-TrkB signaling, which rescued impaired fear memory resulting from hippocampal administration of anti-VGF antibodies or germline VGF ablation in mice. We propose that VGF is a critical component of a positive BDNF-TrkB regulatory loop and, upon its induced expression by memory training, the TLQP-62 peptide rapidly reinforces BDNF-TrkB signaling, regulating hippocampal memory consolidation. Identification of the cellular and molecular mechanisms that regulate long-term memory formation and storage may provide alternative treatment modalities for degenerative and neuropsychiatric memory disorders. The neurotrophin BDNF plays a prominent role in cognitive

  3. Spatial reference- (not working- or procedural-) memory performance of aged rats in the water maze predicts the magnitude of sulpiride-induced facilitation of acetylcholine release by striatal slices.

    Science.gov (United States)

    Cassel, Jean-Christophe; Lazaris, Anelise; Birthelmer, Anja; Jackisch, Rolf

    2007-08-01

    Cluster analysis of water-maze reference-memory performance distinguished subpopulations of young adult (3-5 months), aged (25-27 months) unimpaired (AU) and aged impaired (AI) rats. Working-memory performances of AU and AI rats were close to normal (though young and aged rats differed in exploration strategies). All aged rats showed impaired procedural-memory. Electrically evoked release of tritium was assessed in striatal slices (preloaded with [(3)H]choline) in the presence of oxotremorine, physostigmine, atropine+physostigmine, quinpirole, nomifensine or sulpiride. Aged rats exhibited reduced accumulation of [(3)H]choline (-30%) and weaker transmitter release. Drug effects (highest concentration) were reductions of release by 44% (oxotremorine), 72% (physostigmine), 84% (quinpirole) and 65% (nomifensine) regardless of age. Sulpiride and atropine+physostigmine facilitated the release more efficiently in young rats versus aged rats. The sulpiride-induced facilitation was weaker in AI rats versus AU rats; it significantly correlated with reference-memory performance. The results confirm age-related alterations of cholinergic and dopaminergic striatal functions, and point to the possibility that alterations in the D(2)-mediated dopaminergic regulation of these functions contribute to age-related reference-memory deficits.

  4. The differential effects of emotional salience on direct associative and relational memory during a nap.

    Science.gov (United States)

    Alger, Sara E; Payne, Jessica D

    2016-12-01

    Relational memories are formed from shared components between directly learned memory associations, flexibly linking learned information to better inform future judgments. Sleep has been found to facilitate both direct associative and relational memories. However, the impact of incorporating emotionally salient information into learned material and the interaction of emotional salience and sleep in facilitating both types of memory is unknown. Participants encoded two sets of picture pairs, with either emotionally negative or neutral objects paired with neutral faces. The same objects were present in both sets, paired with two different faces across the sets. Baseline memory for these directly paired associates was tested immediately after encoding, followed by either a 90-min nap opportunity or wakefulness. Five hours after learning, a surprise test assessed relational memory, the indirect association between two faces paired with the same object during encoding, followed by a retest of direct associative memory. Overall, negative information was remembered better than neutral for directly learned pairs. A nap facilitated both preservation of direct associative memories and formation of relational memories, compared to remaining awake. Interestingly, however, this sleep benefit was observed specifically for neutral directly paired associates, while both neutral and negative relational associations benefitted from a nap. Finally, REM sleep played opposing roles in neutral direct and relational associative memory formation, with more REM sleep leading to forgetting of direct associations but promoting relational associations, suggesting that, while not benefitting memory consolidation for directly learned details, REM sleep may foster the memory reorganization needed for relational memory.

  5. Formation of visual memories controlled by gamma power phase-locked to alpha oscillations

    Science.gov (United States)

    Park, Hyojin; Lee, Dong Soo; Kang, Eunjoo; Kang, Hyejin; Hahm, Jarang; Kim, June Sic; Chung, Chun Kee; Jiang, Haiteng; Gross, Joachim; Jensen, Ole

    2016-06-01

    Neuronal oscillations provide a window for understanding the brain dynamics that organize the flow of information from sensory to memory areas. While it has been suggested that gamma power reflects feedforward processing and alpha oscillations feedback control, it remains unknown how these oscillations dynamically interact. Magnetoencephalography (MEG) data was acquired from healthy subjects who were cued to either remember or not remember presented pictures. Our analysis revealed that in anticipation of a picture to be remembered, alpha power decreased while the cross-frequency coupling between gamma power and alpha phase increased. A measure of directionality between alpha phase and gamma power predicted individual ability to encode memory: stronger control of alpha phase over gamma power was associated with better memory. These findings demonstrate that encoding of visual information is reflected by a state determined by the interaction between alpha and gamma activity.

  6. Tequila, a neurotrypsin ortholog, regulates long-term memory formation in Drosophila.

    Science.gov (United States)

    Didelot, Gérard; Molinari, Florence; Tchénio, Paul; Comas, Daniel; Milhiet, Elodie; Munnich, Arnold; Colleaux, Laurence; Preat, Thomas

    2006-08-11

    Mutations in the human neurotrypsin gene are associated with autosomal recessive mental retardation. To further understand the pathophysiological consequences of the lack of this serine protease, we studied Tequila (Teq), the Drosophila neurotrypsin ortholog, using associative memory as a behavioral readout. We found that teq inactivation resulted in a long-term memory (LTM)-specific defect. After LTM conditioning of wild-type flies, teq expression transiently increased in the mushroom bodies. Moreover, specific inhibition of teq expression in adult mushroom bodies resulted in a reversible LTM defect. Hence, the Teq pathway is essential for information processing in Drosophila.

  7. EphrinA4 mimetic peptide targeted to EphA binding site impairs the formation of long-term fear memory in lateral amygdala.

    Science.gov (United States)

    Dines, M; Lamprecht, R

    2014-09-30

    Fear conditioning leads to long-term fear memory formation and is a model for studying fear-related psychopathologies conditions such as phobias and posttraumatic stress disorder. Long-term fear memory formation is believed to involve alterations of synaptic efficacy mediated by changes in synaptic transmission and morphology in lateral amygdala (LA). EphrinA4 and its cognate Eph receptors are intimately involved in regulating neuronal morphogenesis, synaptic transmission and plasticity. To assess possible roles of ephrinA4 in fear memory formation we designed and used a specific inhibitory ephrinA4 mimetic peptide (pep-ephrinA4) targeted to EphA binding site. We show that this peptide, composed of the ephrinA4 binding domain, interacts with EphA4 and inhibits ephrinA4-induced phosphorylation of EphA4. Microinjection of the pep-ephrinA4 into rat LA 30 min before training impaired long- but not short-term fear conditioning memory. Microinjection of a control peptide derived from a nonbinding E helix site of ephrinA4, that does not interact with EphA, had no effect on fear memory formation. Microinjection of pep-ephrinA4 into areas adjacent to the amygdala had no effect on fear memory. Acute systemic administration of pep-ephrinA4 1 h after training also impaired long-term fear conditioning memory formation. These results demonstrate that ephrinA4 binding sites in LA are essential for long-term fear memory formation. Moreover, our research shows that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear and anxiety disorders.

  8. Natural variation in memory formation among Nasonia parasitic wasps : from genes to behaviour

    NARCIS (Netherlands)

    Hoedjes, K.M.

    2014-01-01

      The ability to learn and form memory has been demonstrated in various animal species, ranging from relatively simple invertebrates, such as snails and insects, to more complex vertebrate species, including birds and mammals. The opportunity to acquire new skills or to adapt behaviour through

  9. Ontogeny of Contextual Fear Memory Formation, Specificity, and Persistence in Mice

    Science.gov (United States)

    Akers, Katherine G.; Arruda-Carvalho, Maithe; Josselyn, Sheena A.; Frankland, Paul W.

    2012-01-01

    Pinpointing the precise age when young animals begin to form memories of aversive events is valuable for understanding the onset of anxiety and mood disorders and for detecting early cognitive impairment in models of childhood-onset disorders. Although these disorders are most commonly modeled in mice, we know little regarding the development of…

  10. The Drosophila lingerer protein cooperates with Orb2 in long-term memory formation.

    Science.gov (United States)

    Kimura, Shingo; Sakakibara, Yasufumi; Sato, Kosei; Ote, Manabu; Ito, Hiroki; Koganezawa, Masayuki; Yamamoto, Daisuke

    2015-03-01

    Recently mated Drosophila females were shown to be reluctant to copulate and to exhibit rejecting behavior when courted by a male. Males that experience mate refusal by a mated female subsequently attenuate their courtship effort toward not only mated females but also virgin females. This courtship suppression persists for more than a day, and thus represents long-term memory. The courtship long-term memory has been shown to be impaired in heterozygotes as well as homozygotes of mutants in orb2, a locus encoding a set of CPEB RNA-binding proteins. We show that the impaired courtship long-term memory in orb2-mutant heterozygotes is restored by reducing the activity of lig, another putative RNA-binding protein gene, yet on its own the loss-of-function lig mutation is without effect. We further show that Lig forms a complex with Orb2. We infer that a reduction in the Lig levels compensates the Orb2 deficiency by mitigating the negative feedback for Orb2 expression and thereby alleviating defects in long-term memory.

  11. Natural variation in memory formation among Nasonia parasitic wasps : from genes to behaviour

    NARCIS (Netherlands)

    Hoedjes, K.M.

    2014-01-01

      The ability to learn and form memory has been demonstrated in various animal species, ranging from relatively simple invertebrates, such as snails and insects, to more complex vertebrate species, including birds and mammals. The opportunity to acquire new skills or to adapt behaviour through

  12. Effects of Presentation Format and List Length on Children's False Memories

    Science.gov (United States)

    Swannell, Ellen R.; Dewhurst, Stephen A.

    2013-01-01

    The effect of list length on children's false memories was investigated using list and story versions of the Deese/Roediger-McDermott procedure. Short (7 items) and long (14 items) sequences of semantic associates were presented to children aged 6, 8, and 10 years old either in lists or embedded within a story that emphasized the list theme.…

  13. Insulin Receptor Substrate 2 Is a Negative Regulator of Memory Formation

    Science.gov (United States)

    Irvine, Elaine E.; Drinkwater, Laura; Radwanska, Kasia; Al-Qassab, Hind; Smith, Mark A.; O'Brien, Melissa; Kielar, Catherine; Choudhury, Agharul I.; Krauss, Stefan; Cooper, Jonathan D.; Withers, Dominic J.; Giese, Karl Peter

    2011-01-01

    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…

  14. Hyperlink Format, Categorization Abilities and Memory Span as Contributors to Deaf Users Hypertext Access

    Science.gov (United States)

    Farjardo, Inmaculada; Arfe, Barbara; Benedetti, Patrizia; Altoe, Gianmarco

    2008-01-01

    Sixty deaf and hearing students were asked to search for goods in a Hypertext Supermarket with either graphical or textual links of high typicality, frequency, and familiarity. Additionally, they performed a picture and word categorization task and two working memory span tasks (spatial and verbal). Results showed that deaf students were faster in…

  15. Insulin Receptor Substrate 2 Is a Negative Regulator of Memory Formation

    Science.gov (United States)

    Irvine, Elaine E.; Drinkwater, Laura; Radwanska, Kasia; Al-Qassab, Hind; Smith, Mark A.; O'Brien, Melissa; Kielar, Catherine; Choudhury, Agharul I.; Krauss, Stefan; Cooper, Jonathan D.; Withers, Dominic J.; Giese, Karl Peter

    2011-01-01

    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…

  16. Effects of Electroacupuncture on Learning, Memory and Formation System of Free Radicals in Brain Tissues of Vascular Dementia Model Rats

    Institute of Scientific and Technical Information of China (English)

    王黎; 唐纯志; 赖新生

    2004-01-01

    In order to observe the regulative effect of electro-acupuncture on the formation system of free radicals in the brain tissues and learning and memory in vascular dementia (VD) model rats, the Morris's water labyrinth was used for testing the learning ability and memory in VD model rats made by 4-vessel occlusion method, and the activities or contents of nitric oxide (NO), NO synthase (NOS), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) were determined. Results showed that the mean escape latency in the electro-acupuncture group was markedly reduced in place test, and the times swam the place of the plate-form in the original plate-form quadrant were significantly more than those in the rest three quadrants in spatia1 probe test as compared with the model group. In the electro-acupuncture group and the nimodipine group the contents of NO and MDA and the activity of NOS were decreased, while the activities of SOD and GSH-Px were increased. It is indicated that electro-acupuncture can modulate the production and clearance of free radicals, and improve the ability of learning and memory of the VD model rats.

  17. Inhibition of mGluR1 and IP3Rs impairs long-term memory formation in young chicks.

    Science.gov (United States)

    Baker, K D; Edwards, T M; Rickard, N S

    2008-07-01

    Calcium (Ca(2+)) is involved in a myriad of cellular functions in the brain including synaptic plasticity. However, the role of intracellular Ca(2+) stores in memory processing remains poorly defined. The current study explored a role for glutamate-dependent intracellular Ca(2+) release in memory processing via blockade of metabotropic glutamate receptor subtype 1 (mGluR1) and inositol (1,4,5)-trisphosphate receptors (IP(3)Rs). Using a single-trial discrimination avoidance task developed for the young chick, administration of the specific and potent mGluR1 antagonist JNJ16259685 (500nM, immediately post-training, ic), or the IP(3)R antagonist Xestospongin C (5microM, immediately post-training, ic), impaired retention from 90min post-training. These findings are consistent with mGluR1 activating IP(3)Rs to release intracellular Ca(2+) required for long-term memory formation and have been interpreted within an LTP2 model. The consequences of different patterns of retention loss following ryanodine receptor (RyR) and IP(3)R inhibition are discussed.

  18. Experience-driven formation of parts-based representations in a model of layered visual memory

    Directory of Open Access Journals (Sweden)

    Jenia Jitsev

    2009-09-01

    Full Text Available Growing neuropsychological and neurophysiological evidence suggests that the visual cortex uses parts-based representations to encode, store and retrieve relevant objects. In such a scheme, objects are represented as a set of spatially distributed local features, or parts, arranged in stereotypical fashion. To encode the local appearance and to represent the relations between the constituent parts, there has to be an appropriate memory structure formed by previous experience with visual objects. Here, we propose a model how a hierarchical memory structure supporting efficient storage and rapid recall of parts-based representations can be established by an experience-driven process of self-organization. The process is based on the collaboration of slow bidirectional synaptic plasticity and homeostatic unit activity regulation, both running at the top of fast activity dynamics with winner-take-all character modulated by an oscillatory rhythm. These neural mechanisms lay down the basis for cooperation and competition between the distributed units and their synaptic connections. Choosing human face recognition as a test task, we show that, under the condition of open-ended, unsupervised incremental learning, the system is able to form memory traces for individual faces in a parts-based fashion. On a lower memory layer the synaptic structure is developed to represent local facial features and their interrelations, while the identities of different persons are captured explicitly on a higher layer. An additional property of the resulting representations is the sparseness of both the activity during the recall and the synaptic patterns comprising the memory traces.

  19. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke–Korsakoff syndrome

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-01-01

    Patients with severe Wernicke–Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation. PMID:27576603

  20. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-12-01

    Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

  1. Rapid oriented fibril formation of fish scale collagen facilitates early osteoblastic differentiation of human mesenchymal stem cells.

    Science.gov (United States)

    Matsumoto, Rena; Uemura, Toshimasa; Xu, Zhefeng; Yamaguchi, Isamu; Ikoma, Toshiyuki; Tanaka, Junzo

    2015-08-01

    We studied the effect of fibril formation of fish scale collagen on the osteoblastic differentiation of human mesenchymal stem cells (hMSCs). We found that hMSCs adhered easily to tilapia scale collagen, which remarkably accelerated the early stage of osteoblastic differentiation in hMSCs during in vitro cell culture. Osteoblastic markers such as ALP activity, osteopontin, and bone morphogenetic protein 2 were markedly upregulated when the hMSCs were cultured on a tilapia collagen surface, especially in the early osteoblastic differentiation stage. We hypothesized that this phenomenon occurs due to specific fibril formation of tilapia collagen. Thus, we examined the time course of collagen fibril formation using high-speed atomic force microscopy. Moreover, to elucidate the effect of the orientation of fibril formation on the differentiation of hMSCs, we measured ALP activity of hMSCs cultured on two types of tilapia scale collagen membranes with different degrees of fibril formation. The ALP activity in hMSCs cultured on a fibrous collagen membrane was significantly higher than on a non-fibrous collagen membrane even before adding osteoblastic differentiation medium. These results showed that the degree of the fibril formation of tilapia collagen was essential for the osteoblastic differentiation of hMSCs.

  2. Formation Mechanism of Curved Martensite Structures in Cu-based Shape Memory Alloys

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The curved martensite structures have been observed in CuZnAl-based shape memory alloys by both transmission electron microscope and optical microscope. It was found that the curved martensite structures observed in as-solution treated, as-aged and as-trained alloys usually occurred around dislocation tangles or precipitate, at the plate boundary or grain boundary, and when the growing plates collided with each other or alternate mutually.

  3. Comment on "Tequila, a neurotrypsin ortholog, regulates long-term memory formation in Drosophila".

    Science.gov (United States)

    Sonderegger, Peter; Patthy, Laszlo

    2007-06-22

    Didelot et al. (Reports, 11 August 2006, p. 851) claimed that Drosophila Tequila (Teq) and human neurotrypsin are orthologs and concluded that deficient long-term memory after Teq inactivation indicates that neurotrypsin plays its essential role for human cognitive functions through a similar mechanism. Our analyses suggest that Teq and neurotrypsin are not orthologous, leading us to question their equivalent roles in higher brain function.

  4. Mind Bomb-2 Regulates Hippocampus-dependent Memory Formation and Synaptic Plasticity.

    Science.gov (United States)

    Kim, Somi; Kim, TaeHyun; Lee, Hye-Ryeon; Kong, Young-Yun; Kaang, Bong-Kiun

    2015-11-01

    Notch signaling is a key regulator of neuronal fate during embryonic development, but its function in the adult brain is still largely unknown. Mind bomb-2 (Mib2) is an essential positive regulator of the Notch pathway, which acts in the Notch signal-sending cells. Therefore, genetic deletion of Mib2 in the mouse brain might help understand Notch signaling-mediated cell-cell interactions between neurons and their physiological function. Here we show that deletion of Mib2 in the mouse brain results in impaired hippocampal spatial memory and contextual fear memory. Accordingly, we found impaired hippocampal synaptic plasticity in Mib2 knock-out (KO) mice; however, basal synaptic transmission did not change at the Schaffer collateral-CA1 synapses. Using western blot analysis, we found that the level of cleaved Notch1 was lower in Mib2 KO mice than in wild type (WT) littermates after mild foot shock. Taken together, these data suggest that Mib2 plays a critical role in synaptic plasticity and spatial memory through the Notch signaling pathway.

  5. Gene control of synaptic plasticity and memory formation: implications for diseases and therapeutic strategies.

    Science.gov (United States)

    Vaillend, C; Rampon, C; Davis, S; Laroche, S

    2002-11-01

    There has been nearly a century of interest in the idea that information is stored in the brain as changes in the efficacy of synaptic connections between neurons that are activated during learning. The discovery and detailed report of the phenomenon generally known as long-term potentiation opened a new chapter in the study of synaptic plasticity in the vertebrate brain, and this form of synaptic plasticity has now become the dominant model in the search for the cellular and molecular bases of learning and memory. Accumulating evidence suggests that the rapid activation of the genetic machinery is a key mechanism underlying the enduring modification of neural networks required for the laying down of memory. Here we briefly review these mechanisms and illustrate with a few examples of animal models of neurological disorders how new knowledge about these mechanisms can provide valuable insights into identifying the mechanisms that go awry when memory is deficient, and how, in turn, characterisation of the dysfunctional mechanisms offers prospects to design and evaluate molecular and biobehavioural strategies for therapeutic prevention and rescue.

  6. Impaired spatial and contextual memory formation in galectin-1 deficient mice

    Directory of Open Access Journals (Sweden)

    Sakaguchi Masanori

    2011-09-01

    Full Text Available Abstract Galectins are a 15 member family of carbohydrate-binding proteins that have been implicated in cancer, immunity, inflammation and development. While galectins are expressed in the central nervous system, little is known about their function in the adult brain. Previously we have shown that galectin-1 (gal-1 is expressed in the adult hippocampus, and, in particular, in putative neural stem cells in the subgranular zone. To evaluate how gal-1 might contribute to hippocampal memory function here we studied galectin-1 null mutant (gal-1-/- mice. Compared to their wildtype littermate controls, gal-1-/- mice exhibited impaired spatial learning in the water maze and contextual fear learning. Interestingly, tone fear conditioning was normal in gal-1-/- mice suggesting that loss of gal-1 might especially impact hippocampal learning and memory. Furthermore, gal-1-/- mice exhibited normal motor function, emotion and sensory processing in a battery of other behavioral tests, suggesting that non-mnemonic performance deficits are unlikely to account for the spatial and contextual learning deficits. Together, these data reveal a role for galectin-carbohydrate signalling in hippocampal memory function.

  7. Trial-by-Trial Modulation of Associative Memory Formation by Reward Prediction Error and Reward Anticipation as Revealed by a Biologically Plausible Computational Model

    Science.gov (United States)

    Aberg, Kristoffer C.; Müller, Julia; Schwartz, Sophie

    2017-01-01

    Anticipation and delivery of rewards improves memory formation, but little effort has been made to disentangle their respective contributions to memory enhancement. Moreover, it has been suggested that the effects of reward on memory are mediated by dopaminergic influences on hippocampal plasticity. Yet, evidence linking memory improvements to actual reward computations reflected in the activity of the dopaminergic system, i.e., prediction errors and expected values, is scarce and inconclusive. For example, different previous studies reported that the magnitude of prediction errors during a reinforcement learning task was a positive, negative, or non-significant predictor of successfully encoding simultaneously presented images. Individual sensitivities to reward and punishment have been found to influence the activation of the dopaminergic reward system and could therefore help explain these seemingly discrepant results. Here, we used a novel associative memory task combined with computational modeling and showed independent effects of reward-delivery and reward-anticipation on memory. Strikingly, the computational approach revealed positive influences from both reward delivery, as mediated by prediction error magnitude, and reward anticipation, as mediated by magnitude of expected value, even in the absence of behavioral effects when analyzed using standard methods, i.e., by collapsing memory performance across trials within conditions. We additionally measured trait estimates of reward and punishment sensitivity and found that individuals with increased reward (vs. punishment) sensitivity had better memory for associations encoded during positive (vs. negative) prediction errors when tested after 20 min, but a negative trend when tested after 24 h. In conclusion, modeling trial-by-trial fluctuations in the magnitude of reward, as we did here for prediction errors and expected value computations, provides a comprehensive and biologically plausible description of

  8. Trial-by-Trial Modulation of Associative Memory Formation by Reward Prediction Error and Reward Anticipation as Revealed by a Biologically Plausible Computational Model.

    Science.gov (United States)

    Aberg, Kristoffer C; Müller, Julia; Schwartz, Sophie

    2017-01-01

    Anticipation and delivery of rewards improves memory formation, but little effort has been made to disentangle their respective contributions to memory enhancement. Moreover, it has been suggested that the effects of reward on memory are mediated by dopaminergic influences on hippocampal plasticity. Yet, evidence linking memory improvements to actual reward computations reflected in the activity of the dopaminergic system, i.e., prediction errors and expected values, is scarce and inconclusive. For example, different previous studies reported that the magnitude of prediction errors during a reinforcement learning task was a positive, negative, or non-significant predictor of successfully encoding simultaneously presented images. Individual sensitivities to reward and punishment have been found to influence the activation of the dopaminergic reward system and could therefore help explain these seemingly discrepant results. Here, we used a novel associative memory task combined with computational modeling and showed independent effects of reward-delivery and reward-anticipation on memory. Strikingly, the computational approach revealed positive influences from both reward delivery, as mediated by prediction error magnitude, and reward anticipation, as mediated by magnitude of expected value, even in the absence of behavioral effects when analyzed using standard methods, i.e., by collapsing memory performance across trials within conditions. We additionally measured trait estimates of reward and punishment sensitivity and found that individuals with increased reward (vs. punishment) sensitivity had better memory for associations encoded during positive (vs. negative) prediction errors when tested after 20 min, but a negative trend when tested after 24 h. In conclusion, modeling trial-by-trial fluctuations in the magnitude of reward, as we did here for prediction errors and expected value computations, provides a comprehensive and biologically plausible description of

  9. Serotonin mediation of early memory formation via 5HT2B receptor-induced glycogenolysis in the day-old chick

    Directory of Open Access Journals (Sweden)

    Marie Elizabeth Gibbs

    2014-04-01

    Full Text Available Investigation of the effects of serotonin on memory formation in the chick revealed an action on at least two 5HT receptors. Serotonin injected intracerebrally produced a biphasic effect on memory consolidation with enhancement at low doses and inhibition at higher doses. The non-selective 5HT receptor antagonist methiothepin and the selective 5HT2B/C receptor antagonist SB221284 both inhibited memory, suggesting actions of serotonin on at least 2 different receptor subtypes. The 5HT2B/C and astrocyte-specific 5-HT receptor agonists, fluoxetine and paroxetine, enhanced memory and the effect was attributed to glycogenolysis. Inhibition of glycogenolysis with a low dose of DAB prevented both serotonin and fluoxetine from enhancing memory during short-term memory but not during intermediate memory. The role of serotonin on the 5HT2B/C receptor appears to involve glycogen breakdown in astrocytes during short-term memory, whereas other published evidence attributes the second period of glycogenolysis to noradrenaline.

  10. Serotonin mediation of early memory formation via 5-HT2B receptor-induced glycogenolysis in the day-old chick.

    Science.gov (United States)

    Gibbs, Marie E; Hertz, Leif

    2014-01-01

    Investigation of the effects of serotonin on memory formation in the chick revealed an action on at least two 5-HT receptors. Serotonin injected intracerebrally produced a biphasic effect on memory consolidation with enhancement at low doses and inhibition at higher doses. The non-selective 5-HT receptor antagonist methiothepin and the selective 5-HT2B/C receptor antagonist SB221284 both inhibited memory, suggesting actions of serotonin on at least two different receptor subtypes. The 5-HT2B/C and astrocyte-specific 5-HT receptor agonist, fluoxetine and paroxetine, enhanced memory and the effect was attributed to glycogenolysis. Inhibition of glycogenolysis with a low dose of DAB (1,4-dideoxy-1,4-imino-D-arabinitol) prevented both serotonin and fluoxetine from enhancing memory during short-term memory but not during intermediate memory. The role of serotonin on the 5-HT2B/C receptor appears to involve glycogen breakdown in astrocytes during short-term memory, whereas other published evidence attributes the second period of glycogenolysis to noradrenaline.

  11. Formation of Combined Surface Features of Protrusion Array and Wrinkles atop Shape-Memory Polymer

    Science.gov (United States)

    Sun, L.; Zhao, Y.; Huang, W. M.; Tong, T. H.

    We demonstrate a simple and cost-effective approach to realize two combined surface features of different scales together, namely submillimeter-sized protrusion array and microwrinkles, atop a polystyrene shape-memory polymer. Two different types of protrusions, namely flat-top protrusion and crown-shaped protrusion, were studied. The array of protrusions was produced by the Indentation-Polishing-Heating (IPH) process. Compactly packed steel balls were used for making array of indents. A thin gold layer was sputter deposited atop the polymer surface right after polishing. After heating for shape recovery, array of protrusions with wrinkles on the top due to the buckling of gold layer was produced.

  12. Regulation of germinal center responses, memory B cells and plasma cell formation-an update.

    Science.gov (United States)

    Corcoran, Lynn M; Tarlinton, David M

    2016-04-01

    Progress in understanding humoral immunity has been accelerated by the powerful experimental approaches of genetics, genomics and imaging. Excellent reviews of these advances appeared in 2015 in celebration of the 50th anniversary of the discovery of B cell and T cell lineages in the chicken. Here we provide a contemporary model of B cell differentiation, highlighting recent publications illuminating germinal center (GC), memory B cell and antibody-secreting plasma cell biology. The important contributions of CD4T cells to antibody responses have been thoroughly reviewed elsewhere.

  13. T-type Ca(2+) channels facilitate NO-formation, vasodilatation and NO-mediated modulation of blood pressure

    DEFF Research Database (Denmark)

    Svenningsen, Per; Andersen, Kenneth; Thuesen, Anne D

    2014-01-01

    Voltage-gated calcium channels are involved in the vascular excitation-contraction mechanism and regulation of arterial blood pressure. It was hypothesized that T-type channels promote formation of nitric oxide from the endothelium. The present experiments determine the involvement of T-type chan......Voltage-gated calcium channels are involved in the vascular excitation-contraction mechanism and regulation of arterial blood pressure. It was hypothesized that T-type channels promote formation of nitric oxide from the endothelium. The present experiments determine the involvement of T......-type channels in depolarization-dependent dilatation of mesenteric arteries and blood pressure regulation in Cav3.1 knock-out mice. Nitric oxide-dependent vasodilatation following depolarization-mediated vasoconstriction was reduced significantly in mesenteric arteries from Cav3.1(-/-) compared to wild type...

  14. Long-term avoidance memory formation is associated with a transient increase in mushroom body synaptic complexes in leaf-cutting ants

    Directory of Open Access Journals (Sweden)

    Agustina eFalibene

    2015-04-01

    Full Text Available Long-term behavioral changes related to learning and experience have been shown to be associated with structural remodeling in the brain. Leaf-cutting ants learn to avoid previously preferred plants after they have proved harmful for their symbiotic fungus, a process that involves long-term olfactory memory. We studied the dynamics of brain microarchitectural changes after long-term olfactory memory formation following avoidance learning in Acromyrmex ambiguus. After performing experiments to control for possible neuronal changes related to age and body size, we quantified synaptic complexes (microglomeruli, MG in olfactory regions of the mushroom bodies (MB at different times after learning. Long-term avoidance memory formation was associated with a transient change in MG densities. Two days after learning, MG density was higher than before learning. At days 4 and 15 after learning — when ants still showed plant avoidance — MG densities had decreased to the initial state. The structural reorganization of MG triggered by long-term avoidance memory formation clearly differed from changes promoted by pure exposure to and collection of novel plants with distinct odors. Sensory exposure by the simultaneous collection of several, instead of one, non-harmful plant species resulted in a decrease in MG densities in the olfactory lip. We hypothesize that while sensory exposure leads to MG pruning in the MB olfactory lip, the formation of long-term avoidance memory involves an initial growth of new MG followed by subsequent pruning.

  15. Negative Ion Photoelectron Spectroscopy Reveals Thermodynamic Advantage of Organic Acids in Facilitating Formation of Bisulfate Ion Clusters: Atmospheric Implications

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Gao-Lei; Lin, Wei; Deng, Shihu; Zhang, Jian; Zheng, Weijun; Paesani, Francesco; Wang, Xue B.

    2013-03-07

    Recent lab and field measurements have indicated critical roles of organic acids in enhancing new atmospheric aerosol formation. Such findings have stimulated theoretical studies with the aim of understanding interaction of organic acids with common aerosol nucleation precursors like bisulfate (HSO4-). In this Letter, we report a combined negative ion photoelectron spectroscopic and theoretical investigation of molecular clusters formed by HSO4- with succinic acid (SUA, HO2C(CH2)2CO2H), HSO4-(SUA)n (n = 0-2), along with HSO4-(H2O)n and HSO4-(H2SO4)n. It is found that one SUA molecule can stabilize HSO4- by ca. 39 kcal/mol, triple the corresponding value that one water molecule is capable of (ca. 13 kcal/mol). Molecular dynamics simulations and quantum chemical calculations reveal the most plausible structures of these clusters and attribute the stability of these clusters due to formation of strong hydrogen bonds. This work provides direct experimental evidence showing significant thermodynamic advantage by involving organic acid molecules to promote formation and growth in bisulfate clusters and aerosols.

  16. Negative polarity illusions and the format of hierarchical encodings in memory.

    Science.gov (United States)

    Parker, Dan; Phillips, Colin

    2016-12-01

    Linguistic illusions have provided valuable insights into how we mentally navigate complex representations in memory during language comprehension. Two notable cases involve illusory licensing of agreement and negative polarity items (NPIs), where comprehenders fleetingly accept sentences with unlicensed agreement or an unlicensed NPI, but judge those same sentences as unacceptable after more reflection. Existing accounts have argued that illusions are a consequence of faulty memory access processes, and make the additional assumption that the encoding of the sentence remains fixed over time. This paper challenges the predictions made by these accounts, which assume that illusions should generalize to a broader set of structural environments and a wider range of syntactic and semantic phenomena. We show across seven reading-time and acceptability judgment experiments that NPI illusions can be reliably switched "on" and "off", depending on the amount of time from when the potential licensor is processed until the NPI is encountered. But we also find that the same profile does not extend to agreement illusions. This contrast suggests that the mechanisms responsible for switching the NPI illusion on and off are not shared across all illusions. We argue that the contrast reflects changes over time in the encoding of the semantic/pragmatic representations that can license NPIs. Just as optical illusions have been informative about the visual system, selective linguistic illusions are informative not only about the nature of the access mechanisms, but also about the nature of the encoding mechanisms.

  17. Novel shifts in memory research and their impact on the legal process: introduction to the special issue on memory formation and suggestibility in the legal process.

    Science.gov (United States)

    Otgaar, Henry; Sauerland, Melanie; Petrila, John P

    2013-01-01

    The functioning and frailties of memory are frequently at the centerpiece of much expert testimony about the reliability of eyewitness accounts. Although we have much knowledge about how false memories and suggestibility can affect testimonies, the contributions in this special issue show that when using a sound theoretical framework, novel directions in this field can surface. The papers in this issue can broadly be divided into contributions that are related to: (1) the exact determinants of false memory and suggestibility; (2) new paradigms in legal psychology; (3) positive consequences of memory illusions; and (4) developmental false memory research. Collectively, these contributions have the potential to provide novel shifts in memory research and push this field beyond its current boundaries.

  18. Inferential Costs of Trait Centrality in Impression Formation: Organization in Memory and Misremembering

    OpenAIRE

    Nunes, Ludmila D.; Leonel Garcia-Marques; Ferreira, Mário B.; Tânia Ramos

    2017-01-01

    An extension of the DRM paradigm was used to study the impact of central traits (Asch, 1946) in impression formation. Traits corresponding to the four clusters of the implicit theory of personality—intellectual, positive and negative; and social, positive and negative (Rosenberg et al., 1968)—were used to develop lists containing several traits of one cluster and one central trait prototypical of the opposite cluster. Participants engaging in impression formation relative to participants enga...

  19. Morphological facilitation for regular and irregular verb formations in native and non-native speakers: Little evidence for two distinct mechanisms*

    Science.gov (United States)

    FELDMAN, LAURIE BETH; KOSTIĆ, ALEKSANDAR; BASNIGHT-BROWN, DANA M.; ĐURĐEVIĆ, DUŠICA FILIPOVIĆ; PASTIZZO, MATTHEW JOHN

    2010-01-01

    The authors compared performance on two variants of the primed lexical decision task to investigate morphological processing in native and non-native speakers of English. They examined patterns of facilitation on present tense targets. Primes were regular (billed–bill) past tense formations and two types of irregular past tense forms that varied on preservation of target length (fell–fall; taught–teach). When a forward mask preceded the prime (Exp. 1), language and prime type interacted. Native speakers showed reliable regular and irregular length preserved facilitation relative to orthographic controls. Non-native speakers’ latencies after morphological and orthographic primes did not differ reliably except for regulars. Under cross-modal conditions (Exp. 2), language and prime type interacted. Native but not non-native speakers showed inhibition following orthographically similar primes. Collectively, reliable facilitation for regulars and patterns across verb type and task provided little support for a processing dichotomy (decomposition, non-combinatorial association) based on inflectional regularity in either native or non-native speakers of English. PMID:20526436

  20. Nitric oxide formation does not underlie the memory deficits produced by ibotenate injections into the nucleus basalis of rats.

    Science.gov (United States)

    Harrington, C A; Mobley, S L; Wenk, G L

    1994-04-01

    Basal forebrain (BF) injections of ibotenic (IBO) acid impair memory, whereas quisqualic (QUIS) acid injections do not. The authors investigated whether the cytotoxicity and differential behavioral effects of IBO and QUIS in rats depend on the generation of nitric oxide (NO). Injections of IBO or sodium nitroprusside (NP), but not QUIS, significantly increased BF NO formation, as determined by guanosine 3,5-cyclic monophosphate levels. IBO, alone or coinjected with methylene blue (MB), and QUIS, alone or coinjected with NP, decreased cortical choline acetyltransferase (ChAT) activity and the number of ChAT-positive BF neurons. The BF levels of galanin or neuropeptide Y were unchanged in all lesion groups. QUIS, but not IBO, dose-dependently destroyed NO-producing BF cells. Injections of IBO, with or without MB, impaired choice accuracy in a T-maze alternation task. The results suggest that the generation of NO in the BF does not underlie the spatial working memory deficit produced by IBO.

  1. High polishing selectivity ceria slurry for formation of top electrode in spin-transfer torque magnetic random access memory

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Hao [Advanced Semiconductor Materials and Devices Development Center, Hanyang University, Seoul 133-791 (Korea, Republic of); Department of Electronics and Communication Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Lim, Jae-Hyung [Advanced Semiconductor Materials and Devices Development Center, Hanyang University, Seoul 133-791 (Korea, Republic of); Department of Nanoscale Semiconductor Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Park, Jin-Hyung [Advanced Semiconductor Materials and Devices Development Center, Hanyang University, Seoul 133-791 (Korea, Republic of); Park, Jea-Gun, E-mail: parkjgL@hanyang.ac.kr [Advanced Semiconductor Materials and Devices Development Center, Hanyang University, Seoul 133-791 (Korea, Republic of); Department of Electronics and Communication Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of)

    2012-11-01

    During the formation of the top electrode (T.E.) in spin-transfer torque magnetic random access memory, a slurry with a high polishing rate of SiO{sub 2} and a low polishing rate of metal (T.E. material) is required in the chemical mechanical planarization application area. We used a ceria-based slurry with a polymeric additive to maintain the high polishing rate of SiO{sub 2} while it suppresses the polishing rate of the T.E. material, tantalum and ruthenium. We found ruthenium showed a significantly higher selectivity than tantalum in the ceria-based slurry. X-ray photoelectron spectroscopy was used to investigate the adsorption characteristics of the polymeric additive on the T.E. material. Except for the adsorbed polymeric additive, we found that zeta potential of the T.E. material played a critical role in determining the polishing selectivity of SiO{sub 2}-to-T.E. material. - Highlights: Black-Right-Pointing-Pointer High selective chemical mechanical planarization (CMP) slurry was investigated. Black-Right-Pointing-Pointer The slurry has a high selectivity of SiO{sub 2}-to-metals like tantalum and ruthenium. Black-Right-Pointing-Pointer Spin-transfer-torque magnetic memory requires such high selectivity slurry. Black-Right-Pointing-Pointer Surface zeta potential was used to explain CMP mechanism. Black-Right-Pointing-Pointer tantalum and ruthenium have different rate-determining steps during CMP.

  2. Formation Process of Triangular Morphology of Self-Accommodation Martensite in Ti-Nb-Al Shape Memory Alloy

    Directory of Open Access Journals (Sweden)

    Kamioka Nozomi

    2015-01-01

    Full Text Available The formation process of a habit plane variant (HPV cluster with triangular morphology (T-cluster in Ti- Nb-Al shape memory alloy was investigated by in-situ optical microscopy. Upon cooling the specimen, martensitic transformation occurred and two types of V-shaped clusters and the T-clusters were observed. Two types of V-shaped cluster were the cluster connected by the {111} type I twin (VI and the cluster connected by the type II twin (VII. The T-cluster is formed by the connection of three HPVs by {111} type I twin. The T-cluster is formed by the growth of the third HPV that is nucleated at the tip of a HPV in a VI-cluster and exhibits inward growth. It is suggested that the T-cluster is a derivative of the VI-cluster. This growth behaviour is discussed based on the incompatibility of the clusters.

  3. Sucrose-induced analgesia during early life modulates adulthood learning and memory formation.

    Science.gov (United States)

    Nuseir, Khawla Q; Alzoubi, Karem H; Alabwaini, Jehad; Khabour, Omar F; Kassab, Manal I

    2015-06-01

    This study is aimed at examining the long-term effects of chronic pain during early life (postnatal day 0 to 8weeks), and intervention using sucrose, on cognitive functions during adulthood in rats. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution or paracetamol was administered for analgesia before the paw prick. Control groups include tactile stimulation to account for handling and touching the paws, and sucrose alone was used. All treatments were started on day one of birth and continued for 8weeks. At the end of the treatments, behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM), as well as pain threshold via foot-withdrawal response to a hot plate apparatus. Additionally, the hippocampus was dissected, and blood was collected. Levels of neurotrophins (BDNF, IGF-1 and NT-3) and endorphins were assessed using ELISA. The results show that chronic noxious stimulation resulted in comparable foot-withdrawal latency between noxious and tactile groups. On the other hand, pretreatment with sucrose or paracetamol increased pain threshold significantly both in naive rats and noxiously stimulated rats (Psucrose treatment prevented such impairment (PSucrose significantly increased serum levels of endorphin and enkephalin. Chronic pain decreased levels of BDNF in the hippocampus and this decrease was prevented by sucrose and paracetamol treatments. Hippocampal levels of NT-3 and IGF-1 were not affected by any treatment. In conclusion, chronic pain induction during early life induced short memory impairment, and pretreatment with sucrose prevented this impairment via mechanisms that seem to involve BDNF. As evident in the results, sucrose, whether alone or in the presence of pre-noxious stimulation, increases pain threshold in such circumstances; most likely via a mechanism that involves an increase in endogenous opioids.

  4. FGFR3 promotes angiogenesis-dependent metastasis of hepatocellular carcinoma via facilitating MCP-1-mediated vascular formation.

    Science.gov (United States)

    Liu, Xinyu; Jing, Xiaoqian; Cheng, Xi; Ma, Ding; Jin, Zhijian; Yang, Weiping; Qiu, Weihua

    2016-05-01

    The biological role of fibroblast growth factor receptor 3 (FGFR3) in tumor angiogenesis of hepatocellular carcinoma (HCC) has not been discussed before. Our previous work had indicated FGFR3 was overexpressed in HCC, and silencing FGFR3 in Hu7 cells could regulate tumorigenesis via down-regulating the phosphorylation level of key members of classic signaling pathways including ERK and AKT. In the present work, we explored the role of FGFR3 in angiogenesis-dependent metastasis by using SMMC-7721 and QGY-7703 stable cell lines. Our results indicated FGFR3 could regulate in vitro cell migration ability and in vivo lung metastasis ability of HCC, which was in accordance with increased angiogenesis ability in vitro and in vivo. Using the supernatant from SMMC-7721/FGFR3 cells, we conducted a human angiogenesis protein microarray including 43 angiogenesis factors and found that FGFR3 modulated angiogenesis and metastasis of HCC mainly by promoting the protein level of monocyte chemotactic protein 1 (MCP-1). Silencing FGFR3 by short hairpin RNA (shRNA) could reduce MCP-1 level in lysates and supernatant of QGY-7703 cells and SMMC-7721 cells. Silencing MCP-1 in QGY-7703 or SMMC-7721 cells could induce similar phenotypes compared with silencing FGFR3. Our results suggested FGFR3 promoted metastasis potential of HCC, at least partially if not all, via facilitating MCP-1-mediated angiogenesis, in addition to previously found cell growth and metastasis. MCP-1, a key medium between HCC cells and HUVECs, might be a novel anti-vascular target in HCC.

  5. Memory clinics

    OpenAIRE

    Jolley, D; Benbow, S M; Grizzell, M

    2006-01-01

    Memory clinics were first described in the 1980s. They have become accepted worldwide as useful vehicles for improving practice in the identification, investigation, and treatment of memory disorders, including dementia. They are provided in various settings, the setting determining clientele and practice. All aim to facilitate referral from GPs, other specialists, or by self referral, in the early stages of impairment, and to avoid the stigma associated with psychiatric services. They bring ...

  6. Dopamine facilitates dendritic spine formation by cultured striatal medium spiny neurons through both D1 and D2 dopamine receptors.

    Science.gov (United States)

    Fasano, Caroline; Bourque, Marie-Josée; Lapointe, Gabriel; Leo, Damiana; Thibault, Dominic; Haber, Michael; Kortleven, Christian; Desgroseillers, Luc; Murai, Keith K; Trudeau, Louis-Éric

    2013-04-01

    Variations of dopamine (DA) levels induced by drugs of abuse or in the context of Parkinson's disease modulate the number of dendritic spines in medium spiny neurons (MSNs) of the striatum, showing that DA plays a major role in the structural plasticity of MSNs. However, little is presently known regarding early spine development in MSNs occurring before the arrival of cortical inputs and in particular about the role of DA and D1 (D1R) and D2 (D2R) DA receptors. A cell culture model reconstituting early cellular interactions between MSNs, intrinsic cholinergic interneurons and DA neurons was used to study the role of DA in spine formation. After 5 or 10 days in vitro, the presence of DA neurons increased the number of immature spine-like protrusions. In MSN monocultures, chronic activation of D1R or D2R also increased the number of spines and spinophilin expression in MSNs, suggesting a direct role for these receptors. In DA-MSN cocultures, chronic blockade of D1R or D2R reduced the number of dendritic spines. Interestingly, the combined activation or blockade of both D1R and D2R failed to elicit more extensive spine formation, suggesting that both receptors act through a mechanism that is not additive. Finally, we found increased ionotropic glutamate receptor responsiveness and miniature excitatory postsynaptic current (EPSC) frequency in DA-MSN co-cultures, in parallel with a higher number of spines containing PSD-95, suggesting that the newly formed spines present functional post-synaptic machinery preparing the MSNs to receive additional glutamatergic contacts. These results represent a first step in the understanding of how dopamine neurons promote the structural plasticity of MSNs during the development of basal ganglia circuits.

  7. Post-training Activation of Rac1 in the Basolateral Amygdala Is Required for the Formation of both Short-term and Long-term Auditory Fear Memory

    Directory of Open Access Journals (Sweden)

    Qinqin eGao

    2015-11-01

    Full Text Available Rac1, a member of the Rho family of small GTPases, is crucial for morphological changes of the mature neuronal synapse including spine formation and activity-dependent spine enlargement, while its role in the formation of associated memories, such as conditioned fear memory, is not clear. Here we report that selective deletion of Rac1 in excitatory neurons, but not in parvalbumin inhibitory neurons, impaired short- and long-term memories (STM and LTM of fear conditioning. Conditional knockout of Rac1 before associative fear training in the basolateral amygdala (BLA, a key area for fear memory acquisition and storage, impaired fear memory. The expression of dominant-negative mutant of Rac1, or infusion of Rac1 inhibitor NSC23766 into BLA blocked both STM and LTM of fear conditioning. Furthermore, selective inhibition of Rac1 activation in BLA immediately following fear conditioning impaired STM, demonstrating that fear conditioning-induced Rac1 activation in BLA plays a critical role in the formation of both STM and LTM of conditioned fear.

  8. Loss of Ca2+/calmodulin kinase kinase beta affects the formation of some, but not all, types of hippocampus-dependent long-term memory.

    Science.gov (United States)

    Peters, Marco; Mizuno, Keiko; Ris, Laurence; Angelo, Marco; Godaux, Emile; Giese, K Peter

    2003-10-29

    Long-term memory (LTM) requires activation of the transcription factor cAMP-responsive element binding protein (CREB). Signaling by the Ca2+/calmodulin (CaM) kinase cascade has been implicated in CREB activation and memory consolidation processes in the hippocampus. The CaM kinase kinase beta isoforms belong to the CaM kinase cascade, and we have generated null mutant mice to investigate the role of these kinases in several forms of learning and memory. The null mutants were impaired in spatial training-induced CREB activation and spatial memory formation. Furthermore, the mutants lacked late, but not early, long-term potentiation at the hippocampal CA1 synapse, and they were impaired in LTM, but not short-term memory, for the social transmission of food preferences. We suggest that the CaM kinase kinasebeta isoforms are required for the formation of hippocampal LTM. Surprisingly, however, these kinases were not needed for contextual, trace fear, and passive avoidance LTM. Our results demonstrate that different signaling processes underlie the formation of these types of hippocampal LTM.

  9. Post-Session Administration of USP Methylene Blue Facilitates the Retention of Pathological Fear Extinction and Contextual Memory in Phobic Adults

    Science.gov (United States)

    Telch, Michael J.; Bruchey, Aleksandra K.; Rosenfield, David; Cobb, Adam R.; Smits, Jasper; Pahl, Sandra; Gonzalez-Lima, F.

    2015-01-01

    Objective Preclinical studies have shown that low-dose USP methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. We report on the first controlled experiment to examine the memory-enhancing effects of post-training methylene blue administration on retention of fear extinction and contextual memory following fear extinction training. Method Adults (N = 42) displaying marked claustrophobic fear were randomized to double-blind administration of 260 mg of methylene blue versus placebo immediately following six five-minute extinction trials to an enclosed chamber. Retesting occurred one month later to assess fear renewal as indexed by peak fear during exposure to a non-trained enclosed chamber with the prediction that methylene blue's effects would vary as a function of fear reduction achieved during extinction training. Incidental contextual memory was assessed 1 and 30 days after training to assess the cognitive enhancing effects of methylene blue independent of its effects on fear attenuation. Results Consistent with predictions, participants displaying low end fear at post-training showed significantly less fear at follow-up if they received methylene blue post-training relative to placebo. In contrast, participants displaying moderate to high levels of post-training fear tended to fare worse at follow-up relative to placebo. Methylene blue's enhancement of contextual memory was unrelated to initial or post-training claustrophobic fear. Conclusions Methylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session, but may have a deleterious effect on extinction when administered after an unsuccessful exposure session. PMID:25018057

  10. Polyaspartic acid facilitates oxolation within iron(iii) oxide pre-nucleation clusters and drives the formation of organic-inorganic composites

    Science.gov (United States)

    Scheck, J.; Drechsler, M.; Ma, X.; Stöckl, M. T.; Konsek, J.; Schwaderer, J. B.; Stadler, S. M.; De Yoreo, J. J.; Gebauer, D.

    2016-12-01

    The interplay between polymers and inorganic minerals during the formation of solids is crucial for biomineralization and bio-inspired materials, and advanced material properties can be achieved with organic-inorganic composites. By studying the reaction mechanisms, basic questions on organic-inorganic interactions and their role during material formation can be answered, enabling more target-oriented strategies in future synthetic approaches. Here, we present a comprehensive study on the hydrolysis of iron(iii) in the presence of polyaspartic acid. For the basic investigation of the formation mechanism, a titration assay was used, complemented by microscopic techniques. The polymer is shown to promote precipitation in partly hydrolyzed reaction solutions at the very early stages of the reaction by facilitating iron(iii) hydrolysis. In unhydrolyzed solutions, no significant interactions between the polymer and the inorganic solutes can be observed. We demonstrate that the hydrolysis promotion by the polymer can be understood by facilitating oxolation in olation iron(iii) pre-nucleation clusters. We propose that the adsorption of olation pre-nucleation clusters on the polymer chains and the resulting loss in dynamics and increased proximity of the reactants is the key to this effect. The resulting composite material obtained from the hydrolysis in the presence of the polymer was investigated with additional analytical techniques, namely, scanning and transmission electron microscopies, light microscopy, atomic force microscopy, zeta potential measurements, dynamic light scattering, and thermogravimetric analyses. It consists of elastic, polydisperse nanospheres, ca. 50-200 nm in diameter, and aggregates thereof, exhibiting a high polymer and water content.

  11. Enhancing Curiosity Using Interactive Simulations Combined with Real-Time Formative Assessment Facilitated by Open-Format Questions on Tablet Computers

    CERN Document Server

    Kowalski, F V

    2013-01-01

    Students' curiosity often seems nearly nonexistent in a lecture setting; we discuss a variety of possible reasons for this, but it is the instructor who typically poses questions while only a few students, usually the better ones, respond. As we have developed and implemented the use of InkSurvey to collect real-time formative assessment, we have discovered that it can serve in an unanticipated role: to promote curiosity in engineering physics undergraduates. Curiosity often motivates creative, innovative people. To encourage such curiosity, we solicit questions submitted real-time via InkSurvey and pen-enabled mobile devices (Tablet PCs) in response to interactive simulations (applets) run either before or in class. This provides students with practice in asking questions, increases metacognition, and serves as a rich springboard from which to introduce content and/or address misconceptions. We describe the procedure for measuring curiosity and results from applying this method in a junior level electromagne...

  12. In Situ Grown TiO2 Nanospindles Facilitate the Formation of Holey Reduced Graphene Oxide by Photodegradation.

    Science.gov (United States)

    Peng, Guiming; Ellis, James E; Xu, Gang; Xu, Xueqing; Star, Alexander

    2016-03-23

    Titanium dioxide (TiO2) nanostructures and TiO2/graphene nanocomposites are intensively studied materials for energy conversion, energy storage, and organic contaminant photodegradation. However, for TiO2/graphene composites, impermeability across the graphitic basal plane for electrolytes, metal ions, and gas molecules hinders their practical applications. Herein we report a simple, environmentally friendly synthetic route for mesoporous anatase TiO2 nanospindles, and successfully apply this method to obtain in situ grown TiO2 nanospindles/graphene oxide composite. After a thermal reduction at 400 °C, holes are created in the reduced graphene oxide (RGO) sheets through a photocatalytic oxidation mechanism. The formation of holes in RGO is promoted by photogenerated hydroxyl radicals that oxidize and subsequently decarboxylate the graphitic surface of RGO. The proposed mechanism was supported by photocatalytic electrochemical properties of the nanomaterials. The resulting TiO2/holey RGO composites may overcome the original impermeability of graphene sheets and find applications in catalysis, energy conversion/storage devices, and sensors.

  13. Formation of Exotic Networks of Water Clusters in Helium Droplets Facilitated by the Presence of Neon Atoms

    Energy Technology Data Exchange (ETDEWEB)

    Douberly, Gary E.; Miller, Roger E.; Xantheas, Sotiris S.

    2017-03-08

    Water clusters are formed in helium droplets via the sequential capture of monomers. One or two neon atoms are added to each droplet prior to the addition of water. The infrared spectrum of the droplet ensemble reveals several signatures of polar, water tetramer clusters having dipole moments between 2D and 3D. Comparison with ab initio computations supports the assignment of the cluster networks to noncyclic “3+1” clusters, which are ~5.3 kcal/mol less stable than the global minimum nonpolar cyclic tetramer. The (H2O)3Ne + H2O ring insertion barrier is sufficiently large, such that evaporative helium cooling is capable of kinetically quenching the nonequilibrium tetramer system prior to its rearrangement to the lower energy cyclic species. To this end, the reported process results in the formation of exotic water cluster networks that are either higher in energy than the most stable gas-phase analogs or not even stable in the gas phase.

  14. Formation of Exotic Networks of Water Clusters in Helium Droplets Facilitated by the Presence of Neon Atoms.

    Science.gov (United States)

    Douberly, Gary E; Miller, Roger E; Xantheas, Sotiris S

    2017-03-22

    Water clusters are formed in helium droplets via the sequential capture of monomers. One or two neon atoms are added to each droplet prior to the addition of water. The infrared spectrum of the droplet ensemble reveals several signatures of polar, water tetramer clusters having dipole moments between 2D and 3D. Comparison with ab initio computations supports the assignment of the cluster networks to noncyclic "3 + 1" clusters, which are ∼5.3 kcal/mol less stable than the global minimum nonpolar cyclic tetramer. The (H2O)3Ne + H2O ring insertion barrier is sufficiently large, such that evaporative helium cooling is capable of kinetically quenching the nonequilibrium tetramer system prior to its rearrangement to the lower energy cyclic species. To this end, the reported process results in the formation of exotic water cluster networks that are either higher in energy than the most stable gas-phase analogs or not even stable in the gas phase.

  15. The effects of enhanced zinc on spatial memory and plaque formation in transgenic mice

    Science.gov (United States)

    Linkous, D.H.; Adlard, P.A.; Wanschura, P.B.; Conko, K.M.; Flinn, J.M.

    2009-01-01

    There is considerable evidence suggesting that metals play a central role in the pathogenesis of Alzheimer's disease. Reports suggest that elevated dietary metals may both precipitate and potentiate an Alzheimer's disease phenotype. Despite this, there remain few studies that have examined the behavioral consequences of elevated dietary metals in wild type and Alzheimer's disease animals. To further investigate this in the current study, two separate transgenic models of AD (Tg2576 and TgCRND8), together with wild type littermates were administered 10 ppm (0.153 mM) Zn. Tg2576 animals were maintained on a zinc-enriched diet both pre- and postnatally until 11 months of age, while TgCRND8 animals were treated for five months following weaning. Behavioral testing, consisting of "Atlantis" and "moving" platform versions of the Morris water maze, were conducted at the end of the study, and tissues were collected for immunohistochemical analysis of amyloid-β burden. Our data demonstrate that the provision of a zinc-enriched diet potentiated Alzheimer-like spatial memory impairments in the transgenic animals and was associated with reduced hippocampal amyloid-β plaque deposits. Zinc-related behavioral deficits were also demonstrated in wild type mice, which were sometimes as great as those present in the transgenic animals. However, zinc-related cognitive impairments in transgenic mice were greater than the summation of zinc effects in the wild type mice and the transgene effects.

  16. Does animal-mediated seed dispersal facilitate the formation of Pinus armandii-Quercus aliena var. acuteserrata forests?

    Directory of Open Access Journals (Sweden)

    Fei Yu

    Full Text Available The Pinus armandii and Quercus aliena var. acuteserrata mixed forest is one of the major forest types in the Qinling Mountains, China. P. armandii is considered to be a pioneer species during succession and it is usually invaded by late successional Q. aliena var. acuteserrata. However, the mechanism that underlies its invasion remains unclear. In the present study, we tracked seed dispersal of P. armandii and Q. aliena var. acuteserrata using coded plastic tags in the western, middle and eastern Qinling Mountains to elucidate the invasion process in the mixed forests. Our results indicated that the seeds of both P. armandii and Q. aliena var. acuteserrata were removed rapidly in the Qinling Mountains, and there were no differences in the seed removal rates between the two species. There were significant differences in rodent seed-eating and caching strategies between the two tree species. For P. armandii, seeds were more likely to be eaten in situ than those of Q. aliena var. acuteserrata in all plots. By contrast, the acorns of Q. aliena var. acuteserrata were less frequently eaten in situ, but more likely to be removed and cached. Q. aliena var. acuteserrata acorns had significantly longer dispersal distances than P. armandii seeds in all plots. Although P. armandii seeds were less likely to be dispersed into the Q. aliena var. acuteserrata stands, over 30% of the released acorns were transported into the P. armandii stands where they established five seedlings. Based on the coupled recruitment patterns of P. armandii and Q. aliena var. acuteserrata, we suggest that the animal-mediated seed dispersal contributes to the formation of Pinus armandii-Quercus aliena var. acuteserrata forests.

  17. Long-Term Memory for Place Learning Is Facilitated by Expression of cAMP Response Element-Binding Protein in the Dorsal Hippocampus

    Science.gov (United States)

    Brightwell, Jennifer J.; Smith, Clayton A.; Neve, Rachael L.; Colombo, Paul J.

    2007-01-01

    Extensive research has shown that the hippocampus is necessary for consolidation of long-term spatial memory in rodents. We reported previously that rats using a place strategy to solve a cross maze task showed sustained phosphorylation of hippocampus cyclic AMP response element-binding protein (CREB), a transcription factor implicated in…

  18. Long-Term Memory for Place Learning Is Facilitated by Expression of cAMP Response Element-Binding Protein in the Dorsal Hippocampus

    Science.gov (United States)

    Brightwell, Jennifer J.; Smith, Clayton A.; Neve, Rachael L.; Colombo, Paul J.

    2007-01-01

    Extensive research has shown that the hippocampus is necessary for consolidation of long-term spatial memory in rodents. We reported previously that rats using a place strategy to solve a cross maze task showed sustained phosphorylation of hippocampus cyclic AMP response element-binding protein (CREB), a transcription factor implicated in…

  19. Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers.

    Science.gov (United States)

    Sparkman, Nathan L; Buchanan, Jessica B; Heyen, Jonathan R R; Chen, Jing; Beverly, James L; Johnson, Rodney W

    2006-10-18

    Proinflammatory cytokines inhibit learning and memory but the significance of interleukin-6 (IL-6) in acute cognitive deficits induced by the peripheral innate immune system is not known. To examine the functional role of IL-6 in hippocampus-mediated cognitive impairments associated with peripheral infections, C57BL6/J (IL-6(+/+)) and IL-6 knock-out (IL-6(-/-)) mice were trained in a matching-to-place version of the water maze. After an acquisition phase, IL-6(+/+) mice injected intraperitoneally with lipopolysaccharide (LPS) exhibited deficits in working memory. However, IL-6(-/-) mice were refractory to the LPS-induced impairment in working memory. To determine the mechanism by which IL-6 deficiency conferred protection from disruption in working memory, plasma IL-1beta and tumor necrosis factor alpha (TNFalpha), c-Fos immunoreactivity in the nucleus of the solitary tract (NTS), and steady-state levels of IL-1beta and TNFalpha mRNA in neuronal layers of the hippocampus were determined in IL-6(+/+) and IL-6(-/-) mice after injection of LPS. Plasma IL-1beta and TNFalpha and c-Fos immunoreactivity in the NTS were increased similarly in IL-6(+/+) and IL-6(-/-) mice after LPS, indicating high circulating levels of IL-1beta and TNFalpha and activation of vagal afferent pathways were not sufficient to disrupt working memory in the absence of IL-6. However, the LPS-induced upregulation of IL-1beta and TNFalpha mRNA that was evident in hippocampal tissue of IL-6(+/+) mice was greatly attenuated or entirely absent in IL-6(-/-) mice. Collectively, these data suggest that humoral and neural immune-to-brain communication pathways are intact in IL-6-deficient mice but that, in the absence of IL-6, the central cytokine compartment is hyporesponsive.

  20. A homolog of the vertebrate pituitary adenylate cyclase-activating polypeptide is both necessary and instructive for the rapid formation of associative memory in an invertebrate.

    Science.gov (United States)

    Pirger, Zsolt; László, Zita; Kemenes, Ildikó; Tóth, Gábor; Reglodi, Dóra; Kemenes, György

    2010-10-13

    Similar to other invertebrate and vertebrate animals, cAMP-dependent signaling cascades are key components of long-term memory (LTM) formation in the snail Lymnaea stagnalis, an established experimental model for studying evolutionarily conserved molecular mechanisms of long-term associative memory. Although a great deal is already known about the signaling cascades activated by cAMP, the molecules involved in the learning-induced activation of adenylate cyclase (AC) in Lymnaea remained unknown. Using matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy in combination with biochemical and immunohistochemical methods, recently we have obtained evidence for the existence of a Lymnaea homolog of the vertebrate pituitary adenylate cyclase-activating polypeptide (PACAP) and for the AC-activating effect of PACAP in the Lymnaea nervous system. Here we first tested the hypothesis that PACAP plays an important role in the formation of robust LTM after single-trial classical food-reward conditioning. Application of the PACAP receptor antagonist PACAP6-38 around the time of single-trial training with amyl acetate and sucrose blocked associative LTM, suggesting that in this "strong" food-reward conditioning paradigm the activation of AC by PACAP was necessary for LTM to form. We found that in a "weak" multitrial food-reward conditioning paradigm, lip touch paired with sucrose, memory formation was also dependent on PACAP. Significantly, systemic application of PACAP at the beginning of multitrial tactile conditioning accelerated the formation of transcription-dependent memory. Our findings provide the first evidence to show that in the same nervous system PACAP is both necessary and instructive for fast and robust memory formation after reward classical conditioning.

  1. Influence of memory effect on the state-of-charge estimation of large-format Li-ion batteries based on LiFePO4 cathode

    Science.gov (United States)

    Shi, Wei; Wang, Jiulin; Zheng, Jianming; Jiang, Jiuchun; Viswanathan, Vilayanur; Zhang, Ji-Guang

    2016-04-01

    In this work, we systematically investigated the influence of the memory effect of LiFePO4 cathodes in large-format full batteries. The electrochemical performance of the electrodes used in these batteries was also investigated separately in half-cells to reveal their intrinsic properties. We noticed that the memory effect of LiFePO4/graphite cells depends not only on the maximum state of charge reached during the memory writing process, but is also affected by the depth of discharge reached during the memory writing process. In addition, the voltage deviation in a LiFePO4/graphite full battery is more complex than in a LiFePO4/Li half-cell, especially for a large-format battery, which exhibits a significant current variation in the region near its terminals. Therefore, the memory effect should be taken into account in advanced battery management systems to further extend the long-term cycling stabilities of Li-ion batteries using LiFePO4 cathodes.

  2. Ex vivo study of 5-HT(1A) and 5-HT(7) receptor agonists and antagonists on cAMP accumulation during memory formation and amnesia.

    Science.gov (United States)

    Perez-García, G; Meneses, A

    2008-12-16

    The cyclic adenosine monophosphate (cAMP) is a second messenger and a central component of intracellular signaling pathways that regulate a wide range of biological functions, including memory. Hence, in this work, firstly the time-course of memory formation was determined in an autoshaping learning task, which had allowed the identification of testing times for increases or decreases in performance. Next, untrained, trained and overtrained groups were compared in cAMP production. Moreover, selective stimulation and antagonism of 5-HT(1A) and 5-HT(7) receptors during memory formation and cAMP production were determined. Finally, since there is scarce information about how pharmacological models of amnesia affect cAMP production, the cholinergic or glutamatergic antagonists, scopolamine and dizocilpine, were tested. The major findings of this work showed that when the time-course was determined inasmuch as training and testing sessions occurred, memory performance was graduate and progressive. Notably, for the fourth to seventh (i.e., 48-120 h following autoshaping training session) testing session performance was significantly higher from the previous ones. When animals received 5-HT(1A) and 5-HT(7) receptor agonists and antagonists or amnesic drugs significant increases or decrements in memory performance were observed at 24 and 48 h. Moreover, when ex vivo cAMP production from trained and overtrained groups were compared to untrained ones, significant differences were observed among groups and brain areas. Trained animals treated with 8-OHDPAT, AS19, 8-OHDPAT plus AS19, WAY100635, SB-269970, scopolamine or dizocilpine were compared to similar untrained groups, and eightfold-reduced cAMP production was evident, showing the importance of cAMP production in the signaling case in mammalian memory formation.

  3. Phoenixin-14 enhances memory and mitigates memory impairment induced by Aβ1-42 and scopolamine in mice.

    Science.gov (United States)

    Jiang, J H; He, Z; Peng, Y L; Jin, W D; Wang, Z; Mu, L Y; Chang, M; Wang, R

    2015-12-10

    Phoenixin (PNX) is a recently discovered neuropeptide shown to be involved in regulating the reproductive system, anxiety-related behaviors and pain though its receptor is still unknown. PNX-14, one of the endogenous active isoforms, is reported to regulate gonadotropin releasing hormone (GnRH) receptor expression and GnRH secretion. Because GnRH system is thought to be involved in the regulation of learning and memory processes, we hypothesized that PNX-14 might be mediate learning and memory. Here, we investigated the effects of PNX-14 in memory processes, using novel object recognition (NOR) and object location recognition (OLR) tasks. Our results revealed that intracerebroventricular (i.c.v.) injection of PNX-14 (25nmol) immediately after training not only facilitated memory formation, but also prolonged memory retention in both tasks. The memory-enhancing effects of PNX-14 were also seen when it was infused into the hippocampus. Moreover, these memory-improving effects of PNX-14 could be blocked by a GnRH receptor antagonist (Cetrorelix). The memory-improving effects of PNX-14 were not related to any effects on locomotor activity. Additionally, the results suggested that i.c.v. injection of PNX-14 mitigate the memory impairment induced by the amyloid-β1-42 (Aβ1-42) peptide and scopolamine. The present results indicate that PNX-14 facilitates memory formation and prolongs memory retention through activation of the GnRH receptor, and mitigates the memory-impairing effects of Aβ1-42 and scopolamine, suggesting that PNX-14 may be effective as a drug for enhancing memory and treating Alzheimer׳s disease.

  4. The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Jenny Tosca Thom

    2015-11-01

    Full Text Available Tissue-resident memory T cells (TRM reside in barrier tissues and provide local immediate protective immunity. Here, we show that the salivary gland (SG most-effectively induces CD8+ and CD4+ TRM cells against murine cytomegalovirus (MCMV, which persists in and spreads from this organ. TRM generation depended on local antigen for CD4+, but not CD8+, TRM cells, highlighting major differences in T cell subset-specific demands for TRM development. CMV-specific CD8+ T cells fail to control virus replication upon primary infection in the SG due to CMV-induced MHC I downregulation in glandular epithelial cells. Using intraglandular infection, we challenge this notion and demonstrate that memory CD8+ T cells confer immediate protection against locally introduced MCMV despite active viral immune evasion, owing to early viral tropism to cells that largely withstand MHC I downregulation. Thus, we unravel a yet-unappreciated role for memory CD8+ T cells in protecting mucosal tissues against CMV infection.

  5. The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8(+) T Cells, Facilitating Protection from Local Cytomegalovirus Infection.

    Science.gov (United States)

    Thom, Jenny Tosca; Weber, Thomas Christian; Walton, Senta Maria; Torti, Nicole; Oxenius, Annette

    2015-11-10

    Tissue-resident memory T cells (TRM) reside in barrier tissues and provide local immediate protective immunity. Here, we show that the salivary gland (SG) most-effectively induces CD8(+) and CD4(+) TRM cells against murine cytomegalovirus (MCMV), which persists in and spreads from this organ. TRM generation depended on local antigen for CD4(+), but not CD8(+), TRM cells, highlighting major differences in T cell subset-specific demands for TRM development. CMV-specific CD8(+) T cells fail to control virus replication upon primary infection in the SG due to CMV-induced MHC I downregulation in glandular epithelial cells. Using intraglandular infection, we challenge this notion and demonstrate that memory CD8(+) T cells confer immediate protection against locally introduced MCMV despite active viral immune evasion, owing to early viral tropism to cells that largely withstand MHC I downregulation. Thus, we unravel a yet-unappreciated role for memory CD8(+) T cells in protecting mucosal tissues against CMV infection.

  6. Long-term potentiation and memory processes in the psychological works of Sigmund Freud and in the formation of neuropsychiatric symptoms.

    Science.gov (United States)

    Centonze, D; Siracusano, A; Calabresi, P; Bernardi, G

    2005-01-01

    Far from disproving the model of mind functioning proposed by psychoanalysis, the recent advances in neuropsychiatrical research confirmed the crucial ideas of Sigmund Freud. The hypothesis that the origin of mental illnesses lies in the impossibility for a subject to erase the long-term effects of a remote adverse event is in tune with the view that several psychiatric disturbances reflect the activation of aberrant unconscious memory processes. Freud's insights did not stop here, but went on to describe in an extremely precise manner the neural mechanisms of memory formation almost a century before the description of long-term synaptic potentiation.

  7. Dynamic changes in neurexins' alternative splicing: role of Rho-associated protein kinases and relevance to memory formation.

    Directory of Open Access Journals (Sweden)

    Gabriela Rozic

    Full Text Available The three neurexins genes (NRXN1/2/3 encode polymorphic synaptic membrane proteins that are involved in cognitive functioning. Neurexins' selectivity of function is presumably conferred through differential use of 2 promoters and 5 alternative splicing sites (SS#1/2/3/4/5. In day-old rat brain neurons grown in culture, activation (depolarization induces reversible, calcium dependent, repression of NRXN2α SS#3 insert. The effects of depolarization on NRXN1/2/3α splicing and biochemical pathways mediating them were further studied in these neurons. NRXN1/2/3α splicing in the course of memory formation in vivo was also explored, using fear conditioning paradigm in rats in which the animals were trained to associate an aversive stimulus (electrical shock with a neutral context (a tone, resulting in the expression of fear responses to the neutral context.In the cultured neurons depolarization induced, beside NRXN2α SS#3, repression of SS#3 and SS#4 exons in NRXN3α but not NRXN1α. The repressions were mediated by the calcium/protein kinase C/Rho-associated protein kinase (ROCK pathway. Fear conditioning induced significant and transient repressions of the NRXN1/2/3α SS#4 exons in the rat hippocampus. ROCK inhibition prior to training attenuated the behavioral fear response, the NRXN1/2/3α splicing repressions and subsequent recovery and the levels of excitatory (PSD95 and inhibitory (gephyrin synaptic proteins in the hippocampus. No such effects were observed in the prefrontal cortex. Significant correlations existed between the fear response and hippocampal NRXN3α and NRXN2α SS#4 inserts as well as PSD95 protein levels. Hippocampal NRXN1α SS#4 insert and gephyrin levels did not correlate with the behavioral response but were negatively correlated with each other.These results show for the first time dynamic, experience related changes in NRXN1/2/3α alternative splicing in the rat brain and a role for ROCK in them. Specific neurexins

  8. Crack formation under an electric field in droplets of laponite gel: memory effect and scaling relations.

    Science.gov (United States)

    Khatun, Tajkera; Dutta, Tapati; Tarafdar, Sujata

    2013-12-17

    When a colloidal gel dries through evaporation, cracks are usually formed, which often reveal underlying processes at work during desiccation. Desiccating colloid droplets of a few hundred microliters size show interesting effects of pattern formation and cracking which makes this an active subject of current research. Because aqueous gels of clay are known to be strongly affected by an electric field, one may expect crack patterns to exhibit a field effect. In the present study we allow droplets of laponite gel to dry under a radial electric field. This gives rise to highly reproducible patterns of cracks, which depend on the strength, direction, and time of exposure to the electric field. For a continuously applied DC voltage, cracks always appear on dissipation of a certain constant amount of energy. If the field is switched off before cracks appear, the observed results are shown to obey a number of empirical scaling relations, which enable us to predict the time of appearance and the number of cracks under specified conditions. Scanning electron microscopy (SEM) images of the surface between the macroscopic cracks show the presence of microcracks, which are wider and more numerous when no electric field is applied. The microcracks are reduced in the presence of stronger fields.

  9. Sweet Taste Signaling and the Formation of Memories of Energy Sources

    Directory of Open Access Journals (Sweden)

    Ivan E De Araujo

    2011-11-01

    Full Text Available The last decade witnessed remarkable advances in our knowledge of the gustatory system. Application of molecular biology techniques not only determined the identity of the membrane receptors and downstream effectors that mediate sweetness, but also uncovered the overall logic of gustatory coding in the periphery. However, while the ability to taste sweet may offer the obvious advantage of eliciting rapid and robust intake of sugars, a number of recent studies demonstrate that sweetness is neither necessary nor sufficient for the formation of long-lasting preferences for stimuli associated with sugar intake. Furthermore, uncoupling sweet taste from ensuing energy utilization may disrupt body weight control. This minireview examines recent experiments performed in both rodents and Drosophila revealing the taste-independent rewarding properties of metabolizable sugars. Taken together, these experiments demonstrate the reinforcing actions of sugars in the absence of sweet taste signaling and point to a critical role played by dopamine systems in translating metabolic sensing into behavioral action. From a mechanistic viewpoint, current evidence favors the concept that gastrointestinal and post-absorptive signals contribute in parallel to sweet-independent sugar acceptance and dopamine release.

  10. The contribution of familiarity to recognition memory is a function of test format when using similar foils.

    Science.gov (United States)

    Migo, Ellen; Montaldi, Daniela; Norman, Kenneth A; Quamme, Joel; Mayes, Andrew

    2009-06-01

    Patient Y.R., who suffered hippocampal damage that disrupted recollection but not familiarity, was impaired on a yes/no (YN) object recognition memory test with similar foils. However, she was not impaired on a forced-choice corresponding (FCC) version of the test that paired targets with corresponding similar foils (Holdstock et al., 2002). This dissociation is explained by the Complementary Learning Systems (CLS) neural-network model (Norman & O'Reilly, 2003) if recollection is impaired but familiarity is preserved. The CLS model also predicts that participants relying exclusively on familiarity should be impaired on forced-choice noncorresponding (FCNC) tests, where targets are presented with foils similar to other targets. The present study tests these predictions for all three test formats (YN, FCC, FCNC) in normal participants using two variants of the remember/know procedure. As predicted, performance using familiarity alone was significantly worse than standard recognition on the YN and FCNC tests, but not on the FCC test. Recollection in the form of recall-to-reject was the major process driving YN recognition. This adds support to the interpretation of patient data, according to which hippocampal damage causes a recollection deficit that leads to poor performance on the YN test relative to FCC.

  11. 6-hydroxy-L-nicotine from Arthrobacter nicotinovorans sustain spatial memory formation by decreasing brain oxidative stress in rats.

    Science.gov (United States)

    Hritcu, Lucian; Stefan, Marius; Brandsch, Roderich; Mihasan, Marius

    2013-03-01

    Male Wistar rats were subjected to chronic 6-hydroxy-L-nicotine treatment (6HLN, 0.3 mg/kg, i.p., seven consecutive days) and their memory performance was studied by means of Y-maze and radial arm-maze tasks. 6HLN significantly increased spontaneous alternations in Y-maze task and working memory in radial arm-maze task, suggesting effects on short-term memory, without affecting long-term memory, explored by reference memory in radial arm-maze task. In addition, 6HLN increased antioxidant enzymes activity and decreased production of lipid peroxidation, suggesting antioxidant effects. Also, the linear regression between behavioral measures and oxidative stress markers resulted in significant correlations. Therefore, positive effects of 6HLN on spatial memory may occur by antioxidant actions.

  12. An Agent Memory Model Enabling Rational and Biased Reasoning

    NARCIS (Netherlands)

    Heuvelink, A.; Klein, M.C.A.; Treur, J.

    2008-01-01

    This paper presents an architecture for a memory model that facilitates versatile reasoning mechanisms over the beliefs stored in an agent's belief base. Based on an approach for belief aggregation, a model is introduced for controlling both the formation of abstract and complex beliefs and the

  13. Dataset for the role of sustained attention in memory formation of transgenic mice for Alzheimer׳s disease

    OpenAIRE

    Natalia Mendes Schöwe; Eduardo Moreira de Oliveira; Hudson Sousa Buck; Tania Araujo Viel

    2016-01-01

    Weekly submission of rats to active avoidance apparatus can be considered a neurostimulation strategy, once it can improve memory and can increase the density of receptors from different neurotransmitter systems in brain areas related to memory. These benefits were observed in rats chronically infused with amyloid-β peptide. In the present work it is presented that the same benefit for memory was observed in five months old transgenic mice for Alzheimer’s disease (TG-PDGFB-APPSw,Ind). However...

  14. The Facilitative Effect of Transcranial Direct Current Stimulation on Visuospatial Working Memory in Patients with Diabetic Polyneuropathy: A Pre-post Sham-Controlled Study.

    Science.gov (United States)

    Wu, Yi-Jen; Tseng, Philip; Huang, Han-Wei; Hu, Jon-Fan; Juan, Chi-Hung; Hsu, Kuei-Sen; Lin, Chou-Ching

    2016-01-01

    Diabetes mellitus can lead to diabetic polyneuropathy (DPN) and cognitive deficits that manifest as peripheral and central neuropathy, respectively. In this study we investigated the relationship between visuospatial working memory (VSWM) capacity and DPN severity, and attempted to improve VSWM in DPN patients via the use of transcranial direct current stimulation (tDCS). Sixteen DPN patients and 16 age- and education-matched healthy control subjects received Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) and Montreal Cognitive Assessment (MOCA) for baseline cognitive assessment. A forward- and backward-recall computerized Corsi block tapping task (CBT), both with and without a concurrent motor interference task was used to measure VSWM capacity. Each DPN patient underwent a pre-treatment CBT, followed by tDCS or sham treatment, then a post-treatment CBT on two separate days. We found that although patients with severe DPN (Dyck's grade 2a or 2b) showed comparable general intelligence scores on WAIS-IV as their age- and education-matched healthy counterparts, they nonetheless showed mild cognitive impairment (MCI) on MOCA and working memory deficit on digit-span test of WAIS-IV. Furthermore, patients' peripheral nerve conduction velocity (NCV) was positively correlated with their VSWM span in the most difficult CBT condition that involved backward-recall with motor interference such that patients with worse NCV also had lower VSWM span. Most importantly, anodal tDCS over the right DLPFC was able to improve low-performing patients' VSWM span to be on par with the high-performers, thereby eliminating the correlation between NCV and VSWM. In summary, these findings suggest that (1) MCI and severe peripheral neuropathy can coexist with unequal severity in diabetic patients, (2) the positive correlation of VSWM and NCV suggests a link between peripheral and central neuropathies, and (3) anodal tDCS over the right DLPFC can improve DPN patients' VSWM

  15. The Facilitative Effect of Transcranial Direct Current Stimulation on Visuospatial Working Memory in Patients with Diabetic Polyneuropathy: A Pre–post Sham-Controlled Study

    Science.gov (United States)

    Wu, Yi-Jen; Tseng, Philip; Huang, Han-Wei; Hu, Jon-Fan; Juan, Chi-Hung; Hsu, Kuei-Sen; Lin, Chou-Ching

    2016-01-01

    Diabetes mellitus can lead to diabetic polyneuropathy (DPN) and cognitive deficits that manifest as peripheral and central neuropathy, respectively. In this study we investigated the relationship between visuospatial working memory (VSWM) capacity and DPN severity, and attempted to improve VSWM in DPN patients via the use of transcranial direct current stimulation (tDCS). Sixteen DPN patients and 16 age- and education-matched healthy control subjects received Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) and Montreal Cognitive Assessment (MOCA) for baseline cognitive assessment. A forward- and backward-recall computerized Corsi block tapping task (CBT), both with and without a concurrent motor interference task was used to measure VSWM capacity. Each DPN patient underwent a pre-treatment CBT, followed by tDCS or sham treatment, then a post-treatment CBT on two separate days. We found that although patients with severe DPN (Dyck’s grade 2a or 2b) showed comparable general intelligence scores on WAIS-IV as their age- and education-matched healthy counterparts, they nonetheless showed mild cognitive impairment (MCI) on MOCA and working memory deficit on digit-span test of WAIS-IV. Furthermore, patients’ peripheral nerve conduction velocity (NCV) was positively correlated with their VSWM span in the most difficult CBT condition that involved backward-recall with motor interference such that patients with worse NCV also had lower VSWM span. Most importantly, anodal tDCS over the right DLPFC was able to improve low-performing patients’ VSWM span to be on par with the high-performers, thereby eliminating the correlation between NCV and VSWM. In summary, these findings suggest that (1) MCI and severe peripheral neuropathy can coexist with unequal severity in diabetic patients, (2) the positive correlation of VSWM and NCV suggests a link between peripheral and central neuropathies, and (3) anodal tDCS over the right DLPFC can improve DPN patients’ VSWM

  16. Differentially expressed genes linked to natural variation in long-term memory formation in Cotesia parasitic wasps

    NARCIS (Netherlands)

    Vugt, van J.J.F.A.; Hoedjes, K.M.; Geest, van de H.C.; Schijlen, E.G.W.M.; Vet, L.E.M.; Smid, H.M.

    2015-01-01

    Even though learning and memory are universal traits in the Animal Kingdom, closely related species reveal substantial variation in learning rate and memory dynamics. To determine the genetic background of this natural variation, we studied two congeneric parasitic wasp species, Cotesia glomerata

  17. Differentially expressed genes linked to natural variation in long-term memory formation in Cotesia parasitic wasps

    NARCIS (Netherlands)

    Van Vugt, Joke J. F. A.; Hoedjes, Katja M.; Van de Geest, Henri C.; Schijlen, Elio W. G. M.; Vet, Louise E. M.; Smid, Hans M.

    2015-01-01

    BACKGROUND: Even though learning and memory are universal traits in the Animal Kingdom, closely related species reveal substantial variation in learning rate and memory dynamics. To determine the genetic background of this natural variation, we studied two congeneric parasitic wasp species, Cotesia

  18. Facilitating identity formation, group membership, and learning in science classrooms: What can be learned from out-of-field teaching in an urban school?

    Science.gov (United States)

    Olitsky, Stacy

    2007-03-01

    This paper explores both the obstacles and the possibilities for students developing identities associated with science by engaging in solidarity-building classroom interactions. Data come from ethnographic research conducted in a diverse eighth-grade urban magnet school classroom in which the teacher taught out of field for part of the year. Contrary to expectations, more students participated and reported enjoying science when the teacher was out of field. Analysis of classroom interactions indicated that while in field, the teacher primarily engaged in front stage performances that hid her struggles with the material and accentuated students' views of science as an elite status group. The types of solidarity that developed among students often did not involve science language and sometimes involved students rejecting peers' claims to membership. However, when out of field, the teacher allowed students into her backstage, where her struggles and learning processes were more explicit. These practices lessened the social distance between teacher and students, and reduced the risks of using science language, thereby encouraging solidarity and group membership. This study provides insights into some of the ways that teachers, particularly those in urban settings characterized by diversity, might be more successful at facilitating identity formation and learning in science.

  19. Human immunodeficiency virus type 1-mediated syncytium formation is compatible with adenovirus replication and facilitates efficient dispersion of viral gene products and de novo-synthesized virus particles.

    Science.gov (United States)

    Li, H; Haviv, Y S; Derdeyn, C A; Lam, J; Coolidge, C; Hunter, E; Curiel, D T; Blackwell, J L

    2001-12-10

    Conditionally replicative adenovirus (CRAd) vectors are designed for specific oncolytic replication in tumor tissues with concomitant sparing of normal cells. As such, CRAds offer an unprecedented level of anticancer potential for malignancies that have been refractory to previous cancer gene therapy interventions. CRAd efficacy may, however, be compromised by inefficient dispersion of the replicating vector within the tumor tissue. To address this issue, we evaluated the utility of a fusogenic membrane glycoprotein (FMG), which induces the fusion of neighboring cellular membranes to form multinucleated syncytia. We hypothesized that the FMG-mediated syncytia would facilitate dispersion of the adenovirus (Ad) gene products and viral progeny. To test this, human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, which induce syncytia in the presence of CD4+ target cells, were expressed by an Ad (Ad5HIVenv) in permissive (CD4-positive) and nonpermissive (CD4-negative) cell lines. After validating this Ad-FMG model, the efficiency of Ad replication in the presence or absence of syncytia was evaluated. The results demonstrated that syncytium formation was compatible with Ad replication and dramatically increased the dispersion of virus gene products within the cytoplasm of the syncytia as well as viral particles in the nuclei of the syncytial mass. Moreover, progeny virions were released more efficiently from syncytia compared with nonsyncytial cells. These data demonstrate the utility of FMGs as a dispersion agent and suggest that FMGs can improve the efficacy of CRAd gene therapy.

  20. The effects of the 5-HT(6) receptor agonist EMD and the 5-HT(7) receptor agonist AS19 on memory formation.

    Science.gov (United States)

    Meneses, A; Perez-Garcia, G; Liy-Salmeron, G; Flores-Galvez, D; Castillo, C; Castillo, E

    2008-12-16

    Growing evidence indicates that 5-hydrohytryptamine (5-HT) receptors mediate learning and memory. Particularly interesting are 5-HT(6) and 5-HT(7) receptors, which are localized in brain areas involved in memory formation. Interestingly, recently selective 5-HT(6) and 5-HT(7) receptor agonists and antagonists have become available. Previous evidence indicates that 5-HT(6) or 5-HT(7) receptors antagonists had no effects, improved memory formation and/or reversed amnesia. Herein, the effects of EMD (a 5-HT(6) receptor agonist) and AS19 (a 5-HT(7) receptor agonist) in the associative learning task of autoshaping were studied. Post-training systemic administration of EMD (1-10 mg/kg) or AS19 (1-10 mg/kg) were tested in short-term memory (STM) and long-term memory (LTM). Results showed that only EMD 5.0mg/kg impaired both STM and LTM. AS19 at 1-10 mg/kg significantly impaired STM but not LTM. In those groups used to test only LTM, EMD impaired it; while AS19 improved LTM. Moreover, in the interaction experiments, the STM EMD-impairment effect was partially reversed by the selective 5-HT(6) receptor antagonist SB-399885 (10 mg/kg). The STM AS19-impairment effect (5.0 mg/kg) was not altered by the selective 5-HT(1A) antagonist WAY 100635 (0.3 mg/kg) but reversed by the selective 5-HT(7) receptor antagonist SB-269970 (10.0 mg/kg). The AS19-SB-269970 combination impaired LTM. Taken together these data suggest that the stimulation of 5-HT(6) impaired both STM and LTM. 5-HT(7) receptors stimulation impaired STM but improved LTM. And these results are discussed in the context of their possible neural bases.

  1. Exercise enhances memory consolidation in the aging brain

    Directory of Open Access Journals (Sweden)

    Shikha eSnigdha

    2014-02-01

    Full Text Available Exercise has been shown to reduce age-related losses in cognitive function including learning and memory, but the mechanisms underlying this effect remain poorly understood. Memory formation occurs in stages that include an initial acquisition phase, an intermediate labile phase, and then a process of consolidation which leads to long term memory formation. An effective way to examine the mechanism by which exercise improves memory is to introduce the intervention (exercise, post-acquisition, making it possible to selectively examine memory storage and consolidation. Accordingly we evaluated the effects of post-trial exercise (10 minutes on a treadmill on memory consolidation in aged canines both right after, an hour after, and twenty-four hours after acute exercise training in concurrent discrimination, object location memory (OLM and novel object recognition (NOR tasks. Our study shows that post-trial exercise facilitates memory function by improving memory consolidation in aged animals in a time-dependent manner. The improvements were significant at twenty-four hour post exercise and not right after or one hour after exercise. Aged animals were also tested following chronic exercise (10 min/day for 14 consecutive days on OLM or till criterion were reached (for reversal learning task. We found improvements from a chronic exercise design in both the object location and reversal learning tasks. Our studies suggest that mechanisms to improve overall consolidation and cognitive function remain accessible even with progressing age and can be re-engaged by both acute and chronic exercise.

  2. Exercise enhances memory consolidation in the aging brain.

    Science.gov (United States)

    Snigdha, Shikha; de Rivera, Christina; Milgram, Norton W; Cotman, Carl W

    2014-01-01

    Exercise has been shown to reduce age-related losses in cognitive function including learning and memory, but the mechanisms underlying this effect remain poorly understood. Memory formation occurs in stages that include an initial acquisition phase, an intermediate labile phase, and then a process of consolidation which leads to long-term memory formation. An effective way to examine the mechanism by which exercise improves memory is to introduce the intervention (exercise), post-acquisition, making it possible to selectively examine memory storage and consolidation. Accordingly we evaluated the effects of post-trial exercise (10 min on a treadmill) on memory consolidation in aged canines both right after, an hour after, and 24 h after acute exercise training in concurrent discrimination, object location memory (OLM), and novel object recognition tasks. Our study shows that post-trial exercise facilitates memory function by improving memory consolidation in aged animals in a time-dependent manner. The improvements were significant at 24 h post-exercise and not right after or 1 h after exercise. Aged animals were also tested following chronic exercise (10 min/day for 14 consecutive days) on OLM or till criterion were reached (for reversal learning task). We found improvements from a chronic exercise design in both the object location and reversal learning tasks. Our studies suggest that mechanisms to improve overall consolidation and cognitive function remain accessible even with progressing age and can be re-engaged by both acute and chronic exercise.

  3. The facilitative effect of transcranial direct current stimulation on visuospatial working memory in patients with diabetic polyneuropathy: a pre-post sham-controlled study

    Directory of Open Access Journals (Sweden)

    YI-JEN WU

    2016-09-01

    Full Text Available Diabetes mellitus (DM can lead to diabetic polyneuropathy (DPN and cognitive deficits that manifest as peripheral and central neuropathy, respectively. In this study we investigated the relationship between visuospatial working memory (VSWM capacity and DPN severity, and attempted to improve VSWM in DPN patients via the use of transcranial direct current stimulation (tDCS. Sixteen DPN patients and sixteen age- and education-matched healthy control subjects received Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV and Montreal Cognitive Assessment (MOCA for baseline cognitive assessment. A forward- and backward-recall computerized Corsi block tapping task (CBT, both with and without a concurrent motor interference task was used to measure VSWM capacity. Each DPN patient underwent a pre-treatment CBT, followed by tDCS or sham treatment, then a post-treatment CBT on two separate days. We found that although patients with severe DPN (Dyck’s grade 2a or 2b showed comparable general intelligence scores on WAIS-IV as their age- and education-matched healthy counterparts, they nonetheless showed mild cognitive impairment on MOCA and working memory deficit on digit-span test of WAIS-IV. Furthermore, patients’ peripheral nerve conduction velocity (NCV was positively correlated with their VSWM span in the most difficult CBT condition that involved backward-recall with motor interference such that patients with worse NCV also had lower VSWM span. Most importantly, anodal tDCS over the right DLPFC was able to improve low-performing patients’ VSWM span to be on par with the high-performers, thereby eliminating the correlation between NCV and VSWM. In summary, these findings suggest that 1 mild cognitive impairment and severe peripheral neuropathy can coexist with unequal severity in diabetic patients, 2 the positive correlation of VSWM and NCV suggests a link between peripheral and central neuropathies and 3 anodal tDCS over the right DLPFC can

  4. You can't stop the music: reduced auditory alpha power and coupling between auditory and memory regions facilitate the illusory perception of music during noise.

    Science.gov (United States)

    Müller, Nadia; Keil, Julian; Obleser, Jonas; Schulz, Hannah; Grunwald, Thomas; Bernays, René-Ludwig; Huppertz, Hans-Jürgen; Weisz, Nathan

    2013-10-01

    Our brain has the capacity of providing an experience of hearing even in the absence of auditory stimulation. This can be seen as illusory conscious perception. While increasing evidence postulates that conscious perception requires specific brain states that systematically relate to specific patterns of oscillatory activity, the relationship between auditory illusions and oscillatory activity remains mostly unexplained. To investigate this we recorded brain activity with magnetoencephalography and collected intracranial data from epilepsy patients while participants listened to familiar as well as unknown music that was partly replaced by sections of pink noise. We hypothesized that participants have a stronger experience of hearing music throughout noise when the noise sections are embedded in familiar compared to unfamiliar music. This was supported by the behavioral results showing that participants rated the perception of music during noise as stronger when noise was presented in a familiar context. Time-frequency data show that the illusory perception of music is associated with a decrease in auditory alpha power pointing to increased auditory cortex excitability. Furthermore, the right auditory cortex is concurrently synchronized with the medial temporal lobe, putatively mediating memory aspects associated with the music illusion. We thus assume that neuronal activity in the highly excitable auditory cortex is shaped through extensive communication between the auditory cortex and the medial temporal lobe, thereby generating the illusion of hearing music during noise. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Dataset for the role of sustained attention in memory formation of transgenic mice for Alzheimer׳s disease

    Directory of Open Access Journals (Sweden)

    Natalia Mendes Schöwe

    2016-03-01

    Full Text Available Weekly submission of rats to active avoidance apparatus can be considered a neurostimulation strategy, once it can improve memory and can increase the density of receptors from different neurotransmitter systems in brain areas related to memory. These benefits were observed in rats chronically infused with amyloid-β peptide. In the present work it is presented that the same benefit for memory was observed in five months old transgenic mice for Alzheimer’s disease (TG-PDGFB-APPSw,Ind. However, at this age, no change in density of nicotinic receptors was observed.

  6. Dataset for the role of sustained attention in memory formation of transgenic mice for Alzheimer׳s disease.

    Science.gov (United States)

    Schöwe, Natalia Mendes; de Oliveira, Eduardo Moreira; Buck, Hudson Sousa; Viel, Tania Araujo

    2016-03-01

    Weekly submission of rats to active avoidance apparatus can be considered a neurostimulation strategy, once it can improve memory and can increase the density of receptors from different neurotransmitter systems in brain areas related to memory. These benefits were observed in rats chronically infused with amyloid-β peptide. In the present work it is presented that the same benefit for memory was observed in five months old transgenic mice for Alzheimer's disease (TG-PDGFB-APPSw,Ind). However, at this age, no change in density of nicotinic receptors was observed.

  7. Usage Record Format Recommendation

    CERN Document Server

    Nilsen, J.K.; Muller-Pfeerkorn, R

    2013-01-01

    For resources to be shared, sites must be able to exchange basic accounting and usage data in a common format. This document describes a common format which enables the exchange of basic accounting and usage data from different resources. This record format is intended to facilitate the sharing of usage information, particularly in the area of the accounting of jobs, computing, memory, storage and cloud usage but with a structure that allows an easy extension to other resources. This document describes the Usage Record components both in natural language form and annotated XML. This document does not address how these records should be used, nor does it attempt to dictate the format in which the accounting records are stored. Instead, it denes a common exchange format. Furthermore, nothing is said regarding the communication mechanisms employed to exchange the records, i.e. transport layer, framing, authentication, integrity, etc.

  8. Interactions of the dorsal hippocampus, medial prefrontal cortex and nucleus accumbens in formation of fear memory: difference in inhibitory avoidance learning and contextual fear conditioning.

    Science.gov (United States)

    Yang, Fang-Chi; Liang, K C

    2014-07-01

    Learning active or reactive responses to fear involves different brain circuitry. This study examined how the nuclus accumbens (NAc), dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) may interact in memory processing for these two kinds of responses. Male Wistar rats with cannulae implanted in these areas were trained on a contextual fear conditioning or inhibitory avoidance task that respectively engaged a reactive or active response to fear in the test. Immediately after training, a memory modulating factor released by stress, norepinephrine (NE), was infused into one region and 4% lidocaine into another to examine if an upstream activation effect could be blocked by the downstream suppression. Retention tested 1 day later showed that in both tasks posttraining infusion of NE at different doses into either the DH or mPFC enhanced retention but the enhancement was blocked by concurrent infusion of lidocaine into the other region, suggesting reliance of the effect on functional integrity of both regions. Further, posttraining intra-NAc lidocaine infusion attenuated memory enhancement of NE infused to the DH or mPFC in the inhibitory avoidance task but did not do so in contextual fear conditioning. These results suggest that NE regulation of memory formation for the reactive and active responses to fear may rely on distinct interactions among the DH, mPFC and NAc. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. HDAC inhibitor sodium butyrate sensitizes E1A+Ras-transformed cells to DNA damaging agents by facilitating formation and persistence of γH2AX foci.

    Science.gov (United States)

    Abramova, Maria V; Svetlikova, Svetlana B; Kukushkin, Alexander N; Aksenov, Nikolai D; Pospelova, Tatiana V; Pospelov, Valery A

    2011-12-15

    HDAC inhibitors (HDACi) suppress the growth of tumor cells due to induction of cell cycle arrest, senescence or apoptosis. Recent data demonstrate that HDACi can interfere with DNA Damage Response (DDR) thereby sensitizing the cells to DNA damaging agents. Here, we show that HDACi sodium butyrate (NaBut) potentiates the formation of γH2AX foci predominantly in S-phase E1A+Ras cells. Accumulation of γH2AX foci sensitizes the cells toward such DNA damaging agents as irradiation (IR) and adriamycin. In fact, NaBut potentiates the persistence of γH2AX foci induced by genotoxic agents. The synergizing effects depend on DNA damaging factors and on the order of NaBut treatment. Indeed, NaBut treatment for 24 h leads to an accumulation of G 1-phase cells and a lack of S-phase cells, therefore, adriamycin, a powerful S-phase-specific inhibitor, when added to NaBut-treated cells, is unable to substantially add γH2AX foci. In contrast, IR produces both single- and double-strand DNA breaks at any stage of the cell cycle and was shown to increase γH2AX foci in NaBut-treated cells. Further, a lifetime of IR-induced γH2AX foci depends on the subsequent presence of HDACi. Correspondingly, NaBut withdrawal leads to the extinction of IR-induced γH2AX foci. This necessitates HDACi to hold the IR-induced γH2AX foci unrepaired. However, the IR-induced γH2AX foci persist after long-term NaBut treatment (72 h) even after washing the drug. Thus, although signaling pathways regulating H2AX phosphorylation in NaBut-treated cells remain to be investigated, the obtained results show that NaBut potentiates effects of DNA damaging agents by facilitating formation and persistence of γH2AX foci.

  10. Effects of hippocampal high-frequency electrical stimulation in memory formation and their association with amino acid tissue content and release in normal rats.

    Science.gov (United States)

    Luna-Munguía, Hiram; Meneses, Alfredo; Peña-Ortega, Fernando; Gaona, Andres; Rocha, Luisa

    2012-01-01

    Hippocampal high frequency electrical stimulation (HFS) at 130 Hz has been proposed as a therapeutical strategy to control neurological disorders such as intractable temporal lobe epilepsy (TLE). This study was carried out to determine the effects of hippocampal HFS on the memory process and the probable involvement of amino acids. Using the autoshaping task, we found that animals receiving hippocampal HFS showed augmented short-term, but not long-term memory formation, an effect blocked by bicuculline pretreatment and associated with enhanced tissue levels of amino acids in hippocampus. In addition, microdialysis experiments revealed high extracellular levels of glutamate, aspartate, glycine, taurine, and alanine during the application of hippocampal HFS. In contrast, GABA release augmented during HFS and remained elevated for more than 1 h after the stimulation was ended. HFS had minimal effects on glutamine release. The present results suggest that HFS has an activating effect on specific amino acids in normal hippocampus that may be involved in the enhanced short-term memory formation. These data further provide experimental support for the concept that hippocampus may be a promising target for focal stimulation to treat intractable seizures in humans.

  11. 5-HT6 receptor memory and amnesia: behavioral pharmacology--learning and memory processes.

    Science.gov (United States)

    Meneses, Alfredo; Pérez-García, Georgina; Ponce-Lopez, Teresa; Castillo, Carlos

    2011-01-01

    Growing evidence indicates that antagonists of the 5-hydroxytryptamine (serotonin) receptor6 (5-HT6) improve memory and reverse amnesia, although the mechanisms involved are poorly understood. Hence, in this paper an attempt was made to summarize recent findings. Available evidence indicates that diverse 5-HT6 receptor antagonists produce promnesic and/or antiamnesic effects in diverse conditions, including memory formation, age-related cognitive impairments, memory deficits in diseases such as schizophrenia, Parkinson, and Alzheimer's disease (AD). Notably, some 5-HT6 receptor agonists seem to have promnesic and/or antiamnesic effects. At the present, it is unclear why 5-HT6 receptor agonists and antagonists may facilitate memory or may reverse amnesia in some memory tasks. Certainly, 5-HT6 drugs modulate memory, which are accompanied with neural changes. Likewise, memory, aging, and AD modify 5-HT6 receptors and signaling cascades. Further investigation in different memory tasks, times, and amnesia models together with more complex control groups might provide further clues. Notably, human studies suggest a potential utility of 5-HT6 receptor antagonists in mild-to-moderate AD patients. Even individuals with mild cognitive impairment (MCI) offer a great opportunity to test them.

  12. The role of working memory and declarative memory in trace conditioning.

    Science.gov (United States)

    Connor, David A; Gould, Thomas J

    2016-10-01

    Translational assays of cognition that are similarly implemented in both lower and higher-order species, such as rodents and primates, provide a means to reconcile preclinical modeling of psychiatric neuropathology and clinical research. To this end, Pavlovian conditioning has provided a useful tool for investigating cognitive processes in both lab animal models and humans. This review focuses on trace conditioning, a form of Pavlovian conditioning typified by the insertion of a temporal gap (i.e., trace interval) between presentations of a conditioned stimulus (CS) and an unconditioned stimulus (US). This review aims to discuss pre-clinical and clinical work investigating the mnemonic processes recruited for trace conditioning. Much work suggests that trace conditioning involves unique neurocognitive mechanisms to facilitate formation of trace memories in contrast to standard Pavlovian conditioning. For example, the hippocampus and prefrontal cortex (PFC) appear to play critical roles in trace conditioning. Moreover, cognitive mechanistic accounts in human studies suggest that working memory and declarative memory processes are engaged to facilitate formation of trace memories. The aim of this review is to integrate cognitive and neurobiological accounts of trace conditioning from preclinical and clinical studies to examine involvement of working and declarative memory.

  13. Hunger and memory; CRTC coordinates long-term memory with the physiological state, hunger.

    Science.gov (United States)

    Hirano, Yukinori; Saitoe, Minoru

    2013-09-01

    Animals form and store memory, which advantageously adjusts their behavior later on. Although the growing body of evidences suggests the basic mechanisms of memory, it is not clear whether and in which physiological state memory functions can be altered. Here we discuss our recent study that mild fasting facilitates long-term memory (LTM) formation in Drosophila.(1) Canonical LTM in flies is induced by multiple training with rest intervals, and is mediated by a transcription factor, CREB and its binding protein, CBP. However, fasting allows LTM formation (fLTM) only by single-cycle training, in a manner dependent on another CREB binding protein, CRTC. Although it has been controversial, we are convinced that gene expression in a specific neural structure, called mushroom body (MB), is required for LTMs. We also showed data suggesting that reduced insulin signaling during fasting activates CRTC, thereby inducing fLTM formation. These data provides the conceptual advance that flies adapt their mechanisms for LTM formation according to their internal condition, hunger state. Due to limited food resources in the wild, fLTM could be one of the major form of LTM in natural environment. Furthermore, our data also indicate a novel conception that improvement of memory deficit might be achieved by activation of CRTC.

  14. Microglial production of TNF-alpha is a key element of sustained fear memory.

    Science.gov (United States)

    Yu, Zhiqian; Fukushima, Hotaka; Ono, Chiaki; Sakai, Mai; Kasahara, Yoshiyuki; Kikuchi, Yoshie; Gunawansa, Nicole; Takahashi, Yuta; Matsuoka, Hiroo; Kida, Satoshi; Tomita, Hiroaki

    2017-01-01

    The proinflammatory cytokine productions in the brain are altered in a process of fear memory formation, indicating a possibility that altered microglial function may contribute to fear memory formation. We aimed to investigate whether and how microglial function contributes to fear memory formation. Expression levels of M1- and M2-type microglial marker molecules in microglia isolated from each conditioned mice group were assessed by real-time PCR and immunohistochemistry. Levels of tumor necrosis factor (TNF)-α, but not of other proinflammatory cytokines produced by M1-type microglia, increased in microglia from mice representing retention of fear memory, and returned to basal levels in microglia from mice representing extinction of fear memory. Administration of inhibitors of TNF-α production facilitated extinction of fear memory. On the other hand, expression levels of M2-type microglia-specific cell adhesion molecules, CD206 and CD209, were decreased in microglia from mice representing retention of fear memory, and returned to basal levels in microglia from mice representing extinction of fear memory. Our findings indicate that microglial TNF-α is a key element of sustained fear memory and suggest that TNF-α inhibitors can be candidate molecules for mitigating posttraumatic reactions caused by persistent fear memory.

  15. Dopamine D1 receptor stimulation modulates the formation and retrieval of novel object recognition memory: Role of the prelimbic cortex.

    Science.gov (United States)

    Pezze, Marie A; Marshall, Hayley J; Fone, Kevin C F; Cassaday, Helen J

    2015-11-01

    Previous studies have shown that dopamine D1 receptor antagonists impair novel object recognition memory but the effects of dopamine D1 receptor stimulation remain to be determined. This study investigated the effects of the selective dopamine D1 receptor agonist SKF81297 on acquisition and retrieval in the novel object recognition task in male Wistar rats. SKF81297 (0.4 and 0.8 mg/kg s.c.) given 15 min before the sampling phase impaired novel object recognition evaluated 10 min or 24 h later. The same treatments also reduced novel object recognition memory tested 24 h after the sampling phase and when given 15 min before the choice session. These data indicate that D1 receptor stimulation modulates both the encoding and retrieval of object recognition memory. Microinfusion of SKF81297 (0.025 or 0.05 μg/side) into the prelimbic sub-region of the medial prefrontal cortex (mPFC) in this case 10 min before the sampling phase also impaired novel object recognition memory, suggesting that the mPFC is one important site mediating the effects of D1 receptor stimulation on visual recognition memory.

  16. The role of cannabinoids in modulating emotional and non-emotional memory processes in the hippocampus

    Directory of Open Access Journals (Sweden)

    Irit eAkirav

    2011-06-01

    Full Text Available Cannabinoid agonists generally have a disruptive effect on memory, learning, and operant behavior that is considered to be hippocampus-dependent. Nevertheless, under certain conditions, cannabinoid receptor activation may facilitate neuronal learning processes. For example, CB1 receptors are essential for the extinction of conditioned fear associations, indicating an important role for this receptor in neuronal emotional learning and memory. This review examines the diverse effects of cannabinoids on hippocampal memory and plasticity. It shows how the effects of cannabinoid receptor activation may vary depending on the route of administration, the nature of the task (aversive or not, and whether it involves emotional memory formation (e.g. conditioned fear and extinction learning or non-emotional memory formation (e.g. spatial learning. It also examines the memory stage under investigation (acquisition, consolidation, retrieval, extinction, and the brain areas involved. Differences between the effects of exogenous and endogenous agonists are also discussed. The apparently biphasic effects of cannabinoids on anxiety is noted as this implies that the effects of cannabinoid receptor agonists on hippocampal learning and memory may be attributable to a general modulation of anxiety or stress levels and not to memory per se. The review concludes that cannabinoids have diverse effects on hippocampal memory and plasticity that cannot be categorized simply into an impairing or an enhancing effect. A better understanding of the involvement of cannabinoids in memory processes will help determine whether the benefits of the clinical use of cannabinoids outweigh the risks of possible memory impairments.

  17. Facilitation as a teaching strategy : experiences of facilitators

    Directory of Open Access Journals (Sweden)

    E Lekalakala-Mokgele

    2006-09-01

    Full Text Available Changes in nursing education involve the move from traditional teaching approaches that are teacher-centred to facilitation, a student centred approach. The studentcentred approach is based on a philosophy of teaching and learning that puts the learner on centre-stage. The aim of this study was to identify the challenges of facilitators of learning using facilitation as a teaching method and recommend strategies for their (facilitators development and support. A qualitative, explorative and contextual design was used. Four (4 universities in South Africa which utilize facilitation as a teaching/ learning process were identified and the facilitators were selected to be the sample of the study. The main question posed during in-depth group interviews was: How do you experience facilitation as a teaching/learning method?. Facilitators indicated different experiences and emotions when they first had to facilitate learning. All of them indicated that it was difficult to facilitate at the beginning as they were trained to lecture and that no format for facilitation was available. They experienced frustrations and anxieties as a result. The lack of knowledge of facilitation instilled fear in them. However they indicated that facilitation had many benefits for them and for the students. Amongst the ones mentioned were personal and professional growth. Challenges mentioned were the fear that they waste time and that they do not cover the content. It is therefore important that facilitation be included in the training of nurse educators.

  18. Prenatal stress induces spatial memory deficits and epigenetic changes in the hippocampus indicative of heterochromatin formation and reduced gene expression.

    Science.gov (United States)

    Benoit, Jamie D; Rakic, Pasko; Frick, Karyn M

    2015-03-15

    Stress during pregnancy has a wide variety of negative effects in both human [1] and animal offspring [2]. These effects are especially apparent in various forms of learning and memory such as object recognition [3] and spatial memory [4]. The cognitive effects of prenatal stress (PNS) may be mediated through epigenetic changes such as histone acetylation and DNA methylation [5]. As such, the present study investigated the effects of chronic unpredictable PNS on memory and epigenetic measures in adult offspring. Mice that underwent PNS exhibited impaired spatial memory in the Morris water maze, as well as sex-specific changes in levels of DNA methyltransferase (DNMT) 1 protein, and acetylated histone H3 (AcH3) in the hippocampus, and serum corticosterone. Male mice exposed to PNS exhibited decreased hippocampal AcH3, whereas female PNS mice displayed a further reduction in AcH3, as well as heightened hippocampal DNMT1 protein levels and corticosterone levels. These data suggest that PNS may epigenetically reduce transcription in the hippocampus, particularly in females in whom this effect may be related to increased baseline stress hormone levels, and which may underlie the sexual dimorphism in rates of mental illness in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Formation of a Mental Abacus for Computation and Its Use as a Memory Device for Digits: A Developmental Study.

    Science.gov (United States)

    Hatano, Giyoo; And Others

    1987-01-01

    Examined whether representational changes in digit memory are functions of children's expertise in mental abacus operation when abacus operators reproduced series of digits forward or backward. Found skilled operators equally facile with forward and backward reproduction, but novices slower going backward. Suggests advanced operators apply their…

  20. Direct formation of gold nanoparticles on substrates using a novel ZnO sacrificial templated-growth hydrothermal approach and their properties in organic memory device

    Science.gov (United States)

    Goh, Lean Poh; Razak, Khairunisak Abdul; Ridhuan, Nur Syafinaz; Cheong, Kuan Yew; Ooi, Poh Choon; Aw, Kean Chin

    2012-10-01

    This study describes a novel fabrication technique to grow gold nanoparticles (AuNPs) directly on seeded ZnO sacrificial template/polymethylsilsesquioxanes (PMSSQ)/Si using low-temperature hydrothermal reaction at 80°C for 4 h. The effect of non-annealing and various annealing temperatures, 200°C, 300°C, and 400°C, of the ZnO-seeded template on AuNP size and distribution was systematically studied. Another PMMSQ layer was spin-coated on AuNPs to study the memory properties of organic insulator-embedded AuNPs. Well-distributed and controllable AuNP sizes were successfully grown directly on the substrate, as observed using a field emission scanning electron microscope followed by an elemental analysis study. A phase analysis study confirmed that the ZnO sacrificial template was eliminated during the hydrothermal reaction. The AuNP formation mechanism using this hydrothermal reaction approach was proposed. In this study, the AuNPs were charge-trapped sites and showed excellent memory effects when embedded in PMSSQ. Optimum memory properties of PMMSQ-embedded AuNPs were obtained for AuNPs synthesized on a seeded ZnO template annealed at 300°C, with 54 electrons trapped per AuNP and excellent current-voltage response between an erased and programmed device.

  1. [Formation and interaction of memory traces of the "results" of action in the situation of choosing the direction of movement in space].

    Science.gov (United States)

    Iantareva, L I

    1980-01-01

    The formation of choice between runs to the left or to the right side in rats was studied in aspect of the problem of interaction between memory traces of the signal of locomotion direction and its "result". First a run to the left was elaborated to a tone; the second run--to the right--was elaborated with alternating presentation of light and tone. The closer to the correct choice the longer was the time of performance of both competing reactions. This fact is considered as a result of interaction between memory traces of "results" in their competition for the common final path. The process of singling out of the model of afferent parameters of the "result" of the run to the right was optimized by a preliminary consolidation of memory trace of light's physical parameters used as a signal of its efficiency. The experience of locomotion to the right acquired in these conditions, proved to be resistent against amnesing effect of electric shock.

  2. Gender-specific effects of CGP 55845, GABAB receptor antagonist, on neuromuscular coordination, learning and memory formation in albino mouse following neonatal hypoxia-ischemia insult.

    Science.gov (United States)

    Gillani, Quratul Ane; Akbar, Atif; Ali, Muhammad; Iqbal, Furhan

    2015-06-01

    GABAB receptor antagonists are experimentally proved as spatial memory enhancers in mouse models but their role has not been described following hypoxic-ischemic insult. 10-day-old albino mice were subjected to Murine model of hypoxia and ischemia. Following brain damage, mice were fed on normal rodent diet till they were 13 weeks old. At this time point, mice were divided into two groups. Group 1 received saline and group 2 received intraperitoneally CGP 55845 (1 mg/ml solvent/Kg body weight) for 12 days. Behavioural observations were made during rota rod, open field and Morris water maze test along with brain infarct measurement in both CGP 55845 treated and untreated groups. It was observed that application of GABAB receptor antagonist improved the over all motor function in male and female albino mice but effects were more pronounced in males. In open field, CGP 55845-treated female mice showed poor performance. CGP 55845 had no significant effect on learning and memory formation during Morris water maze test and also on brain infract size in both genders following hypoxia ischemia encephalopathy. Effects of CGP 55845 can be further explored in a dose and duration dependent manner to improve the learning and memory in albino mice following neonatal brain damage.

  3. Formats

    Directory of Open Access Journals (Sweden)

    Gehmann, Ulrich

    2012-03-01

    Full Text Available In the following, a new conceptual framework for investigating nowadays’ “technical” phenomena shall be introduced, that of formats. The thesis is that processes of formatting account for our recent conditions of life, and will do so in the very next future. It are processes whose foundations have been laid in modernity and which will further unfold for the time being. These processes are embedded in the format of the value chain, a circumstance making them resilient to change. In addition, they are resilient in themselves since forming interconnected systems of reciprocal causal circuits.Which leads to an overall situation that our entire “Lebenswelt” became formatted to an extent we don’t fully realize, even influencing our very percep-tion of it.

  4. Effects of 5-HT drugs in prefrontal cortex during memory formation and the ketamine amnesia-model.

    Science.gov (United States)

    Liy-Salmeron, Gustavo; Meneses, Alfredo

    2008-01-01

    This article describes a series of experiments investigating the effects of systemic or intraprefrontal administration of serotonergic agents on ketamine induced memory deficits in rats. First, rats were trained on an operant autoshaping task. Immediately after training, rats were injected with different doses of drug or saline. Following drug administration, rats were tested after 1.5 h for short-term memory (STM) and 24 h for long-term memory (LTM) of conditioned response. An increase or decrease in number of conditioned responses was an index of retention. The major results of this work show that ketamine impaired STM and this effect was reversed, by either systemic or intraprefrontal cortex administration of the agonist 5-HT(1A/7) 8-OH-DPAT, the 5-HT receptor antagonists MDL100907 (5-HT(2A)), SB-399885 (5-HT(6)), and SB-269970 (5-HT(7)). The ketamine STM-impairment effect was not altered by the 5-HT(1A) antagonist WAY 100635 or the 5-HT(1B) antagonist SB-224289. Notably, prefrontal cortex inhibition of translation or transcription interrupted STM without affecting LTM suggesting different signaling mechanisms. The interacting effect of NMDA and serotonin agents in memory function is an interesting and important area of study; both receptors are considered to be important targets for the development of antipsychotic medication. Particularly, 5-HT(1A/7), 5-HT(2A) 5-HT(6), and 5-HT(7) receptors present in prefrontal cortex, represent important targets for development of drugs for the treatment of SMT-deficits.

  5. H3K9me3 Inhibition Improves Memory, Promotes Spine Formation, and Increases BDNF Levels in the Aged Hippocampus.

    Science.gov (United States)

    Snigdha, Shikha; Prieto, G Aleph; Petrosyan, Arpine; Loertscher, Brad M; Dieskau, André P; Overman, Larry E; Cotman, Carl W

    2016-03-23

    An increasing number of studies show that an altered epigenetic landscape may cause impairments in regulation of learning and memory-related genes within the aged hippocampus, eventually resulting in cognitive deficits in the aged brain. One such epigenetic repressive mark is trimethylation of H3K9 (H3K9me3), which is typically implicated in gene silencing. Here, we identify, for the first time, an essential role for H3K9me3 and its histone methyl transferase (SUV39H1) in mediating hippocampal memory functions. Pharmacological inhibition of SUV39H1 using a novel and selective inhibitor decreased levels of H3K9me3 in the hippocampus of aged mice, and improved performance in the objection location memory and fear conditioning tasks and in a complex spatial environment learning task. The inhibition of SUV39H1 induced an increase in spine density of thin and stubby but not mushroom spines in the hippocampus of aged animals and increased surface GluR1 levels in hippocampal synaptosomes, a key index of spine plasticity. Furthermore, there were changes at BDNF exon I gene promoter, in concert with overall BDNF levels in the hippocampus of drug-treated animals compared with control animals. Together, these data demonstrate that SUV39H1 inhibition and the concomitant H3K9me3 downregulation mediate gene transcription in the hippocampus and reverse age-dependent deficits in hippocampal memory. Cognitive decline is a debilitating condition associated with not only neurodegenerative diseases but also aging in general. However, effective treatments have been slow to emerge so far. In this study, we demonstrate that epigenetic regulation of key synaptic proteins may be an underlying, yet reversible, cause of this decline. Our findings suggest that histone 3 trimethylation is a probable target for pharmacological intervention that can counteract cognitive decline in the aging brain. Finally, we provide support to the hypothesis that, by manipulating the enzyme that regulates H3K9

  6. Using Formative Assessment to Facilitate Learner Self-Regulation: A Case Study of Assessment Practices and Student Perceptions in Hong Kong

    Science.gov (United States)

    Jing Jing, Ma

    2017-01-01

    One of the key aims of formative assessment in higher education is to enable students to become self-regulated learners (Nicol & Macfarlane-Dick, 2006). Based on Nicol and Macfarlane-Dick's (2006) framework, this exploratory study investigates which formative assessment practices proposed by them were used by one college EFL writing teacher to…

  7. Timed and targeted differential regulation of nitric oxide synthase (NOS) and anti-NOS genes by reward conditioning leading to long-term memory formation.

    Science.gov (United States)

    Korneev, Sergei A; Straub, Volko; Kemenes, Ildikó; Korneeva, Elena I; Ott, Swidbert R; Benjamin, Paul R; O'Shea, Michael

    2005-02-02

    In a number of neuronal models of learning, signaling by the neurotransmitter nitric oxide (NO), synthesized by the enzyme neuronal NO synthase (nNOS), is essential for the formation of long-term memory (LTM). Using the molluscan model system Lymnaea, we investigate here whether LTM formation is associated with specific changes in the activity of members of the NOS gene family: Lym-nNOS1, Lym-nNOS2, and the antisense RNA-producing pseudogene (anti-NOS). We show that expression of the Lym-nNOS1 gene is transiently upregulated in cerebral ganglia after conditioning. The activation of the gene is precisely timed and occurs at the end of a critical period during which NO is required for memory consolidation. Moreover, we demonstrate that this induction of the Lym-nNOS1 gene is targeted to an identified modulatory neuron called the cerebral giant cell (CGC). This neuron gates the conditioned feeding response and is an essential part of the neural network involved in LTM formation. We also show that the expression of the anti-NOS gene, which functions as a negative regulator of nNOS expression, is downregulated in the CGC by training at 4 h after conditioning, during the critical period of NO requirement. This appears to be the first report of the timed and targeted differential regulation of the activity of a group of related genes involved in the production of a neurotransmitter that is necessary for learning, measured in an identified neuron of known function. We also provide the first example of the behavioral regulation of a pseudogene.

  8. Dynamic neural systems enable adaptive, flexible memories.

    NARCIS (Netherlands)

    Kroes, M.C.W.; Fernandez, G.S.E.

    2012-01-01

    Almost all studies on memory formation have implicitly put forward a rather static view on memory. However, memories are not stable but sensitive to changes over time. Here we argue that memory alterations arise from the inherent predictive function of memory. Within this framework, we draw an

  9. Herbal Extracts Combination (WNK Prevents Decline in Spatial Learning and Memory in APP/PS1 Mice through Improvement of Hippocampal Aβ Plaque Formation, Histopathology, and Ultrastructure

    Directory of Open Access Journals (Sweden)

    Wei-hong Cong

    2012-01-01

    Full Text Available To investigate the cognitive enhancement effect of WNK, an extracts combination of P. ginseng,  G. biloba, and C. sativus L. and possible mechanisms, 5-month-old APP/PS1 transgenic mice were used in this study. After 3 months of administration, all mice received Morris water maze (MWM training and a probe test. Mouse brain sections were detected by immunohistochemistry, HE staining, and transmission electron microscopy. MWM results showed significant difference between transgenic mice and nontransgenic littermates (P<0.05, P<0.01. WNK-treated mice exhibited enhanced maze performance over the training progression, especially better spatial memory retention in probe test compared to transgenic mice (P<0.05, P<0.01 and better spatial learning and memory at the fourth day of MWM test compared to EGB761- (G. biloba extract- treated ones (P<0.05. Hippocampal Aβ plaque burden significantly differed between APP/PS1 and littermate mice (P<0.001, while decreased Aβ plaque appeared in WNK- or EGB761-treated transgenic brains (P<0.05. Neurodegenerative changes were evident from light microscopic and ultrastructural observations in transgenic brains, which were improved by WNK or EGB761 treatment. These data indicate WNK can reduce the decline in spatial cognition, which might be due to its effects on reducing Aβ plaque formation and ameliorating histopathology and ultrastructure in hippocampus of APP/PS1 mouse brain.

  10. Glycosaminoglycan-mediated coacervation of tropoelastin abolishes the critical concentration, accelerates coacervate formation, and facilitates spherule fusion: implications for tropoelastin microassembly.

    Science.gov (United States)

    Tu, Yidong; Weiss, Anthony S

    2008-07-01

    Elastogenesis and elastin repair depend on the secretion of tropoelastin from the cell, yet cellular production is low in the many biological systems that have been studied. To address the apparent paradox of a paucity of tropoelastin for cell surface microassembly, we examined the effects of the glycosaminoglycans heparin, heparan sulfate, and chondroitin sulfate B, on tropoelastin aggregate formation through coacervation. We found a significant effect, particularly of heparin, on the minimum or critical concentration of tropoelastin, which was required for microassembly, lowering critical concentration to a point that it was no longer detectable. The assemblies resulted in protein droplet formation that was visually indistinguishable from the spherules that typify coacervation. The spherules readily coalesced in the presence of heparin and higher concentrations of tropoelastin, resulting in an almost continuous layer of coacervated tropoelastin. Four stages of droplet behavior were observed: early droplet formation, approximately 6 mum droplet formation, and fusion of droplets followed by the formation of a coalesced layer. We conclude that glycosaminoglycans in the extracellular matrix have the capacity to promote coacervation at low concentrations of tropoelastin.

  11. Domain architecture of protein-disulfide isomerase facilitates its dual role as an oxidase and an isomerase in Ero1p-mediated disulfide formation

    DEFF Research Database (Denmark)

    Kulp, M. S.; Frickel, E. M.; Ellgaard, Lars

    2006-01-01

    Native disulfide bond formation in eukaryotes is dependent on protein-disulfide isomerase (PDI) and its homologs, which contain varying combinations of catalytically active and inactive thioredoxin domains. However, the specific contribution of PDI to the formation of new disulfides versus...... reduction/rearrangement of non-native disulfides is poorly understood. We analyzed the role of individual PDI domains in disulfide bond formation in a reaction driven by their natural oxidant, Ero1p. We found that Ero1p oxidizes the isolated PDI catalytic thioredoxin domains, A and A' at the same rate....... In contrast, we found that in the context of full-length PDI, there is an asymmetry in the rate of oxidation of the two active sites. This asymmetry is the result of a dual effect: an enhanced rate of oxidation of the second catalytic (A') domain and the substrate-mediated inhibition of oxidation of the first...

  12. Behavioral and Neural Analysis of GABA in the Acquisition, Consolidation, Reconsolidation, and Extinction of Fear Memory

    Science.gov (United States)

    Makkar, Steve R; Zhang, Shirley Q; Cranney, Jacquelyn

    2010-01-01

    The current review systematically documents the role of γ-amino-butyric acid (GABA) in different aspects of fear memory—acquisition and consolidation, reconsolidation, and extinction, and attempts to resolve apparent contradictions in the data in order to identify the function of GABAA receptors in fear memory. First, numerous studies have shown that pre- and post-training administration of drugs that facilitate GABAergic transmission disrupt the initial formation of fear memories, indicating a role for GABAA receptors, possibly within the amygdala and hippocampus, in the acquisition and consolidation of fear memories. Similarly, recent evidence indicates that these drugs are also detrimental to the restorage of fear memories after their reactivation. This suggests a role for GABAA receptors in the reconsolidation of fear memories, although the precise neural circuits are yet to be identified. Finally, research regarding the role of GABA in extinction has shown that GABAergic transmission is also disruptive to the formation of newly acquired extinction memories. We argue that contradictions to these patterns are the result of variations in (a) the location of drug infusion, (b) the dosage of the drug and/or (c) the time point of drug administration. The question of whether these GABA-induced memory deficits reflect deficits in retrieval is discussed. Overall, the evidence implies that the processes mediating memory stability consequent to initial fear learning, memory reactivation, and extinction training are dependent on a common mechanism of reduced GABAergic neurotransmission. PMID:20410874

  13. Rac1 modulates the formation of primordial follicles by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice.

    Science.gov (United States)

    Zhao, Lihua; Du, Xinhua; Huang, Kun; Zhang, Tuo; Teng, Zhen; Niu, Wanbao; Wang, Chao; Xia, Guoliang

    2016-04-06

    The size of the primordial follicle pool determines the reproductive potential of mammalian females, and establishment of the pool is highly dependent on specific genes expression. However, the molecular mechanisms by which the essential genes are regulated coordinately to ensure primordial follicle assembly remain a mystery. Here, we show that the small GTPase Rac1 plays an indispensable role in controlling the formation of primordial follicles in mouse ovary. Employing fetal mouse ovary organ culture system, we demonstrate that disruption of Rac1 retarded the breakdown of germline cell cysts while Rac1 overexpression accelerated the formation of primordial follicles. In addition, in vivo inhibitor injection resulted in the formation of multi-oocyte follicles. Subsequent investigation showed that Rac1 induced nuclear import of STAT3 by physical binding. In turn, nuclear STAT3 directly activated the transcription of essential oocyte-specific genes, including Jagged1, GDF9, BMP15 and Nobox. Further, GDF9 and BMP15 regulated the translation of Notch2 via mTORC1 activation in pregranulosa cells. Overexression or addition of Jagged1, GDF9 and BMP15 not only reversed the effect of Rac1 disruption, but also accelerated primordial follicle formation via Notch2 signaling activation. Collectively, these results indicate that Rac1 plays important roles as a key regulator in follicular assembly.

  14. Phage Anti-Immunocomplex Assay (PHAIA) for clomazone: Two-site recognition increases assay specificity and facilitates adaptation into a rapid on-site format

    Science.gov (United States)

    Rossotti, M.A.; Carlomagno, M.; González-Techera, A.; Hammock, B.D.; Last, J.; González-Sapienza, G.

    2010-01-01

    The impact of the use of herbicides in agriculture can be minimized by compliance with good management practices that reduce the amount used and their release into the environment. Simple tests that provide real time on-site information about these chemicals are a major aid for these programs. In this work we show that PHAIA, a method that uses phage-borne peptides to detect the formation of antibody-analyte immunocomplexes, is an advantageous technology to produce such field tests. A monoclonal antibody to the herbicide clomazone was raised and used in the development of conventional competitive and noncompetitive PHAIA immunoassays. The sensitivity attained with the PHAIA format was over ten times higher than that of the competitive format. The cross-reactivity of the two methods was also compared by using structurally related compounds, and we observed that the two-site binding of PHAIA “double-checks” the recognition of the analyte, thereby increasing the assay specificity. The positive readout of the noncompetitive PHAIA method allowed adaptation of the assay into a rapid and simple format where as little as 0.4 ng/ml of clomazone (more than 10-fold lower than the proposed standard) in water samples from a rice field could be easily detected by simple visual inspection. PMID:20886819

  15. Phage anti-immunocomplex assay for clomazone: two-site recognition increasing assay specificity and facilitating adaptation into an on-site format.

    Science.gov (United States)

    Rossotti, M A; Carlomagno, M; González-Techera, A; Hammock, B D; Last, J; González-Sapienza, G

    2010-11-01

    The impact of the use of herbicides in agriculture can be minimized by compliance with good management practices that reduce the amount used and their release into the environment. Simple tests that provide real time on-site information about these chemicals are a major aid for these programs. In this work, we show that phage anti-immunocomplex assay (PHAIA), a method that uses phage-borne peptides to detect the formation of antibody-analyte immunocomplexes, is an advantageous technology to produce such field tests. A monoclonal antibody to the herbicide clomazone was raised and used in the development of conventional competitive and noncompetitive PHAIA immunoassays. The sensitivity attained with the PHAIA format was over 10 times higher than that of the competitive format. The cross-reactivity of the two methods was also compared using structurally related compounds, and we observed that the two-site binding of PHAIA "double-checks" the recognition of the analyte, thereby increasing the assay specificity. The positive readout of the noncompetitive PHAIA method allowed adaptation of the assay into a rapid and simple format where as little as 0.4 ng/mL clomazone (more than 10-fold lower than the proposed standard) in water samples from a rice field could be easily detected by simple visual inspection.

  16. Wisp2/CCN5 up-regulated in the central nervous system of GM3-only mice facilitates neurite formation in Neuro2a cells via integrin-Akt signaling

    Energy Technology Data Exchange (ETDEWEB)

    Ohkawa, Yuki, E-mail: tomilbio@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ohmi, Yuhsuke, E-mail: ooumi82@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Tajima, Orie, E-mail: oriet@isc.chubu.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto-cho, Kasugai 487-8501 (Japan); Yamauchi, Yoshio, E-mail: yyoshio@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Furukawa, Keiko, E-mail: keikofu@isc.chubu.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto-cho, Kasugai 487-8501 (Japan); Furukawa, Koichi, E-mail: koichi@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan)

    2011-08-05

    Highlights: {yields} Wisp2/CCN5 was up-regulated in nervous tissues of GM3-only mutant mice. {yields} Wisp2/CCN5 was found in neurons more strongly in the mutant mice. {yields} Wisp2/CCN5 induces Akt phosphorylation via integrins and facilitates neurite formation. {yields} Wisp2/CCN5 conferred resistance to H{sub 2}O{sub 2}-induced apoptosis. {yields} Up-regulation of Wisp2/CCN5 in GM3-only mice seemed for protection of brains from neurodegeneration. -- Abstract: Wisp2/CCN5 belongs to CCN family proteins which are involved in cell proliferation, angiogenesis, tumorigenesis and wound healing. Although a number of studies on the roles of Wisp2/CCN5 in cancers have been reported, no study on the expression and function of Wisp2/CCN5 in the central nervous system has been reported. In this study, we focused on Wisp2/CCN5 that was up-regulated in nervous tissues in GM3-only mice. Over-expression of Wisp2/CCN5 enhanced neurite outgrowth potently after serum withdrawal with increased phosphorylation levels of Akt and ERKs. When cells were cultured with recombinant Wisp2/CCN5 proteins, more and longer neurites were formed than in the controls. Thus, we demonstrated for the first time that Wisp2/CCN5 facilitates neurite formation in a mouse neuroblastoma cell line, Neuro2a. Akt phosphorylation induced by recombinant Wisp2/CCN5 was suppressed after knockdown of integrin {beta}1. Moreover, Wisp2/CCN5-over-expressing cells were resistant to apoptosis induced by H{sub 2}O{sub 2}. These results suggested that secreted Wisp2/CCN5 induces Akt and ERK phosphorylation via integrins, and consequently facilitates neurite formation and conferred resistance to apoptosis. Up-regulation of Wisp2/CCN5 in GM3-only mice should be, therefore, a reaction to protect nervous tissues from neurodegeneration caused by ganglioside deficiency.

  17. In sync: gamma oscillations and emotional memory

    Directory of Open Access Journals (Sweden)

    Drew Battenfield Headley

    2013-11-01

    Full Text Available Emotional experiences leave vivid memories that can last a lifetime. The emotional facilitation of memory has been attributed to the engagement of diffusely projecting neuromodulatory systems that enhance the consolidation of synaptic plasticity in regions activated by the experience. This process requires the propagation of signals between brain regions, and for those signals to induce long-lasting synaptic plasticity. Both of these demands are met by gamma oscillations, which reflect synchronous population activity on a fast timescale (35-120 Hz. Regions known to participate in the formation of emotional memories, such as the basolateral amygdala, also promote gamma-band activation throughout cortical and subcortical circuits. Recent studies have demonstrated that gamma oscillations are enhanced during emotional situations, coherent between regions engaged by salient stimuli, and predict subsequent memory for cues associated with aversive stimuli. Furthermore, neutral stimuli that come to predict emotional events develop enhanced gamma oscillations, reflecting altered processing in the brain, which may underpin how past emotional experiences color future learning and memory.

  18. Neuronal filopodium formation induced by the membrane glycoprotein M6a (Gpm6a) is facilitated by coronin-1a, Rac1, and p21-activated kinase 1 (Pak1).

    Science.gov (United States)

    Alvarez Juliá, Anabel; Frasch, Alberto C; Fuchsova, Beata

    2016-04-01

    Stress-responsive neuronal membrane glycoprotein M6a (Gpm6a) functions in neurite extension, filopodium and spine formation and synaptogenesis. The mechanisms of Gpm6a action in these processes are incompletely understood. Previously, we identified the actin regulator coronin-1a (Coro1a) as a putative Gpm6a interacting partner. Here, we used co-immunoprecipitation assays with the anti-Coro1a antibody to show that Coro1a associates with Gpm6a in rat hippocampal neurons. By immunofluorescence microscopy, we demonstrated that in hippocampal neurons Coro1a localizes in F-actin-enriched regions and some of Coro1a spots co-localize with Gpm6a labeling. Notably, the over-expression of a dominant-negative form of Coro1a as well as its down-regulation by siRNA interfered with Gpm6a-induced filopodium formation. Coro1a is known to regulate the plasma membrane translocation and activation of small GTPase Rac1. We show that Coro1a co-immunoprecipitates with Rac1 together with Gpm6a. Pharmacological inhibition of Rac1 resulted in a significant decrease in filopodium formation by Gpm6a. The same was observed upon the co-expression of Gpm6a with the inactive GDP-bound form of Rac1. In this case, the elevated membrane recruitment of GDP-bound Rac1 was detected as well. Moreover, the kinase activity of the p21-activated kinase 1 (Pak1), a main downstream effector of Rac1 that acts downstream of Coro1a, was required for Gpm6a-induced filopodium formation. Taken together, our results provide evidence that a signaling pathway including Coro1a, Rac1, and Pak1 facilitates Gpm6a-induced filopodium formation. Formation of filopodia by membrane glycoprotein M6a (Gpm6a) requires actin regulator coronin-1a (Coro1a), known to regulate plasma membrane localization and activation of Rac1 and its downstream effector Pak1. Coro1a associates with Gpm6a. Blockage of Coro1a, Rac1, or Pak1 interferes with Gpm6a-induced filopodium formation. Moreover, Gpm6a facilitates Rac1 membrane recruitment

  19. DnaK and DnaJ facilitated the folding process and reduced inclusion body formation of magnesium transporter CorA overexpressed in Escherichia coli.

    Science.gov (United States)

    Chen, Yong; Song, Jinmei; Sui, Sen-fang; Wang, Da-Neng

    2003-12-01

    Overexpression of CorA, the major magnesium transporter from bacterial inner membrane, in Escherichia coli resulted in the synthesis of 60mg of protein per liter of culture, most of which however was in the form of inclusion bodies. The levels of inclusion body formation were reduced by lowering the cell culture temperature. To dissect CorA inclusion body formation and the folding process involved, we co-expressed the protein with various chaperones and other folding modulators. Expression of DnaK/DnaJ (Hsp70) prevented inclusion bodies from forming and resulted in the integration of more CorA into the membrane. GroEL/GroES (Hsp60/Hsp10) were less effective at reducing CorA inclusion body formation. Co-expression with either Ffh/4.5S-RNA, the signal recognition particle, or SecA, the ATPase that drives protein insertion into the membrane, had little effect on CorA folding. These results indicate: (1) that CorA inclusion bodies form immediately after synthesis at 37 degrees C, (2) that CorA solubility in the cytosol can be increased by co-expressing a chaperone system, (3) membrane targeting is probably not a rate-limiting factor, and (4) that membrane insertion becomes a limitation only when large amounts of soluble CorA are present in the cytosol. These co-expression systems can be used for producing other membrane proteins in large quantities.

  20. Negative Affect Impairs Associative Memory but Not Item Memory

    Science.gov (United States)

    Bisby, James A.; Burgess, Neil

    2014-01-01

    The formation of associations between items and their context has been proposed to rely on mechanisms distinct from those supporting memory for a single item. Although emotional experiences can profoundly affect memory, our understanding of how it interacts with different aspects of memory remains unclear. We performed three experiments to examine…

  1. Disruption of the dorsolateral prefrontal cortex facilitates the consolidation of procedural skills.

    Science.gov (United States)

    Galea, Joseph M; Albert, Neil B; Ditye, Thomas; Miall, R Chris

    2010-06-01

    In explicit sequence learning tasks, an improvement in performance (skill) typically occurs after sleep-leading to the recent literature on sleep-dependent motor consolidation. Consolidation can also be facilitated during wakefulness if declarative knowledge for the sequence is reduced through a secondary cognitive task. Accordingly, declarative and procedural consolidation processes appear to mutually interact. Here we used TMS to test the hypothesis that functions in the dorsolateral prefrontal cortex (DLPFC) that support declarative memory formation indirectly reduce the formation of procedural representations. We hypothesize that disrupting the DLPFC immediately after sequence learning would degrade the retention or the consolidation of the sequence within the declarative memory system and thus facilitate consolidation within procedural memory systems, evident as wakeful off-line skill improvement. Inhibitory theta-burst TMS was applied to the left DLPFC (n = 10), to the right DLPFC (n = 10), or to an occipital cortical control site (n = 10) immediately after training on the serial reaction time task (SRTT). All groups were retested after eight daytime hours without sleep. TMS of either left or right DLPFC lead to skill improvements on the SRTT. Increase in skill was greater following right DLPFC stimulation than left DLPFC stimulation; there was no improvement in skill for the control group. Across all participants, free recall of the sequence was inversely related to the improvements in performance on the SRTT. These results support the hypothesis of interference between declarative and procedural consolidation processes and are discussed in the framework of the interactions between memory systems.

  2. Formation of the Nanocrystalline Structure in an Equiatomic NiTi Shape-Memory Alloy by Thermomechanical Processing

    Science.gov (United States)

    Mohammad Sharifi, E.; Kermanpur, A.; Karimzadeh, F.; Esmaili, A.

    2014-04-01

    The microstructural evolution during cold rolling followed by annealing of an equiatomic NiTi shape-memory alloy was investigated. The high purity Ni50Ti50 alloy was cast by a copper boat vacuum induction-melting technique. The as-cast ingots were then homogenized, hot rolled, and annealed to prepare the suitable initial microstructure. Thereafter, annealed specimens were cold rolled up to 70 % thickness reduction at room temperature. Post-deformation annealing was conducted at 400 °C for 1 h. The microstructure was characterized using scanning electron microscopy, transmission electron microscopy, x-ray diffraction, and differential scanning calorimetry techniques. The initial microstructure was free from segregation and Ti- or Ni-rich precipitates and was composed of coarse grains with an average size of 50 μm. The cold rolling of NiTi alloy resulted in a partial amorphization and the deformation-induced grain refinement. A nanocrystalline structure with the grain size of about 20-70 nm was formed during the post-deformation annealing.

  3. Deficiency of Cks1 Leads to Learning and Long-Term Memory Defects and p27 Dependent Formation of Neuronal Cofilin Aggregates.

    Science.gov (United States)

    Kukalev, Alexander; Ng, Yiu-Ming; Ju, Limei; Saidi, Amal; Lane, Sophie; Mondragon, Angeles; Dormann, Dirk; Walker, Sophie E; Grey, William; Ho, Philip Wing-Lok; Stephens, David N; Carr, Antony M; Lamsa, Karri; Tse, Eric; Yu, Veronica P C C

    2017-01-01

    In mitotic cells, the cyclin-dependent kinase (CDK) subunit protein CKS1 regulates S phase entry by mediating degradation of the CDK inhibitor p27. Although mature neurons lack mitotic CDKs, we found that CKS1 was actively expressed in post-mitotic neurons of the adult hippocampus. Interestingly, Cks1 knockout (Cks1-/-) mice exhibited poor long-term memory, and diminished maintenance of long-term potentiation in the hippocampal circuits. Furthermore, there was neuronal accumulation of cofilin-actin rods or cofilin aggregates, which are associated with defective dendritic spine maturation and synaptic loss. We further demonstrated that it was the increased p27 level that activated cofilin by suppressing the RhoA kinase-mediated inhibitory phosphorylation of cofilin, resulting in the formation of cofilin aggregates in the Cks1-/- neuronal cells. Consistent with reports that the peptidyl-prolyl-isomerase PIN1 competes with CKS1 for p27 binding, we found that inhibition of PIN1 diminished the formation of cofilin aggregates through decreasing p27 levels, thereby activating RhoA and increasing cofilin phosphorylation. Our results revealed that CKS1 is involved in normal glutamatergic synapse development and dendritic spine maturation in adult hippocampus through modulating p27 stability. © The Author 2016. Published by Oxford University Press.

  4. Evaluation of passive oxide layer formation-biocompatibility relationship in NiTi shape memory alloys: geometry and body location dependency.

    Science.gov (United States)

    Toker, S M; Canadinc, D; Maier, H J; Birer, O

    2014-03-01

    A systematic set of ex-situ experiments were carried out on Nickel-Titanium (NiTi) shape memory alloy (SMA) in order to identify the dependence of its biocompatibility on sample geometry and body location. NiTi samples with three different geometries were immersed into three different fluids simulating different body parts. The changes observed in alloy surface and chemical content of fluids upon immersion experiments designed for four different time periods were analyzed in terms of ion release, oxide layer formation, and chemical composition of the surface layer. The results indicate that both sample geometry and immersion fluid significantly affect the alloy biocompatibility, as evidenced by the passive oxide layer formation on the alloy surface and ion release from the samples. Upon a 30 day immersion period, all three types of NiTi samples exhibited lower ion release than the critical value for clinic applications. However; a significant amount of ion release was detected in the case of gastric fluid, warranting a thorough investigation prior to utility of NiTi in gastrointestinal treatments involving long-time contact with tissue. Furthermore, certain geometries appear to be safer than the others for each fluid, providing a new set of guidelines to follow while designing implants making use of NiTi SMAs to be employed in treatments targeting specific body parts. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Hippocampal sleep features: relations to human memory function.

    Science.gov (United States)

    Ferrara, Michele; Moroni, Fabio; De Gennaro, Luigi; Nobili, Lino

    2012-01-01

    The recent spread of intracranial electroencephalographic (EEG) recording techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific patterns of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, non-REM sleep) in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples) that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate

  6. Hippocampal sleep features: relations to human memory function

    Directory of Open Access Journals (Sweden)

    Michele eFerrara

    2012-04-01

    Full Text Available The recent spread of intracranial EEG recordings techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific pattern of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, NREM sleep in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate sleep

  7. Memory dynamics under stress.

    Science.gov (United States)

    Quaedflieg, Conny W E M; Schwabe, Lars

    2017-06-19

    Stressful events have a major impact on memory. They modulate memory formation in a time-dependent manner, closely linked to the temporal profile of action of major stress mediators, in particular catecholamines and glucocorticoids. Shortly after stressor onset, rapidly acting catecholamines and fast, non-genomic glucocorticoid actions direct cognitive resources to the processing and consolidation of the ongoing threat. In parallel, control of memory is biased towards rather rigid systems, promoting habitual forms of memory allowing efficient processing under stress, at the expense of "cognitive" systems supporting memory flexibility and specificity. In this review, we discuss the implications of this shift in the balance of multiple memory systems for the dynamics of the memory trace. Specifically, stress appears to hinder the incorporation of contextual details into the memory trace, to impede the integration of new information into existing knowledge structures, to impair the flexible generalisation across past experiences, and to hamper the modification of memories in light of new information. Delayed, genomic glucocorticoid actions might reverse the control of memory, thus restoring homeostasis and "cognitive" control of memory again.

  8. Memory Storage and Neural Systems.

    Science.gov (United States)

    Alkon, Daniel L.

    1989-01-01

    Investigates memory storage and molecular nature of associative-memory formation by analyzing Pavlovian conditioning in marine snails and rabbits. Presented is the design of a computer-based memory system (neural networks) using the rules acquired in the investigation. Reports that the artificial network recognized patterns well. (YP)

  9. Stress effects on memory: an update and integration.

    Science.gov (United States)

    Schwabe, Lars; Joëls, Marian; Roozendaal, Benno; Wolf, Oliver T; Oitzl, Melly S

    2012-08-01

    It is well known that stressful experiences may affect learning and memory processes. Less clear is the exact nature of these stress effects on memory: both enhancing and impairing effects have been reported. These opposite effects may be explained if the different time courses of stress hormone, in particular catecholamine and glucocorticoid, actions are taken into account. Integrating two popular models, we argue here that rapid catecholamine and non-genomic glucocorticoid actions interact in the basolateral amygdala to shift the organism into a 'memory formation mode' that facilitates the consolidation of stressful experiences into long-term memory. The undisturbed consolidation of these experiences is then promoted by genomic glucocorticoid actions that induce a 'memory storage mode', which suppresses competing cognitive processes and thus reduces interference by unrelated material. Highlighting some current trends in the field, we further argue that stress affects learning and memory processes beyond the basolateral amygdala and hippocampus and that stress may pre-program subsequent memory performance when it is experienced during critical periods of brain development.

  10. Targeted Reactivation during Sleep Differentially Affects Negative Memories in Socially Anxious and Healthy Children and Adolescents.

    Science.gov (United States)

    Groch, Sabine; Preiss, Andrea; McMakin, Dana L; Rasch, Björn; Walitza, Susanne; Huber, Reto; Wilhelm, Ines

    2017-03-01

    Cognitive models propose a negative memory bias as one key factor contributing to the emergence and maintenance of social anxiety disorder (SAD). The long-term consolidation of memories relies on memory reactivations during sleep. We investigated in SAD patients and healthy controls the role of memory<