Mechanisms of Memory Enhancement

PubMed Central

Stern, Sarah A.

2012-01-01

The ongoing quest for memory enhancement is one that grows necessary as the global population increasingly ages. The extraordinary progress that has been made in the past few decades elucidating the underlying mechanisms of how long-term memories are formed has provided insight into how memories might also be enhanced. Capitalizing on this knowledge, it has been postulated that targeting many of the same mechanisms, including CREB activation, AMPA/NMDA receptor trafficking, neuromodulation (e.g. via dopamine, adrenaline, cortisol or acetylcholine) and metabolic processes (e.g. via glucose and insulin) may all lead to the enhancement of memory. These and other mechanisms and/or approaches have been tested via genetic or pharmacological methods in animal models, and several have been investigated in humans as well. In addition, a number of behavioral methods, including exercise and reconsolidation, may also serve to strengthen and enhance memories. By capitalizing on this knowledge and continuing to investigate these promising avenues, memory enhancement may indeed be achieved in the future. PMID:23151999

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

NASA Astrophysics Data System (ADS)

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.

Memory for Lectures: How Lecture Format Impacts the Learning Experience

PubMed Central

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. PMID:26561235

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

PubMed

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.

Attentional influences on memory formation: A tale of a not-so-simple story.

PubMed

Ortiz-Tudela, J; Milliken, B; Jiménez, L; Lupiáñez, J

2018-05-01

Is there a learning mechanism triggered by mere expectation violation? Is there some form of memory enhancement inherent to an event mismatching our predictions? Across seven experiments, we explore this issue by means of a validity paradigm. Although our manipulation clearly succeeded in generating an expectation and breaking it, the memory consequences of that expectation mismatch are not so obvious. We report here evidence of a null effect of expectation on memory formation. Our results (1) show that enhanced memory for unexpected events is not easily achieved and (2) call for a reevaluation of previous accounts of memory enhancements based on prediction error or difficulty of processing. Limitations of this study and possible implications for the field are discussed in detail.

Post-encoding emotional arousal enhances consolidation of item memory, but not reality-monitoring source memory.

PubMed

Wang, Bo; Sun, Bukuan

2017-03-01

The current study examined whether the effect of post-encoding emotional arousal on item memory extends to reality-monitoring source memory and, if so, whether the effect depends on emotionality of learning stimuli and testing format. In Experiment 1, participants encoded neutral words and imagined or viewed their corresponding object pictures. Then they watched a neutral, positive, or negative video. The 24-hour delayed test showed that emotional arousal had little effect on both item memory and reality-monitoring source memory. Experiment 2 was similar except that participants encoded neutral, positive, and negative words and imagined or viewed their corresponding object pictures. The results showed that positive and negative emotional arousal induced after encoding enhanced consolidation of item memory, but not reality-monitoring source memory, regardless of emotionality of learning stimuli. Experiment 3, identical to Experiment 2 except that participants were tested only on source memory for all the encoded items, still showed that post-encoding emotional arousal had little effect on consolidation of reality-monitoring source memory. Taken together, regardless of emotionality of learning stimuli and regardless of testing format of source memory (conjunction test vs. independent test), the facilitatory effect of post-encoding emotional arousal on item memory does not generalize to reality-monitoring source memory.

Serotonin–mushroom body circuit modulating the formation of anesthesia-resistant memory in Drosophila

PubMed Central

Lee, Pei-Tseng; Lin, Hsuan-Wen; Chang, Yu-Hsuan; Fu, Tsai-Feng; Dubnau, Josh; Hirsh, Jay; Lee, Tzumin; Chiang, Ann-Shyn

2011-01-01

Pavlovian olfactory learning in Drosophila produces two genetically distinct forms of intermediate-term memories: anesthesia-sensitive memory, which requires the amnesiac gene, and anesthesia-resistant memory (ARM), which requires the radish gene. Here, we report that ARM is specifically enhanced or inhibited in flies with elevated or reduced serotonin (5HT) levels, respectively. The requirement for 5HT was additive with the memory defect of the amnesiac mutation but was occluded by the radish mutation. This result suggests that 5HT and Radish protein act on the same pathway for ARM formation. Three supporting lines of evidence indicate that ARM formation requires 5HT released from only two dorsal paired medial (DPM) neurons onto the mushroom bodies (MBs), the olfactory learning and memory center in Drosophila: (i) DPM neurons were 5HT-antibody immunopositive; (ii) temporal inhibition of 5HT synthesis or release from DPM neurons, but not from other serotonergic neurons, impaired ARM formation; (iii) knocking down the expression of d5HT1A serotonin receptors in α/β MB neurons, which are innervated by DPM neurons, inhibited ARM formation. Thus, in addition to the Amnesiac peptide required for anesthesia-sensitive memory formation, the two DPM neurons also release 5HT acting on MB neurons for ARM formation. PMID:21808003

Hippocampal 5-HT Input Regulates Memory Formation and Schaffer Collateral Excitation.

PubMed

Teixeira, Catia M; Rosen, Zev B; Suri, Deepika; Sun, Qian; Hersh, Marc; Sargin, Derya; Dincheva, Iva; Morgan, Ashlea A; Spivack, Stephen; Krok, Anne C; Hirschfeld-Stoler, Tessa; Lambe, Evelyn K; Siegelbaum, Steven A; Ansorge, Mark S

2018-06-06

The efficacy and duration of memory storage is regulated by neuromodulatory transmitter actions. While the modulatory transmitter serotonin (5-HT) plays an important role in implicit forms of memory in the invertebrate Aplysia, its function in explicit memory mediated by the mammalian hippocampus is less clear. Specifically, the consequences elicited by the spatio-temporal gradient of endogenous 5-HT release are not known. Here we applied optogenetic techniques in mice to gain insight into this fundamental biological process. We find that activation of serotonergic terminals in the hippocampal CA1 region both potentiates excitatory transmission at CA3-to-CA1 synapses and enhances spatial memory. Conversely, optogenetic silencing of CA1 5-HT terminals inhibits spatial memory. We furthermore find that synaptic potentiation is mediated by 5-HT4 receptors and that systemic modulation of 5-HT4 receptor function can bidirectionally impact memory formation. Collectively, these data reveal powerful modulatory influence of serotonergic synaptic input on hippocampal function and memory formation. Copyright © 2018 Elsevier Inc. All rights reserved.

How mood challenges emotional memory formation: an fMRI investigation.

PubMed

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. Copyright © 2011 Elsevier Inc. All rights reserved.

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

PubMed Central

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

The development of neural correlates for memory formation

PubMed Central

Ofen, Noa

2012-01-01

A growing body of literature considers the development of episodic memory systems in the brain; the majority are neuroimaging studies conducted during memory encoding in order to explore developmental trajectories in memory formation. This review considers evidence from behavioral studies of memory development, neural correlates of memory formation in adults, and structural brain development, all of which form the foundation of a developmental cognitive neuroscience approach to memory development. I then aim to integrate the current evidence from developmental functional neuroimaging studies of memory formation with respect to three hypotheses. First, memory development reflects the development in the use of memory strategies, linked to prefrontal cortex. Second, developmental effects within the medial temporal lobes are more complex, and correspond to current notions about the nature in which the MTL support the formation of memory. Third, neurocognitive changes in content representation influence memory. Open issues and current directions are discussed. PMID:22414608

Auditory closed-loop stimulation of the sleep slow oscillation enhances memory.

PubMed

Ngo, Hong-Viet V; Martinetz, Thomas; Born, Jan; Mölle, Matthias

2013-05-08

Brain rhythms regulate information processing in different states to enable learning and memory formation. The <1 Hz sleep slow oscillation hallmarks slow-wave sleep and is critical to memory consolidation. Here we show in sleeping humans that auditory stimulation in phase with the ongoing rhythmic occurrence of slow oscillation up states profoundly enhances the slow oscillation rhythm, phase-coupled spindle activity, and, consequently, the consolidation of declarative memory. Stimulation out of phase with the ongoing slow oscillation rhythm remained ineffective. Closed-loop in-phase stimulation provides a straight-forward tool to enhance sleep rhythms and their functional efficacy. Copyright © 2013 Elsevier Inc. All rights reserved.

Enhancing early consolidation of human episodic memory by theta EEG neurofeedback.

PubMed

Rozengurt, Roman; Shtoots, Limor; Sheriff, Aviv; Sadka, Ofir; Levy, Daniel A

2017-11-01

Consolidation of newly formed memories is readily disrupted, but can it be enhanced? Given the prominent role of hippocampal theta oscillations in memory formation and retrieval, we hypothesized that upregulating theta power during early stages of consolidation might benefit memory stability and persistence. We used EEG neurofeedback to enable participants to selectively increase theta power in their EEG spectra following episodic memory encoding, while other participants engaged in low beta-focused neurofeedback or passively viewed a neutral nature movie. Free recall assessments immediately following the interventions, 24h later and 7d later all indicated benefit to memory of theta neurofeedback, relative to low beta neurofeedback or passive movie-viewing control conditions. The degree of benefit to memory was correlated with the extent of theta power modulation, but not with other spectral changes. Theta enhancement may provide optimal conditions for stabilization of new hippocampus-dependent memories. Copyright © 2017 Elsevier Inc. All rights reserved.

Post-Training Intrahippocampal Inhibition of Class I Histone Deacetylases Enhances Long-Term Object-Location Memory

ERIC Educational Resources Information Center

Hawk, Joshua D.; Florian, Cedrick; Abel, Ted

2011-01-01

Long-term memory formation involves covalent modification of the histone proteins that package DNA. Reducing histone acetylation by mutating histone acetyltransferases impairs long-term memory, and enhancing histone acetylation by inhibiting histone deacetylases (HDACs) improves long-term memory. Previous studies using HDAC inhibitors to enhance…

Source memory enhancement for emotional words.

PubMed

Doerksen, S; Shimamura, A P

2001-03-01

The influence of emotional stimuli on source memory was investigated by using emotionally valenced words. The words were colored blue or yellow (Experiment 1) or surrounded by a blue or yellow frame (Experiment 2). Participants were asked to associate the words with the colors. In both experiments, emotionally valenced words elicited enhanced free recall compared with nonvalenced words; however, recognition memory was not affected. Source memory for the associated color was also enhanced for emotional words, suggesting that even memory for contextual information is benefited by emotional stimuli. This effect was not due to the ease of semantic clustering of emotional words because semantically related words were not associated with enhanced source memory, despite enhanced recall (Experiment 3). It is suggested that enhancement resulted from facilitated arousal or attention, which may act to increase organization processes important for source memory.

Level of processing modulates the neural correlates of emotional memory formation

PubMed Central

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

2010-01-01

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 employed a levels-of-processing manipulation to characterize the impact of emotion on encoding with and without the influence of elaborative processes. Participants viewed emotionally negative, neutral, and positive scenes under two conditions: a shallow condition focused on the perceptual features of the scenes and a deep condition that queried their semantic meaning. Recognition memory was tested 2 days later. Results showed that emotional memory enhancements were greatest in the shallow condition. FMRI analyses revealed that the right amygdala predicted subsequent emotional memory in the shallow more than deep condition, whereas the right ventrolateral prefrontal cortex demonstrated the reverse pattern. Furthermore, the association of these regions with the hippocampus was modulated by valence: the amygdala-hippocampal link was strongest for negative stimuli, whereas the prefrontal-hippocampal link was strongest for positive stimuli. Taken together, these results suggest two distinct activation patterns underlying emotional memory formation: an amygdala component that promotes memory during shallow encoding, especially for negative information, and a prefrontal component that provides extra benefits during deep encoding, especially for positive information. PMID:20350176

Level of processing modulates the neural correlates of emotional memory formation.

PubMed

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

2011-04-01

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 encoding with and without the influence of elaborative processes. Participants viewed emotionally negative, neutral, and positive scenes under two conditions: a shallow condition focused on the perceptual features of the scenes and a deep condition that queried their semantic meaning. Recognition memory was tested 2 days later. Results showed that emotional memory enhancements were greatest in the shallow condition. fMRI analyses revealed that the right amygdala predicted subsequent emotional memory in the shallow more than deep condition, whereas the right ventrolateral PFC demonstrated the reverse pattern. Furthermore, the association of these regions with the hippocampus was modulated by valence: the amygdala-hippocampal link was strongest for negative stimuli, whereas the prefrontal-hippocampal link was strongest for positive stimuli. Taken together, these results suggest two distinct activation patterns underlying emotional memory formation: an amygdala component that promotes memory during shallow encoding, especially for negative information, and a prefrontal component that provides extra benefits during deep encoding, especially for positive information.

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

PubMed

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.

Memory formation orchestrates the wiring of adult-born hippocampal neurons into brain circuits.

PubMed

Petsophonsakul, Petnoi; Richetin, Kevin; Andraini, Trinovita; Roybon, Laurent; Rampon, Claire

2017-08-01

During memory formation, structural rearrangements of dendritic spines provide a mean to durably modulate synaptic connectivity within neuronal networks. New neurons generated throughout the adult life in the dentate gyrus of the hippocampus contribute to learning and memory. As these neurons become incorporated into the network, they generate huge numbers of new connections that modify hippocampal circuitry and functioning. However, it is yet unclear as to how the dynamic process of memory formation influences their synaptic integration into neuronal circuits. New memories are established according to a multistep process during which new information is first acquired and then consolidated to form a stable memory trace. Upon recall, memory is transiently destabilized and vulnerable to modification. Using contextual fear conditioning, we found that learning was associated with an acceleration of dendritic spines formation of adult-born neurons, and that spine connectivity becomes strengthened after memory consolidation. Moreover, we observed that afferent connectivity onto adult-born neurons is enhanced after memory retrieval, while extinction training induces a change of spine shapes. Together, these findings reveal that the neuronal activity supporting memory processes strongly influences the structural dendritic integration of adult-born neurons into pre-existing neuronal circuits. Such change of afferent connectivity is likely to impact the overall wiring of hippocampal network, and consequently, to regulate hippocampal function.

Enhancement of fear memory by retrieval through reconsolidation

PubMed Central

Fukushima, Hotaka; Zhang, Yue; Archbold, Georgia; Ishikawa, Rie; Nader, Karim; Kida, Satoshi

2014-01-01

Memory retrieval is considered to have roles in memory enhancement. Recently, memory reconsolidation was suggested to reinforce or integrate new information into reactivated memory. Here, we show that reactivated inhibitory avoidance (IA) memory is enhanced through reconsolidation under conditions in which memory extinction is not induced. This memory enhancement is mediated by neurons in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) through the simultaneous activation of calcineurin-induced proteasome-dependent protein degradation and cAMP responsive element binding protein-mediated gene expression. Interestingly, the amygdala is required for memory reconsolidation and enhancement, whereas the hippocampus and mPFC are required for only memory enhancement. Furthermore, memory enhancement triggered by retrieval utilizes distinct mechanisms to strengthen IA memory by additional learning that depends only on the amygdala. Our findings indicate that reconsolidation functions to strengthen the original memory and show the dynamic nature of reactivated memory through protein degradation and gene expression in multiple brain regions. DOI: http://dx.doi.org/10.7554/eLife.02736.001 PMID:24963141

Arousal-Enhanced Location Memory for Pictures

PubMed Central

Mather, Mara; Nesmith, Kathryn

2008-01-01

Four experiments revealed arousal-enhanced location memory for pictures. After an incidental encoding task, participants were more likely to remember the locations of positive and negative arousing pictures than the locations of non-arousing pictures, indicating better binding of location to picture. This arousal-enhanced binding effect did not have a cost for the binding of nearby pictures to their locations. Thus, arousal can enhance binding of an arousing picture’s content to its location without interfering with picture-location binding for nearby pictures. In addition, arousal-enhanced picture-location memory binding is not just a side effect of enhanced memory for the picture itself, as it occurs both when recognition memory is good and when it is poor. PMID:19190722

Memory Enhancement by Targeting Cdk5 Regulation of NR2B

PubMed Central

Plattner, Florian; Hernandéz, Adan; Kistler, Tara M.; Pozo, Karine; Zhong, Ping; Yuen, Eunice Y.; Tan, Chunfeng; Hawasli, Ammar H.; Cooke, Sam F.; Nishi, Akinori; Guo, Ailan; Wiederhold, Thorsten; Yan, Zhen; Bibb, James A.

2014-01-01

SUMMARY Many psychiatric and neurological disorders are characterized by learning and memory deficits, for which cognitive enhancement is considered a valid treatment strategy. The N-methyl-D-aspartate receptor (NMDAR) is a prime target for the development of cognitive enhancers due to its fundamental role in learning and memory. In particular, the NMDAR subunit NR2B improves synaptic plasticity and memory when over-expressed in neurons. However, NR2B regulation is not well understood and no therapies potentiating NMDAR function have been developed. Here, we show that serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5). Cdk5-dependent NR2B phosphorylation is regulated by neuronal activity and controls the receptor’s cell surface expression. Disrupting NR2B-Cdk5 interaction using a small interfering peptide (siP) increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation in vivo. Our results reveal a novel regulatory mechanism critical to NR2B function that can be targeted for the development of cognitive enhancers. PMID:24607229

Voluntary Running Exercise-Mediated Enhanced Neurogenesis Does Not Obliterate Retrograde Spatial Memory.

PubMed

Kodali, Maheedhar; Megahed, Tarick; Mishra, Vikas; Shuai, Bing; Hattiangady, Bharathi; Shetty, Ashok K

2016-08-03

Running exercise (RE) improves cognition, formation of anterograde memories, and mood, alongside enhancing hippocampal neurogenesis. A previous investigation in a mouse model showed that RE-induced increased neurogenesis erases retrograde memory (Akers et al., 2014). However, it is unknown whether RE-induced forgetting is common to all species. We ascertained whether voluntary RE-induced enhanced neurogenesis interferes with the recall of spatial memory in rats. Young rats assigned to either sedentary (SED) or running exercise (RE) groups were first subjected to eight learning sessions in a water maze. A probe test (PT) conducted 24 h after the final training session confirmed that animals in either group had a similar ability for the recall of short-term memory. Following this, rats in the RE group were housed in larger cages fitted with running wheels, whereas rats in the SED group remained in standard cages. Animals in the RE group ran an average of 78 km in 4 weeks. A second PT performed 4 weeks after the first PT revealed comparable ability for memory recall between animals in the RE and SED groups, which was evidenced through multiple measures of memory retrieval function. The RE group displayed a 1.5- to 2.1-fold higher hippocampal neurogenesis than SED rats. Additionally, both moderate and brisk RE did not interfere with the recall of memory, although increasing amounts of RE proportionally enhanced neurogenesis. In conclusion, RE does not impair memory recall ability in a rat model despite substantially increasing neurogenesis. Running exercise (RE) improves new memory formation along with an increased neurogenesis in the hippocampus. In view of a recent study showing that RE-mediated increased hippocampal neurogenesis promotes forgetfulness in a mouse model, we ascertained whether a similar adverse phenomenon exists in a rat model. Memory recall ability examined 4 weeks after learning confirmed that animals that had run a mean of 78 km and displayed a 1

Coordinated prefrontal-hippocampal activity and navigation strategy-related prefrontal firing during spatial memory formation.

PubMed

Negrón-Oyarzo, Ignacio; Espinosa, Nelson; Aguilar, Marcelo; Fuenzalida, Marco; Aboitiz, Francisco; Fuentealba, Pablo

2018-06-18

Learning the location of relevant places in the environment is crucial for survival. Such capacity is supported by a distributed network comprising the prefrontal cortex and hippocampus, yet it is not fully understood how these structures cooperate during spatial reference memory formation. Hence, we examined neural activity in the prefrontal-hippocampal circuit in mice during acquisition of spatial reference memory. We found that interregional oscillatory coupling increased with learning, specifically in the slow-gamma frequency (20 to 40 Hz) band during spatial navigation. In addition, mice used both spatial and nonspatial strategies to navigate and solve the task, yet prefrontal neuronal spiking and oscillatory phase coupling were selectively enhanced in the spatial navigation strategy. Lastly, a representation of the behavioral goal emerged in prefrontal spiking patterns exclusively in the spatial navigation strategy. These results suggest that reference memory formation is supported by enhanced cortical connectivity and evolving prefrontal spiking representations of behavioral goals.

Nogo receptor 1 regulates formation of lasting memories.

PubMed

Karlén, Alexandra; Karlsson, Tobias E; Mattsson, Anna; Lundströmer, Karin; Codeluppi, Simone; Pham, Therese M; Bäckman, Cristina M; Ogren, Sven Ove; Aberg, Elin; Hoffman, Alexander F; Sherling, Michael A; Lupica, Carl R; Hoffer, Barry J; Spenger, Christian; Josephson, Anna; Brené, Stefan; Olson, Lars

2009-12-01

Formation of lasting memories is believed to rely on structural alterations at the synaptic level. We had found that increased neuronal activity down-regulates Nogo receptor-1 (NgR1) in brain regions linked to memory formation and storage, and postulated this to be required for formation of lasting memories. We now show that mice with inducible overexpression of NgR1 in forebrain neurons have normal long-term potentiation and normal 24-h memory, but severely impaired month-long memory in both passive avoidance and swim maze tests. Blocking transgene expression normalizes these memory impairments. Nogo, Lingo-1, Troy, endogenous NgR1, and BDNF mRNA expression levels were not altered by transgene expression, suggesting that the impaired ability to form lasting memories is directly coupled to inability to down-regulate NgR1. Regulation of NgR1 may therefore serve as a key regulator of memory consolidation. Understanding the molecular underpinnings of synaptic rearrangements that carry lasting memories may facilitate development of treatments for memory dysfunction.

Nogo receptor 1 regulates formation of lasting memories

PubMed Central

Karlén, Alexandra; Karlsson, Tobias E.; Mattsson, Anna; Lundströmer, Karin; Codeluppi, Simone; Pham, Therese M.; Bäckman, Cristina M.; Ögren, Sven Ove; Åberg, Elin; Hoffman, Alexander F.; Sherling, Michael A.; Lupica, Carl R.; Hoffer, Barry J.; Spenger, Christian; Josephson, Anna; Brené, Stefan; Olson, Lars

2009-01-01

Formation of lasting memories is believed to rely on structural alterations at the synaptic level. We had found that increased neuronal activity down-regulates Nogo receptor-1 (NgR1) in brain regions linked to memory formation and storage, and postulated this to be required for formation of lasting memories. We now show that mice with inducible overexpression of NgR1 in forebrain neurons have normal long-term potentiation and normal 24-h memory, but severely impaired month-long memory in both passive avoidance and swim maze tests. Blocking transgene expression normalizes these memory impairments. Nogo, Lingo-1, Troy, endogenous NgR1, and BDNF mRNA expression levels were not altered by transgene expression, suggesting that the impaired ability to form lasting memories is directly coupled to inability to down-regulate NgR1. Regulation of NgR1 may therefore serve as a key regulator of memory consolidation. Understanding the molecular underpinnings of synaptic rearrangements that carry lasting memories may facilitate development of treatments for memory dysfunction. PMID:19915139

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

PubMed Central

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

Critical Period of Memory Enhancement during Taste Avoidance Conditioning in Lymnaea stagnalis

PubMed Central

Sunada, Hiroshi; Lukowiak, Ken; Sakakibara, Manabu

2013-01-01

The present study investigated the optimal training procedure leading to long-lasting taste avoidance behavior in Lymnaea. A training procedure comprising 5 repeated pairings of a conditional stimulus (CS, sucrose), with an unconditional stimulus (US, a tactile stimulation to the animal’s head), over a 4-day period resulted in an enhanced memory formation than 10 CS-US repeated pairings over a 2-day period or 20 CS-US repeated pairings on a single day. Backward conditioning (US-CS) pairings did not result in conditioning. Thus, this taste avoidance conditioning was CS-US pairing specific. Food avoidance behavior was not observed following training, however, if snails were immediately subjected to a cold-block (4°C for 10 min). It was critical that the cold-block be applied within 10 min to block long-term memory (LTM) formation. Further, exposure to the cold-block 180 min after training also blocked both STM and LTM formation. The effects of the cold-block on subsequent learning and memory formation were also examined. We found no long lasting effects of the cold-block on subsequent memory formation. If protein kinase C was activated before the conditioning paradigm, snails could still acquire STM despite exposure to the cold-block. PMID:24098373

The epigenetic basis of memory formation and storage.

PubMed

Jarome, Timothy J; Thomas, Jasmyne S; Lubin, Farah D

2014-01-01

The formation of long-term memory requires a series of cellular and molecular changes that involve transcriptional regulation of gene expression. While these changes in gene transcription were initially thought to be largely regulated by the activation of transcription factors by intracellular signaling molecules, epigenetic mechanisms have emerged as an important regulator of transcriptional processes across multiple brain regions to form a memory circuit for a learned event or experience. Due to their self-perpetuating nature and ability to bidirectionally control gene expression, these epigenetic mechanisms have the potential to not only regulate initial memory formation but also modify and update memory over time. This chapter focuses on the established, but poorly understood, role for epigenetic mechanisms such as posttranslational modifications of histone proteins and DNA methylation at the different stages of memory storage. Additionally, this chapter emphasizes how these mechanisms interact to control the ideal epigenetic environment for memory formation and modification in neurons. The reader will gain insights into the limitations in our current understanding of epigenetic regulation of memory storage, especially in terms of their cell-type specificity and the lack of understanding in the interactions of various epigenetic modifiers to one another to impact gene expression changes during memory formation.

Hippocampal Metaplasticity Is Required for the Formation of Temporal Associative Memories

PubMed Central

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

2014-01-01

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. PMID:25505329

The interaction of rhinal cortex and hippocampus in human declarative memory formation.

PubMed

Fell, Jürgen; Klaver, Peter; Elger, Christian E; Fernández, Guillén

2002-01-01

Human declarative memory formation crucially depends on processes within the medial temporal lobe (MTL). These processes can be monitored in real-time by recordings from depth electrodes implanted in the MTL of patients with epilepsy who undergo presurgical evaluation. In our studies, patients performed a word memorization task during depth EEG recording. Afterwards, the difference between event-related potentials (ERPs) corresponding to subsequently remembered versus forgotten words was analyzed. These kind of studies revealed that successful memory encoding is characterized by an early process generated by the rhinal cortex within 300 ms following stimulus onset. This rhinal process precedes a hippocampal process, which starts about 200 ms later. Further investigation revealed that the rhinal process seems to be a correlate of semantic preprocessing which supports memory formation, whereas the hippocampal process appears to be a correlate of an exclusively mnemonic operation. These studies yielded only indirect evidence for an interaction of rhinal cortex and hippocampus. Direct evidence for a memory related cooperation between both structures, however, has been found in a study analyzing so called gamma activity, EEG oscillations of around 40 Hz. This investigation showed that successful as opposed to unsuccessful memory formation is accompanied by an initial enhancement of rhinal-hippocampal phase synchronization, which is followed by a later desynchronization. Present knowledge about the function of phase synchronized gamma activity suggests that this phase coupling and decoupling initiates and later terminates communication between the two MTL structures. Phase synchronized rhinal-hippocampal gamma activity may, moreover, accomplish Hebbian synaptic modifications and thus provide an initial step of declarative memory formation on the synaptic level.

Predicting episodic memory formation for movie events

PubMed Central

Tang, Hanlin; Singer, Jed; Ison, Matias J.; Pivazyan, Gnel; Romaine, Melissa; Frias, Rosa; Meller, Elizabeth; Boulin, Adrianna; Carroll, James; Perron, Victoria; Dowcett, Sarah; Arellano, Marlise; Kreiman, Gabriel

2016-01-01

Episodic memories are long lasting and full of detail, yet imperfect and malleable. We quantitatively evaluated recollection of short audiovisual segments from movies as a proxy to real-life memory formation in 161 subjects at 15 minutes up to a year after encoding. Memories were reproducible within and across individuals, showed the typical decay with time elapsed between encoding and testing, were fallible yet accurate, and were insensitive to low-level stimulus manipulations but sensitive to high-level stimulus properties. Remarkably, memorability was also high for single movie frames, even one year post-encoding. To evaluate what determines the efficacy of long-term memory formation, we developed an extensive set of content annotations that included actions, emotional valence, visual cues and auditory cues. These annotations enabled us to document the content properties that showed a stronger correlation with recognition memory and to build a machine-learning computational model that accounted for episodic memory formation in single events for group averages and individual subjects with an accuracy of up to 80%. These results provide initial steps towards the development of a quantitative computational theory capable of explaining the subjective filtering steps that lead to how humans learn and consolidate memories. PMID:27686330

Predicting episodic memory formation for movie events.

PubMed

Tang, Hanlin; Singer, Jed; Ison, Matias J; Pivazyan, Gnel; Romaine, Melissa; Frias, Rosa; Meller, Elizabeth; Boulin, Adrianna; Carroll, James; Perron, Victoria; Dowcett, Sarah; Arellano, Marlise; Kreiman, Gabriel

2016-09-30

Episodic memories are long lasting and full of detail, yet imperfect and malleable. We quantitatively evaluated recollection of short audiovisual segments from movies as a proxy to real-life memory formation in 161 subjects at 15 minutes up to a year after encoding. Memories were reproducible within and across individuals, showed the typical decay with time elapsed between encoding and testing, were fallible yet accurate, and were insensitive to low-level stimulus manipulations but sensitive to high-level stimulus properties. Remarkably, memorability was also high for single movie frames, even one year post-encoding. To evaluate what determines the efficacy of long-term memory formation, we developed an extensive set of content annotations that included actions, emotional valence, visual cues and auditory cues. These annotations enabled us to document the content properties that showed a stronger correlation with recognition memory and to build a machine-learning computational model that accounted for episodic memory formation in single events for group averages and individual subjects with an accuracy of up to 80%. These results provide initial steps towards the development of a quantitative computational theory capable of explaining the subjective filtering steps that lead to how humans learn and consolidate memories.

Autophagy Enhances Memory Erasure through Synaptic Destabilization.

PubMed

Shehata, Mohammad; Abdou, Kareem; Choko, Kiriko; Matsuo, Mina; Nishizono, Hirofumi; Inokuchi, Kaoru

2018-04-11

There is substantial interest in memory reconsolidation as a target for the treatment of anxiety disorders, such as post-traumatic stress disorder. However, its applicability is restricted by reconsolidation-resistant boundary conditions that constrain the initial memory destabilization. In this study, we investigated whether the induction of synaptic protein degradation through autophagy modulation, a major protein degradation pathway, can enhance memory destabilization upon retrieval and whether it can be used to overcome these conditions. Here, using male mice in an auditory fear reconsolidation model, we showed that autophagy contributes to memory destabilization and its induction can be used to enhance erasure of a reconsolidation-resistant auditory fear memory that depended on AMPAR endocytosis. Using male mice in a contextual fear reconsolidation model, autophagy induction in the amygdala or in the hippocampus enhanced fear or contextual memory destabilization, respectively. The latter correlated with AMPAR degradation in the spines of the contextual memory-ensemble cells. Using male rats in an in vivo LTP reconsolidation model, autophagy induction enhanced synaptic destabilization in an NMDAR-dependent manner. These data indicate that induction of synaptic protein degradation can enhance both synaptic and memory destabilization upon reactivation and that autophagy inducers have the potential to be used as a therapeutic tool in the treatment of anxiety disorders. SIGNIFICANCE STATEMENT It has been reported that inhibiting synaptic protein degradation prevents memory destabilization. However, whether the reverse relation is true and whether it can be used to enhance memory destabilization are still unknown. Here we addressed this question on the behavioral, molecular, and synaptic levels, and showed that induction of autophagy, a major protein degradation pathway, can enhance memory and synaptic destabilization upon reactivation. We also show that autophagy

Mindfulness Enhances Episodic Memory Performance: Evidence from a Multimethod Investigation.

PubMed

Brown, Kirk Warren; Goodman, Robert J; Ryan, Richard M; Anālayo, Bhikkhu

2016-01-01

Training in mindfulness, classically described as a receptive attentiveness to present events and experiences, has been shown to improve attention and working memory. Both are key to long-term memory formation, and the present three-study series used multiple methods to examine whether mindfulness would enhance episodic memory, a key form of long-term memory. In Study 1 (N = 143), a self-reported state of mindful attention predicted better recognition performance in the Remember-Know (R-K) paradigm. In Study 2 (N = 93), very brief training in a focused attention form of mindfulness also produced better recognition memory performance on the R-K task relative to a randomized, well-matched active control condition. Study 3 (N = 57) extended these findings by showing that relative to randomized active and inactive control conditions the effect of very brief mindfulness training generalized to free-recall memory performance. This study also found evidence for mediation of the mindfulness training-episodic memory relation by intrinsic motivation. These findings indicate that mindful attention can beneficially impact motivation and episodic memory, with potential implications for educational and occupational performance.

A role for autophagy in long-term spatial memory formation in male rodents.

PubMed

Hylin, Michael J; Zhao, Jing; Tangavelou, Karthikeyan; Rozas, Natalia S; Hood, Kimberly N; MacGowan, Jacalyn S; Moore, Anthony N; Dash, Pramod K

2018-03-01

A hallmark of long-term memory formation is the requirement for protein synthesis. Administration of protein synthesis inhibitors impairs long-term memory formation without influencing short-term memory. Rapamycin is a specific inhibitor of target of rapamycin complex 1 (TORC1) that has been shown to block protein synthesis and impair long-term memory. In addition to regulating protein synthesis, TORC1 also phosphorylates Unc-51-like autophagy activating kinase-1 (Ulk-1) to suppress autophagy. As autophagy can be activated by rapamycin (and rapamycin inhibits long-term memory), our aim was to test the hypothesis that autophagy inhibitors would enhance long-term memory. To examine if learning alters autophagosome number, we used male reporter mice carrying the GFP-LC3 transgene. Using these mice, we observed that training in the Morris water maze task increases the number of autophagosomes, a finding contrary to our expectations. For learning and memory studies, male Long Evans rats were used due to their relatively larger size (compared to mice), making it easier to perform intrahippocampal infusions in awake, moving animals. When the autophagy inhibitors 3-methyladenine (3-MA) or Spautin-1 were administered bilaterally into the hippocampii prior to training in the Morris water maze task, the drugs did not alter learning. In contrast, when memory was tested 24 hours later by a probe trial, significant impairments were observed. In addition, intrahippocampal infusion of an autophagy activator peptide (TAT-Beclin-1) improved long-term memory. These results indicate that autophagy is not necessary for learning, but is required for long-term memory formation. © 2017 Wiley Periodicals, Inc.

Four-Week Strategy-Based Training to Enhance Prospective Memory in Older Adults: Targeting Intention Retention Is More Beneficial than Targeting Intention Formation.

PubMed

Ihle, Andreas; Albiński, Rafal; Gurynowicz, Kamila; Kliegel, Matthias

2018-01-01

So far, training of prospective memory (PM) focused on very short instances (single sessions) and targeted the intention-formation phase only. We aimed to compare the effectiveness of 2 different 4-week strategy-based PM training types, namely imagery training (targeting the encoding of the PM intention in the intention-formation phase) versus rehearsal training (targeting the maintenance of the PM intention in the intention-retention phase) in older adults. We used a 4-week training protocol (8 sessions in total, 2 sessions per week). From the 44 participants, 21 were randomly assigned to the imagery training (vividly imagining a mental picture to memorize the connection between the PM cue words and related actions during intention formation) and 23 to the rehearsal training (rehearsing the PM cue words during intention retention). The criterion PM task was assessed before and after the training. Comparing the effectiveness of both training types, we found a significant time by training type interaction on PM accuracy in terms of PM cue detection, F(1, 42) = 6.07, p = 0.018, η2p = 0.13. Subsequent analyses revealed that the rehearsal training was more effective in enhancing PM accuracy in terms of PM cue detection than the imagery training. Strategy-based PM training in older adults targeting the maintenance of the PM intention in the intention-retention phase may be more effective in enhancing PM accuracy in terms of PM cue detection than the strategy targeting the encoding of the PM intention in the intention-formation phase. This suggests that for successful prospective remembering, older adults may need more support to keep the PM cues active in memory while working on the ongoing task than to initially encode the PM intention. © 2018 S. Karger AG, Basel.

Emotional Arousal Does Not Enhance Association-Memory

ERIC Educational Resources Information Center

Madan, Christopher R.; Caplan, Jeremy B.; Lau, Christine S. M.; Fujiwara, Esther

2012-01-01

Emotionally arousing information is remembered better than neutral information. This enhancement effect has been shown for memory for items. In contrast, studies of association-memory have found both impairments and enhancements of association-memory by arousal. We aimed to resolve these conflicting results by using a cued-recall paradigm combined…

Kisspeptin-13 enhances memory and mitigates memory impairment induced by Aβ1-42 in mice novel object and object location recognition tasks.

PubMed

Jiang, J H; He, Z; Peng, Y L; Jin, W D; Wang, Z; Han, R W; Chang, M; Wang, R

2015-09-01

Kisspeptin (KP), the endogenous ligand of GPR54, is a recently discovered neuropeptide shown to be involved in regulating reproductive system, anxiety-related behavior, locomotion, food intake, and suppression of metastasis across a range of cancers. KP is transcribed within the hippocampus, and GPR54 has been found in the amygdala and hippocampus, suggesting that KP might be involved in mediating learning and memory. However, the role of KP in cognition was largely unclear. Here, we investigated the role of KP-13, one of the endogenous active isoforms, in memory processes, and determined whether KP-13 could mitigate memory impairment induced by Aβ1-42 in mice, using novel object recognition (NOR) and object location recognition (OLR) tasks. Intracerebroventricular (i.c.v.) infusion of KP-13 (2μg) immediately after training not only facilitated memory formation, but also prolonged memory retention in both tasks. The memory-improving effects of KP-13 could be blocked by the GPR54 receptor antagonist, kisspeptin-234 (234), and GnRH receptors antagonist, Cetrorelix, suggesting pharmacological specificity. Then the memory-enhancing effects were also presented after infusion of KP-13 into the hippocampus. Moreover, we found that i.c.v. injection of KP-13 was able to reverse the memory impairment induced by Aβ1-42, which was inhibited by 234. To sum up, the results of our work indicate that KP-13 could facilitate memory formation and prolong memory retention through activation of the GPR54 and GnRH receptors, and suppress memory-impairing effect of Aβ1-42 through activation of the GPR54, suggesting that KP-13 may be a potential drug for enhancing memory and treating Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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. Copyright © 2014 the authors 0270-6474/14/3416762-12$15.00/0.

Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders.

PubMed

McLean, Samantha L; Grayson, Ben; Marsh, Samuel; Zarroug, Samah H O; Harte, Michael K; Neill, Jo C

2016-04-01

Cholinergic dysfunction has been shown to be central to the pathophysiology of Alzheimer's disease and has also been postulated to contribute to cognitive dysfunction observed in various psychiatric disorders, including schizophrenia. Deficits are found across a number of cognitive domains and in spite of several attempts to develop new therapies, these remain an unmet clinical need. In the current study we investigated the efficacy of donepezil, risperidone and selective nicotinic α7 and α4β2 receptor agonists to reverse a delay-induced deficit in recognition memory. Adult female Hooded Lister rats received drug treatments and were tested in the novel object recognition (NOR) task following a 6h inter-trial interval (ITI). In all treatment groups, there was no preference for the left or right identical objects in the acquisition trial. Risperidone failed to enhance recognition memory in this paradigm whereas donepezil was effective such that rats discriminated between the novel and familiar object in the retention trial following a 6h ITI. Although a narrow dose range of PNU-282987 and RJR-2403 was tested, only one dose of each increased recognition memory, the highest dose of PNU-282987 (10mg/kg) and the lowest dose of RJR-2403 (0.1mg/kg), indicative of enhanced cognitive performance. Interestingly, these compounds were also efficacious when administered either before the acquisition or the retention trial of the task, suggesting an important role for nicotinic receptor subtypes in the formation and retrieval of recognition memory. Copyright © 2016. Published by Elsevier B.V.

Age differences and format effects in working memory.

PubMed

Foos, Paul W; Goolkasian, Paula

2010-07-01

Format effects refer to lower recall of printed words from working memory when compared to spoken words or pictures. These effects have been attributed to an attenuation of attention to printed words. The present experiment compares younger and older adults' recall of three or six items presented as pictures, spoken words, printed words, and alternating case WoRdS. The latter stimuli have been shown to increase attention to printed words and, thus, reduce format effects. The question of interest was whether these stimuli would also reduce format effects for older adults whose working memory capacity has fewer attentional resources to allocate. Results showed that older adults performed as well as younger adults with three items but less well with six and that format effects were reduced for both age groups, but more for young, when alternating case words were used. Other findings regarding executive control of working memory are discussed. The obtained differences support models of reduced capacity in older adult working memory.

The Role of Ephs and Ephrins in Memory Formation.

PubMed

Dines, Monica; Lamprecht, Raphael

2016-04-01

The ability to efficiently store memories in the brain is a fundamental process and its impairment is associated with multiple human mental disorders. Evidence indicates that long-term memory formation involves alterations of synaptic efficacy produced by modifications in neural transmission and morphology. The Eph receptors and their cognate ephrin ligands have been shown to be involved in these key neuronal processes by regulating events such as presynaptic transmitter release, postsynaptic glutamate receptor conductance and trafficking, synaptic glutamate reuptake, and dendritic spine morphogenesis. Recent findings show that Ephs and ephrins are needed for memory formation in different organisms. These proteins participate in the formation of various types of memories that are subserved by different neurons and brain regions. Ephs and ephrins are involved in brain disorders and diseases with memory impairment symptoms, including Alzheimer's disease and anxiety. Drugs that agonize or antagonize Ephs/ephrins signaling have been developed and could serve as therapeutic agents to treat such diseases. Ephs and ephrins may therefore induce cellular alterations mandatory for memory formation and serve as a target for pharmacological intervention for treatment of memory-related brain diseases. © The Author 2015. Published by Oxford University Press on behalf of CINP.

The Role of Ephs and Ephrins in Memory Formation

PubMed Central

Dines, Monica

2016-01-01

The ability to efficiently store memories in the brain is a fundamental process and its impairment is associated with multiple human mental disorders. Evidence indicates that long-term memory formation involves alterations of synaptic efficacy produced by modifications in neural transmission and morphology. The Eph receptors and their cognate ephrin ligands have been shown to be involved in these key neuronal processes by regulating events such as presynaptic transmitter release, postsynaptic glutamate receptor conductance and trafficking, synaptic glutamate reuptake, and dendritic spine morphogenesis. Recent findings show that Ephs and ephrins are needed for memory formation in different organisms. These proteins participate in the formation of various types of memories that are subserved by different neurons and brain regions. Ephs and ephrins are involved in brain disorders and diseases with memory impairment symptoms, including Alzheimer’s disease and anxiety. Drugs that agonize or antagonize Ephs/ephrins signaling have been developed and could serve as therapeutic agents to treat such diseases. Ephs and ephrins may therefore induce cellular alterations mandatory for memory formation and serve as a target for pharmacological intervention for treatment of memory-related brain diseases. PMID:26371183

Distributed learning enhances relational memory consolidation.

PubMed

Litman, Leib; Davachi, Lila

2008-09-01

It has long been known that distributed learning (DL) provides a mnemonic advantage over massed learning (ML). However, the underlying mechanisms that drive this robust mnemonic effect remain largely unknown. In two experiments, we show that DL across a 24 hr interval does not enhance immediate memory performance but instead slows the rate of forgetting relative to ML. Furthermore, we demonstrate that this savings in forgetting is specific to relational, but not item, memory. In the context of extant theories and knowledge of memory consolidation, these results suggest that an important mechanism underlying the mnemonic benefit of DL is enhanced memory consolidation. We speculate that synaptic strengthening mechanisms supporting long-term memory consolidation may be differentially mediated by the spacing of memory reactivation. These findings have broad implications for the scientific study of episodic memory consolidation and, more generally, for educational curriculum development and policy.

Mindfulness Enhances Episodic Memory Performance: Evidence from a Multimethod Investigation

PubMed Central

Goodman, Robert J.; Ryan, Richard M.; Anālayo, Bhikkhu

2016-01-01

Training in mindfulness, classically described as a receptive attentiveness to present events and experiences, has been shown to improve attention and working memory. Both are key to long-term memory formation, and the present three-study series used multiple methods to examine whether mindfulness would enhance episodic memory, a key form of long-term memory. In Study 1 (N = 143), a self-reported state of mindful attention predicted better recognition performance in the Remember-Know (R-K) paradigm. In Study 2 (N = 93), very brief training in a focused attention form of mindfulness also produced better recognition memory performance on the R-K task relative to a randomized, well-matched active control condition. Study 3 (N = 57) extended these findings by showing that relative to randomized active and inactive control conditions the effect of very brief mindfulness training generalized to free-recall memory performance. This study also found evidence for mediation of the mindfulness training—episodic memory relation by intrinsic motivation. These findings indicate that mindful attention can beneficially impact motivation and episodic memory, with potential implications for educational and occupational performance. PMID:27115491

Opposing roles for GABAA and GABAC receptors in short-term memory formation in young chicks.

PubMed

Gibbs, M E; Johnston, G A R

2005-01-01

The inhibitory neurotransmitter GABA has both inhibitory and enhancing effects on short-term memory for a bead discrimination task in the young chick. Low doses of GABA (1-3 pmol/hemisphere) injected into the multimodal association area of the chick forebrain, inhibit strongly reinforced memory, whereas higher doses (30-100 pmol/hemisphere) enhance weakly reinforced memory. The effect of both high and low doses of GABA is clearly on short-term memory in terms of both the time of injection and in the time that the memory loss occurs. We argue on the basis of relative sensitivities to GABA and to selective GABA receptor antagonists that low doses of GABA act at GABAC receptors (EC50 approximately 1 microM) and the higher doses of GABA act via GABAA receptors (EC50 approximately 10 microM). The selective GABAA receptor antagonist bicuculline inhibited strongly reinforced memory in a dose and time dependent manner, whereas the selective GABAC receptor antagonists TPMPA and P4MPA enhanced weakly reinforced in a dose and time dependent manner. Confirmation that different levels of GABA affect different receptor subtypes was demonstrated by the shift in the GABA dose-response curves to the selective antagonists. It is clear that GABA is involved in the control of short-term memory formation and its action, enhancing or inhibiting, depends on the level of GABA released at the time of learning.

IL-15 signaling promotes adoptive effector T-cell survival and memory formation in irradiation-induced lymphopenia.

PubMed

Xu, Aizhang; Bhanumathy, Kalpana Kalyanasundaram; Wu, Jie; Ye, Zhenmin; Freywald, Andrew; Leary, Scot C; Li, Rongxiu; Xiang, Jim

2016-01-01

Lymphopenia promotes naïve T-cell homeostatic proliferation and adoptive effector T-cell survival and memory formation. IL-7 plays a critical role in homeostatic proliferation, survival and memory formation of naïve T-cells in lymphopenia, and its underlying molecular mechanism has also been well studied. However, the mechanism for adoptively transferred effector T-cell survival and memory formation is not fully understood. Here, we transferred in vitro-activated transgenic OT-I CD8(+) effector T-cells into irradiation (600 rads)-induced lymphopenic C57BL/6, IL-7 knockout (KO) and IL-15 KO mice, and investigated the survival and memory formation of transferred T-cells in lymphopenia. We demonstrate that transferred T-cells prolong their survival and enhance their memory in lymphopenic mice, in a manner that depends on IL-15 signaling, but not IL-7. We determine that in vitro stimulation of naïve or effector T-cells with IL-7 and IL-15 reduces IL-7Rα, and increases and/or maintains IL-15Rβ expression, respectively. Consistent with these findings, the expression of IL-7Rα and IL-15Rβ is down- and up-regulated, respectively, in vivo on transferred T-cells in an early phase post T-cell transfer in lymphopenia. We further show that in vitro IL-15 restimulation-induced memory T-cells (compared to IL-2 restimulation-induced effector T-cells) and in vivo transferred T-cells in irradiated IL-15-sufficient C57BL/6 mice (compared to IL-15-deficient IL-15 KO mice) have increased mitochondrial content, but less NADH and lower mitochondrial potential (ΔΨm), and demonstrate greater phosphorylation of signal transducers and activators of transcription-5 (STAT5) and Unc-51-like kinase-1 (ULK1), and higher expression of B-cell leukemia/lymphoma-2 (Bcl2) and memory-, autophagy- and mitochondrial biogenesis-related molecules. Irradiation-induced lymphopenia promotes effector T-cell survival via IL-15 signaling the STAT5/Bcl2 pathway, enhances T-cell memory formation via IL

A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation.

PubMed

Cambon, Karine; Hansen, Stine M; Venero, Cesar; Herrero, A Isabel; Skibo, Galina; Berezin, Vladimir; Bock, Elisabeth; Sandi, Carmen

2004-04-28

The neural cell adhesion molecule (NCAM) plays a critical role in development and plasticity of the nervous system and is involved in the mechanisms of learning and memory. Here, we show that intracerebroventricular administration of the FG loop (FGL), a synthetic 15 amino acid peptide corresponding to the binding site of NCAM for the fibroblast growth factor receptor 1 (FGFR1), immediately after training rats in fear conditioning or water maze learning, induced a long-lasting improvement of memory. In primary cultures of hippocampal neurons, FGL enhanced the presynaptic function through activation of FGFR1 and promoted synapse formation. These results provide the first evidence for a memory-facilitating effect resulting from a treatment that mimics NCAM function. They suggest that increased efficacy of synaptic transmission and formation of new synapses probably mediate the cognition-enhancing properties displayed by the peptide.

NMDA receptor- and ERK-dependent histone methylation changes in the lateral amygdala bidirectionally regulate fear memory formation.

PubMed

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

2014-07-01

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 consolidation. Here we found increases in histone H3 lysine 9 dimethylation (H3K9me2) levels in the LA at 1 h following auditory fear conditioning, which continued to be temporally regulated up to 25 h following behavioral training. Additionally, we demonstrate that inhibiting the H3K9me2 histone lysine methyltransferase G9a (H/KMTs-G9a) in the LA impaired fear memory, while blocking the H3K9me2 histone lysine demethylase LSD1 (H/KDM-LSD1) enhanced fear memory, suggesting that H3K9me2 in the LA can bidirectionally regulate fear memory formation. Furthermore, we show that NMDAR activity differentially regulated the recruitment of H/KMT-G9a, H/KDM-LSD1, and subsequent H3K9me2 levels at a target gene promoter. This was largely regulated by GluN2B- but not GluN2A-containing NMDARs via ERK activation. Moreover, fear memory deficits associated with NMDAR or ERK blockade were successfully rescued through pharmacologically inhibiting LSD1, suggesting that enhancements of H3K9me2 levels within the LA can rescue fear memory impairments that result from hypofunctioning NMDARs or loss of ERK signaling. Together, the present study suggests that histone lysine methylation regulation in the LA via NMDAR-ERK-dependent signaling is involved in fear memory formation. © 2014 Gupta-Agarwal et al.; Published by Cold Spring Harbor Laboratory Press.

Epigenetic Mechanisms of Memory Formation and Reconsolidation

PubMed Central

Jarome, Timothy J.; Lubin, Farah D.

2014-01-01

Memory consolidation involves transcriptional control of genes in neurons to stabilize a newly formed memory. Following retrieval, a once consolidated memory destabilizes and again requires gene transcription changes in order to restabilize, a process referred to as reconsolidation. Understanding the molecular mechanisms of gene transcription during the consolidation and reconsolidation processes could provide crucial insights into normal memory formation and memory dysfunction associated with psychiatric disorders. In the past decade, modifications of epigenetic markers such as DNA methylation and posttranslational modifications of histone proteins have emerged as critical transcriptional regulators of gene expression during initial memory formation and after retrieval. In light of the rapidly growing literature in this exciting area of research, we here examine the most recent and latest evidence demonstrating how memory acquisition and retrieval trigger epigenetic changes during the consolidation and reconsolidation phases to impact behavior. In particular we focus on the reconsolidation process, where we discuss the already identified epigenetic regulators of gene transcription during memory reconsolidation, while exploring other potential epigenetic modifications that may also be involved, and expand on how these epigenetic modifications may be precisely and temporally controlled by important signaling cascades critical to the reconsolidation process. Finally, we explore the possibility that epigenetic mechanisms may serve to regulate a system or circuit level reconsolidation process and may be involved in retrieval-dependent memory updating. Hence, we propose that epigenetic mechanisms coordinate changes in neuronal gene transcription, not only during the initial memory consolidation phase, but are triggered by retrieval to regulate molecular and cellular processes during memory reconsolidation. PMID:25130533

Diagnosing criterion-level effects on memory: what aspects of memory are enhanced by repeated retrieval?

PubMed

Vaughn, Kalif E; Rawson, Katherine A

2011-09-01

Previous research has shown that increasing the criterion level (i.e., the number of times an item must be correctly retrieved during practice) improves subsequent memory, but which specific components of memory does increased criterion level enhance? In two experiments, we examined the extent to which the criterion level affects associative memory, target memory, and cue memory. Participants studied Lithuanian-English word pairs via cued recall with restudy until items were correctly recalled one to five times. In Experiment 1, participants took one of four recall tests and one of three recognition tests after a 2-day delay. In Experiment 2, participants took only recognition tests after a 1-week delay. In both experiments, increasing the criterion level enhanced associative memory, as indicated by enhanced performance on forward and backward cued-recall tests and on tests of associative recognition. An increased criterion level also improved target memory, as indicated by enhanced free recall and recognition of targets, and improved cue memory, as indicated by enhanced free recall and recognition of cues.

Pre-stimulus thalamic theta power predicts human memory formation.

PubMed

Sweeney-Reed, Catherine M; Zaehle, Tino; Voges, Jürgen; Schmitt, Friedhelm C; Buentjen, Lars; Kopitzki, Klaus; Richardson-Klavehn, Alan; Hinrichs, Hermann; Heinze, Hans-Jochen; Knight, Robert T; Rugg, Michael D

2016-09-01

Pre-stimulus theta (4-8Hz) power in the hippocampus and neocortex predicts whether a memory for a subsequent event will be formed. Anatomical studies reveal thalamus-hippocampal connectivity, and lesion, neuroimaging, and electrophysiological studies show that memory processing involves the dorsomedial (DMTN) and anterior thalamic nuclei (ATN). The small size and deep location of these nuclei have limited real-time study of their activity, however, and it is unknown whether pre-stimulus theta power predictive of successful memory formation is also found in these subcortical structures. We recorded human electrophysiological data from the DMTN and ATN of 7 patients receiving deep brain stimulation for refractory epilepsy. We found that greater pre-stimulus theta power in the right DMTN was associated with successful memory encoding, predicting both behavioral outcome and post-stimulus correlates of successful memory formation. In particular, significant correlations were observed between right DMTN theta power and both frontal theta and right ATN gamma (32-50Hz) phase alignment, and frontal-ATN theta-gamma cross-frequency coupling. We draw the following primary conclusions. Our results provide direct electrophysiological evidence in humans of a role for the DMTN as well as the ATN in memory formation. Furthermore, prediction of subsequent memory performance by pre-stimulus thalamic oscillations provides evidence that post-stimulus differences in thalamic activity that index successful and unsuccessful encoding reflect brain processes specifically underpinning memory formation. Finally, the findings broaden the understanding of brain states that facilitate memory encoding to include subcortical as well as cortical structures. Copyright © 2016 Elsevier Inc. All rights reserved.

Does Stress Enhance or Impair Memory Consolidation?

PubMed Central

Trammell, Janet P.; Clore, Gerald L.

2014-01-01

Three experiments examined the hypothesis that stress-induced arousal enhances long term memory for experiences associated with an arousing events. Contrary to expectations, in each experiment exposure to a stressor (arm immersion in ice water) interfered with, rather than enhanced, long term memory for associated material. Despite varying the stimuli (words, pictures), their emotional value (positive, negative, neutral), the time between learning and stress inductions (0 to 1 minute), and opportunities for post-learning rehearsal, each experiment produced a significant reversal of the hypothesized effect. That is, in each experiment, exposure to a stressor interfered with, rather than enhanced, long term memory for associated material. We conclude that the relationship between stress and memory consolidation is more bounded than previously believed. PMID:23895111

Does stress enhance or impair memory consolidation?

PubMed

Trammell, Janet P; Clore, Gerald L

2014-01-01

Three experiments examined the hypothesis that stress-induced arousal enhances long-term memory for experiences associated with arousing events. Contrary to expectations, in each experiment exposure to a stressor (arm immersion in ice water) interfered with, rather than enhanced, long-term memory for associated material. Despite varying the stimuli (words, pictures), their emotional value (positive, negative, neutral), the time between learning and stress inductions (0 to 1 minute), and opportunities for post-learning rehearsal, each experiment produced a significant reversal of the hypothesised effect. That is, in each experiment, exposure to a stressor interfered with, rather than enhanced, long-term memory for associated material. We conclude that the relationship between stress and memory consolidation is more bounded than previously believed.

Histone Deacetylase Inhibition Induces Odor Preference Memory Extension and Maintains Enhanced AMPA Receptor Expression in the Rat Pup Model

ERIC Educational Resources Information Center

Bhattacharya, Sriya; Mukherjee, Bandhan; Doré, Jules J. E.; Yuan, Qi; Harley, Carolyn W.; McLean, John H.

2017-01-01

Histone deacetylase (HDAC) plays a role in synaptic plasticity and long-term memory formation. We hypothesized that trichostatin-A (TSA), an HDAC inhibitor, would promote long-term odor preference memory and maintain enhanced GluA1 receptor levels that have been hypothesized to support memory. We used an early odor preference learning model in…

The roles of Eph receptors in contextual fear conditioning memory formation.

PubMed

Dines, Monica; Grinberg, Svetlana; Vassiliev, Maria; Ram, Alon; Tamir, Tal; Lamprecht, Raphael

2015-10-01

Eph receptors regulate glutamate receptors functions, neuronal morphology and synaptic plasticity, cellular events believed to be involved in memory formation. In this study we aim to explore the roles of Eph receptors in learning and memory. Toward that end, we examined the roles of EphB2 and EphA4 receptors, key regulators of synaptic functions, in fear conditioning memory formation. We show that mice lacking EphB2 (EphB2(-/-)) are impaired in short- and long-term contextual fear conditioning memory. Mice that express a carboxy-terminally truncated form of EphB2 that lacks forward signaling, instead of the full EphB2, are impaired in long-term, but not short-term, contextual fear conditioning memory. Long-term contextual fear conditioning memory is attenuated in CaMKII-cre;EphA4(lx/-) mice where EphA4 is removed from all pyramidal neurons of the forebrain. Mutant mice with targeted kinase-dead EphA4 (EphA4(KD)) exhibit intact long-term contextual fear conditioning memory showing that EphA4 kinase-mediated forward signaling is not needed for contextual fear memory formation. The ability to form long-term conditioned taste aversion (CTA) memory is not impaired in the EphB2(-/-) and CaMKII-cre;EphA4(lx/-) mice. We conclude that EphB2 forward signaling is required for long-term contextual fear conditioning memory formation. In contrast, EphB2 mediates short-term contextual fear conditioning memory formation in a forward signaling-independent manner. EphA4 mediates long-term contextual fear conditioning memory formation in a kinase-independent manner. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed Central

Bechay, Kiro; Rusche, James R.; Jacques, Vincent; Kudugunti, Shashi; Miao, Wenyan; Weinberger, Norman M.; McGaugh, James L.

2015-01-01

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

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

PubMed

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

17β-Estradiol and Agonism of G-protein-Coupled Estrogen Receptor Enhance Hippocampal Memory via Different Cell-Signaling Mechanisms

PubMed Central

Kim, Jaekyoon; Szinte, Julia S.; Boulware, Marissa I.

2016-01-01

The ability of 17β-estradiol (E2) to enhance hippocampal object recognition and spatial memory depends on rapid activation of extracellular signal-regulated kinase (ERK) in the dorsal hippocampus (DH). Although this activation can be mediated by the intracellular estrogen receptors ERα and ERβ, little is known about the role that the membrane estrogen receptor GPER plays in regulating ERK or E2-mediated memory formation. In this study, post-training DH infusion of the GPER agonist G-1 enhanced object recognition and spatial memory in ovariectomized female mice, whereas the GPER antagonist G-15 impaired memory, suggesting that GPER activation, like E2, promotes hippocampal memory formation. However, unlike E2, G-1 did not increase ERK phosphorylation, but instead significantly increased phosphorylation of c-Jun N-terminal kinase (JNK) in the DH. Moreover, DH infusion of the JNK inhibitor SP600125 prevented G-1 from enhancing object recognition and spatial memory, but the ERK inhibitor U0126 did not. These data suggest that GPER enhances memory via different cell-signaling mechanisms than E2. This conclusion was supported by data showing that the ability of E2 to facilitate memory and activate ERK signaling was not blocked by G-15 or SP600125, which demonstrates that the memory-enhancing effects of E2 are not dependent on JNK or GPER activation in the DH. Together, these data indicate that GPER regulates memory independently from ERα and ERβ by activating JNK signaling, rather than ERK signaling. Thus, the findings suggest that GPER in the DH may not function as an estrogen receptor to regulate object recognition and spatial memory. SIGNIFICANCE STATEMENT Although 17β-estradiol has long been known to regulate memory function, the molecular mechanisms underlying estrogenic memory modulation remain largely unknown. Here, we examined whether the putative membrane estrogen receptor GPER acts like the classical estrogen receptors, ERα and ERβ, to facilitate

Memory formation during anaesthesia: plausibility of a neurophysiological basis

PubMed Central

Veselis, R. A.

2015-01-01

As opposed to conscious, personally relevant (explicit) memories that we can recall at will, implicit (unconscious) memories are prototypical of ‘hidden’ memory; memories that exist, but that we do not know we possess. Nevertheless, our behaviour can be affected by these memories; in fact, these memories allow us to function in an ever-changing world. It is still unclear from behavioural studies whether similar memories can be formed during anaesthesia. Thus, a relevant question is whether implicit memory formation is a realistic possibility during anaesthesia, considering the underlying neurophysiology. A different conceptualization of memory taxonomy is presented, the serial parallel independent model of Tulving, which focuses on dynamic information processing with interactions among different memory systems rather than static classification of different types of memories. The neurophysiological basis for subliminal information processing is considered in the context of brain function as embodied in network interactions. Function of sensory cortices and thalamic activity during anaesthesia are reviewed. The role of sensory and perisensory cortices, in particular the auditory cortex, in support of memory function is discussed. Although improbable, with the current knowledge of neurophysiology one cannot rule out the possibility of memory formation during anaesthesia. PMID:25735711

Epigenetic mechanisms of memory formation and reconsolidation.

PubMed

Jarome, Timothy J; Lubin, Farah D

2014-11-01

Memory consolidation involves transcriptional control of genes in neurons to stabilize a newly formed memory. Following retrieval, a once consolidated memory destabilizes and again requires gene transcription changes in order to restabilize, a process referred to as reconsolidation. Understanding the molecular mechanisms of gene transcription during the consolidation and reconsolidation processes could provide crucial insights into normal memory formation and memory dysfunction associated with psychiatric disorders. In the past decade, modifications of epigenetic markers such as DNA methylation and posttranslational modifications of histone proteins have emerged as critical transcriptional regulators of gene expression during initial memory formation and after retrieval. In light of the rapidly growing literature in this exciting area of research, we here examine the most recent and latest evidence demonstrating how memory acquisition and retrieval trigger epigenetic changes during the consolidation and reconsolidation phases to impact behavior. In particular we focus on the reconsolidation process, where we discuss the already identified epigenetic regulators of gene transcription during memory reconsolidation, while exploring other potential epigenetic modifications that may also be involved, and expand on how these epigenetic modifications may be precisely and temporally controlled by important signaling cascades critical to the reconsolidation process. Finally, we explore the possibility that epigenetic mechanisms may serve to regulate a system or circuit level reconsolidation process and may be involved in retrieval-dependent memory updating. Hence, we propose that epigenetic mechanisms coordinate changes in neuronal gene transcription, not only during the initial memory consolidation phase, but are triggered by retrieval to regulate molecular and cellular processes during memory reconsolidation. Copyright © 2014 Elsevier Inc. All rights reserved.

Epigenetic mechanisms: critical contributors to long-term memory formation.

PubMed

Lubin, Farah D; Gupta, Swati; Parrish, R Ryley; Grissom, Nicola M; Davis, Robin L

2011-12-01

Recent advances in chromatin biology have identified a role for epigenetic mechanisms in the regulation of neuronal gene expression changes, a necessary process for proper synaptic plasticity and memory formation. Experimental evidence for dynamic chromatin remodeling influencing gene transcription in postmitotic neurons grew from initial reports describing posttranslational modifications of histones, including phosphorylation and acetylation occurring in various brain regions during memory consolidation. An accumulation of recent studies, however, has also highlighted the importance of other epigenetic modifications, such as DNA methylation and histone methylation, as playing a role in memory formation. This present review examines learning-induced gene transcription by chromatin remodeling underlying long-lasting changes in neurons, with direct implications for the study of epigenetic mechanisms in long-term memory formation and behavior. Furthermore, the study of epigenetic gene regulation, in conjunction with transcription factor activation, can provide complementary lines of evidence to further understanding transcriptional mechanisms subserving memory storage.

Manipulating memory CD8 T cell numbers by timed enhancement of IL-2 signals1

PubMed Central

Kim, Marie T.; Kurup, Samarchith P.; Starbeck-Miller, Gabriel R.; Harty, John T.

2016-01-01

Due to the growing burden of tumors and chronic infections, manipulating CD8 T cell responses for clinical use has become an important goal for immunologists. Here, we show that dendritic cell (DC) immunization coupled with relatively early (days 1–3) or late (days 4–6) administration of enhanced IL-2-signals both increase peak effector CD8 T cell numbers, but only early IL-2 signals enhance memory numbers. IL-2 signals delivered at relatively late time points drive terminal differentiation, marked Bim mediated contraction and do not increase memory T cell numbers. In contrast, early IL-2 signals induce effector cell metabolic profiles more conducive to memory formation. Of note, down-regulation of CD80 and CD86 was observed on DCs in vivo following early IL-2 treatment. Mechanistically, early IL-2 treatment enhanced CTLA-4 expression on regulatory T (Treg) cells, and CTLA-4 blockade alongside IL-2 treatment in vivo prevented the decrease in CD80 and CD86, supporting a cell-extrinsic role of CTLA-4 in down-regulating B7-ligand expression on DCs. Finally, DC immunization followed by early IL-2 treatment and αCTLA-4 blockade resulted in lower memory CD8 T cell numbers compared to the DC + early IL-2 treatment group. These data suggest that curtailed signaling through the B7-CD28 co-stimulatory axis during CD8 T cell activation limits terminal differentiation and preserves memory CD8 T cell formation and thus, should be considered in future T cell vaccination strategies. PMID:27439516

Depletion of perineuronal nets enhances recognition memory and long-term depression in the perirhinal cortex

PubMed Central

Romberg, Carola; Yang, Sujeong; Melani, Riccardo; Andrews, Melissa R.; Horner, Alexa E.; Spillantini, Maria G.; Bussey, Timothy J.; Fawcett, James W.; Pizzorusso, Tommaso; Saksida, Lisa M.

2013-01-01

Perineuronal nets are extracellular matrix structures surrounding cortical neuronal cell bodies and proximal dendrites, and are involved in the control of brain plasticity and the closure of critical periods. Expression of the link protein Crtl1/Hapln1 in neurons has recently been identified as the key event triggering the formation of perineuronal nets. Here we show that the genetic attenuation of perineuronal nets in adult brain Crtl1 knockout mice enhances long term object recognition memory and facilitates long-term depression in the perirhinal cortex, a neural correlate of object recognition memory. Identical prolongation of memory follows localised digestion of perineuronal nets with chondroitinase ABC, an enzyme that degrades the chondroitin sulphate proteoglycans (CSPGs) components of PNNs. The memory-enhancing effect of chondroitinase ABC treatment attenuated over time, suggesting that regeneration of PNNs gradually restored control plasticity levels. Our findings indicate that perineuronal nets regulate both memory and experience-driven synaptic plasticity in adulthood. PMID:23595763

Effects of Interfacial Fluorination on Performance Enhancement of High-k-Based Charge Trap Flash Memory

NASA Astrophysics Data System (ADS)

Wang, Chenjie; Huo, Zongliang; Liu, Ziyu; Liu, Yu; Cui, Yanxiang; Wang, Yumei; Li, Fanghua; Liu, Ming

2013-07-01

The effects of interfacial fluorination on the metal/Al2O3/HfO2/SiO2/Si (MAHOS) memory structure have been investigated. By comparing MAHOS memories with and without interfacial fluorination, it was identified that the deterioration of the performance and reliability of MAHOS memories is mainly due to the formation of an interfacial layer that generates excess oxygen vacancies at the interface. Interfacial fluorination suppresses the growth of the interfacial layer, which is confirmed by X-ray photoelectron spectroscopy depth profile analysis, increases enhanced program/erase efficiency, and improves data retention characteristics. Moreover, it was observed that fluorination at the SiO-HfO interface achieves a more effective performance enhancement than that at the HfO-AlO interface.

Self-imagining enhances recognition memory in memory-impaired individuals with neurological damage.

PubMed

Grilli, Matthew D; Glisky, Elizabeth L

2010-11-01

The ability to imagine an elaborative event from a personal perspective relies on several cognitive processes that may potentially enhance subsequent memory for the event, including visual imagery, semantic elaboration, emotional processing, and self-referential processing. In an effort to find a novel strategy for enhancing memory in memory-impaired individuals with neurological damage, we investigated the mnemonic benefit of a method we refer to as self-imagining-the imagining of an event from a realistic, personal perspective. Fourteen individuals with neurologically based memory deficits and 14 healthy control participants intentionally encoded neutral and emotional sentences under three instructions: structural-baseline processing, semantic processing, and self-imagining. Findings revealed a robust "self-imagination effect (SIE)," as self-imagination enhanced recognition memory relative to deep semantic elaboration in both memory-impaired individuals, F(1, 13) = 32.11, p < .001, η2 = .71; and healthy controls, F(1, 13) = 5.57, p < .05, η2 = .30. In addition, results indicated that mnemonic benefits of self-imagination were not limited by severity of the memory disorder nor were they related to self-reported vividness of visual imagery, semantic processing, or emotional content of the materials. The findings suggest that the SIE may depend on unique mnemonic mechanisms possibly related to self-referential processing and that imagining an event from a personal perspective makes that event particularly memorable even for those individuals with severe memory deficits. Self-imagining may thus provide an effective rehabilitation strategy for individuals with memory impairment.

The lasting memory enhancements of retrospective attention

PubMed Central

Reaves, Sarah; Strunk, Jonathan; Phillips, Shekinah; Verhaeghen, Paul; Duarte, Audrey

2016-01-01

Behavioral research has shown that spatial cues that orient attention toward task relevant items being maintained in visual short-term memory (VSTM) enhance item memory accuracy. However, it is unknown if these retrospective attentional cues (“retro-cues”) enhance memory beyond typical short-term memory delays. It is also unknown whether retro-cues affect the spatial information associated with VSTM representations. Emerging evidence suggests that processes that affect short-term memory maintenance may also affect long-term memory (LTM) but little work has investigated the role of attention in LTM. In the current event-related potential (ERP) study, we investigated the duration of retrospective attention effects and the impact of retrospective attention manipulations on VSTM representations. Results revealed that retro-cueing improved both VSTM and LTM memory accuracy and that posterior maximal ERPs observed during VSTM maintenance predicted subsequent LTM performance. N2pc ERPs associated with attentional selection were attenuated by retro-cueing suggesting that retrospective attention may disrupt maintenance of spatial configural information in VSTM. Collectively, these findings suggest that retrospective attention can alter the structure of memory representations, which impacts memory performance beyond short-term memory delays. PMID:27038756

The lasting memory enhancements of retrospective attention.

PubMed

Reaves, Sarah; Strunk, Jonathan; Phillips, Shekinah; Verhaeghen, Paul; Duarte, Audrey

2016-07-01

Behavioral research has shown that spatial cues that orient attention toward task relevant items being maintained in visual short-term memory (VSTM) enhance item memory accuracy. However, it is unknown if these retrospective attentional cues ("retro-cues") enhance memory beyond typical short-term memory delays. It is also unknown whether retro-cues affect the spatial information associated with VSTM representations. Emerging evidence suggests that processes that affect short-term memory maintenance may also affect long-term memory (LTM) but little work has investigated the role of attention in LTM. In the current event-related potential (ERP) study, we investigated the duration of retrospective attention effects and the impact of retrospective attention manipulations on VSTM representations. Results revealed that retro-cueing improved both VSTM and LTM memory accuracy and that posterior maximal ERPs observed during VSTM maintenance predicted subsequent LTM performance. N2pc ERPs associated with attentional selection were attenuated by retro-cueing suggesting that retrospective attention may disrupt maintenance of spatial configural information in VSTM. Collectively, these findings suggest that retrospective attention can alter the structure of memory representations, which impacts memory performance beyond short-term memory delays. Copyright © 2016 Elsevier B.V. All rights reserved.

Sleep Enhances Explicit Recollection in Recognition Memory

ERIC Educational Resources Information Center

Drosopoulos, Spyridon; Wagner, Ullrich; Born, Jan

2005-01-01

Recognition memory is considered to be supported by two different memory processes, i.e., the explicit recollection of information about a previous event and an implicit process of recognition based on a contextual sense of familiarity. Both types of memory supposedly rely on distinct memory systems. Sleep is known to enhance the consolidation of…

Self-Imagining Enhances Recognition Memory in Memory-Impaired Individuals with Neurological Damage

PubMed Central

Grilli, Matthew D.; Glisky, Elizabeth L.

2010-01-01

Objective The ability to imagine an elaborative event from a personal perspective relies on a number of cognitive processes that may potentially enhance subsequent memory for the event, including visual imagery, semantic elaboration, emotional processing, and self-referential processing. In an effort to find a novel strategy for enhancing memory in memory-impaired individuals with neurological damage, the present study investigated the mnemonic benefit of a method we refer to as “self-imagining” – or the imagining of an event from a realistic, personal perspective. Method Fourteen individuals with neurologically-based memory deficits and fourteen healthy control participants intentionally encoded neutral and emotional sentences under three instructions: structural-baseline processing, semantic processing, and self-imagining. Results Findings revealed a robust “self-imagination effect” as self-imagination enhanced recognition memory relative to deep semantic elaboration in both memory-impaired individuals, F (1, 13) = 32.11, p < .001, η2 = .71, and healthy controls, F (1, 13) = 5.57, p < .05, η2 = .30. In addition, results indicated that mnemonic benefits of self-imagination were not limited by severity of the memory disorder nor were they related to self-reported vividness of visual imagery, semantic processing, or emotional content of the materials. Conclusions The findings suggest that the self-imagination effect may depend on unique mnemonic mechanisms possibly related to self-referential processing, and that imagining an event from a personal perspective makes that event particularly memorable even for those individuals with severe memory deficits. Self-imagining may thus provide an effective rehabilitation strategy for individuals with memory impairment. PMID:20873930

Overexpression of Protein Kinase Mζ in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats.

PubMed

Schuette, Sven R M; Fernández-Fernández, Diego; Lamla, Thorsten; Rosenbrock, Holger; Hobson, Scott

2016-04-13

The persistently active protein kinase Mζ (PKMζ) has been found to be involved in the formation and maintenance of long-term memory. Most of the studies investigating PKMζ, however, have used either putatively unselective inhibitors or conventional knock-out animal models in which compensatory mechanisms may occur. Here, we overexpressed an active form of PKMζ in rat hippocampus, a structure highly involved in memory formation, and embedded in several neural networks. We investigated PKMζ's influence on synaptic plasticity using electrophysiological recordings of basal transmission, paired pulse facilitation, and LTP and combined this with behavioral cognitive experiments addressing formation and retention of both contextual memory during aversive conditioning and spatial memory during spontaneous exploration. We demonstrate that hippocampal slices overexpressing PKMζ show enhanced basal transmission, suggesting a potential role of PKMζ in postsynaptic AMPAR trafficking. Moreover, the PKMζ-overexpressing slices augmented LTP and this effect was not abolished by protein-synthesis blockers, indicating that PKMζ induces enhanced LTP formation in a protein-synthesis-independent manner. In addition, we found selectively enhanced long-term memory for contextual but not cued fear memory, underlining the theory of the hippocampus' involvement in the contextual aspect of aversive reinforced tasks. Memory for spatial orientation during spontaneous exploration remained unaltered, suggesting that PKMζ may not affect the neural circuits underlying spontaneous tasks that are different from aversive tasks. In this study, using an overexpression strategy as opposed to an inhibitor-based approach, we demonstrate an important modulatory role of PKMζ in synaptic plasticity and selective memory processing. Most of the literature investigating protein kinase Mζ (PKMζ) used inhibitors with selectivity that has been called into question or conventional knock-out animal

Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory

PubMed Central

Yin, Xi; Gao, Yuan; Shi, Hai-Shui; Song, Li; Wang, Jie-Chao; Shao, Juan; Geng, Xu-Hong; Xue, Gai; Li, Jian-Li; Hou, Yan-Ning

2016-01-01

Histone modifications have been implicated in learning and memory. Our previous transcriptome data showed that expression of sirtuins 6 (SIRT6), a member of Histone deacetylases (HDACs) family in the hippocampal cornu ammonis 1 (CA1) was decreased after contextual fear conditioning. However, the role of SIRT6 in the formation of memory is still elusive. In the present study, we found that contextual fear conditioning inhibited translational expression of SIRT6 in the CA1. Microinfusion of lentiviral vector-expressing SIRT6 into theCA1 region selectively enhanced the expression of SIRT6 and impaired the formation of long-term contextual fear memory without affecting short-term fear memory. The overexpression of SIRT6 in the CA1 had no effect on anxiety-like behaviors or locomotor activity. Also, we also found that SIRT6 overexpression significantly inhibited the expression of insulin-like factor 2 (IGF2) and amounts of proteins and/or phosphoproteins (e.g. Akt, pAkt, mTOR and p-mTOR) related to the IGF2 signal pathway in the CA1. These results demonstrate that the overexpression of SIRT6 in the CA1 impaired the formation of long-term fear memory, and SIRT6 in the CA1 may negatively modulate the formation of contextual fear memory via inhibiting the IGF signaling pathway. PMID:26732053

17β-Estradiol and Agonism of G-protein-Coupled Estrogen Receptor Enhance Hippocampal Memory via Different Cell-Signaling Mechanisms.

PubMed

Kim, Jaekyoon; Szinte, Julia S; Boulware, Marissa I; Frick, Karyn M

2016-03-16

The ability of 17β-estradiol (E2) to enhance hippocampal object recognition and spatial memory depends on rapid activation of extracellular signal-regulated kinase (ERK) in the dorsal hippocampus (DH). Although this activation can be mediated by the intracellular estrogen receptors ERα and ERβ, little is known about the role that the membrane estrogen receptor GPER plays in regulating ERK or E2-mediated memory formation. In this study, post-training DH infusion of the GPER agonist G-1 enhanced object recognition and spatial memory in ovariectomized female mice, whereas the GPER antagonist G-15 impaired memory, suggesting that GPER activation, like E2, promotes hippocampal memory formation. However, unlike E2, G-1 did not increase ERK phosphorylation, but instead significantly increased phosphorylation of c-Jun N-terminal kinase (JNK) in the DH. Moreover, DH infusion of the JNK inhibitor SP600125 prevented G-1 from enhancing object recognition and spatial memory, but the ERK inhibitor U0126 did not. These data suggest that GPER enhances memory via different cell-signaling mechanisms than E2. This conclusion was supported by data showing that the ability of E2 to facilitate memory and activate ERK signaling was not blocked by G-15 or SP600125, which demonstrates that the memory-enhancing effects of E2 are not dependent on JNK or GPER activation in the DH. Together, these data indicate that GPER regulates memory independently from ERα and ERβ by activating JNK signaling, rather than ERK signaling. Thus, the findings suggest that GPER in the DH may not function as an estrogen receptor to regulate object recognition and spatial memory. Although 17β-estradiol has long been known to regulate memory function, the molecular mechanisms underlying estrogenic memory modulation remain largely unknown. Here, we examined whether the putative membrane estrogen receptor GPER acts like the classical estrogen receptors, ERα and ERβ, to facilitate hippocampal memory in female

Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory.

PubMed

Benn, Abigail; Barker, Gareth R I; Stuart, Sarah A; Roloff, Eva V L; Teschemacher, Anja G; Warburton, E Clea; Robinson, Emma S J

2016-05-04

Finding effective cognitive enhancers is a major health challenge; however, modulating glutamatergic neurotransmission has the potential to enhance performance in recognition memory tasks. Previous studies using glutamate receptor antagonists have revealed that the medial prefrontal cortex (mPFC) plays a central role in associative recognition memory. The present study investigates short-term recognition memory using optogenetics to target glutamatergic neurons within the rodent mPFC specifically. Selective stimulation of glutamatergic neurons during the online maintenance of information enhanced associative recognition memory in normal animals. This cognitive enhancing effect was replicated by local infusions of the AMPAkine CX516, but not CX546, which differ in their effects on EPSPs. This suggests that enhancing the amplitude, but not the duration, of excitatory synaptic currents improves memory performance. Increasing glutamate release through infusions of the mGluR7 presynaptic receptor antagonist MMPIP had no effect on performance. These results provide new mechanistic information that could guide the targeting of future cognitive enhancers. Our work suggests that improved associative-recognition memory can be achieved by enhancing endogenous glutamatergic neuronal activity selectively using an optogenetic approach. We build on these observations to recapitulate this effect using drug treatments that enhance the amplitude of EPSPs; however, drugs that alter the duration of the EPSP or increase glutamate release lack efficacy. This suggests that both neural and temporal specificity are needed to achieve cognitive enhancement. Copyright © 2016 Benn et al.

Strategies To Enhance Memory Based on Brain-Research.

ERIC Educational Resources Information Center

Banikowski, Alison K.; Mehring, Teresa A.

1999-01-01

This article reviews the literature on three aspects of memory: (1) an information processing model of memory (including the sensory register, attention, short-term memory, and long-term memory); (2) instructional strategies designed to enhance memory (which stress gaining students' attention and active involvement); and (3) reasons why…

Memory formation during anaesthesia: plausibility of a neurophysiological basis.

PubMed

Veselis, R A

2015-07-01

As opposed to conscious, personally relevant (explicit) memories that we can recall at will, implicit (unconscious) memories are prototypical of 'hidden' memory; memories that exist, but that we do not know we possess. Nevertheless, our behaviour can be affected by these memories; in fact, these memories allow us to function in an ever-changing world. It is still unclear from behavioural studies whether similar memories can be formed during anaesthesia. Thus, a relevant question is whether implicit memory formation is a realistic possibility during anaesthesia, considering the underlying neurophysiology. A different conceptualization of memory taxonomy is presented, the serial parallel independent model of Tulving, which focuses on dynamic information processing with interactions among different memory systems rather than static classification of different types of memories. The neurophysiological basis for subliminal information processing is considered in the context of brain function as embodied in network interactions. Function of sensory cortices and thalamic activity during anaesthesia are reviewed. The role of sensory and perisensory cortices, in particular the auditory cortex, in support of memory function is discussed. Although improbable, with the current knowledge of neurophysiology one cannot rule out the possibility of memory formation during anaesthesia. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Memory Transformation Enhances Reinforcement Learning in Dynamic Environments.

PubMed

Santoro, Adam; Frankland, Paul W; Richards, Blake A

2016-11-30

Over the course of systems consolidation, there is a switch from a reliance on detailed episodic memories to generalized schematic memories. This switch is sometimes referred to as "memory transformation." Here we demonstrate a previously unappreciated benefit of memory transformation, namely, its ability to enhance reinforcement learning in a dynamic environment. We developed a neural network that is trained to find rewards in a foraging task where reward locations are continuously changing. The network can use memories for specific locations (episodic memories) and statistical patterns of locations (schematic memories) to guide its search. We find that switching from an episodic to a schematic strategy over time leads to enhanced performance due to the tendency for the reward location to be highly correlated with itself in the short-term, but regress to a stable distribution in the long-term. We also show that the statistics of the environment determine the optimal utilization of both types of memory. Our work recasts the theoretical question of why memory transformation occurs, shifting the focus from the avoidance of memory interference toward the enhancement of reinforcement learning across multiple timescales. As time passes, memories transform from a highly detailed state to a more gist-like state, in a process called "memory transformation." Theories of memory transformation speak to its advantages in terms of reducing memory interference, increasing memory robustness, and building models of the environment. However, the role of memory transformation from the perspective of an agent that continuously acts and receives reward in its environment is not well explored. In this work, we demonstrate a view of memory transformation that defines it as a way of optimizing behavior across multiple timescales. Copyright © 2016 the authors 0270-6474/16/3612228-15$15.00/0.

Random walk with memory enhancement and decay

NASA Astrophysics Data System (ADS)

Tan, Zhi-Jie; Zou, Xian-Wu; Huang, Sheng-You; Zhang, Wei; Jin, Zhun-Zhi

2002-04-01

A model of random walk with memory enhancement and decay was presented on the basis of the characteristics of the biological intelligent walks. In this model, the movement of the walker is determined by the difference between the remaining information at the jumping-out site and jumping-in site. The amount of the memory information si(t) at a site i is enhanced with the increment of visiting times to that site, and decays with time t by the rate e-βt, where β is the memory decay exponent. When β=0, there exists a transition from Brownian motion (BM) to the compact growth of walking trajectory with the density of information energy u increasing. But for β>0, this transition does not appear and the walk with memory enhancement and decay can be considered as the BM of the mass center of the cluster composed of remembered sites in the late stage.

Memory enhancing drugs and Alzheimer's disease: enhancing the self or preventing the loss of it?

PubMed

Dekkers, Wim; Rikkert, Marcel Olde

2007-06-01

In this paper we analyse some ethical and philosophical questions related to the development of memory enhancing drugs (MEDs) and anti-dementia drugs. The world of memory enhancement is coloured by utopian thinking and by the desire for quicker, sharper, and more reliable memories. Dementia is characterized by decline, fragility, vulnerability, a loss of the most important cognitive functions and even a loss of self. While MEDs are being developed for self-improvement, in Alzheimer's Disease (AD) the self is being lost. Despite this it is precisely those patients with AD and other forms of dementia that provide the subjects for scientific research on memory improvement. Biomedical research in the field of MEDs and anti-dementia drugs appears to provide a strong impetus for rethinking what we mean by 'memory', 'enhancement', 'therapy', and 'self'. We conclude (1) that the enhancement of memory is still in its infancy, (2) that current MEDs and anti-dementia drugs are at best partially and minimally effective under specific conditions, (3) that 'memory' and 'enhancement' are ambiguous terms, (4) that there is no clear-cut distinction between enhancement and therapy, and (5) that the research into MEDs and anti-dementia drugs encourages a reductionistic view of the human mind and of the self.

NF-κB mediates Gadd45β expression and DNA demethylation in the hippocampus during fear memory formation.

PubMed

Jarome, Timothy J; Butler, Anderson A; Nichols, Jessica N; Pacheco, Natasha L; Lubin, Farah D

2015-01-01

Gadd45-mediated DNA demethylation mechanisms have been implicated in the process of memory formation. However, the transcriptional mechanisms involved in the regulation of Gadd45 gene expression during memory formation remain unexplored. NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) controls transcription of genes in neurons and is a critical regulator of synaptic plasticity and memory formation. In silico analysis revealed several NF-κB (p65/RelA and cRel) consensus sequences within the Gadd45β gene promoter. Whether NF-κB activity regulates Gadd45 expression and associated DNA demethylation in neurons during memory formation is unknown. Here, we found that learning in a fear conditioning paradigm increased Gadd45β gene expression and brain-derivedneurotrophic factor (BDNF) DNA demethylation in area CA1 of the hippocampus, both of which were prevented with pharmacological inhibition of NF-κB activity. Further experiments found that conditional mutations in p65/RelA impaired fear memory formation but did not alter changes in Gadd45β expression. The learning-induced increases in Gadd45β mRNA levels, Gadd45β binding at the BDNF gene and BDNF DNA demethylation were blocked in area CA1 of the c-rel knockout mice. Additionally, local siRNA-mediated knockdown of c-rel in area CA1 prevented fear conditioning-induced increases in Gadd45β expression and BDNF DNA demethylation, suggesting that c-Rel containing NF-κB transcription factor complex is responsible for Gadd45β regulation during memory formation. Together, these results support a novel transcriptional role for NF-κB in regulation of Gadd45β expression and DNA demethylation in hippocampal neurons during fear memory.

Working memory can enhance unconscious visual perception.

PubMed

Pan, Yi; Cheng, Qiu-Ping; Luo, Qian-Ying

2012-06-01

We demonstrate that unconscious processing of a stimulus property can be enhanced when there is a match between the contents of working memory and the stimulus presented in the visual field. Participants first held a cue (a colored circle) in working memory and then searched for a brief masked target shape presented simultaneously with a distractor shape. When participants reported having no awareness of the target shape at all, search performance was more accurate in the valid condition, where the target matched the cue in color, than in the neutral condition, where the target mismatched the cue. This effect cannot be attributed to bottom-up perceptual priming from the presentation of a memory cue, because unconscious perception was not enhanced when the cue was merely perceptually identified but not actively held in working memory. These findings suggest that reentrant feedback from the contents of working memory modulates unconscious visual perception.

Effects of lentivirus-mediated CREB expression in the dorsolateral striatum: memory enhancement and evidence for competitive and cooperative interactions with the hippocampus.

PubMed

Kathirvelu, Balachandar; Colombo, Paul J

2013-11-01

Neural systems specialized for memory may interact during memory formation or recall, and the results of interactions are important determinants of how systems control behavioral output. In two experiments, we used lentivirus-mediated expression of the transcription factor CREB (LV-CREB) to test if localized manipulations of cellular plasticity influence interactions between the hippocampus and dorsolateral striatum. In Experiment 1, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for response learning, and impairs memory for place learning. LV-CREB in the dorsolateral striatum had no effect on response learning, but impaired place memory; a finding consistent with competition between the striatum and hippocampus. In Experiment 2, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for cue learning, and impairs memory for contextual fear conditioning. LV-CREB in the dorsolateral striatum enhanced memory for cue learning and, in contrast to our prediction, also enhanced memory for contextual fear conditioning, consistent with a cooperative interaction between the striatum and hippocampus. Overall, the current experiments demonstrate that infusion of LV-CREB in the dorsolateral striatum (1) increases levels of CREB protein locally, (2) does not alter acquisition of place, response, cue, or contextual fear conditioning, (3) facilitates memory for cue learning and contextual fear conditioning, and (4) impairs memory for place learning. Taken together, the present results provide evidence that LV-CREB in the dorsolateral striatum can enhance memory formation and cause both competitive and cooperative interactions with the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

How the bimodal format of presentation affects working memory: an overview.

PubMed

Mastroberardino, Serena; Santangelo, Valerio; Botta, Fabiano; Marucci, Francesco S; Olivetti Belardinelli, Marta

2008-03-01

The best format in which information that has to be recalled is presented has been investigated in several studies, which focused on the impact of bimodal stimulation on working memory performance. An enhancement of participant's performance in terms of correct recall has been repeatedly found, when bimodal formats of presentation (i.e., audiovisual) were compared to unimodal formats (i.e, either visual or auditory), in providing implications for multimedial learning. Several theoretical frameworks have been suggested in order to account for the bimodal advantage, ranging from those emphasizing early stages of processing (such as automatic alerting effects or multisensory integration processes) to those centred on late stages of processing (as postulated by the dual coding theory). The aim of this paper is to review previous contributions to this topic, providing a comprehensive theoretical framework, which is updated by the latest empirical studies.

Enhancing Memory in Your Students: COMPOSE Yourself!

ERIC Educational Resources Information Center

Rotter, Kathleen M.

2009-01-01

The essence of teaching is, in fact, creating new memories for your students. The teacher's role is to help students store the correct information (memories) in ways that make recall and future access and use likely. Therefore, choosing techniques to enhance memory is possibly the most critical aspect of instructional design. COMPOSE is an acronym…

Autophagy is essential for effector CD8 T cell survival and memory formation

PubMed Central

Xu, Xiaojin; Araki, Koichi; Li, Shuzhao; Han, Jin-Hwan; Ye, Lilin; Tan, Wendy G.; Konieczny, Bogumila T.; Bruinsma, Monique W.; Martinez, Jennifer; Pearce, Erika L; Green, Douglas R.; Jones, Dean P.; Virgin, Herbert W.; Ahmed, Rafi

2014-01-01

The importance of autophagy in memory CD8 T cell differentiation in vivo is not well defined. We show here that autophagy is dynamically regulated in virus-specific CD8 T cells during acute lymphocytic choriomeningitis virus infection. Autophagy decreased in activated proliferating T cells, and was then upregulated at the peak of the effector T cell response. Consistent with this model, deletion of the key autophagy genes Atg7 or Atg5 in virus-specific CD8 T cells had minimal effect on generating effector cells but greatly enhanced their death during the contraction phase resulting in compromised memory formation. These findings provide insight into when autophagy is needed during effector and memory T cell differentiation in vivo and also warrant a re-examination of our current concepts about the relationship between T cell activation and autophagy. PMID:25362489

The effect of rearing environment on memory formation.

PubMed

Rothwell, Cailin M; Spencer, Gaynor E; Lukowiak, Ken

2018-05-22

Lymnaea stagnalis is a well-studied model system for determining how changes in the environment influence associative learning and memory formation. For example, some wild strains of L. stagnalis , collected from separate geographic locations, show superior memory-forming abilities compared with others. Here, we studied memory formation in two laboratory-bred L. stagnalis strains, derived from the same original population in The Netherlands. The two strains were reared in two different laboratories at the University of Calgary (C-strain) and at Brock University (B-strain) for many years and we found that they differed in their memory-forming ability. Specifically, the C-strain required only two training sessions to form long-term memory (LTM) whereas the B-strain required four sessions to form LTM. Additionally, the LTM formed by the B-strain persisted for a shorter amount of time than the memory formed by the C-strain. Thus, despite being derived from the same original population, the C- and B-strains have developed different memory-forming abilities. Next, we raised the two strains from embryos away from home (i.e. in the other laboratory) over two generations and assessed their memory-forming abilities. The B-strain reared and maintained at the University of Calgary demonstrated improved memory-forming ability within a single generation, while the C-strain reared at Brock University retained their normal LTM-forming ability across two subsequent generations. This suggests that local environmental factors may contribute to the behavioural divergence observed between these two laboratory-bred strains. © 2018. Published by The Company of Biologists Ltd.

Shp2 in Forebrain Neurons Regulates Synaptic Plasticity, Locomotion, and Memory Formation in Mice

PubMed Central

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

2015-01-01

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. PMID:25713104

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

PubMed

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. © 2014 S. Karger AG, Basel.

Neuropeptide S enhances memory and mitigates memory impairment induced by MK801, scopolamine or Aβ₁₋₄₂ in mice novel object and object location recognition tasks.

PubMed

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

2013-07-01

Neuropeptide S (NPS), the endogenous ligand of NPSR, has been shown to promote arousal and anxiolytic-like effects. According to the predominant distribution of NPSR in brain tissues associated with learning and memory, NPS has been reported to modulate cognitive function in rodents. Here, we investigated the role of NPS in memory formation, and determined whether NPS could mitigate memory impairment induced by selective N-methyl-D-aspartate receptor antagonist MK801, muscarinic cholinergic receptor antagonist scopolamine or Aβ₁₋₄₂ in mice, using novel object and object location recognition tasks. Intracerebroventricular (i.c.v.) injection of 1 nmol NPS 5 min after training not only facilitated object recognition memory formation, but also prolonged memory retention in both tasks. The improvement of object recognition memory induced by NPS could be blocked by the selective NPSR antagonist SHA 68, indicating pharmacological specificity. Then, we found that i.c.v. injection of NPS reversed memory disruption induced by MK801, scopolamine or Aβ₁₋₄₂ in both tasks. In summary, our results indicate that NPS facilitates memory formation and prolongs the retention of memory through activation of the NPSR, and mitigates amnesia induced by blockage of glutamatergic or cholinergic system or by Aβ₁₋₄₂, suggesting that NPS/NPSR system may be a new target for enhancing memory and treating amnesia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Emotionally Negative Pictures Enhance Gist Memory

PubMed Central

Bookbinder, S. H.; Brainerd, C. J.

2016-01-01

In prior work on how true and false memory are influenced by emotion, valence and arousal have often been conflated. Thus, it is difficult to say which specific effects are due to valence and which are due to arousal. In the present research, we used a picture-memory paradigm that allowed emotional valence to be manipulated with arousal held constant. Negatively-valenced pictures elevated both true and false memory, relative to positive and neutral pictures. Conjoint recognition modeling revealed that negative valence (a) reduced erroneous suppression of true memories and (b) increased the familiarity of the semantic content of both true and false memories. Overall, negative valence impaired the verbatim side of episodic memory but enhanced the gist side, and these effects persisted even after a week-long delay. PMID:27454002

Accounting for Immediate Emotional Memory Enhancement

ERIC Educational Resources Information Center

Talmi, Deborah; McGarry, Lucy M.

2012-01-01

Memory for emotional events is usually very good even when tested shortly after study, before it is altered by the influence of emotional arousal on consolidation. Immediate emotion-enhanced memory may stem from the influence of emotion on cognitive processes at encoding and retrieval. Our goal was to test which cognitive factors are necessary and…

Emotionally negative pictures enhance gist memory.

PubMed

Bookbinder, S H; Brainerd, C J

2017-02-01

In prior work on how true and false memory are influenced by emotion, valence and arousal have often been conflated. Thus, it is difficult to say which specific effects are caused by valence and which are caused by arousal. In the present research, we used a picture-memory paradigm that allowed emotional valence to be manipulated with arousal held constant. Negatively valenced pictures elevated both true and false memory, relative to positive and neutral pictures. Conjoint recognition modeling revealed that negative valence (a) reduced erroneous suppression of true memories and (b) increased the familiarity of the semantic content of both true and false memories. Overall, negative valence impaired the verbatim side of episodic memory but enhanced the gist side, and these effects persisted even after a week-long delay. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Smad4 SUMOylation is essential for memory formation through upregulation of the skeletal myopathy gene TPM2.

PubMed

Hsu, Wei L; Ma, Yun L; Liu, Yen C; Lee, Eminy H Y

2017-11-28

Smad4 is a critical effector of TGF-β signaling that regulates a variety of cellular functions. However, its role in the brain has rarely been studied. Here, we examined the molecular mechanisms underlying the post-translational regulation of Smad4 function by SUMOylation, and its role in spatial memory formation. In the hippocampus, Smad4 is SUMOylated by the E3 ligase PIAS1 at Lys-113 and Lys-159. Both spatial training and NMDA injection enhanced Smad4 SUMOylation. Inhibition of Smad4 SUMOylation impaired spatial learning and memory in rats by downregulating TPM2, a gene associated with skeletal myopathies. Similarly, knockdown of TPM2 expression impaired spatial learning and memory, while TPM2 mRNA and protein expression increased after spatial training. Among the TPM2 mutations associated with skeletal myopathies, the TPM2E122K mutation was found to reduce TPM2 expression and impair spatial learning and memory in rats. We have identified a novel role of Smad4 SUMOylation and TPM2 in learning and memory formation. These results suggest that patients with skeletal myopathies who carry the TPM2E122K mutation may also have deficits in learning and memory functions.

Neural and Cellular Mechanisms of Fear and Extinction Memory Formation

PubMed Central

Orsini, Caitlin A.; Maren, Stephen

2012-01-01

Over the course of natural history, countless animal species have evolved adaptive behavioral systems to cope with dangerous situations and promote survival. Emotional memories are central to these defense systems because they are rapidly acquired and prepare organisms for future threat. Unfortunately, the persistence and intrusion of memories of fearful experiences are quite common and can lead to pathogenic conditions, such as anxiety and phobias. Over the course of the last thirty years, neuroscientists and psychologists alike have attempted to understand the mechanisms by which the brain encodes and maintains these aversive memories. Of equal interest, though, is the neurobiology of extinction memory formation as this may shape current therapeutic techniques. Here we review the extant literature on the neurobiology of fear and extinction memory formation, with a strong focus on the cellular and molecular mechanisms underlying these processes. PMID:22230704

Effects of Anodal Transcranial Direct Current Stimulation and Serotonergic Enhancement on Memory Performance in Young and Older Adults.

PubMed

Prehn, Kristin; Stengl, Helena; Grittner, Ulrike; Kosiolek, René; Ölschläger, Anja; Weidemann, Alexandra; Flöel, Agnes

2017-01-01

In the absence of effective therapies for dementia and its precursors, enhancing neuroplasticity by means of non-invasive brain stimulation such as anodal transcranial direct current stimulation (atDCS) might be a promising approach to counteract or delay the onset of cognitive decline, but effect sizes have been moderate so far. Previous reports indicate that increasing serotonin levels may enhance atDCS-induced neuroplasticity. However, evidence for serotonergic modulation of atDCS effects on memory is still lacking. Here, we conducted a double-blind, randomized, sham-/placebo-controlled trial to investigate the impact of a selective serotonin reuptake inhibitor (SSRI; single dose of 20 mg citalopram) and atDCS over the right temporoparietal cortex (1 mA, 20 min) on memory formation. Twenty young and 20 older subjects completed an object-location learning task in each of the four conditions: sham+placebo, sham+SSRI, atDCS+placebo, and atDCS+SSRI. Outcome measures were performance in immediate (primary outcome) and delayed cued recall. While we found an SSRI effect, but no statistically significant effect of atDCS on immediate recall scores, young and older adults benefited most from the combined application (comparisons: atDCS+SSRI>atDCS+placebo and atDCS+SSRI>sham+placebo). Thus, our data provide evidence that atDCS improves memory formation if serotonergic neurotransmission is enhanced simultaneously. Further studies are needed to assess whether these findings extend to clinical populations with memory impairment and translate into clinically relevant improvements after long-term serotonergic enhancement and repeated stimulation.

Effects of Anodal Transcranial Direct Current Stimulation and Serotonergic Enhancement on Memory Performance in Young and Older Adults

PubMed Central

Prehn, Kristin; Stengl, Helena; Grittner, Ulrike; Kosiolek, René; Ölschläger, Anja; Weidemann, Alexandra; Flöel, Agnes

2017-01-01

In the absence of effective therapies for dementia and its precursors, enhancing neuroplasticity by means of non-invasive brain stimulation such as anodal transcranial direct current stimulation (atDCS) might be a promising approach to counteract or delay the onset of cognitive decline, but effect sizes have been moderate so far. Previous reports indicate that increasing serotonin levels may enhance atDCS-induced neuroplasticity. However, evidence for serotonergic modulation of atDCS effects on memory is still lacking. Here, we conducted a double-blind, randomized, sham-/placebo-controlled trial to investigate the impact of a selective serotonin reuptake inhibitor (SSRI; single dose of 20 mg citalopram) and atDCS over the right temporoparietal cortex (1 mA, 20 min) on memory formation. Twenty young and 20 older subjects completed an object-location learning task in each of the four conditions: sham+placebo, sham+SSRI, atDCS+placebo, and atDCS+SSRI. Outcome measures were performance in immediate (primary outcome) and delayed cued recall. While we found an SSRI effect, but no statistically significant effect of atDCS on immediate recall scores, young and older adults benefited most from the combined application (comparisons: atDCS+SSRI>atDCS+placebo and atDCS+SSRI>sham+placebo). Thus, our data provide evidence that atDCS improves memory formation if serotonergic neurotransmission is enhanced simultaneously. Further studies are needed to assess whether these findings extend to clinical populations with memory impairment and translate into clinically relevant improvements after long-term serotonergic enhancement and repeated stimulation. PMID:27555381

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

PubMed

van Geldorp, Bonnie; Heringa, Sophie M; van den Berg, Esther; Olde Rikkert, Marcel G M; Biessels, Geert Jan; Kessels, Roy P C

2015-01-01

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 study, we examined WM and episodic memory formation in normal aging and in patients with early Alzheimer's disease (mild cognitive impairment, MCI; and Alzheimer's dementia, AD). In the first study, 26 young adults (mean age 29.6 years) were compared to 18 middle-aged adults (mean age 52.2 years) and 25 older adults (mean age 72.8 years). We used an associative delayed-match-to-sample WM task, which requires participants to maintain two pairs of faces and houses presented on a computer screen for short (3 s) or long (6 s) maintenance intervals. After the WM task, an unexpected subsequent associative memory task was administered (two-alternative forced choice). In the second study, 27 patients with AD and 19 patients with MCI were compared to 25 older controls, using the same paradigm as that in Experiment 1. Older adults performed worse than both middle-aged and young adults. No effect of delay was observed in the healthy adults, and pairs that were processed during long maintenance intervals were not better remembered in the subsequent memory task. In the MCI and AD patients, longer maintenance intervals hampered the task performance. Also, both patient groups performed significantly worse than controls on the episodic memory task as well as the associative WM task. Aging and AD present with a decline in WM binding, a finding that extends similar results in episodic memory. Longer delays in the WM task did not affect episodic memory formation. We conclude that WM deficits are found when WM capacity is exceeded, which may occur during associative processing.

Disrupting Jagged1-Notch signaling impairs spatial memory formation in adult mice.

PubMed

Sargin, Derya; Botly, Leigh C P; Higgs, Gemma; Marsolais, Alexander; Frankland, Paul W; Egan, Sean E; Josselyn, Sheena A

2013-07-01

It is well-known that Notch signaling plays a critical role in brain development and growing evidence implicates this signaling pathway in adult synaptic plasticity and memory formation. The Notch1 receptor is activated by two subclasses of ligands, Delta-like (including Dll1 and Dll4) and Jagged (including Jag1 and Jag2). Ligand-induced Notch1 receptor signaling is modulated by a family of Fringe proteins, including Lunatic fringe (Lfng). Although Dll1, Jag1 and Lfng are critical regulators of Notch signaling, their relative contribution to memory formation in the adult brain is unknown. To investigate the roles of these important components of Notch signaling in memory formation, we examined spatial and fear memory formation in adult mice with reduced expression of Dll1, Jag1, Lfng and Dll1 plus Lfng. We also examined motor activity, anxiety-like behavior and sensorimotor gating using the acoustic startle response in these mice. Of the lines of mutant mice tested, we found that only mice with reduced Jag1 expression (mice heterozygous for a null mutation in Jag1, Jag1(+/-)) showed a selective impairment in spatial memory formation. Importantly, all other behavior including open field activity, conditioned fear memory (both context and discrete cue), acoustic startle response and prepulse inhibition, was normal in this line of mice. These results provide the first in vivo evidence that Jag1-Notch signaling is critical for memory formation in the adult brain. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement.

PubMed

Adamsky, Adar; Kol, Adi; Kreisel, Tirzah; Doron, Adi; Ozeri-Engelhard, Nofar; Melcer, Talia; Refaeli, Ron; Horn, Henrike; Regev, Limor; Groysman, Maya; London, Michael; Goshen, Inbal

2018-05-18

Astrocytes respond to neuronal activity and were shown to be necessary for plasticity and memory. To test whether astrocytic activity is also sufficient to generate synaptic potentiation and enhance memory, we expressed the Gq-coupled receptor hM3Dq in CA1 astrocytes, allowing their activation by a designer drug. We discovered that astrocytic activation is not only necessary for synaptic plasticity, but also sufficient to induce NMDA-dependent de novo long-term potentiation in the hippocampus that persisted after astrocytic activation ceased. In vivo, astrocytic activation enhanced memory allocation; i.e., it increased neuronal activity in a task-specific way only when coupled with learning, but not in home-caged mice. Furthermore, astrocytic activation using either a chemogenetic or an optogenetic tool during acquisition resulted in memory recall enhancement on the following day. Conversely, directly increasing neuronal activity resulted in dramatic memory impairment. Our findings that astrocytes induce plasticity and enhance memory may have important clinical implications for cognitive augmentation treatments. Copyright © 2018 Elsevier Inc. All rights reserved.

Genes and signaling pathways involved in memory enhancement in mutant mice

PubMed Central

2014-01-01

Mutant mice have been used successfully as a tool for investigating the mechanisms of memory at multiple levels, from genes to behavior. In most cases, manipulating a gene expressed in the brain impairs cognitive functions such as memory and their underlying cellular mechanisms, including synaptic plasticity. However, a remarkable number of mutations have been shown to enhance memory in mice. Understanding how to improve a system provides valuable insights into how the system works under normal conditions, because this involves understanding what the crucial components are. Therefore, more can be learned about the basic mechanisms of memory by studying mutant mice with enhanced memory. This review will summarize the genes and signaling pathways that are altered in the mutants with enhanced memory, as well as their roles in synaptic plasticity. Finally, I will discuss how knowledge of memory-enhancing mechanisms could be used to develop treatments for cognitive disorders associated with impaired plasticity. PMID:24894914

Exploring the use of memory colors for image enhancement

NASA Astrophysics Data System (ADS)

Xue, Su; Tan, Minghui; McNamara, Ann; Dorsey, Julie; Rushmeier, Holly

2014-02-01

Memory colors refer to those colors recalled in association with familiar objects. While some previous work introduces this concept to assist digital image enhancement, their basis, i.e., on-screen memory colors, are not appropriately investigated. In addition, the resulting adjustment methods developed are not evaluated from a perceptual view of point. In this paper, we first perform a context-free perceptual experiment to establish the overall distributions of screen memory colors for three pervasive objects. Then, we use a context-based experiment to locate the most representative memory colors; at the same time, we investigate the interactions of memory colors between different objects. Finally, we show a simple yet effective application using representative memory colors to enhance digital images. A user study is performed to evaluate the performance of our technique.

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

PubMed Central

Chen, Yan-Chu; Ma, Yun-Li; Lin, Cheng-Hsiung; Cheng, Sin-Jhong; Hsu, Wei-Lun; Lee, Eminy H.-Y.

2017-01-01

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. PMID:28744198

Enhancement of Immune Memory Responses to Respiratory Infection

DTIC Science & Technology

2017-08-01

Unlimited Distribution 13. SUPPLEMENTARY NOTES 14. ABSTRACT Maintenance of long - term immunological memory against pathogens is crucial for the rapid...highly expressed in memory B cells in mice, and Atg7 is required for maintenance of long - term memory B cells needed to protect against influenza...AWARD NUMBER: W81XWH-16-1-0360 TITLE: Enhancement of Immune Memory Responses to Respiratory Infection PRINCIPAL INVESTIGATORs: Dr Min Chen PhD

Enhanced dimension-specific visual working memory in grapheme–color synesthesia☆

PubMed Central

Terhune, Devin Blair; Wudarczyk, Olga Anna; Kochuparampil, Priya; Cohen Kadosh, Roi

2013-01-01

There is emerging evidence that the encoding of visual information and the maintenance of this information in a temporarily accessible state in working memory rely on the same neural mechanisms. A consequence of this overlap is that atypical forms of perception should influence working memory. We examined this by investigating whether having grapheme–color synesthesia, a condition characterized by the involuntary experience of color photisms when reading or representing graphemes, would confer benefits on working memory. Two competing hypotheses propose that superior memory in synesthesia results from information being coded in two information channels (dual-coding) or from superior dimension-specific visual processing (enhanced processing). We discriminated between these hypotheses in three n-back experiments in which controls and synesthetes viewed inducer and non-inducer graphemes and maintained color or grapheme information in working memory. Synesthetes displayed superior color working memory than controls for both grapheme types, whereas the two groups did not differ in grapheme working memory. Further analyses excluded the possibilities of enhanced working memory among synesthetes being due to greater color discrimination, stimulus color familiarity, or bidirectionality. These results reveal enhanced dimension-specific visual working memory in this population and supply further evidence for a close relationship between sensory processing and the maintenance of sensory information in working memory. PMID:23892185

Word Imageability Enhances Association-memory by Increasing Hippocampal Engagement.

PubMed

Caplan, Jeremy B; Madan, Christopher R

2016-10-01

The hippocampus is thought to support association-memory, particularly when tested with cued recall. One of the most well-known and studied factors that influences accuracy of verbal association-memory is imageability; participants remember pairs of high-imageability words better than pairs of low-imageability words. High-imageability words are also remembered better in tests of item-memory. However, we previously found that item-memory effects could not explain the enhancement in cued recall, suggesting that imageability enhances association-memory strength. Here we report an fMRI study designed to ask, what is the role of the hippocampus in the memory advantage for associations due to imageability? We tested two alternative hypotheses: (1) Recruitment Hypothesis: High-imageability pairs are remembered better because they recruit the underlying hippocampal association-memory function more effectively. Alternatively, (2) Bypassing Hypothesis: Imageability functions by making the association-forming process easier, enhancing memory in a way that bypasses the hippocampus, as has been found, for example, with explicit unitization imagery strategies. Results found, first, hippocampal BOLD signal was greater during study and recall of high- than low-imageability word pairs. Second, the difference in activity between recalled and forgotten pairs showed a main effect, but no significant interaction with imageability, challenging the bypassing hypothesis, but consistent with the predictions derived from the recruitment hypothesis. Our findings suggest that certain stimulus properties, like imageability, may leverage, rather than avoid, the associative function of the hippocampus to support superior association-memory.

Dissociation between Complete Hippocampal Context Memory Formation and Context Fear Acquisition

ERIC Educational Resources Information Center

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…

Glucocorticoids in the prefrontal cortex enhance memory consolidation and impair working memory by a common neural mechanism

PubMed Central

Barsegyan, Areg; Mackenzie, Scott M.; Kurose, Brian D.; McGaugh, James L.; Roozendaal, Benno

2010-01-01

It is well established that acute administration of adrenocortical hormones enhances the consolidation of memories of emotional experiences and, concurrently, impairs working memory. These different glucocorticoid effects on these two memory functions have generally been considered to be independently regulated processes. Here we report that a glucocorticoid receptor agonist administered into the medial prefrontal cortex (mPFC) of male Sprague-Dawley rats both enhances memory consolidation and impairs working memory. Both memory effects are mediated by activation of a membrane-bound steroid receptor and depend on noradrenergic activity within the mPFC to increase levels of cAMP-dependent protein kinase. These findings provide direct evidence that glucocorticoid effects on both memory consolidation and working memory share a common neural influence within the mPFC. PMID:20810923

Negative emotion elicited in high school students enhances consolidation of item memory, but not source memory.

PubMed

Wang, Bo

2015-05-01

The study examined the effect of negative emotion on consolidation of both item and source memory. Participants learned words read by either a male or female. Then they watched either a negative or a neutral video clip. Memory tests were carried out either 25min or 24h after learning. The study yielded the following findings. First, negative emotion enhanced consolidation of item memory as measured by recognition memory in the 25-min delay, and enhanced consolidation of item memory as measured by free recall in both the 25-min and the 24-h delay. Second, negative emotion had little effect on consolidation of source memory, either in the 25-min or the 24-h delay. These findings provide evidence for the differential effects of negative emotion on item memory and source memory and have implications for using emotion as a strategy to intervene memory consolidation. Copyright © 2015 Elsevier Inc. All rights reserved.

Emotion strengthens high priority memory traces but weakens low priority memory traces

PubMed Central

Sakaki, Michiko; Fryer, Kellie; Mather, Mara

2014-01-01

When encountering emotional events, memory for those events is typically enhanced. But it has been unclear how emotionally arousing events influence memory for preceding information. Does emotional arousal induce retrograde amnesia or retrograde enhancement? The current study revealed that this depends on the top-down goal relevance of the preceding information. Across three studies, we found that emotional arousal induced by one image facilitated memory for the preceding neutral item when people prioritized that neutral item. In contrast, an emotional image impaired memory for the preceding neutral item when people did not prioritize that neutral item. Emotional arousal elicited by negative and positive pictures both showed this pattern of enhancing or impairing memory for the preceding stimulus depending on its priority. These results indicate that emotional arousal amplifies the effects of top-down priority in memory formation. PMID:24311478

Emotion strengthens high-priority memory traces but weakens low-priority memory traces.

PubMed

Sakaki, Michiko; Fryer, Kellie; Mather, Mara

2014-02-01

When people encounter emotional events, their memory for those events is typically enhanced. But it has been unclear how emotionally arousing events influence memory for preceding information. Does emotional arousal induce retrograde amnesia or retrograde enhancement? The current study revealed that this depends on the top-down goal relevance of the preceding information. Across three studies, we found that emotional arousal induced by one image facilitated memory for the preceding neutral item when people prioritized that neutral item. In contrast, an emotionally arousing image impaired memory for the preceding neutral item when people did not prioritize that neutral item. Emotional arousal elicited by both negative and positive pictures showed this pattern of enhancing or impairing memory for the preceding stimulus depending on its priority. These results indicate that emotional arousal amplifies the effects of top-down priority in memory formation.

Reward Retroactively Enhances Memory Consolidation for Related Items

ERIC Educational Resources Information Center

Patil, Anuya; Murty, Vishnu P.; Dunsmoor, Joseph E.; Phelps, Elizabeth A.; Davachi, Lila

2017-01-01

Reward motivation has been shown to modulate episodic memory processes in order to support future adaptive behavior. However, for a memory system to be truly adaptive, it should enhance memory for rewarded events as well as for neutral events that may seem inconsequential at the time of encoding but can gain importance later. Here, we investigated…

Animal model of methylphenidate's long-term memory-enhancing effects.

PubMed

Carmack, Stephanie A; Howell, Kristin K; Rasaei, Kleou; Reas, Emilie T; Anagnostaras, Stephan G

2014-01-16

Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a critical target of therapeutic intervention in ADHD. We examined the effects of a wide range of doses of MPH (0.01-10 mg/kg, i.p.) on Pavlovian fear learning, a leading model of memory. MPH's effects were then compared to those of atomoxetine (0.1-10 mg/kg, i.p.), bupropion (0.5-20 mg/kg, i.p.), and citalopram (0.01-10 mg/kg, i.p.). At low, clinically relevant doses, MPH enhanced fear memory; at high doses it impaired memory. MPH's memory-enhancing effects were not confounded by its effects on locomotion or anxiety. Further, MPH-induced memory enhancement seemed to require both dopamine and norepinephrine transporter inhibition. Finally, the addictive potential of MPH (1 mg/kg and 10 mg/kg) was compared to those of two other psychostimulants, amphetamine (0.005 mg/kg and 1.5 mg/kg) and cocaine (0.15 mg/kg and 15 mg/kg), using a conditioned place preference and behavioral sensitization paradigm. We found that memory-enhancing effects of psychostimulants observed at low doses are readily dissociable from their reinforcing and locomotor activating effects at high doses. Together, our data suggest that fear conditioning will be an especially fruitful platform for modeling the effects of psychostimulants on LTM in drug development.

Oscillatory Reinstatement Enhances Declarative Memory.

PubMed

Javadi, Amir-Homayoun; Glen, James C; Halkiopoulos, Sara; Schulz, Mei; Spiers, Hugo J

2017-10-11

Declarative memory recall is thought to involve the reinstatement of neural activity patterns that occurred previously during encoding. Consistent with this view, greater similarity between patterns of activity recorded during encoding and retrieval has been found to predict better memory performance in a number of studies. Recent models have argued that neural oscillations may be crucial to reinstatement for successful memory retrieval. However, to date, no causal evidence has been provided to support this theory, nor has the impact of oscillatory electrical brain stimulation during encoding and retrieval been assessed. To explore this we used transcranial alternating current stimulation over the left dorsolateral prefrontal cortex of human participants [ n = 70, 45 females; age mean (SD) = 22.12 (2.16)] during a declarative memory task. Participants received either the same frequency during encoding and retrieval (60-60 or 90-90 Hz) or different frequencies (60-90 or 90-60 Hz). When frequencies matched there was a significant memory improvement (at both 60 and 90 Hz) relative to sham stimulation. No improvement occurred when frequencies mismatched. Our results provide support for the role of oscillatory reinstatement in memory retrieval. SIGNIFICANCE STATEMENT Recent neurobiological models of memory have argued that large-scale neural oscillations are reinstated to support successful memory retrieval. Here we used transcranial alternating current stimulation (tACS) to test these models. tACS has recently been shown to induce neural oscillations at the frequency stimulated. We stimulated over the left dorsolateral prefrontal cortex during a declarative memory task involving learning a set of words. We found that tACS applied at the same frequency during encoding and retrieval enhances memory. We also find no difference between the two applied frequencies. Thus our results are consistent with the proposal that reinstatement of neural oscillations during retrieval

State of the art on targeted memory reactivation: Sleep your way to enhanced cognition.

PubMed

Schouten, Daphne I; Pereira, Sofia I R; Tops, Mattie; Louzada, Fernando M

2017-04-01

Targeted memory reactivation is a fairly simple technique that has the potential to influence the course of memory formation through application of cues during sleep. Studies have shown that cueing memory during sleep can lead to either an enhanced or decreased representation of the information encoded in the targeted networks, depending on experimental variations. The effects have been associated with sleep parameters and accompanied by activation of memory related brain areas. The findings suggest a causal role of neuronal replay in memory consolidation and provide evidence for the active system consolidation hypothesis. However, the observed inconsistencies across studies suggest that further research is warranted regarding the underlying neural mechanisms and optimal conditions for the application of targeted memory reactivation. The goal of the present review is to integrate the currently available experimental data and to provide an overview of this technique's limitations and pitfalls, as well as its potential applications in everyday use and clinical treatment. Exploring the open questions herein identified should lead to insight into safer and more effective ways of adjusting memory representations to better suit individual needs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhanced dimension-specific visual working memory in grapheme-color synesthesia.

PubMed

Terhune, Devin Blair; Wudarczyk, Olga Anna; Kochuparampil, Priya; Cohen Kadosh, Roi

2013-10-01

There is emerging evidence that the encoding of visual information and the maintenance of this information in a temporarily accessible state in working memory rely on the same neural mechanisms. A consequence of this overlap is that atypical forms of perception should influence working memory. We examined this by investigating whether having grapheme-color synesthesia, a condition characterized by the involuntary experience of color photisms when reading or representing graphemes, would confer benefits on working memory. Two competing hypotheses propose that superior memory in synesthesia results from information being coded in two information channels (dual-coding) or from superior dimension-specific visual processing (enhanced processing). We discriminated between these hypotheses in three n-back experiments in which controls and synesthetes viewed inducer and non-inducer graphemes and maintained color or grapheme information in working memory. Synesthetes displayed superior color working memory than controls for both grapheme types, whereas the two groups did not differ in grapheme working memory. Further analyses excluded the possibilities of enhanced working memory among synesthetes being due to greater color discrimination, stimulus color familiarity, or bidirectionality. These results reveal enhanced dimension-specific visual working memory in this population and supply further evidence for a close relationship between sensory processing and the maintenance of sensory information in working memory. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Arp2/3 and VASP Are Essential for Fear Memory Formation in Lateral Amygdala.

PubMed

Basu, Sreetama; Kustanovich, Irina; Lamprecht, Raphael

2016-01-01

The actin cytoskeleton is involved in key neuronal functions such as synaptic transmission and morphogenesis. However, the roles and regulation of actin cytoskeleton in memory formation remain to be clarified. In this study, we unveil the mechanism whereby actin cytoskeleton is regulated to form memory by exploring the roles of the major actin-regulatory proteins Arp2/3, VASP, and formins in long-term memory formation. Inhibition of Arp2/3, involved in actin filament branching and neuronal morphogenesis, in lateral amygdala (LA) with the specific inhibitor CK-666 during fear conditioning impaired long-term, but not short-term, fear memory. The inactive isomer CK-689 had no effect on memory formation. We observed that Arp2/3 is colocalized with the actin-regulatory protein profilin in LA neurons of fear-conditioned rats. VASP binding to profilin is needed for profilin-mediated stabilization of actin cytoskeleton and dendritic spine morphology. Microinjection of poly-proline peptide [G(GP 5 ) 3 ] into LA, to interfere with VASP binding to profilin, impaired long-term but not short-term fear memory formation. Control peptide [G(GA 5 ) 3 ] had no effect. Inhibiting formins, which regulate linear actin elongation, in LA during fear conditioning by microinjecting the formin-specific inhibitor SMIFH2 into LA had no effect on long-term fear memory formation. We conclude that Arp2/3 and VASP, through the profilin binding site, are essential for the formation of long-term fear memory in LA and propose a model whereby these proteins subserve cellular events, leading to memory consolidation.

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

ERIC Educational Resources Information Center

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…

VGF and Its C-Terminal Peptide TLQP-62 Regulate Memory Formation in Hippocampus via a BDNF-TrkB-Dependent Mechanism.

PubMed

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

VGF and Its C-Terminal Peptide TLQP-62 Regulate Memory Formation in Hippocampus via a BDNF-TrkB-Dependent Mechanism

PubMed Central

Lin, Wei-Jye; Jiang, Cheng; Sadahiro, Masato; Bozdagi, Ozlem; Vulchanova, Lucy; Alberini, Cristina M.

2015-01-01

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. SIGNIFICANCE STATEMENT 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

Consistency of handedness, regardless of direction, predicts baseline memory accuracy and potential for memory enhancement.

PubMed

Lyle, Keith B; Hanaver-Torrez, Shelley D; Hackländer, Ryan P; Edlin, James M

2012-01-01

Research has shown that consistently right-handed individuals have poorer memory than do inconsistently right- or left-handed individuals under baseline conditions but more reliably exhibit enhanced memory retrieval after making a series of saccadic eye movements. From this it could be that consistent versus inconsistent handedness, regardless of left/right direction, is an important individual difference factor in memory. Or, more specifically, it could be the presence or absence of consistent right-handedness that matters for memory. To resolve this ambiguity, we compared consistent and inconsistent left- and right-handers on associative recognition tests taken after saccades or a no-saccades control activity. Consistent-handers exhibited poorer memory than did inconsistent-handers following the control activity, and saccades enhanced retrieval for consistent-handers only. Saccades impaired retrieval for inconsistent-handers. None of these effects depended on left/right direction. Hence, this study establishes handedness consistency, regardless of direction, as an important individual difference factor in memory.

Collaboration enhances later individual memory for emotional material.

PubMed

Bärthel, Gwennis A; Wessel, Ineke; Huntjens, Rafaële J C; Verwoerd, Johan

2017-05-01

Research on collaborative remembering suggests that collaboration hampers group memory (i.e., collaborative inhibition), yet enhances later individual memory. Studies examining collaborative effects on memory for emotional stimuli are scarce, especially concerning later individual memory. In the present study, female undergraduates watched an emotional movie and recalled it either collaboratively (n = 60) or individually (n = 60), followed by an individual free recall test and a recognition test. We replicated the standard collaborative inhibition effect. Further, in line with the literature, the collaborative condition displayed better post-collaborative individual memory. More importantly, in post-collaborative free recall, the centrality of the information to the movie plot did not play an important role. Recognition rendered slightly different results. Although collaboration rendered more correct recognition for more central details, it did not enhance recognition of background details. Secondly, the collaborative and individual conditions did not differ with respect to overlap of unique correct items in free recall. Yet, during recognition former collaborators more unanimously endorsed correct answers, as well as errors. Finally, extraversion, neuroticism, social anxiety, and depressive symptoms did not moderate the influence of collaboration on memory. Implications for the fields of forensic and clinical psychology are discussed.

Animal model of methylphenidate's long-term memory-enhancing effects

PubMed Central

Carmack, Stephanie A.; Howell, Kristin K.; Rasaei, Kleou; Reas, Emilie T.; Anagnostaras, Stephan G.

2014-01-01

Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a critical target of therapeutic intervention in ADHD. We examined the effects of a wide range of doses of MPH (0.01–10 mg/kg, i.p.) on Pavlovian fear learning, a leading model of memory. MPH's effects were then compared to those of atomoxetine (0.1–10 mg/kg, i.p.), bupropion (0.5–20 mg/kg, i.p.), and citalopram (0.01–10 mg/kg, i.p.). At low, clinically relevant doses, MPH enhanced fear memory; at high doses it impaired memory. MPH's memory-enhancing effects were not confounded by its effects on locomotion or anxiety. Further, MPH-induced memory enhancement seemed to require both dopamine and norepinephrine transporter inhibition. Finally, the addictive potential of MPH (1 mg/kg and 10 mg/kg) was compared to those of two other psychostimulants, amphetamine (0.005 mg/kg and 1.5 mg/kg) and cocaine (0.15 mg/kg and 15 mg/kg), using a conditioned place preference and behavioral sensitization paradigm. We found that memory-enhancing effects of psychostimulants observed at low doses are readily dissociable from their reinforcing and locomotor activating effects at high doses. Together, our data suggest that fear conditioning will be an especially fruitful platform for modeling the effects of psychostimulants on LTM in drug development. PMID:24434869

Social importance enhances prospective memory: evidence from an event-based task.

PubMed

Walter, Stefan; Meier, Beat

2017-07-01

Prospective memory performance can be enhanced by task importance, for example by promising a reward. Typically, this comes at costs in the ongoing task. However, previous research has suggested that social importance (e.g., providing a social motive) can enhance prospective memory performance without additional monitoring costs in activity-based and time-based tasks. The aim of the present study was to investigate the influence of social importance in an event-based task. We compared four conditions: social importance, promising a reward, both social importance and promising a reward, and standard prospective memory instructions (control condition). The results showed enhanced prospective memory performance for all importance conditions compared to the control condition. Although ongoing task performance was slowed in all conditions with a prospective memory task when compared to a baseline condition with no prospective memory task, additional costs occurred only when both the social importance and reward were present simultaneously. Alone, neither social importance nor promising a reward produced an additional slowing when compared to the cost in the standard (control) condition. Thus, social importance and reward can enhance event-based prospective memory at no additional cost.

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

PubMed

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

Exogenous temporal cues enhance recognition memory in an object-based manner.

PubMed

Ohyama, Junji; Watanabe, Katsumi

2010-11-01

Exogenous attention enhances the perception of attended items in both a space-based and an object-based manner. Exogenous attention also improves recognition memory for attended items in the space-based mode. However, it has not been examined whether object-based exogenous attention enhances recognition memory. To address this issue, we examined whether a sudden visual change in a task-irrelevant stimulus (an exogenous cue) would affect participants' recognition memory for items that were serially presented around a cued time. The results showed that recognition accuracy for an item was strongly enhanced when the visual cue occurred at the same location and time as the item (Experiments 1 and 2). The memory enhancement effect occurred when the exogenous visual cue and an item belonged to the same object (Experiments 3 and 4) and even when the cue was counterpredictive of the timing of an item to be asked about (Experiment 5). The present study suggests that an exogenous temporal cue automatically enhances the recognition accuracy for an item that is presented at close temporal proximity to the cue and that recognition memory enhancement occurs in an object-based manner.

Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue

PubMed Central

Rojas, Julio C.; Bruchey, Aleksandra K.; Gonzalez-Lima, F.

2011-01-01

This paper provides the first review of the memory-enhancing and neuroprotective metabolic mechanisms of action of methylene blue in vivo. These mechanisms have important implications as a new neurobiological approach to improve normal memory and to treat memory impairment and neurodegeneration associated with mitochondrial dysfunction. Methylene blue’s action is unique because its neurobiological effects are not determined by regular drug-receptor interactions or drug-response paradigms. Methylene blue shows a hormetic dose-response, with opposite effects at low and high doses. At low doses, methylene blue is an electron cycler in the mitochondrial electron transport chain, with unparalleled antioxidant and cell respiration-enhancing properties that affect the function of the nervous system in a versatile manner. A major role of the respiratory enzyme cytochrome oxidase on the memory-enhancing effects of methylene blue is supported by available data. The memory-enhancing effects have been associated with improvement of memory consolidation in a network-specific and use-dependent fashion. In addition, low doses of methylene blue have also been used for neuroprotection against mitochondrial dysfunction in humans and experimental models of disease. The unique auto-oxidizing property of methylene blue and its pleiotropic effects on a number of tissue oxidases explain its potent neuroprotective effects at low doses. The evidence reviewed supports a mechanistic role of low-dose methylene blue as a promising and safe intervention for improving memory and for the treatment of acute and chronic conditions characterized by increased oxidative stress, neurodegeneration and memory impairment. PMID:22067440

Regulation of Memory Formation by the Transcription Factor XBP1.

PubMed

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.

Self-Referencing Enhances Memory Specificity with Age

PubMed Central

Hamami, Ayala; Serbun, Sarah J.; Gutchess, Angela H.

2011-01-01

Self-referencing has been identified as an advantageous mnemonic strategy for young and older adults. However, little research has investigated the ways in which self-referencing may influence older adults’ memory for details, which is typically impaired with age, beyond memory for the item itself. Experiment 1 assessed the effects of self- and other-referencing on memory for visually detailed pictures of objects in thirty-two young and thirty-two older adults. Results indicate that self- and close other-referencing similarly enhance general (item) and specific (detail) recognition for both young and older adults relative to the distant other condition. Experiment 2 extended these findings to source memory, with young and older adults encoding verbal information in self-referent, semantic, and structural conditions. Findings suggest that self-referencing provides an age-equivalent boost in general memory and specific memory for specific source details. We conclude that the mnemonic benefits of referencing the self extend to specific memory for visual and verbal information across the lifespan. PMID:21480719

Level of Processing Modulates the Neural Correlates of Emotional Memory Formation

ERIC Educational Resources Information Center

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…

The "memory kinases": roles of PKC isoforms in signal processing and memory formation.

PubMed

Sun, Miao-Kun; Alkon, Daniel L

2014-01-01

The protein kinase C (PKC) isoforms, which play an essential role in transmembrane signal conduction, can be viewed as a family of "memory kinases." Evidence is emerging that they are critically involved in memory acquisition and maintenance, in addition to their involvement in other functions of cells. Deficits in PKC signal cascades in neurons are one of the earliest abnormalities in the brains of patients suffering from Alzheimer's disease. Their dysfunction is also involved in several other types of memory impairments, including those related to emotion, mental retardation, brain injury, and vascular dementia/ischemic stroke. Inhibition of PKC activity leads to a reduced capacity of many types of learning and memory, but may have therapeutic values in treating substance abuse or aversive memories. PKC activators, on the other hand, have been shown to possess memory-enhancing and antidementia actions. PKC pharmacology may, therefore, represent an attractive area for developing effective cognitive drugs for the treatment of many types of memory disorders and dementias. © 2014 Elsevier Inc. All rights reserved.

Emotional Memories Are Not All Created Equal: Evidence for Selective Memory Enhancement

ERIC Educational Resources Information Center

Anderson, Adam K.; Grabski, Wojtek; Lacka, Dominika; Yamaguchi, Yuki

2006-01-01

Human brain imaging studies have shown that greater amygdala activation to emotional relative to neutral events leads to enhanced episodic memory. Other studies have shown that fearful faces also elicit greater amygdala activation relative to neutral faces. To the extent that amygdala recruitment is sufficient to enhance recollection, these…

Arousal Enhanced Memory Retention Is Eliminated Following Temporal Lobe Resection

ERIC Educational Resources Information Center

Ahs, Fredrik; Kumlien, Eva; Fredrikson, Mats

2010-01-01

The amygdala, situated in the anterior medial temporal lobe (MTL), is involved in the emotional enhancement of memory. The present study evaluated whether anterior MTL-resections attenuated arousal induced memory enhancement for pictures. Also, the effect of MTL-resections on response latencies at retrieval was assessed. Thirty-one patients with…

Astrocyte-neuron lactate transport is required for long-term memory formation.

PubMed

Suzuki, Akinobu; Stern, Sarah A; Bozdagi, Ozlem; Huntley, George W; Walker, Ruth H; Magistretti, Pierre J; Alberini, Cristina M

2011-03-04

We report that, in the rat hippocampus, learning leads to a significant increase in extracellular lactate levels that derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by L-lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc, and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation. Copyright © 2011 Elsevier Inc. All rights reserved.

Astrocyte-neuron lactate transport is required for long-term memory formation

PubMed Central

Suzuki, Akinobu; Stern, Sarah A.; Bozdagi, Ozlem; Huntley, George W.; Walker, Ruth H.; Magistretti, Pierre J.; Alberini, Cristina M.

2011-01-01

SUMMARY We report that in the rat hippocampus learning leads to a significant increase in extracellular lactate levels, which derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in-vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation. PMID:21376239

DNA methylation in memory formation: Emerging insights

PubMed Central

Heyward, Frankie D.; Sweatt, J. David

2016-01-01

The establishment of synaptic plasticity and long-term memory requires lasting cellular and molecular modifications that, as a whole, must endure despite the rapid turnover of their constituent parts. Such a molecular feat must be mediated by a stable, self-perpetuating, cellular information storage mechanism. DNA methylation, being the archetypal cellular information storage mechanism, has been heavily implicated as being necessary for stable activity-dependent transcriptional alterations within the central nervous system (CNS). This review details the foundational discoveries from both gene-targeted, as well as whole-genome sequencing, studies that have successfully brought DNA methylation to our attention as a chief regulator of activity- and experience-dependent transcriptional alterations within the CNS. We present a hypothetical framework with which the disparate experimental findings dealing with distinct manipulations of the DNA methylation, and their effect on memory, might be resolved while taking into account the unique impact activity-dependent alterations in DNA methylation potentially have on both memory promoting and memory-suppressing gene expression. And last, we discuss potential avenues for future inquiry into the role of DNA methylation during remote memory formation. PMID:25832671

Gene repressive mechanisms in the mouse brain involved in memory formation

PubMed Central

Yu, Nam-Kyung; Kaang, Bong-Kiun

2016-01-01

Gene regulation in the brain is essential for long-term plasticity and memory formation. Despite this established notion, the quantitative translational map in the brain during memory formation has not been reported. To systematically probe the changes in protein synthesis during memory formation, our recent study exploited ribosome profiling using the mouse hippocampal tissues at multiple time points after a learning event. Analysis of the resulting database revealed novel types of gene regulation after learning. First, the translation of a group of genes was rapidly suppressed without change in mRNA levels. At later time points, the expression of another group of genes was downregulated through reduction in mRNA levels. This reduction was predicted to be downstream of inhibition of ESR1 (Estrogen Receptor 1) signaling. Overexpressing Nrsn1, one of the genes whose translation was suppressed, or activating ESR1 by injecting an agonist interfered with memory formation, suggesting the functional importance of these findings. Moreover, the translation of genes encoding the translational machineries was found to be suppressed, among other genes in the mouse hippocampus. Together, this unbiased approach has revealed previously unidentified characteristics of gene regulation in the brain and highlighted the importance of repressive controls. [BMB Reports 2016; 49(4): 199-200] PMID:26949020

Gene repressive mechanisms in the mouse brain involved in memory formation.

PubMed

Yu, Nam-Kyung; Kaang, Bong-Kiun

2016-04-01

Gene regulation in the brain is essential for long-term plasticity and memory formation. Despite this established notion, the quantitative translational map in the brain during memory formation has not been reported. To systematically probe the changes in protein synthesis during memory formation, our recent study exploited ribosome profiling using the mouse hippocampal tissues at multiple time points after a learning event. Analysis of the resulting database revealed novel types of gene regulation after learning. First, the translation of a group of genes was rapidly suppressed without change in mRNA levels. At later time points, the expression of another group of genes was downregulated through reduction in mRNA levels. This reduction was predicted to be downstream of inhibition of ESR1 (Estrogen Receptor 1) signaling. Overexpressing Nrsn1, one of the genes whose translation was suppressed, or activating ESR1 by injecting an agonist interfered with memory formation, suggesting the functional importance of these findings. Moreover, the translation of genes encoding the translational machineries was found to be suppressed, among other genes in the mouse hippocampus. Together, this unbiased approach has revealed previously unidentified characteristics of gene regulation in the brain and highlighted the importance of repressive controls. [BMB Reports 2016; 49(4): 199-200].

Molecular mechanisms underlying formation of long-term reward memories and extinction memories in the honeybee (Apis mellifera)

PubMed Central

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 flower's characteristic features with a reward in a way that resembles olfactory appetitive classical conditioning, a learning paradigm that is used to study mechanisms underlying learning and memory formation in the honeybee. Due to a plethora of studies on appetitive classical conditioning and phenomena related to it, the honeybee is one of the best characterized invertebrate model organisms from a learning psychological point of view. Moreover, classical conditioning and associated behavioral phenomena are surprisingly similar in honeybees and vertebrates, suggesting a convergence of underlying neuronal processes, including the molecular mechanisms that contribute to them. Here I review current thinking on the molecular mechanisms underlying long-term memory (LTM) formation in honeybees following classical conditioning and extinction, demonstrating that an in-depth analysis of the molecular mechanisms of classical conditioning in honeybees might add to our understanding of associative learning in honeybees and vertebrates. PMID:25225299

A single dose of cocaine enhances prospective memory performance.

PubMed

Hutten, Nadia Rpw; Kuypers, Kim Pc; van Wel, Janelle Hp; Theunissen, Eef L; Toennes, Stefan W; Verkes, Robbert-Jan; Ramaekers, Johannes G

2018-06-01

Prospective memory is the ability to recall intended actions or events at the right time or in the right context. While cannabis is known to impair prospective memory, the acute effect of cocaine is unknown. In addition, it is not clear whether changes in prospective memory represent specific alterations in memory processing or result from more general effects on cognition that spread across multiple domains such as arousal and attention. The main objective of the study was, therefore, to determine whether drug-induced changes in prospective memory are memory specific or associated with more general drug-induced changes in attention and arousal. A placebo-controlled, three-way, cross-over study including 15 regular poly-drug users was set up to test the influence of oral cocaine (300 mg) and vaporised cannabis (300+150 'booster' µg/kg bodyweight) on an event-based prospective memory task. Attentional performance was assessed using a divided attention task and subjective arousal was assessed with the Profile of Mood States questionnaire. Results showed that cocaine enhanced prospective memory, attention and arousal. Mean performance of prospective memory and attention, as well as levels of arousal were lowest during treatment with cannabis as compared with placebo and cocaine as evinced by a significantly increased trend across treatment conditions. Prospective memory performance was only weakly positively associated to measures of attention and arousal. Together, these results indicate that cocaine enhancement of prospective memory performance cannot be fully explained by parallel changes in arousal and attention levels, and is likely to represent a direct change in the neural network underlying prospective memory.

Cell-adhesion molecules in memory formation.

PubMed

Schmidt, R

1995-01-23

After learning events the CNS of higher organisms selects, which acquired informations are permanently stored as a memory trace. This period of memory consolidation is susceptible to interference by biochemical inhibitors of transcription and translation. Ependymin is a specific CNS glycoprotein functionally involved in memory consolidation in goldfish: after active shock-avoidance conditioning ependymin mRNA is rapidly induced in meningeal fibroblasts followed by enhanced synthesis and secretion of several closely related forms of the protein. Intracranial injections of anti-ependymin antisera or antisense oligodeoxynucleotides interfere specifically with memory consolidation, indicating that only de novo synthesized ependymin molecules are involved. Ependymin is capable of directing the growth of central axons in vitro and participates in neuronal regeneration in situ, presumably by its HNK-1 cell-adhesion epitope. Experiments reviewed in this article suggest a model that involves two regulation mechanisms for the function of ependymin in behavioural plasticity: while hormones appear to determine, how much of this cell adhesion molecule is synthesized after learning, local changes of metal cation concentrations in the micro-environment of activated neurons may polymerize ependymin at those synapses, that have to be consolidated to improve their efficacy for future use.

Oscillatory theta activity during memory formation and its impact on overnight consolidation: a missing link?

PubMed

Heib, Dominik P J; Hoedlmoser, Kerstin; Anderer, Peter; Gruber, Georg; Zeitlhofer, Josef; Schabus, Manuel

2015-08-01

Sleep has been shown to promote memory consolidation driven by certain oscillatory patterns, such as sleep spindles. However, sleep does not consolidate all newly encoded information uniformly but rather "selects" certain memories for consolidation. It is assumed that such selection depends on salience tags attached to the new memories before sleep. However, little is known about the underlying neuronal processes reflecting presleep memory tagging. The current study sought to address the question of whether event-related changes in spectral theta power (theta ERSP) during presleep memory formation could reflect memory tagging that influences subsequent consolidation during sleep. Twenty-four participants memorized 160 word pairs before sleep; in a separate laboratory visit, they performed a nonlearning control task. Memory performance was tested twice, directly before and after 8 hr of sleep. Results indicate that participants who improved their memory performance overnight displayed stronger theta ERSP during the memory task in comparison with the control task. They also displayed stronger memory task-related increases in fast sleep spindle activity. Furthermore, presleep theta activity was directly linked to fast sleep spindle activity, indicating that processes during memory formation might indeed reflect memory tagging that influences subsequent consolidation during sleep. Interestingly, our results further indicate that the suggested relation between sleep spindles and overnight performance change is not as direct as once believed. Rather, it appears to be mediated by processes beginning during presleep memory formation. We conclude that theta ERSP during presleep memory formation reflects cortico-hippocampal interactions that lead to a better long-term accessibility by tagging memories for sleep spindle-related reprocessing.

Adrenergic enhancement of consolidation of object recognition memory.

PubMed

Dornelles, Arethuza; de Lima, Maria Noemia Martins; Grazziotin, Manoela; Presti-Torres, Juliana; Garcia, Vanessa Athaide; Scalco, Felipe Siciliani; Roesler, Rafael; Schröder, Nadja

2007-07-01

Extensive evidence indicates that epinephrine (EPI) modulates memory consolidation for emotionally arousing tasks in animals and human subjects. However, previous studies have not examined the effects of EPI on consolidation of recognition memory. Here we report that systemic administration of EPI enhances consolidation of memory for a novel object recognition (NOR) task under different training conditions. Control male rats given a systemic injection of saline (0.9% NaCl) immediately after NOR training showed significant memory retention when tested at 1.5 or 24, but not 96h after training. In contrast, rats given a post-training injection of EPI showed significant retention of NOR at all delays. In a second experiment using a different training condition, rats treated with EPI, but not SAL-treated animals, showed significant NOR retention at both 1.5 and 24-h delays. We next showed that the EPI-induced enhancement of retention tested at 96h after training was prevented by pretraining systemic administration of the beta-adrenoceptor antagonist propranolol. The findings suggest that, as previously observed in experiments using aversively motivated tasks, epinephrine modulates consolidation of recognition memory and that the effects require activation of beta-adrenoceptors.

Brief, pre-learning stress reduces false memory production and enhances true memory selectively in females.

PubMed

Zoladz, Phillip R; Peters, David M; Kalchik, Andrea E; Hoffman, Mackenzie M; Aufdenkampe, Rachael L; Woelke, Sarah A; Wolters, Nicholas E; Talbot, Jeffery N

2014-04-10

Some of the previous research on stress-memory interactions has suggested that stress increases the production of false memories. However, as accumulating work has shown that the effects of stress on learning and memory depend critically on the timing of the stressor, we hypothesized that brief stress administered immediately before learning would reduce, rather than increase, false memory production. In the present study, participants submerged their dominant hand in a bath of ice cold water (stress) or sat quietly (no stress) for 3 min. Then, participants completed a short-term memory task, the Deese-Roediger-McDermott paradigm, in which they were presented with 10 different lists of semantically related words (e.g., candy, sour, sugar) and, after each list, were tested for their memory of presented words (e.g., candy), non-presented unrelated "distractor" words (e.g., hat), and non-presented semantically related "critical lure" words (e.g., sweet). Stress, overall, significantly reduced the number of critical lures recalled (i.e., false memory) by participants. In addition, stress enhanced memory for the presented words (i.e., true memory) in female, but not male, participants. These findings reveal that stress does not unequivocally enhance false memory production and that the timing of the stressor is an important variable that could mediate such effects. Such results could have important implications for understanding the dependability of eyewitness accounts of events that are observed following stress. Copyright © 2014 Elsevier Inc. All rights reserved.

Methylphenidate produces selective enhancement of declarative memory consolidation in healthy volunteers.

PubMed

Linssen, A M W; Vuurman, E F P M; Sambeth, A; Riedel, W J

2012-06-01

Methylphenidate inhibits the reuptake of dopamine and noradrenaline and is used to treat children with attention deficit hyperactivity disorder (ADHD). Besides reducing behavioral symptoms, it improves their cognitive function. There are also observations of methylphenidate-induced cognition enhancement in healthy adults, although studies in this area are relatively sparse. We assessed the possible memory-enhancing properties of methylphenidate. In the current study, the possible enhancing effects of three doses of methylphenidate on declarative and working memory, attention, response inhibition and planning were investigated in healthy volunteers. In a double blind placebo-controlled crossover study, 19 healthy young male volunteers were tested after a single dose of placebo or 10, 20 or 40 mg of methylphenidate. Cognitive performance testing included a word learning test as a measure of declarative memory, a spatial working memory test, a set-shifting test, a stop signal test and a computerized version of the Tower of London planning test. Declarative memory consolidation was significantly improved relative to placebo after 20 and 40 mg of methylphenidate. Methylphenidate also improved set shifting and stopped signal task performance but did not affect spatial working memory or planning. To the best of our knowledge, this is the first study reporting enhanced declarative memory consolidation after methylphenidate in a dose-related fashion over a dose range that is presumed to reflect a wide range of dopamine reuptake inhibition.

Sleep in Children Enhances Preferentially Emotional Declarative But Not Procedural Memories

ERIC Educational Resources Information Center

Prehn-Kristensen, Alexander; Goder, Robert; Chirobeja, Stefania; Bressman, Inka; Ferstl, Roman; Baving, Lioba

2009-01-01

Although the consolidation of several memory systems is enhanced by sleep in adults, recent studies suggest that sleep supports declarative memory but not procedural memory in children. In the current study, the influence of sleep on emotional declarative memory (recognition task) and procedural memory (mirror tracing task) in 20 healthy children…

Epigenetic Regulation of Memory Formation and Maintenance

ERIC Educational Resources Information Center

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…

Metaplasticity contributes to memory formation in the hippocampus.

PubMed

Crestani, Ana P; Krueger, Jamie N; Barragan, Eden V; Nakazawa, Yuki; Nemes, Sonya E; Quillfeldt, Jorge A; Gray, John A; Wiltgen, Brian J

2018-05-16

Prior learning can modify the plasticity mechanisms that are used to encode new information. For example, NMDA receptor (NMDAR) activation is typically required for new spatial and contextual learning in the hippocampus. However, once animals have acquired this information, they can learn new tasks even if NMDARs are blocked. This finding suggests that behavioral training alters cellular plasticity mechanisms such that NMDARs are not required for subsequent learning. The mechanisms that mediate this change are currently unknown. To address this issue, we tested the idea that changes in intrinsic excitability (induced by learning) facilitate the encoding of new memories via metabotropic glutamate receptor (mGluR) activation. Consistent with this hypothesis, hippocampal neurons exhibited increases in intrinsic excitability after learning that lasted for several days. This increase was selective and only observed in neurons that were activated by the learning event. When animals were trained on a new task during this period, excitable neurons were reactivated and memory formation required the activation of mGluRs instead of NMDARs. These data suggest that increases in intrinsic excitability may serve as a metaplastic mechanism for memory formation.

Social Relevance Enhances Memory for Impressions in Older Adults

PubMed Central

Cassidy, Brittany S.; Gutchess, Angela H.

2012-01-01

Previous research has demonstrated that older adults have difficulty retrieving contextual material over items alone. Recent research suggests this deficit can be reduced by adding emotional context, allowing for the possibility that memory for social impressions may show less age-related decline than memory for other types of contextual information. Two studies investigated how orienting to social or self-relevant aspects of information contributed to the learning and retrieval of impressions in young and older adults. Participants encoded impressions of others in conditions varying in the use of self-reference (Experiment 1) and interpersonal meaningfulness (Experiment 2), and completed memory tasks requiring the retrieval of specific traits. For both experiments, age groups remembered similar numbers of impressions. In Experiment 1, using more self-relevant encoding contexts increased memory for impressions over orienting to stimuli in a non-social way, regardless of age. In Experiment 2, older adults had enhanced memory for impressions presented in an interpersonally meaningful relative to a personally irrelevant way, whereas young adults were unaffected by this manipulation. The results provide evidence that increasing social relevance ameliorates age differences in memory for impressions, and enhances older adults’ ability to successfully retrieve contextual information. PMID:22364168

Social relevance enhances memory for impressions in older adults.

PubMed

Cassidy, Brittany S; Gutchess, Angela H

2012-01-01

Previous research has demonstrated that older adults have difficulty retrieving contextual material over items alone. Recent research suggests this deficit can be reduced by adding emotional context, allowing for the possibility that memory for social impressions may show less age-related decline than memory for other types of contextual information. Two studies investigated how orienting to social or self-relevant aspects of information contributed to the learning and retrieval of impressions in young and older adults. Participants encoded impressions of others in conditions varying in the use of self-reference (Experiment 1) and interpersonal meaningfulness (Experiment 2), and completed memory tasks requiring the retrieval of specific traits. For both experiments, age groups remembered similar numbers of impressions. In Experiment 1 using more self-relevant encoding contexts increased memory for impressions over orienting to stimuli in a non-social way, regardless of age. In Experiment 2 older adults had enhanced memory for impressions presented in an interpersonally meaningful relative to a personally irrelevant way, whereas young adults were unaffected by this manipulation. The results provide evidence that increasing social relevance ameliorates age differences in memory for impressions, and enhances older adults' ability to successfully retrieve contextual information.

Transient acidosis while retrieving a fear-related memory enhances its lability

PubMed Central

Du, Jianyang; Price, Margaret P; Taugher, Rebecca J; Grigsby, Daniel; Ash, Jamison J; Stark, Austin C; Hossain Saad, Md Zubayer; Singh, Kritika; Mandal, Juthika; Wemmie, John A; Welsh, Michael J

2017-01-01

Attenuating the strength of fearful memories could benefit people disabled by memories of past trauma. Pavlovian conditioning experiments indicate that a retrieval cue can return a conditioned aversive memory to a labile state. However, means to enhance retrieval and render a memory more labile are unknown. We hypothesized that augmenting synaptic signaling during retrieval would increase memory lability. To enhance synaptic transmission, mice inhaled CO2 to induce an acidosis and activate acid sensing ion channels. Transient acidification increased the retrieval-induced lability of an aversive memory. The labile memory could then be weakened by an extinction protocol or strengthened by reconditioning. Coupling CO2 inhalation to retrieval increased activation of amygdala neurons bearing the memory trace and increased the synaptic exchange from Ca2+-impermeable to Ca2+-permeable AMPA receptors. The results suggest that transient acidosis during retrieval renders the memory of an aversive event more labile and suggest a strategy to modify debilitating memories. DOI: http://dx.doi.org/10.7554/eLife.22564.001 PMID:28650315

Test Expectation Enhances Memory Consolidation across Both Sleep and Wake

PubMed Central

Wamsley, Erin J.; Hamilton, Kelly; Graveline, Yvette; Manceor, Stephanie; Parr, Elaine

2016-01-01

Memory consolidation benefits from post-training sleep. However, recent studies suggest that sleep does not uniformly benefit all memory, but instead prioritizes information that is important to the individual. Here, we examined the effect of test expectation on memory consolidation across sleep and wakefulness. Following reports that information with strong “future relevance” is preferentially consolidated during sleep, we hypothesized that test expectation would enhance memory consolidation across a period of sleep, but not across wakefulness. To the contrary, we found that expectation of a future test enhanced memory for both spatial and motor learning, but that this effect was equivalent across both wake and sleep retention intervals. These observations differ from those of least two prior studies, and fail to support the hypothesis that the “future relevance” of learned material moderates its consolidation selectively during sleep. PMID:27760193

Adaptive memory: enhanced location memory after survival processing.

PubMed

Nairne, James S; Vanarsdall, Joshua E; Pandeirada, Josefa N S; Blunt, Janell R

2012-03-01

Two experiments investigated whether survival processing enhances memory for location. From an adaptive perspective, remembering that food has been located in a particular area, or that potential predators are likely to be found in a given territory, should increase the chances of subsequent survival. Participants were shown pictures of food or animals located at various positions on a computer screen. The task was to rate the ease of collecting the food or capturing the animals relative to a central fixation point. Surprise retention tests revealed that people remembered the locations of the items better when the collection or capturing task was described as relevant to survival. These data extend the generality of survival processing advantages to a new domain (location memory) by means of a task that does not involve rating the relevance of words to a scenario. 2012 APA, all rights reserved

Carbonic anhydrase activation enhances object recognition memory in mice through phosphorylation of the extracellular signal-regulated kinase in the cortex and the hippocampus.

PubMed

Canto de Souza, Lucas; Provensi, Gustavo; Vullo, Daniela; Carta, Fabrizio; Scozzafava, Andrea; Costa, Alessia; Schmidt, Scheila Daiane; Passani, Maria Beatrice; Supuran, Claudiu T; Blandina, Patrizio

2017-05-15

Rats injected with by d-phenylalanine, a carbonic anhydrase (CA) activator, enhanced spatial learning, whereas rats given acetazolamide, a CA inhibitor, exhibited impairments of fear memory consolidation. However, the related mechanisms are unclear. We investigated if CAs are involved in a non-spatial recognition memory task assessed using the object recognition test (ORT). Systemic administration of acetazolamide to male CD1 mice caused amnesia in the ORT and reduced CA activity in brain homogenates, while treatment with d-phenylalanine enhanced memory and increased CA activity. We provided also the first evidence that d-phenylalanine administration rapidly activated extracellular signal-regulated kinase (ERK) pathways, a critical step for memory formation, in the cortex and the hippocampus, two brain areas involved in memory processing. Effects elicited by d-phenylalanine were completely blunted by co-administration of acetazolamide, but not of 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate (C18), a CA inhibitor that, differently from acetazolamide, does not cross the blood brain barrier. Our results strongly suggest that brain but not peripheral CAs activation potentiates memory as a result of ERK pathway enhanced activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sleep deprivation increases formation of false memory.

PubMed

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 < 0.050). These findings reiterate the importance of adequate 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.

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

ERIC Educational Resources Information Center

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…

Temporal binding function of dorsal CA1 is critical for declarative memory formation

PubMed Central

Sellami, Azza; Al Abed, Alice Shaam; Brayda-Bruno, Laurent; Etchamendy, Nicole; Valério, Stéphane; Oulé, Marie; Pantaléon, Laura; Lamothe, Valérie; Potier, Mylène; Bernard, Katy; Jabourian, Maritza; Herry, Cyril; Mons, Nicole; Piazza, Pier-Vincenzo; Eichenbaum, Howard; Marighetto, Aline

2017-01-01

Temporal binding, the process that enables association between discontiguous stimuli in memory, and relational organization, a process that enables the flexibility of declarative memories, are both hippocampus-dependent and decline in aging. However, how these two processes are related in supporting declarative memory formation and how they are compromised in age-related memory loss remain hypothetical. We here identify a causal link between these two features of declarative memory: Temporal binding is a necessary condition for the relational organization of discontiguous events. We demonstrate that the formation of a relational memory is limited by the capability of temporal binding, which depends on dorsal (d)CA1 activity over time intervals and diminishes in aging. Conversely, relational representation is successful even in aged individuals when the demand on temporal binding is minimized, showing that relational/declarative memory per se is not impaired in aging. Thus, bridging temporal intervals by dCA1 activity is a critical foundation of relational representation, and a deterioration of this mechanism is responsible for the age-associated memory impairment. PMID:28874586

Temporal binding function of dorsal CA1 is critical for declarative memory formation.

PubMed

Sellami, Azza; Al Abed, Alice Shaam; Brayda-Bruno, Laurent; Etchamendy, Nicole; Valério, Stéphane; Oulé, Marie; Pantaléon, Laura; Lamothe, Valérie; Potier, Mylène; Bernard, Katy; Jabourian, Maritza; Herry, Cyril; Mons, Nicole; Piazza, Pier-Vincenzo; Eichenbaum, Howard; Marighetto, Aline

2017-09-19

Temporal binding, the process that enables association between discontiguous stimuli in memory, and relational organization, a process that enables the flexibility of declarative memories, are both hippocampus-dependent and decline in aging. However, how these two processes are related in supporting declarative memory formation and how they are compromised in age-related memory loss remain hypothetical. We here identify a causal link between these two features of declarative memory: Temporal binding is a necessary condition for the relational organization of discontiguous events. We demonstrate that the formation of a relational memory is limited by the capability of temporal binding, which depends on dorsal (d)CA1 activity over time intervals and diminishes in aging. Conversely, relational representation is successful even in aged individuals when the demand on temporal binding is minimized, showing that relational/declarative memory per se is not impaired in aging. Thus, bridging temporal intervals by dCA1 activity is a critical foundation of relational representation, and a deterioration of this mechanism is responsible for the age-associated memory impairment.

Working memory-driven attention improves spatial resolution: Support for perceptual enhancement.

PubMed

Pan, Yi; Luo, Qianying; Cheng, Min

2016-08-01

Previous research has indicated that attention can be biased toward those stimuli matching the contents of working memory and thereby facilitates visual processing at the location of the memory-matching stimuli. However, whether this working memory-driven attentional modulation takes place on early perceptual processes remains unclear. Our present results showed that working memory-driven attention improved identification of a brief Landolt target presented alone in the visual field. Because the suprathreshold target appeared without any external noise added (i.e., no distractors or masks), the results suggest that working memory-driven attention enhances the target signal at early perceptual stages of visual processing. Furthermore, given that performance in the Landolt target identification task indexes spatial resolution, this attentional facilitation indicates that working memory-driven attention can boost early perceptual processing via enhancement of spatial resolution at the attended location.

Enhanced associative memory for colour (but not shape or location) in synaesthesia.

PubMed

Pritchard, Jamie; Rothen, Nicolas; Coolbear, Daniel; Ward, Jamie

2013-05-01

People with grapheme-colour synaesthesia have been shown to have enhanced memory on a range of tasks using both stimuli that induce synaesthesia (e.g. words) and, more surprisingly, stimuli that do not (e.g. certain abstract visual stimuli). This study examines the latter by using multi-featured stimuli consisting of shape, colour and location conjunctions (e.g. shape A+colour A+location A; shape B+colour B+location B) presented in a recognition memory paradigm. This enables distractor items to be created in which one of these features is 'unbound' with respect to the others (e.g. shape A+colour B+location A; shape A+colour A+location C). Synaesthetes had higher recognition rates suggesting an enhanced ability to bind certain visual features together into memory. Importantly, synaesthetes' false alarm rates were lower only when colour was the unbound feature, not shape or location. We suggest that synaesthetes are "colour experts" and that enhanced perception can lead to enhanced memory in very specific ways; but, not for instance, an enhanced ability to form associations per se. The results support contemporary models that propose a continuum between perception and memory. Copyright © 2013 Elsevier B.V. All rights reserved.

Epigenetic regulation of memory formation and maintenance

PubMed Central

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 and functional plasticity. This plasticity is dependent on a well-regulated program of neurotransmitter release, post-synaptic receptor activation, intracellular signaling cascades, gene transcription, and subsequent protein synthesis. In the last decade, epigenetic markers like DNA methylation and post-translational modifications of histone tails have emerged as important regulators of the memory process. Their ability to regulate gene transcription dynamically in response to neuronal activation supports the consolidation of long-term memory. Furthermore, the persistent and self-propagating nature of these mechanisms, particularly DNA methylation, suggests a molecular mechanism for memory maintenance. In this review, we will examine the evidence that supports a role of epigenetic mechanisms in learning and memory. In doing so, we hope to emphasize (1) the widespread involvement of these mechanisms across different behavioral paradigms and distinct brain regions, (2) the temporal and genetic specificity of these mechanisms in response to upstream signaling cascades, and (3) the functional outcome these mechanisms may have on structural and functional plasticity. Finally, we consider the future directions of neuroepigenetic research as it relates to neuronal storage of information. PMID:23322554

Enhancing quantum sensing sensitivity by a quantum memory

PubMed Central

Zaiser, Sebastian; Rendler, Torsten; Jakobi, Ingmar; Wolf, Thomas; Lee, Sang-Yun; Wagner, Samuel; Bergholm, Ville; Schulte-Herbrüggen, Thomas; Neumann, Philipp; Wrachtrup, Jörg

2016-01-01

In quantum sensing, precision is typically limited by the maximum time interval over which phase can be accumulated. Memories have been used to enhance this time interval beyond the coherence lifetime and thus gain precision. Here, we demonstrate that by using a quantum memory an increased sensitivity can also be achieved. To this end, we use entanglement in a hybrid spin system comprising a sensing and a memory qubit associated with a single nitrogen-vacancy centre in diamond. With the memory we retain the full quantum state even after coherence decay of the sensor, which enables coherent interaction with distinct weakly coupled nuclear spin qubits. We benchmark the performance of our hybrid quantum system against use of the sensing qubit alone by gradually increasing the entanglement of sensor and memory. We further apply this quantum sensor-memory pair for high-resolution NMR spectroscopy of single 13C nuclear spins. PMID:27506596

Consistency of Handedness, Regardless of Direction, Predicts Baseline Memory Accuracy and Potential for Memory Enhancement

ERIC Educational Resources Information Center

Lyle, Keith B.; Hanaver-Torrez, Shelley D.; Hacklander, Ryan P.; Edlin, James M.

2012-01-01

Research has shown that consistently right-handed individuals have poorer memory than do inconsistently right- or left-handed individuals under baseline conditions but more reliably exhibit enhanced memory retrieval after making a series of saccadic eye movements. From this it could be that consistent versus inconsistent handedness, regardless of…

Pharmacological Enhancement of Memory and Executive Functioning in Laboratory Animals

PubMed Central

Floresco, Stan B; Jentsch, James D

2011-01-01

Investigating how different pharmacological compounds may enhance learning, memory, and higher-order cognitive functions in laboratory animals is the first critical step toward the development of cognitive enhancers that may be used to ameliorate impairments in these functions in patients suffering from neuropsychiatric disorders. Rather than focus on one aspect of cognition, or class of drug, in this review we provide a broad overview of how distinct classes of pharmacological compounds may enhance different types of memory and executive functioning, particularly those mediated by the prefrontal cortex. These include recognition memory, attention, working memory, and different components of behavioral flexibility. A key emphasis is placed on comparing and contrasting the effects of certain drugs on different cognitive and mnemonic functions, highlighting methodological issues associated with this type of research, tasks used to investigate these functions, and avenues for future research. Viewed collectively, studies of the neuropharmacological basis of cognition in rodents and non-human primates have identified targets that will hopefully open new avenues for the treatment of cognitive disabilities in persons affected by mental disorders. PMID:20844477

Roles of calcium/calmodulin-dependent kinase II in long-term memory formation in crickets.

PubMed

Mizunami, Makoto; Nemoto, Yuko; Terao, Kanta; Hamanaka, Yoshitaka; Matsumoto, Yukihisa

2014-01-01

Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) is a key molecule in many systems of learning and memory in vertebrates, but roles of CaMKII in invertebrates have not been characterized in detail. We have suggested that serial activation of NO/cGMP signaling, cyclic nucleotide-gated channel, Ca(2+)/CaM and cAMP signaling participates in long-term memory (LTM) formation in olfactory conditioning in crickets, and here we show participation of CaMKII in LTM formation and propose its site of action in the biochemical cascades. Crickets subjected to 3-trial conditioning to associate an odor with reward exhibited memory that lasts for a few days, which is characterized as protein synthesis-dependent LTM. In contrast, animals subjected to 1-trial conditioning exhibited memory that lasts for only several hours (mid-term memory, MTM). Injection of a CaMKII inhibitor prior to 3-trial conditioning impaired 1-day memory retention but not 1-hour memory retention, suggesting that CaMKII participates in LTM formation but not in MTM formation. Animals injected with a cGMP analogue, calcium ionophore or cAMP analogue prior to 1-trial conditioning exhibited 1-day retention, and co-injection of a CaMKII inhibitor impaired induction of LTM by the cGMP analogue or that by the calcium ionophore but not that by the cAMP analogue, suggesting that CaMKII is downstream of cGMP production and Ca(2+) influx and upstream of cAMP production in biochemical cascades for LTM formation. Animals injected with an adenylyl cyclase (AC) activator prior to 1-trial conditioning exhibited 1-day retention. Interestingly, a CaMKII inhibitor impaired LTM induction by the AC activator, although AC is expected to be a downstream target of CaMKII. The results suggest that CaMKII interacts with AC to facilitate cAMP production for LTM formation. We propose that CaMKII serves as a key molecule for interplay between Ca(2+) signaling and cAMP signaling for LTM formation, a new role of CaMKII in

Money Enhances Memory Consolidation--But Only for Boring Material

ERIC Educational Resources Information Center

Murayama, Kou; Kuhbandner, Christof

2011-01-01

Money's ability to enhance memory has received increased attention in recent research. However, previous studies have not directly addressed the time-dependent nature of monetary effects on memory, which are suggested to exist by research in cognitive neuroscience, and the possible detrimental effects of monetary rewards on learning interesting…

The effects of refreshing and elaboration on working memory performance, and their contributions to long-term memory formation.

PubMed

Bartsch, Lea M; Singmann, Henrik; Oberauer, Klaus

2018-03-19

Refreshing and elaboration are cognitive processes assumed to underlie verbal working-memory maintenance and assumed to support long-term memory formation. Whereas refreshing refers to the attentional focussing on representations, elaboration refers to linking representations in working memory into existing semantic networks. We measured the impact of instructed refreshing and elaboration on working and long-term memory separately, and investigated to what extent both processes are distinct in their contributions to working as well as long-term memory. Compared with a no-processing baseline, immediate memory was improved by repeating the items, but not by refreshing them. There was no credible effect of elaboration on working memory, except when items were repeated at the same time. Long-term memory benefited from elaboration, but not from refreshing the words. The results replicate the long-term memory benefit for elaboration, but do not support its beneficial role for working memory. Further, refreshing preserves immediate memory, but does not improve it beyond the level achieved without any processing.

Synaptic clustering within dendrites: an emerging theory of memory formation

PubMed Central

Kastellakis, George; Cai, Denise J.; Mednick, Sara C.; Silva, Alcino J.; Poirazi, Panayiota

2015-01-01

It is generally accepted that complex memories are stored in distributed representations throughout the brain, however the mechanisms underlying these representations are not understood. Here, we review recent findings regarding the subcellular mechanisms implicated in memory formation, which provide evidence for a dendrite-centered theory of memory. Plasticity-related phenomena which affect synaptic properties, such as synaptic tagging and capture, synaptic clustering, branch strength potentiation and spinogenesis provide the foundation for a model of memory storage that relies heavily on processes operating at the dendrite level. The emerging picture suggests that clusters of functionally related synapses may serve as key computational and memory storage units in the brain. We discuss both experimental evidence and theoretical models that support this hypothesis and explore its advantages for neuronal function. PMID:25576663

Brain STAT5 signaling modulates learning and memory formation.

PubMed

Furigo, Isadora C; Melo, Helen M; Lyra E Silva, Natalia M; Ramos-Lobo, Angela M; Teixeira, Pryscila D S; Buonfiglio, Daniella C; Wasinski, Frederick; Lima, Eliana R; Higuti, Eliza; Peroni, Cibele N; Bartolini, Paolo; Soares, Carlos R J; Metzger, Martin; de Felice, Fernanda G; Donato, Jose

2018-06-01

The signal transducer and activator of transcription 5 (STAT5) is a transcription factor recruited by numerous cytokines. STAT5 is important for several physiological functions, including body and tissue growth, mammary gland development, immune system and lipid metabolism. However, the role of STAT5 signaling for brain functions is still poorly investigated, especially regarding cognitive aspects. Therefore, the objective of the present study was to investigate whether brain STAT5 signaling modulates learning and memory formation. For this purpose, brain-specific STAT5 knockout (STAT5 KO) mice were studied in well-established memory tests. Initially, we confirmed a robust reduction in STAT5a and STAT5b mRNA levels in different brain structures of STAT5 KO mice. STAT5 KO mice showed no significant alterations in metabolism, growth, somatotropic axis and spontaneous locomotor activity. In contrast, brain-specific STAT5 ablation impaired learning and memory formation in the novel object recognition, Barnes maze and contextual fear conditioning tests. To unravel possible mechanisms that might underlie the memory deficits of STAT5 KO mice, we assessed neurogenesis in the hippocampus, but no significant differences were observed between groups. On the other hand, reduced insulin-like growth factor-1 (IGF-1) mRNA expression was found in the hippocampus and hypothalamus of STAT5 KO mice. These findings collectively indicate that brain STAT5 signaling is required to attain normal learning and memory. Therefore, STAT5 is an important downstream cellular mechanism shared by several cytokines to regulate cognitive functions.

Enhanced recognition memory in grapheme-color synaesthesia for different categories of visual stimuli.

PubMed

Ward, Jamie; Hovard, Peter; Jones, Alicia; Rothen, Nicolas

2013-01-01

Memory has been shown to be enhanced in grapheme-color synaesthesia, and this enhancement extends to certain visual stimuli (that don't induce synaesthesia) as well as stimuli comprised of graphemes (which do). Previous studies have used a variety of testing procedures to assess memory in synaesthesia (e.g., free recall, recognition, associative learning) making it hard to know the extent to which memory benefits are attributable to the stimulus properties themselves, the testing method, participant strategies, or some combination of these factors. In the first experiment, we use the same testing procedure (recognition memory) for a variety of stimuli (written words, non-words, scenes, and fractals) and also check which memorization strategies were used. We demonstrate that grapheme-color synaesthetes show enhanced memory across all these stimuli, but this is not found for a non-visual type of synaesthesia (lexical-gustatory). In the second experiment, the memory advantage for scenes is explored further by manipulating the properties of the old and new images (changing color, orientation, or object presence). Again, grapheme-color synaesthetes show a memory advantage for scenes across all manipulations. Although recognition memory is generally enhanced in this study, the largest effects were found for abstract visual images (fractals) and scenes for which color can be used to discriminate old/new status.

Modifying Memory: Selectively Enhancing and Updating Personal Memories for a Museum Tour by Reactivating Them

PubMed Central

St. Jacques, Peggy L.; Schacter, Daniel L.

2013-01-01

Memory can be modified when reactivated, but little is known about how the properties and extent of reactivation can selectively affect subsequent memory. We developed a novel museum paradigm to directly investigate reactivation-induced plasticity for personal memories. Participants reactivated memories triggered by photos taken from a camera they wore during a museum tour and made relatedness judgments on novel photos taken from a different tour of the same museum. Subsequent recognition memory for events at the museum was better for memories that were highly reactivated (i.e., the retrieval cues during reactivation matched the encoding experience) than for memories that were reactivated at a lower level (i.e., the retrieval cues during reactivation mismatched the encoding experience), but reactivation also increased false recognition of photographs depicting stops that were not experienced during the museum tour. Reactivation thus enables memories to be selectively enhanced and distorted via updating, thereby supporting the dynamic and flexible nature of memory. PMID:23406611

Effects of hippocampal high-frequency electrical stimulation in memory formation and their association with amino acid tissue content and release in normal rats.

PubMed

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. Copyright © 2010 Wiley Periodicals, Inc., Inc.

The effect of Twitter exposure on false memory formation.

PubMed

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.

Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory

PubMed Central

Ko, Hyoung-Gon; Jang, Deok-Jin; Son, Junehee; Kwak, Chuljung; Choi, Jun-Hyeok; Ji, Young-Hoon; Lee, Yun-Sil; Son, Hyeon; Kaang, Bong-Kiun

2009-01-01

Newborn neurons in the subgranular zone (SGZ) of the hippocampus incorporate into the dentate gyrus and mature. Numerous studies have focused on hippocampal neurogenesis because of its importance in learning and memory. However, it is largely unknown whether hippocampal neurogenesis is involved in memory extinction per se. Here, we sought to examine the possibility that hippocampal neurogenesis may play a critical role in the formation and extinction of hippocampus-dependent contextual fear memory. By methylazoxymethanol acetate (MAM) or gamma-ray irradiation, hippocampal neurogenesis was impaired in adult mice. Under our experimental conditions, only a severe impairment of hippocampal neurogenesis inhibited the formation of contextual fear memory. However, the extinction of contextual fear memory was not affected. These results suggest that although adult newborn neurons contribute to contextual fear memory, they may not be involved in the extinction or erasure of hippocampus-dependent contextual fear memory. PMID:19138433

Green tea and cocoa enhance cognition in Lymnaea

PubMed Central

Swinton, Erin; de Freitas, Emily; Swinton, Cayley; Shymansky, Tamila; Hiles, Emily; Zhang, Jack; Rothwell, Cailin; Lukowiak, Ken

2018-01-01

ABSTRACT A flavonoid, (-)-epicatechi (Epi), enhances long-term memory (LTM) formation in Lymnaea and reverses memory obstruction caused by stress. Many foods contain substantial amounts of Epi, (e.g. green tea and cocoa). In humans eating such foods may directly or indirectly enhance cognition. We directly test whether operant conditioning training Lymnaea in these natural foods result in the same effects as training snails in pure Epi. We found that exposure to products containing high concentrations of Epi (e.g. green tea and cocoa) during training enhanced memory formation and could even reverse a learning and memory deficit brought about by stress. Epi can be photo-inactivated by exposure to ultraviolet light. We found that following photo-inactivation of Epi, memory enhancement did not occur. Photo-inactivation of foods containing Epi (e,g. green tea) blocked their ability to enhance LTM. Our data are thus consistent with the hypothesis that dietary sources of Epi can have positive benefits on cognitive ability and be able to reverse memory aversive states. PMID:29497476

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

PubMed

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.

How To Create and Conduct a Memory Enhancement Program.

ERIC Educational Resources Information Center

Meyer, Genevieve R.; Ober-Reynolds, Sharman

This report describes Memory Enhancement Group workshops which have been conducted at the Senior Health and Peer Counseling Center in Santa Monica, California and gives basic data regarding outcomes of the workshops. It provides a model of memory as a three-step process of registration or becoming aware, consolidation, and retrieval. It presents…

Remembering the snake in the grass: Threat enhances recognition but not source memory.

PubMed

Meyer, Miriam Magdalena; Bell, Raoul; Buchner, Axel

2015-12-01

Research on the influence of emotion on source memory has yielded inconsistent findings. The object-based framework (Mather, 2007) predicts that negatively arousing stimuli attract attention, resulting in enhanced within-object binding, and, thereby, enhanced source memory for intrinsic context features of emotional stimuli. To test this prediction, we presented pictures of threatening and harmless animals, the color of which had been experimentally manipulated. In a memory test, old-new recognition for the animals and source memory for their color was assessed. In all 3 experiments, old-new recognition was better for the more threatening material, which supports previous reports of an emotional memory enhancement. This recognition advantage was due to the emotional properties of the stimulus material, and not specific for snake stimuli. However, inconsistent with the prediction of the object-based framework, intrinsic source memory was not affected by emotion. (c) 2015 APA, all rights reserved).

Portable wireless neurofeedback system of EEG alpha rhythm enhances memory.

PubMed

Wei, Ting-Ying; Chang, Da-Wei; Liu, You-De; Liu, Chen-Wei; Young, Chung-Ping; Liang, Sheng-Fu; Shaw, Fu-Zen

2017-11-13

Effect of neurofeedback training (NFT) on enhancement of cognitive function or amelioration of clinical symptoms is inconclusive. The trainability of brain rhythm using a neurofeedback system is uncertainty because various experimental designs are used in previous studies. The current study aimed to develop a portable wireless NFT system for alpha rhythm and to validate effect of the NFT system on memory with a sham-controlled group. The proposed system contained an EEG signal analysis device and a smartphone with wireless Bluetooth low-energy technology. Instantaneous 1-s EEG power and contiguous 5-min EEG power throughout the training were developed as feedback information. The training performance and its progression were kept to boost usability of our device. Participants were blinded and randomly assigned into either the control group receiving random 4-Hz power or Alpha group receiving 8-12-Hz power. Working memory and episodic memory were assessed by the backward digital span task and word-pair task, respectively. The portable neurofeedback system had advantages of a tiny size and long-term recording and demonstrated trainability of alpha rhythm in terms of significant increase of power and duration of 8-12 Hz. Moreover, accuracies of the backward digital span task and word-pair task showed significant enhancement in the Alpha group after training compared to the control group. Our tiny portable device demonstrated success trainability of alpha rhythm and enhanced two kinds of memories. The present study suggest that the portable neurofeedback system provides an alternative intervention for memory enhancement.

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

PubMed

Boury-Jamot, Benjamin; Halfon, Olivier; Magistretti, Pierre J; Boutrel, Benjamin

2016-12-01

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. © 2016 WILEY Periodicals, Inc.

Enhanced recognition memory in grapheme-color synaesthesia for different categories of visual stimuli

PubMed Central

Ward, Jamie; Hovard, Peter; Jones, Alicia; Rothen, Nicolas

2013-01-01

Memory has been shown to be enhanced in grapheme-color synaesthesia, and this enhancement extends to certain visual stimuli (that don't induce synaesthesia) as well as stimuli comprised of graphemes (which do). Previous studies have used a variety of testing procedures to assess memory in synaesthesia (e.g., free recall, recognition, associative learning) making it hard to know the extent to which memory benefits are attributable to the stimulus properties themselves, the testing method, participant strategies, or some combination of these factors. In the first experiment, we use the same testing procedure (recognition memory) for a variety of stimuli (written words, non-words, scenes, and fractals) and also check which memorization strategies were used. We demonstrate that grapheme-color synaesthetes show enhanced memory across all these stimuli, but this is not found for a non-visual type of synaesthesia (lexical-gustatory). In the second experiment, the memory advantage for scenes is explored further by manipulating the properties of the old and new images (changing color, orientation, or object presence). Again, grapheme-color synaesthetes show a memory advantage for scenes across all manipulations. Although recognition memory is generally enhanced in this study, the largest effects were found for abstract visual images (fractals) and scenes for which color can be used to discriminate old/new status. PMID:24187542

Entrainment of prefrontal beta oscillations induces an endogenous echo and impairs memory formation.

PubMed

Hanslmayr, Simon; Matuschek, Jonas; Fellner, Marie-Christin

2014-04-14

Brain oscillations across all frequency bands play a key role for memory formation. Specifically, desynchronization of local neuronal assemblies in the left inferior prefrontal cortex (PFC) in the beta frequency (∼18 Hz) has been shown to be central for encoding of verbal memories. However, it remains elusive whether prefrontal beta desynchronization is causally relevant for memory formation and whether these endogenous beta oscillations can be entrained by external stimulation. By using combined EEG-TMS (transcranial magnetic stimulation), we here address these fundamental questions in human participants performing a word-list learning task. Confirming our predictions, memory encoding was selectively impaired when the left inferior frontal gyrus (IFG) was driven at beta (18.7 Hz) compared to stimulation at other frequencies (6.8 Hz and 10.7 Hz) and to ineffective sham stimulation (18.7 Hz). Furthermore, a sustained oscillatory "echo" in the left IFG, which outlasted the stimulation period by approximately 1.5 s, was observed solely after beta stimulation. The strength of this beta echo was related to memory impairment on a between-subjects level. These results show endogenous oscillatory entrainment effects and behavioral impairment selectively in beta frequency for stimulation of the left IFG, demonstrating an intimate causal relationship between prefrontal beta desynchronization and memory formation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Formation of spatial and nonspatial memory in different condensed versions of short-term learning in Morris water maze.

PubMed

Zots, M A; Ivashkina, O I; Ivanova, A A; Anokhin, K V

2014-03-01

We studied the formation of spatial and nonspatial memory in mice during learning in three different condensed versions of Morris water maze task. Learning in combined version caused the formation of both spatial and nonspatial memory, whereas learning in condensed versions (spatial and nonspatial) led to memory formation specific for the version.

Memory for time and place contributes to enhanced confidence in memories for emotional events

PubMed Central

Rimmele, Ulrike; Davachi, Lila; Phelps, Elizabeth A.

2012-01-01

Emotion strengthens the subjective sense of remembering. However, these confidently remembered emotional memories have not been found be more accurate for some types of contextual details. We investigated whether the subjective sense of recollecting negative stimuli is coupled with enhanced memory accuracy for three specific types of central contextual details using the remember/know paradigm and confidence ratings. Our results indicate that the subjective sense of remembering is indeed coupled with better recollection of spatial location and temporal context. In contrast, we found a double-dissociation between the subjective sense of remembering and memory accuracy for colored dots placed in the conceptual center of negative and neutral scenes. These findings show that the enhanced subjective recollective experience for negative stimuli reliably indicates objective recollection for spatial location and temporal context, but not for other types of details, whereas for neutral stimuli, the subjective sense of remembering is coupled with all the types of details assessed. Translating this finding to flashbulb memories, we found that, over time, more participants correctly remembered the location where they learned about the terrorist attacks on 9/11 than any other canonical feature. Likewise participants’ confidence was higher in their memory for location vs. other canonical features. These findings indicate that the strong recollective experience of a negative event corresponds to an accurate memory for some kinds of contextual details, but not other kinds. This discrepancy provides further evidence that the subjective sense of remembering negative events is driven by a different mechanism than the subjective sense of remembering neutral events. PMID:22642353

Distributed Learning Enhances Relational Memory Consolidation

ERIC Educational Resources Information Center

Litman, Leib; Davachi, Lila

2008-01-01

It has long been known that distributed learning (DL) provides a mnemonic advantage over massed learning (ML). However, the underlying mechanisms that drive this robust mnemonic effect remain largely unknown. In two experiments, we show that DL across a 24 hr interval does not enhance immediate memory performance but instead slows the rate of…

Epigenetic regulation of estrogen-dependent memory

PubMed Central

Fortress, Ashley M.; Frick, Karyn M.

2014-01-01

Hippocampal memory formation is highly regulated by post-translational histone modifications and DNA methylation. Accordingly, these epigenetic processes play a major role in the effects of modulatory factors, such as sex steroid hormones, on hippocampal memory. Our laboratory recently demonstrated that the ability of the potent estrogen 17β-estradiol (E2) to enhance hippocampal-dependent novel object recognition memory in ovariectomized female mice requires ERK-dependent histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although these data provide valuable insight into the chromatin modifications that mediate the memory-enhancing effects of E2, epigenetic regulation of gene expression is enormously complex. Therefore, more research is needed to fully understand how E2 and other hormones employ epigenetic alterations to shape behavior. This review discusses the epigenetic alterations shown thus far to regulate hippocampal memory, briefly reviews the effects of E2 on hippocampal function, and describes in detail our work on epigenetic regulation of estrogenic memory enhancement. PMID:24878494

Selective inhibition of phosphodiesterase 5 enhances glutamatergic synaptic plasticity and memory in mice.

PubMed

Uthayathas, Subramaniam; Parameshwaran, Kodeeswaran; Karuppagounder, Senthilkumar S; Ahuja, Manuj; Dhanasekaran, Muralikrishnan; Suppiramaniam, Vishnu

2013-11-01

Phosphodiesterases (PDEs) belong to a family of proteins that control metabolism of cyclic nucleotides. Targeting PDE5, for enhancing cellular function, is one of the therapeutic strategies for male erectile dysfunction. We have investigated whether in vivo inhibition of PDE5, which is expressed in several brain regions, will enhance memory and synaptic transmission in the hippocampus of healthy mice. We have found that acute administration of sildenafil, a specific PDE5 inhibitor, enhanced hippocampus-dependent memory tasks. To elucidate the underlying mechanism in the memory enhancement, effects of sildenafil on long-term potentiation (LTP) were measured. The level of LTP was significantly elevated, with concomitant increases in basal synaptic transmission, in mice treated with sildenafil (1 mg/kg/day) for 15 days compared to control mice. These results suggest that moderate PDE5 inhibition enhances memory by increasing synaptic plasticity and transmission in the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

Nobiletin improves emotional and novelty recognition memory but not spatial referential memory.

PubMed

Kang, Jiyun; Shin, Jung-Won; Kim, Yoo-Rim; Swanberg, Kelley M; Kim, Yooseung; Bae, Jae Ryong; Kim, Young Ki; Lee, Jinwon; Kim, Soo-Yeon; Sohn, Nak-Won; Maeng, Sungho

2017-01-01

How to maintain and enhance cognitive functions for both aged and young populations is a highly interesting subject. But candidate memory-enhancing reagents are tested almost exclusively on lesioned or aged animals. Also, there is insufficient information on the type of memory these reagents can improve. Working memory, located in the prefrontal cortex, manages short-term sensory information, but, by gaining significant relevance, this information is converted to long-term memory by hippocampal formation and/or amygdala, followed by tagging with space-time or emotional cues, respectively. Nobiletin is a product of citrus peel known for cognitive-enhancing effects in various pharmacological and neurodegenerative disease models, yet, it is not well studied in non-lesioned animals and the type of memory that nobiletin can improve remains unclear. In this study, 8-week-old male mice were tested using behavioral measurements for working, spatial referential, emotional and visual recognition memory after daily administration of nobiletin. While nobiletin did not induce any change of spontaneous activity in the open field test, freezing by fear conditioning and novel object recognition increased. However, the effectiveness of spatial navigation in the Y-maze and Morris water maze was not improved. These results mean that nobiletin can specifically improve memories of emotionally salient information associated with fear and novelty, but not of spatial information without emotional saliency. Accordingly, the use of nobiletin on normal subjects as a memory enhancer would be more effective on emotional types but may have limited value for the improvement of episodic memories.

Emotional content enhances true but not false memory for categorized stimuli.

PubMed

Choi, Hae-Yoon; Kensinger, Elizabeth A; Rajaram, Suparna

2013-04-01

Past research has shown that emotion enhances true memory, but that emotion can either increase or decrease false memory. Two theoretical possibilities-the distinctiveness of emotional stimuli and the conceptual relatedness of emotional content-have been implicated as being responsible for influencing both true and false memory for emotional content. In the present study, we sought to identify the mechanisms that underlie these mixed findings by equating the thematic relatedness of the study materials across each type of valence used (negative, positive, or neutral). In three experiments, categorically bound stimuli (e.g., funeral, pets, and office items) were used for this purpose. When the encoding task required the processing of thematic relatedness, a significant true-memory enhancement for emotional content emerged in recognition memory, but no emotional boost to false memory (exp. 1). This pattern persisted for true memory with a longer retention interval between study and test (24 h), and false recognition was reduced for emotional items (exp. 2). Finally, better recognition memory for emotional items once again emerged when the encoding task (arousal ratings) required the processing of the emotional aspect of the study items, with no emotional boost to false recognition (EXP. 3). Together, these findings suggest that when emotional and neutral stimuli are equivalently high in thematic relatedness, emotion continues to improve true memory, but it does not override other types of grouping to increase false memory.

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

PubMed

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.

Brain oscillations track the formation of episodic memories in the real world.

PubMed

Griffiths, Benjamin; Mazaheri, Ali; Debener, Stefan; Hanslmayr, Simon

2016-12-01

Despite the well-known influence of environmental context on episodic memory, little has been done to increase contextual richness within the lab. This leaves a blind spot lingering over the neuronal correlates of episodic memory formation in day-to-day life. To address this, we presented participants with a series of words to memorise along a pre-designated route across campus while a mobile EEG system acquired ongoing neural activity. Replicating lab-based subsequent memory effects (SMEs), we identified significant low to mid frequency power decreases (<30Hz), including beta power decreases over the left inferior frontal gyrus. When investigating the oscillatory correlates of temporal and spatial context binding, we found that items strongly bound to spatial context exhibited significantly greater theta power decreases than items strongly bound to temporal context. These findings expand upon lab-based studies by demonstrating the influence of real world contextual factors that underpin memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.

A flavanoid component of chocolate quickly reverses an imposed memory deficit.

PubMed

Knezevic, Bogdan; Komatsuzaki, Yoshimasa; de Freitas, Emily; Lukowiak, Ken

2016-03-01

The ability to remember is influenced by environmental and lifestyle factors, such as stress and diet. A flavanol contained in chocolate, epicatechin (Epi), has been shown to enhance long-term memory (LTM) formation in Lymnaea. Combining two stressors (low-calcium pond water and crowding) blocks learning and all forms of memory; that is, this combination of environmentally relevant stressors creates a memory-unfriendly state. We tested the hypothesis that Epi will immediately reverse the memory-unfriendly state, i.e. that snails in the memory-deficit state when trained in Epi will immediately become competent to learn and form memory. We found that Epi not only reverses the memory-deficit state but also further enhances LTM formation. Thus, a naturally occurring bioactive plant compound can overcome a memory-unfriendly state. This supports the idea that bioactive substances may mitigate memory-making deficits that, for example, occur with ageing. © 2016. Published by The Company of Biologists Ltd.

The human hippocampal formation mediates short-term memory of colour-location associations.

PubMed

Finke, Carsten; Braun, Mischa; Ostendorf, Florian; Lehmann, Thomas-Nicolas; Hoffmann, Karl-Titus; Kopp, Ute; Ploner, Christoph J

2008-01-31

The medial temporal lobe (MTL) has long been considered essential for declarative long-term memory, whereas the fronto-parietal cortex is generally seen as the anatomical substrate of short-term memory. This traditional dichotomy is questioned by recent studies suggesting a possible role of the MTL for short-term memory. In addition, there is no consensus on a possible specialization of MTL sub-regions for memory of associative information. Here, we investigated short-term memory for single features and feature associations in three humans with post-surgical lesions affecting the right hippocampal formation and in 10 healthy controls. We used three delayed-match-to-sample tasks with two delays (900/5000 ms) and three set sizes (2/4/6 items). Subjects were instructed to remember either colours, locations or colour-location associations. In colour-only and location-only conditions, performance of patients did not differ from controls. By contrast, a significant group difference was found in the association condition at 5000 ms delay. This difference was largely independent of set size, thus suggesting that it cannot be explained by the increased complexity of the association condition. These findings show that the hippocampal formation plays a significant role for short-term memory of simple visuo-spatial associations, and suggest a specialization of MTL sub-regions for associative memory.

Caffeine in floral nectar enhances a pollinator's memory of reward.

PubMed

Wright, G A; Baker, D D; Palmer, M J; Stabler, D; Mustard, J A; Power, E F; Borland, A M; Stevenson, P C

2013-03-08

Plant defense compounds occur in floral nectar, but their ecological role is not well understood. We provide evidence that plant compounds pharmacologically alter pollinator behavior by enhancing their memory of reward. Honeybees rewarded with caffeine, which occurs naturally in nectar of Coffea and Citrus species, were three times as likely to remember a learned floral scent as were honeybees rewarded with sucrose alone. Caffeine potentiated responses of mushroom body neurons involved in olfactory learning and memory by acting as an adenosine receptor antagonist. Caffeine concentrations in nectar did not exceed the bees' bitter taste threshold, implying that pollinators impose selection for nectar that is pharmacologically active but not repellent. By using a drug to enhance memories of reward, plants secure pollinator fidelity and improve reproductive success.

Music-based memory enhancement in Alzheimer's disease: promise and limitations.

PubMed

Simmons-Stern, Nicholas R; Deason, Rebecca G; Brandler, Brian J; Frustace, Bruno S; O'Connor, Maureen K; Ally, Brandon A; Budson, Andrew E

2012-12-01

In a previous study (Simmons-Stern, Budson & Ally, 2010), we found that patients with Alzheimer's disease (AD) better recognized visually presented lyrics when the lyrics were also sung rather than spoken at encoding. The present study sought to further investigate the effects of music on memory in patients with AD by making the content of the song lyrics relevant for the daily life of an older adult and by examining how musical encoding alters several different aspects of episodic memory. Patients with AD and healthy older adults studied visually presented novel song lyrics related to instrumental activities of daily living (IADL) that were accompanied by either a sung or a spoken recording. Overall, participants performed better on a memory test of general lyric content for lyrics that were studied sung as compared to spoken. However, on a memory test of specific lyric content, participants performed equally well for sung and spoken lyrics. We interpret these results in terms of a dual-process model of recognition memory such that the general content questions represent a familiarity-based representation that is preferentially sensitive to enhancement via music, while the specific content questions represent a recollection-based representation unaided by musical encoding. Additionally, in a test of basic recognition memory for the audio stimuli, patients with AD demonstrated equal discrimination for sung and spoken stimuli. We propose that the perceptual distinctiveness of musical stimuli enhanced metamemorial awareness in AD patients via a non-selective distinctiveness heuristic, thereby reducing false recognition while at the same time reducing true recognition and eliminating the mnemonic benefit of music. These results are discussed in the context of potential music-based memory enhancement interventions for the care of patients with AD. Published by Elsevier Ltd.

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

PubMed Central

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

The time course of ventrolateral prefrontal cortex involvement in memory formation.

PubMed

Machizawa, Maro G; Kalla, Roger; Walsh, Vincent; Otten, Leun J

2010-03-01

Human neuroimaging studies have implicated a number of brain regions in long-term memory formation. Foremost among these is ventrolateral prefrontal cortex. Here, we used double-pulse transcranial magnetic stimulation (TMS) to assess whether the contribution of this part of cortex is crucial for laying down new memories and, if so, to examine the time course of this process. Healthy adult volunteers performed an incidental encoding task (living/nonliving judgments) on sequences of words. In separate series, the task was performed either on its own or while TMS was applied to one of two sites of experimental interest (left/right anterior inferior frontal gyrus) or a control site (vertex). TMS pulses were delivered at 350, 750, or 1,150 ms following word onset. After a delay of 15 min, memory for the items was probed with a recognition memory test including confidence judgments. TMS to all three sites nonspecifically affected the speed and accuracy with which judgments were made during the encoding task. However, only TMS to prefrontal cortex affected later memory performance. Stimulation of left or right inferior frontal gyrus at all three time points reduced the likelihood that a word would later be recognized by a small, but significant, amount (approximately 4%). These findings indicate that bilateral ventrolateral prefrontal cortex plays an essential role in memory formation, exerting its influence between > or = 350 and 1,150 ms after an event is encountered.

Enhancing memory and imagination improves problem solving among individuals with depression.

PubMed

McFarland, Craig P; Primosch, Mark; Maxson, Chelsey M; Stewart, Brandon T

2017-08-01

Recent work has revealed links between memory, imagination, and problem solving, and suggests that increasing access to detailed memories can lead to improved imagination and problem-solving performance. Depression is often associated with overgeneral memory and imagination, along with problem-solving deficits. In this study, we tested the hypothesis that an interview designed to elicit detailed recollections would enhance imagination and problem solving among both depressed and nondepressed participants. In a within-subjects design, participants completed a control interview or an episodic specificity induction prior to completing memory, imagination, and problem-solving tasks. Results revealed that compared to the control interview, the episodic specificity induction fostered increased detail generation in memory and imagination and more relevant steps on the problem-solving task among depressed and nondepressed participants. This study builds on previous work by demonstrating that a brief interview can enhance problem solving among individuals with depression and supports the notion that episodic memory plays a key role in problem solving. It should be noted, however, that the results of the interview are relatively short-lived.

Pharmacological enhancement of memory or cognition in normal subjects

PubMed Central

Lynch, Gary; Cox, Conor D.; Gall, Christine M.

2014-01-01

The possibility of expanding memory or cognitive capabilities above the levels in high functioning individuals is a topic of intense discussion among scientists and in society at large. The majority of animal studies use behavioral endpoint measures; this has produced valuable information but limited predictability for human outcomes. Accordingly, several groups are pursuing a complementary strategy with treatments targeting synaptic events associated with memory encoding or forebrain network operations. Transcription and translation figure prominently in substrate work directed at enhancement. Notably, the question of why new proteins would be needed for a now-forming memory given that learning-driven synthesis presumably occurred throughout the immediate past has been largely ignored. Despite this conceptual problem, and some controversy, recent studies have reinvigorated the idea that selective gene manipulation is a plausible route to enhancement. Efforts to improve memory by facilitating synaptic encoding of information have also progressed, in part due of breakthroughs on mechanisms that stabilize learning-related, long-term potentiation (LTP). These advances point to a reductionistic hypothesis for a diversity of experimental results on enhancement, and identify under-explored possibilities. Cognitive enhancement remains an elusive goal, in part due to the difficulty of defining the target. The popular view of cognition as a collection of definable computations seems to miss the fluid, integrative process experienced by high functioning individuals. The neurobiological approach obviates these psychological issues to directly test the consequences of improving throughput in networks underlying higher order behaviors. The few relevant studies testing drugs that selectively promote excitatory transmission indicate that it is possible to expand cortical networks engaged by complex tasks and that this is accompanied by capabilities not found in normal animals

Epigenetic mechanisms in experience-driven memory formation and behavior.

PubMed

Puckett, Rosemary E; Lubin, Farah D

2011-10-01

Epigenetic mechanisms have long been associated with the regulation of gene-expression changes accompanying normal neuronal development and cellular differentiation; however, until recently these mechanisms were believed to be statically quiet in the adult brain. Behavioral neuroscientists have now begun to investigate these epigenetic mechanisms as potential regulators of gene-transcription changes in the CNS subserving synaptic plasticity and long-term memory (LTM) formation. Experimental evidence from learning and memory animal models has demonstrated that active chromatin remodeling occurs in terminally differentiated postmitotic neurons, suggesting that these molecular processes are indeed intimately involved in several stages of LTM formation, including consolidation, reconsolidation and extinction. Such chromatin modifications include the phosphorylation, acetylation and methylation of histone proteins and the methylation of associated DNA to subsequently affect transcriptional gene readout triggered by learning. The present article examines how such learning-induced epigenetic changes contribute to LTM formation and influence behavior. In particular, this article is a survey of the specific epigenetic mechanisms that have been demonstrated to regulate gene expression for both transcription factors and growth factors in the CNS, which are critical for LTM formation and storage, as well as how aberrant epigenetic processing can contribute to psychological states such as schizophrenia and drug addiction. Together, the findings highlighted in this article support a novel role for epigenetic mechanisms in the adult CNS serving as potential key molecular regulators of gene-transcription changes necessary for LTM formation and adult behavior.

Context odor presentation during sleep enhances memory in honeybees.

PubMed

Zwaka, Hanna; Bartels, Ruth; Gora, Jacob; Franck, Vivien; Culo, Ana; Götsch, Moritz; Menzel, Randolf

2015-11-02

Sleep plays an important role in stabilizing new memory traces after learning [1-3]. Here we investigate whether sleep's role in memory processing is similar in evolutionarily distant species and demonstrate that a context trigger during deep-sleep phases improves memory in invertebrates, as it does in humans. We show that in honeybees (Apis mellifera), exposure to an odor during deep sleep that has been present during learning improves memory performance the following day. Presentation of the context odor during wake phases or novel odors during sleep does not enhance memory. In humans, memory consolidation can be triggered by presentation of a context odor during slow-wave sleep that had been present during learning [3-5]. Our results reveal that deep-sleep phases in honeybees have the potential to prompt memory consolidation, just as they do in humans. This study provides strong evidence for a conserved role of sleep-and how it affects memory processes-from insects to mammals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ventromedial prefrontal cortex stimulation enhances memory and hippocampal neurogenesis in the middle-aged rats

PubMed Central

Liu, Albert; Jain, Neeraj; Vyas, Ajai; Lim, Lee Wei

2015-01-01

Memory dysfunction is a key symptom of age-related dementia. Although recent studies have suggested positive effects of electrical stimulation for memory enhancement, its potential targets remain largely unknown. In this study, we hypothesized that spatially targeted deep brain stimulation of ventromedial prefrontal cortex enhanced memory functions in a middle-aged rat model. Our results show that acute stimulation enhanced the short-, but not the long-term memory in the novel-object recognition task. Interestingly, after chronic high-frequency stimulation, both the short- and long-term memories were robustly improved in the novel-object recognition test and Morris water-maze spatial task compared to sham. Our results also demonstrated that chronic ventromedial prefrontal cortex high-frequency stimulation upregulated neurogenesis-associated genes along with enhanced hippocampal cell proliferation. Importantly, these memory behaviors were strongly correlated with the hippocampal neurogenesis. Overall, these findings suggest that chronic ventromedial prefrontal cortex high-frequency stimulation may serve as a novel effective therapeutic target for dementia-related disorders. DOI: http://dx.doi.org/10.7554/eLife.04803.001 PMID:25768425

Identification of a novel protein for memory regulation in the hippocampus.

PubMed

Zhang, Xue-Han; Zhang, Hui; Tu, Yanyang; Gao, Xiang; Zhou, Changfu; Jin, Meilei; Zhao, Guoping; Jing, Naihe; Li, Bao-Ming; Yu, Lei

2005-08-26

Memory formation, maintenance, and retrieval are a dynamic process, reflecting a combined outcome of new memory formation on one hand, and older memory suppression/clearance on the other. Although much knowledge has been gained regarding new memory formation, less is known about the molecular components and processes that serve the function of memory suppression/clearance. Here, we report the identification of a novel protein, termed hippyragranin (HGN), that is expressed in the rat hippocampus and its expression is reduced by hippocampal denervation. Inhibition of HGN by antisense oligonucleotide in area CA1 results in enhanced performance in Morris water maze, as well as elevated long-term potentiation. These results suggest that HGN is involved in negative memory regulation.

Effects of cortisol suppression on sleep-associated consolidation of neutral and emotional memory.

PubMed

Wagner, Ullrich; Degirmenci, Metin; Drosopoulos, Spyridon; Perras, Boris; Born, Jan

2005-12-01

Previous research indicates that hippocampus-dependent declarative memory benefits from early nocturnal sleep, when slow-wave sleep (SWS) prevails and cortisol release is minimal, whereas amygdala-dependent emotional memory is enhanced through late sleep, when rapid eye movement (REM) sleep predominates. The role of the strong cortisol rise accompanying late sleep for emotional memory consolidation has not yet been investigated. Effects of the cortisol synthesis inhibitor metyrapone on sleep-associated consolidation of memory for neutral and emotional texts were investigated in a randomized, double-blind, placebo-controlled study in 14 healthy men. Learning took place immediately before treatment, which was followed by 8 hours of sleep. Retrieval was tested at 11 am the next morning. Metyrapone suppressed cortisol during sleep and blocked particularly the late-night rise in cortisol. It reduced SWS and concomitantly impaired the consolidation of neutral texts. Emotional texts were spared from this impairing influence, however. Metyrapone even amplified emotional enhancement in text recall indicating amygdala-dependent memory. Cortisol blockade during sleep impairs hippocampus-dependent declarative memory formation but enhances amygdala-dependent emotional memory formation. The natural cortisol rise during late sleep may thus protect from overshooting emotional memory formation, a mechanism possibly pertinent to the development of posttraumatic stress disorder.

Audiovisual semantic congruency during encoding enhances memory performance.

PubMed

Heikkilä, Jenni; Alho, Kimmo; Hyvönen, Heidi; Tiippana, Kaisa

2015-01-01

Studies of memory and learning have usually focused on a single sensory modality, although human perception is multisensory in nature. In the present study, we investigated the effects of audiovisual encoding on later unisensory recognition memory performance. The participants were to memorize auditory or visual stimuli (sounds, pictures, spoken words, or written words), each of which co-occurred with either a semantically congruent stimulus, incongruent stimulus, or a neutral (non-semantic noise) stimulus in the other modality during encoding. Subsequent memory performance was overall better when the stimulus to be memorized was initially accompanied by a semantically congruent stimulus in the other modality than when it was accompanied by a neutral stimulus. These results suggest that semantically congruent multisensory experiences enhance encoding of both nonverbal and verbal materials, resulting in an improvement in their later recognition memory.

Stress enhances the consolidation of extinction memory in a predictive learning task

PubMed Central

Hamacher-Dang, Tanja C.; Engler, Harald; Schedlowski, Manfred; Wolf, Oliver T.

2013-01-01

Extinction is not always permanent, as indicated by several types of recovery effects, such as the renewal effect, which may occur after a context change and points towards the importance of contextual cues. Strengthening the retrieval of extinction memory is a crucial aim of extinction-based psychotherapeutic treatments of anxiety disorders to prevent relapse. Stress is known to modulate learning and memory, with mostly enhancing effects on memory consolidation. However, whether such a consolidation-enhancing effect of acute stress can also be found for extinction memory has not yet been examined in humans. In this study, we investigated the effect of stress after extinction learning on the retrieval of extinction memory in a predictive learning renewal paradigm. Participants took the part of being the doctor of a fictitious patient and learned to predict whether certain food stimuli were associated with “stomach trouble” in two different restaurants (contexts). On the first day, critical stimuli were associated with stomach trouble in context A (acquisition phase). On the second day, these associations were extinguished in context B. Directly after extinction, participants were either exposed to a stressor (socially evaluated cold pressor test; n = 22) or a control condition (n = 24). On the third day, we tested retrieval of critical associations in contexts A and B. Participants exposed to stress after extinction exhibited a reduced recovery of responding at test in context B, suggesting that stress may context-dependently enhance the consolidation of extinction memory. Furthermore, the increase in cortisol in response to the stressor was negatively correlated with the recovery of responding in context A. Our findings suggest that in parallel to the known effects of stress on the consolidation of episodic memory, stress also enhances the consolidation of extinction memory, which might be relevant for potential applications in extinction-based psychotherapy

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

PubMed

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.

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

PubMed Central

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

2014-01-01

Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesised to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluR2 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 GluR2-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 GluR2-independent target of ZIP (possibly PKCλ) in the mPFC during early memory formation. PMID:24729442

Differential effects of beta-adrenergic receptor blockade in the medial prefrontal cortex during aversive and incidental taste memory formation.

PubMed

Reyes-López, J; Nuñez-Jaramillo, L; Morán-Guel, E; Miranda, M I

2010-08-11

The medial prefrontal cortex (mPFC) is a brain area crucial for memory, attention, and decision making. Specifically, the noradrenergic system in this cortex is involved in aversive learning, as well as in the retrieval of these memories. Some evidence suggests that this area has an important role during taste memory, particularly during conditioned taste aversion (CTA), a model of aversive memory. Despite some previous evidence, there is scarce information about the role of adrenergic receptors in the mPFC during formation of aversive taste memory and appetitive/incidental taste memory. The goal of this research was to evaluate the role of mPFC beta-adrenergic receptors during CTA acquisition/consolidation or CTA retrieval, as well as during incidental taste memory formation using the model of latent inhibition of CTA. The results showed that infusions in the mPFC of the beta-adrenergic antagonist propranolol before CTA acquisition impaired both short- and long-term aversive taste memory formation, and also that propranolol infusions before the memory test impaired CTA retrieval. However, propranolol infusions before pre-exposure to the taste during the latent inhibition procedure had no effect on incidental taste memory acquisition or consolidation. These data indicate that beta-adrenergic receptors in the mPFC have different functions during taste memory formation: they have an important role during aversive taste association as well as during aversive retrieval but not during incidental taste memory formation. Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Structural Components of Synaptic Plasticity and Memory Consolidation

PubMed Central

Bailey, Craig H.; Kandel, Eric R.; Harris, Kristen M.

2015-01-01

Consolidation of implicit memory in the invertebrate Aplysia and explicit memory in the mammalian hippocampus are associated with remodeling and growth of preexisting synapses and the formation of new synapses. Here, we compare and contrast structural components of the synaptic plasticity that underlies these two distinct forms of memory. In both cases, the structural changes involve time-dependent processes. Thus, some modifications are transient and may contribute to early formative stages of long-term memory, whereas others are more stable, longer lasting, and likely to confer persistence to memory storage. In addition, we explore the possibility that trans-synaptic signaling mechanisms governing de novo synapse formation during development can be reused in the adult for the purposes of structural synaptic plasticity and memory storage. Finally, we discuss how these mechanisms set in motion structural rearrangements that prepare a synapse to strengthen the same memory and, perhaps, to allow it to take part in other memories as a basis for understanding how their anatomical representation results in the enhanced expression and storage of memories in the brain. PMID:26134321

Context memory formation requires activity-dependent protein degradation in the hippocampus.

PubMed

Cullen, Patrick K; Ferrara, Nicole C; Pullins, Shane E; Helmstetter, Fred J

2017-11-01

Numerous studies have indicated that the consolidation of contextual fear memories supported by an aversive outcome like footshock requires de novo protein synthesis as well as protein degradation mediated by the ubiquitin-proteasome system (UPS). Context memory formed in the absence of an aversive stimulus by simple exposure to a novel environment requires de novo protein synthesis in both the dorsal (dHPC) and ventral (vHPC) hippocampus. However, the role of UPS-mediated protein degradation in the consolidation of context memory in the absence of a strong aversive stimulus has not been investigated. In the present study, we used the context preexposure facilitation effect (CPFE) procedure, which allows for the dissociation of context learning from context-shock learning, to investigate the role of activity-dependent protein degradation in the dHPC and vHPC during the formation of a context memory. We report that blocking protein degradation with the proteasome inhibitor clasto-lactacystin β-lactone (βLac) or blocking protein synthesis with anisomycin (ANI) immediately after context preexposure significantly impaired context memory formation. Additionally, we examined 20S proteasome activity at different time points following context exposure and saw that the activity of proteasomes in the dHPC increases immediately after stimulus exposure while the vHPC exhibits a biphasic pattern of proteolytic activity. Taken together, these data suggest that the requirement of increased proteolysis during memory consolidation is not driven by processes triggered by the strong aversive outcome (i.e., shock) normally used to support fear conditioning. © 2017 Cullen et al.; Published by Cold Spring Harbor Laboratory Press.

Rapid formation and flexible expression of memories of subliminal word pairs.

PubMed

Reber, Thomas P; Henke, Katharina

2011-01-01

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.

Stretchable degradable and electroactive shape memory copolymers with tunable recovery temperature enhance myogenic differentiation.

PubMed

Deng, Zexing; Guo, Yi; Zhao, Xin; Li, Longchao; Dong, Ruonan; Guo, Baolin; Ma, Peter X

2016-12-01

Development of flexible degradable electroactive shape memory polymers (ESMPs) with tunable switching temperature (around body temperature) for tissue engineering is still a challenge. Here we designed and synthesized a series of shape memory copolymers with electroactivity, super stretchability and tunable recovery temperature based on poly(ε-caprolactone) (PCL) with different molecular weight and conductive amino capped aniline trimer, and demonstrated their potential to enhance myogenic differentiation from C2C12 myoblast cells. We characterized the copolymers by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance ( 1 H NMR), cyclic voltammetry (CV), ultraviolet-visible spectroscopy (UV-vis), differential scanning calorimetry (DSC), shape memory test, tensile test and in vitro enzymatic degradation study. The electroactive biodegradable shape memory copolymers showed great elasticity, tunable recovery temperature around 37°C, and good shape memory properties. Furthermore, proliferation and differentiation of C2C12 myoblasts were investigated on electroactive copolymers films, and they greatly enhanced the proliferation, myotube formation and related myogenic differentiation genes expression of C2C12 myoblasts compared to the pure PCL with molecular weight of 80,000. Our study suggests that these electroactive, highly stretchable, biodegradable shape memory polymers with tunable recovery temperature near the body temperature have great potential in skeletal muscle tissue engineering application. Conducting polymers can regulate cell behavior such cell adhesion, proliferation, and differentiation with or without electrical stimulation. Therefore, they have great potential for electrical signal sensitive tissue regeneration. Although conducting biomaterials with degradability have been developed, highly stretchable and electroactive degradable copolymers for soft tissue engineering have been rarely reported. On the other hand, shape

Epigenetic regulation of estrogen-dependent memory.

PubMed

Fortress, Ashley M; Frick, Karyn M

2014-10-01

Hippocampal memory formation is highly regulated by post-translational histone modifications and DNA methylation. Accordingly, these epigenetic processes play a major role in the effects of modulatory factors, such as sex steroid hormones, on hippocampal memory. Our laboratory recently demonstrated that the ability of the potent estrogen 17β-estradiol (E2) to enhance hippocampal-dependent novel object recognition memory in ovariectomized female mice requires ERK-dependent histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although these data provide valuable insight into the chromatin modifications that mediate the memory-enhancing effects of E2, epigenetic regulation of gene expression is enormously complex. Therefore, more research is needed to fully understand how E2 and other hormones employ epigenetic alterations to shape behavior. This review discusses the epigenetic alterations shown thus far to regulate hippocampal memory, briefly reviews the effects of E2 on hippocampal function, and describes in detail our work on epigenetic regulation of estrogenic memory enhancement. Copyright © 2014 Elsevier Inc. All rights reserved.

Familiarity enhances visual working memory for faces.

PubMed

Jackson, Margaret C; Raymond, Jane E

2008-06-01

Although it is intuitive that familiarity with complex visual objects should aid their preservation in visual working memory (WM), empirical evidence for this is lacking. This study used a conventional change-detection procedure to assess visual WM for unfamiliar and famous faces in healthy adults. Across experiments, faces were upright or inverted and a low- or high-load concurrent verbal WM task was administered to suppress contribution from verbal WM. Even with a high verbal memory load, visual WM performance was significantly better and capacity estimated as significantly greater for famous versus unfamiliar faces. Face inversion abolished this effect. Thus, neither strategic, explicit support from verbal WM nor low-level feature processing easily accounts for the observed benefit of high familiarity for visual WM. These results demonstrate that storage of items in visual WM can be enhanced if robust visual representations of them already exist in long-term memory.

Video Game Training Enhances Visuospatial Working Memory and Episodic Memory in Older Adults

PubMed Central

Toril, Pilar; Reales, José M.; Mayas, Julia; Ballesteros, Soledad

2016-01-01

In this longitudinal intervention study with experimental and control groups, we investigated the effects of video game training on the visuospatial working memory (WM) and episodic memory of healthy older adults. Participants were 19 volunteer older adults, who received 15 1-h video game training sessions with a series of video games selected from a commercial package (Lumosity), and a control group of 20 healthy older adults. The results showed that the performance of the trainees improved significantly in all the practiced video games. Most importantly, we found significant enhancements after training in the trained group and no change in the control group in two computerized tasks designed to assess visuospatial WM, namely the Corsi blocks task and the Jigsaw puzzle task. The episodic memory and short-term memory of the trainees also improved. Gains in some WM and episodic memory tasks were maintained during a 3-month follow-up period. These results suggest that the aging brain still retains some degree of plasticity, and that video game training might be an effective intervention tool to improve WM and other cognitive functions in older adults. PMID:27199723

Utility of Nutraceutical Products Marketed for Cognitive and Memory Enhancement

PubMed Central

McDougall, Graham J.; Austin-Wells, Vonnette; Zimmerman, Teena

2008-01-01

This article identifies a convenience sample of 14 memory-enhancing herbal products that were found to be available commercially, examines their active ingredients, states their claims, and evaluates the available evidence to determine their efficacy. The analyses identified four problematic areas. First, a majority of the products use cognitive terminology, which leads consumers to anticipate an intended cognitive benefit. Second, some ingredients are completely homeopathic and contain components not known outside of the homeopathic field. Third, the evidence of treatment efficacy is often contradictory, because products are recommended for purposes other than cognitive or memory loss. Finally, the manufacturers of the product have usually conducted the research on individual products. Until more research is available, it is suggested that holistic nursing professionals exercise caution in recommending nutraceuticals to their patients/clients for the use of cognitive improvement or memory enhancement. PMID:16251490

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

PubMed Central

Hales, J. B.

2011-01-01

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. PMID:21248058

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

PubMed Central

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

A Role of Protein Degradation in Memory Consolidation after Initial Learning and Extinction Learning in the Honeybee ("Apis mellifera")

ERIC Educational Resources Information Center

Felsenberg, Johannes; Dombrowski, Vincent; Eisenhardt, Dorothea

2012-01-01

Protein degradation is known to affect memory formation after extinction learning. We demonstrate here that an inhibitor of protein degradation, MG132, interferes with memory formation after extinction learning in a classical appetitive conditioning paradigm. In addition, we find an enhancement of memory formation when the same inhibitor is…

Levosimendan enhances memory through antioxidant effect in rat model: behavioral and molecular study.

PubMed

Rababa'h, Abeer M; Alzoubi, Karem H; Atmeh, Ala'a

2018-06-01

Impairment of learning and memory has been associated with accumulation of reactive oxygen species in the body. It has also been found that antioxidants enhance learning and memory. Levosimendan is a cardiac inotropic and vasodilator agent that has pleotropic effects including antioxidant, anti-inflammatory, and smooth muscle vasodilatory actions. In this study, we investigated the effect of levosimendan on learning and memory in rats. Levosimendan (12 µg/kg, intraperitoneally) or vehicle was administered once a week for 8 weeks. The radial arm water maze was used to assess spatial learning and memory. In addition, hippocampus levels of antioxidant biomarkers/enzyme - reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase, superoxide dismutase, catalase, and thiobarbituric acid reactive substance - were assessed. Levosimendan significantly enhanced short-term (30 min) and long-term (5 h) memory. Levosimendan also significantly increased levels of glutathione peroxidase and GSH and decreased thiobarbituric acid reactive substance. There were no significant effects on the level of other oxidative stress biomarkers. In conclusion, levosimendan enhanced short-term and long-term memory by potentiating antioxidant defense mechanism in the hippocampus.

Unforgettable Ultimatums? Expectation Violations Promote Enhanced Social Memory Following Economic Bargaining

PubMed Central

Chang, Luke J.; Sanfey, Alan G.

2009-01-01

Recent work in the field of neuroeconomics has examined how people make decisions in interactive settings. However, less is currently known about how these social decisions influence subsequent memory for these interactions. We investigated this question by using functional magnetic resonance imaging to scan participants as they viewed photographs of people they had either recently played an Ultimatum Game with in the role of Responder, or that they had never seen before. Based on previous work that has investigated “cheater detection”, we were interested in whether participants demonstrated a relative enhanced memory for partners that made either fair or unfair proposals. We found no evidence, either behaviorally or neurally, supporting enhanced memory based on the amount of money offered by the Proposer. However, we did find that participants’ initial expectations about the offers they would experience in the game influenced their memory. Participants demonstrated relatively enhanced subjective memory for partners that made proposals that were contradictory to their initial expectations. In addition, we observed two distinct brain systems that were associated with partners that either offered more or less than the participants’ expectations. Viewing pictures of partners that exceeded initial expectations was associated with the bilateral anterior insula, anterior cingulate cortex/premotor area, striatum, and bilateral posterior hippocampi, while viewing partners that offered less than initial expectations was associated with bilateral temporal-parietal junction, right STS, bilateral posterior insula, and precuneus. These results suggest that memory for social interaction may not be guided by a specific cheater detection system, but rather a more general expectation violation system. PMID:19876405

Cholinergic dependence of taste memory formation: evidence of two distinct processes.

PubMed

Gutiérrez, Ranier; Rodriguez-Ortiz, Carlos J; De La Cruz, Vanesa; Núñez-Jaramillo, Luis; Bermudez-Rattoni, Federico

2003-11-01

Learning the aversive or positive consequences associated with novel taste solutions has a strong significance for an animal's survival. A lack of recognition of a taste's consequences could prevent ingestion of potential edibles or encounter death. We used conditioned taste aversion (CTA) and attenuation of neophobia (AN) to study aversive and safe taste memory formation. To determine if muscarinic receptors in the insular cortex participate differentially in both tasks, we infused the muscarinic antagonists scopolamine at distinct times before or after the presentation of a strong concentration of saccharin, followed by either an i.p. injection of a malaise-inducing agent or no injection. Our results showed that blockade of muscarinic receptors before taste presentation disrupts both learning tasks. However, the same treatment after the taste prevents AN but not CTA. These results clearly demonstrate that cortical cholinergic activity participates in the acquisition of both safe and aversive memory formation, and that cortical muscarinic receptors seem to be necessary for safe but not for aversive taste memory consolidation. These results suggest that the taste memory trace is processed in the insular cortex simultaneously by at least two independent mechanisms, and that their interaction would determine the degree of aversion or preference learned to a novel taste.

On the formation of collective memories: the role of a dominant narrator.

PubMed

Cuc, Alexandru; Ozuru, Yasuhiro; Manier, David; Hirst, William

2006-06-01

To test our hypothesis that conversations can contribute to the formation of collective memory, we asked participants to study stories and to recall them individually (pregroup recollection), then as a group (group recounting), and then once again individually (postgroup recollection). One way that postgroup collective memories can be formed under these circumstances is if unshared pregroup recollections in the group recounting influences others' postgroup recollections. In the present research, we explored (using tests of recall and recognition) whether the presence of a dominant narrator can facilitate the emergence of unshared pregroup recollections in a group recounting and whether this emergence is associated with changes in postgroup recollections. We argue that the formation of a collective memory through conversation is not inevitable but is limited by cognitive factors, such as conditions for social contagion, and by situational factors, such as the presence of a narrator.

Negative affect impairs associative memory but not item memory.

PubMed

Bisby, James A; Burgess, Neil

2013-12-17

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 the effects of emotion on memory for items and their associations. By presenting neutral and negative items with background contexts, Experiment 1 demonstrated that item memory was facilitated by emotional affect, whereas memory for an associated context was reduced. In Experiment 2, arousal was manipulated independently of the memoranda, by a threat of shock, whereby encoding trials occurred under conditions of threat or safety. Memory for context was equally impaired by the presence of negative affect, whether induced by threat of shock or a negative item, relative to retrieval of the context of a neutral item in safety. In Experiment 3, participants were presented with neutral and negative items as paired associates, including all combinations of neutral and negative items. The results showed both above effects: compared to a neutral item, memory for the associate of a negative item (a second item here, context in Experiments 1 and 2) is impaired, whereas retrieval of the item itself is enhanced. Our findings suggest that negative affect impairs associative memory while recognition of a negative item is enhanced. They support dual-processing models in which negative affect or stress impairs hippocampal-dependent associative memory while the storage of negative sensory/perceptual representations is spared or even strengthened.

Rapid Formation and Flexible Expression of Memories of Subliminal Word Pairs

PubMed Central

Reber, Thomas P.; Henke, Katharina

2011-01-01

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. PMID:22125545

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

PubMed

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.

Synaptic Scaling Enables Dynamically Distinct Short- and Long-Term Memory Formation

PubMed Central

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

2013-01-01

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. PMID:24204240

Music-Based Memory Enhancement in Alzheimer’s Disease: Promise and Limitations

PubMed Central

Simmons-Stern, Nicholas R.; Deason, Rebecca G.; Brandler, Brian J.; Frustace, Bruno S.; O’Connor, Maureen K.; Ally, Brandon A.; Budson, Andrew E.

2012-01-01

In a previous study (Simmons-Stern, Budson, & Ally 2010), we found that patients with Alzheimer’s disease (AD) better recognized visually presented lyrics when the lyrics were also sung rather than spoken at encoding. The present study sought to further investigate the effects of music on memory in patients with AD by making the content of the song lyrics relevant for the daily life of an older adult and by examining how musical encoding alters several different aspects of episodic memory. Patients with AD and healthy older adults studied visually presented novel song lyrics related to instrumental activities of daily living (IADL) that were accompanied by either a sung or a spoken recording. Overall, participants performed better on a memory test of general lyric content for lyrics that were studied sung as compared to spoken. However, on a memory test of specific lyric content, participants performed equally well for sung and spoken lyrics. We interpret these results in terms of a dual-process model of recognition memory such that the general content questions represent a familiarity-based representation that is preferentially sensitive to enhancement via music, while the specific content questions represent a recollection-based representation unaided by musical encoding. Additionally, in a test of basic recognition memory for the audio stimuli, patients with AD demonstrated equal discrimination for sung and spoken stimuli. We propose that the perceptual distinctiveness of musical stimuli enhanced metamemorial awareness in AD patients via a non-selective distinctiveness heuristic, thereby reducing false recognition while at the same time reducing true recognition and eliminating the mnemonic benefit of music. These results are discussed in the context of potential music-based memory enhancement interventions for the care of patients with AD. PMID:23000133

Methylprednisolone as a memory enhancer in rats: Effects on aversive memory, long-term potentiation and calcium influx.

PubMed

de Vargas, Liane da Silva; Gonçalves, Rithiele; Lara, Marcus Vinícius S; Costa-Ferro, Zaquer S M; Salamoni, Simone Denise; Domingues, Michelle Flores; Piovesan, Angela Regina; de Assis, Dênis Reis; Vinade, Lucia; Corrado, Alexandre P; Alves-Do-Prado, Wilson; Correia-de-Sá, Paulo; da Costa, Jaderson Costa; Izquierdo, Ivan; Dal Belo, Cháriston A; Mello-Carpes, Pâmela B

2017-09-01

It is well recognized that stress or glucocorticoids hormones treatment can modulate memory performance in both directions, either impairing or enhancing it. Despite the high number of studies aiming at explaining the effects of glucocorticoids on memory, this has not yet been completely elucidated. Here, we demonstrate that a low daily dose of methylprednisolone (MP, 5mg/kg, i.p.) administered for 10-days favors aversive memory persistence in adult rats, without any effect on the exploring behavior, locomotor activity, anxiety levels and pain perception. Enhanced performance on the inhibitory avoidance task was correlated with long-term potentiation (LTP), a phenomenon that was strengthen in hippocampal slices of rats injected with MP (5mg/kg) during 10days. Additionally, in vitro incubation with MP (30-300µM) concentration-dependently increased intracellular [Ca 2+ ] i in cultured hippocampal neurons depolarized by KCl (35mM). In conclusion, a low daily dose of MP for 10days may promote aversive memory persistence in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice.

PubMed

Morimura, Naoko; Yasuda, Hiroki; Yamaguchi, Kazuhiko; Katayama, Kei-Ichi; Hatayama, Minoru; Tomioka, Naoko H; Odagawa, Maya; Kamiya, Akiko; Iwayama, Yoshimi; Maekawa, Motoko; Nakamura, Kazuhiko; Matsuzaki, Hideo; Tsujii, Masatsugu; Yamada, Kazuyuki; Yoshikawa, Takeo; Aruga, Jun

2017-06-12

Lrfn2/SALM1 is a PSD-95-interacting synapse adhesion molecule, and human LRFN2 is associated with learning disabilities. However its role in higher brain function and underlying mechanisms remain unknown. Here, we show that Lrfn2 knockout mice exhibit autism-like behavioural abnormalities, including social withdrawal, decreased vocal communications, increased stereotyped activities and prepulse inhibition deficits, together with enhanced learning and memory. In the hippocampus, the levels of synaptic PSD-95 and GluA1 are decreased. The synapses are structurally and functionally immature with spindle shaped spines, smaller postsynaptic densities, reduced AMPA/NMDA ratio, and enhanced LTP. In vitro experiments reveal that synaptic surface expression of AMPAR depends on the direct interaction between Lrfn2 and PSD-95. Furthermore, we detect functionally defective LRFN2 missense mutations in autism and schizophrenia patients. Together, these findings indicate that Lrfn2/LRFN2 serve as core components of excitatory synapse maturation and maintenance, and their dysfunction causes immature/silent synapses with pathophysiological state.

Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice

PubMed Central

Morimura, Naoko; Yasuda, Hiroki; Yamaguchi, Kazuhiko; Katayama, Kei-ichi; Hatayama, Minoru; Tomioka, Naoko H.; Odagawa, Maya; Kamiya, Akiko; Iwayama, Yoshimi; Maekawa, Motoko; Nakamura, Kazuhiko; Matsuzaki, Hideo; Tsujii, Masatsugu; Yamada, Kazuyuki; Yoshikawa, Takeo; Aruga, Jun

2017-01-01

Lrfn2/SALM1 is a PSD-95-interacting synapse adhesion molecule, and human LRFN2 is associated with learning disabilities. However its role in higher brain function and underlying mechanisms remain unknown. Here, we show that Lrfn2 knockout mice exhibit autism-like behavioural abnormalities, including social withdrawal, decreased vocal communications, increased stereotyped activities and prepulse inhibition deficits, together with enhanced learning and memory. In the hippocampus, the levels of synaptic PSD-95 and GluA1 are decreased. The synapses are structurally and functionally immature with spindle shaped spines, smaller postsynaptic densities, reduced AMPA/NMDA ratio, and enhanced LTP. In vitro experiments reveal that synaptic surface expression of AMPAR depends on the direct interaction between Lrfn2 and PSD-95. Furthermore, we detect functionally defective LRFN2 missense mutations in autism and schizophrenia patients. Together, these findings indicate that Lrfn2/LRFN2 serve as core components of excitatory synapse maturation and maintenance, and their dysfunction causes immature/silent synapses with pathophysiological state. PMID:28604739

Divided attention can enhance memory encoding: the attentional boost effect in implicit memory.

PubMed

Spataro, Pietro; Mulligan, Neil W; Rossi-Arnaud, Clelia

2013-07-01

Distraction during encoding has long been known to disrupt later memory performance. Contrary to this long-standing result, we show that detecting an infrequent target in a dual-task paradigm actually improves memory encoding for a concurrently presented word, above and beyond the performance reached in the full-attention condition. This absolute facilitation was obtained in 2 perceptual implicit tasks (lexical decision and word fragment completion) but not in a conceptual implicit task (semantic classification). In the case of recognition memory, the facilitation was relative, bringing accuracy in the divided attention condition up to the level of accuracy in the full attention condition. The findings follow from the hypothesis that the attentional boost effect reflects enhanced visual encoding of the study stimulus consequent to the transient orienting response to the dual-task target. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Diminishing-cues retrieval practice: A memory-enhancing technique that works when regular testing doesn't.

PubMed

Fiechter, Joshua L; Benjamin, Aaron S

2017-08-28

Retrieval practice has been shown to be a highly effective tool for enhancing memory, a fact that has led to major changes to educational practice and technology. However, when initial learning is poor, initial retrieval practice is unlikely to be successful and long-term benefits of retrieval practice are compromised or nonexistent. Here, we investigate the benefit of a scaffolded retrieval technique called diminishing-cues retrieval practice (Finley, Benjamin, Hays, Bjork, & Kornell, Journal of Memory and Language, 64, 289-298, 2011). Under learning conditions that favored a strong testing effect, diminishing cues and standard retrieval practice both enhanced memory performance relative to restudy. Critically, under learning conditions where standard retrieval practice was not helpful, diminishing cues enhanced memory performance substantially. These experiments demonstrate that diminishing-cues retrieval practice can widen the range of conditions under which testing can benefit memory, and so can serve as a model for the broader application of testing-based techniques for enhancing learning.

In sync: gamma oscillations and emotional memory.

PubMed

Headley, Drew B; Paré, Denis

2013-11-21

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.

Sleep Enhances Recognition Memory for Conspecifics as Bound into Spatial Context

PubMed Central

Sawangjit, Anuck; Kelemen, Eduard; Born, Jan; Inostroza, Marion

2017-01-01

Social memory refers to the fundamental ability of social species to recognize their conspecifics in quite different contexts. Sleep has been shown to benefit consolidation, especially of hippocampus-dependent episodic memory whereas effects of sleep on social memory are less well studied. Here, we examined the effect of sleep on memory for conspecifics in rats. To discriminate interactions between the consolidation of social memory and of spatial context during sleep, adult Long Evans rats performed on a social discrimination task in a radial arm maze. The Learning phase comprised three 10-min sampling sessions in which the rats explored a juvenile rat presented at a different arm of the maze in each session. Then the rats were allowed to sleep (n = 18) or stayed awake (n = 18) for 120 min. During the following 10-min Test phase, the familiar juvenile rat (of the Learning phase) was presented along with a novel juvenile rat, each rat at an opposite arm of the maze. Significant social recognition memory, as indicated by preferential exploration of the novel over the familiar conspecific, occurred only after post-learning sleep, but not after wakefulness. Sleep, compared with wakefulness, significantly enhanced social recognition during the first minute of the Test phase. However, memory expression depended on the spatial configuration: Significant social recognition memory emerged only after sleep when the rat encountered the novel conspecific at a place different from that of the familiar juvenile in the last sampling session before sleep. Though unspecific retrieval-related effects cannot entirely be excluded, our findings suggest that sleep, rather than independently enhancing social and spatial aspects of memory, consolidates social memory by acting on an episodic representation that binds the memory of the conspecific together with the spatial context in which it was recently encountered. PMID:28270755

The influence of cannabinoids on learning and memory processes of the dorsal striatum.

PubMed

Goodman, Jarid; Packard, Mark G

2015-11-01

Extensive evidence indicates that the mammalian endocannabinoid system plays an integral role in learning and memory. Our understanding of how cannabinoids influence memory comes predominantly from studies examining cognitive and emotional memory systems mediated by the hippocampus and amygdala, respectively. However, recent evidence suggests that cannabinoids also affect habit or stimulus-response (S-R) memory mediated by the dorsal striatum. Studies implementing a variety of maze tasks in rats indicate that systemic or intra-dorsolateral striatum infusions of cannabinoid receptor agonists or antagonists impair habit memory. In mice, cannabinoid 1 (CB1) receptor knockdown can enhance or impair habit formation, whereas Δ(9)THC tolerance enhances habit formation. Studies in human cannabis users also suggest an enhancement of S-R/habit memory. A tentative conclusion based on the available data is that acute disruption of the endocannabinoid system with either agonists or antagonists impairs, whereas chronic cannabinoid exposure enhances, dorsal striatum-dependent S-R/habit memory. CB1 receptors are required for multiple forms of striatal synaptic plasticity implicated in memory, including short-term and long-term depression. Interactions with the hippocampus-dependent memory system may also have a role in some of the observed effects of cannabinoids on habit memory. The impairing effect often observed with acute cannabinoid administration argues for cannabinoid-based treatments for human psychopathologies associated with a dysfunctional habit memory system (e.g. post-traumatic stress disorder and drug addiction/relapse). In addition, the enhancing effect of repeated cannabinoid exposure on habit memory suggests a novel neurobehavioral mechanism for marijuana addiction involving the dorsal striatum-dependent memory system. Copyright © 2015 Elsevier Inc. All rights reserved.

Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes

PubMed Central

Garcia-Alvarez, Gisela; Shetty, Mahesh S.; Lu, Bo; Yap, Kenrick An Fu; Oh-Hora, Masatsugu; Sajikumar, Sreedharan; Bichler, Zoë; Fivaz, Marc

2015-01-01

Recent findings point to a central role of the endoplasmic reticulum-resident STIM (Stromal Interaction Molecule) proteins in shaping the structure and function of excitatory synapses in the mammalian brain. The impact of the Stim genes on cognitive functions remains, however, poorly understood. To explore the function of the Stim genes in learning and memory, we generated three mouse strains with conditional deletion (cKO) of Stim1 and/or Stim2 in the forebrain. Stim1, Stim2, and double Stim1/Stim2 cKO mice show no obvious brain structural defects or locomotor impairment. Analysis of spatial reference memory in the Morris water maze revealed a mild learning delay in Stim1 cKO mice, while learning and memory in Stim2 cKO mice was indistinguishable from their control littermates. Deletion of both Stim genes in the forebrain resulted, however, in a pronounced impairment in spatial learning and memory reflecting a synergistic effect of the Stim genes on the underlying neural circuits. Notably, long-term potentiation (LTP) at CA3-CA1 hippocampal synapses was markedly enhanced in Stim1/Stim2 cKO mice and was associated with increased phosphorylation of the AMPA receptor subunit GluA1, the transcriptional regulator CREB and the L-type Voltage-dependent Ca2+ channel Cav1.2 on protein kinase A (PKA) sites. We conclude that STIM1 and STIM2 are key regulators of PKA signaling and synaptic plasticity in neural circuits encoding spatial memory. Our findings also reveal an inverse correlation between LTP and spatial learning/memory and suggest that abnormal enhancement of cAMP/PKA signaling and synaptic efficacy disrupts the formation of new memories. PMID:26236206

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Busby, Y., E-mail: yan.busby@unamur.be; Pireaux, J.-J.; Nau, S.

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 filamentsmore » 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.« less

Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells.

PubMed

Drobek, Ales; Moudra, Alena; Mueller, Daniel; Huranova, Martina; Horkova, Veronika; Pribikova, Michaela; Ivanek, Robert; Oberle, Susanne; Zehn, Dietmar; McCoy, Kathy D; Draber, Peter; Stepanek, Ondrej

2018-05-11

Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10-20% of all peripheral CD8 + T cells in mice. Their origin, biological roles, and relationship to naïve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing T-cell receptor repertoires and using retrogenic monoclonal T-cell populations, we demonstrate that the virtual memory T-cell formation is a so far unappreciated cell fate decision checkpoint. We describe two molecular mechanisms driving the formation of virtual memory T cells. First, virtual memory T cells originate exclusively from strongly self-reactive T cells. Second, the stoichiometry of the CD8 interaction with Lck regulates the size of the virtual memory T-cell compartment via modulating the self-reactivity of individual T cells. Although virtual memory T cells descend from the highly self-reactive clones and acquire a partial memory program, they are not more potent in inducing experimental autoimmune diabetes than naïve T cells. These data underline the importance of the variable level of self-reactivity in polyclonal T cells for the generation of functional T-cell diversity. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

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

PubMed

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.

Deleting HDAC3 Rescues Long-Term Memory Impairments Induced by Disruption of the Neuron-Specific Chromatin Remodeling Subunit BAF53b

ERIC Educational Resources Information Center

Shu, Guanhua; Kramár, Enikö A.; López, Alberto J.; Huynh, Grace; Wood, Marcelo A.; Kwapis, Janine L.

2018-01-01

Multiple epigenetic mechanisms, including histone acetylation and nucleosome remodeling, are known to be involved in long-term memory formation. Enhancing histone acetylation by deleting histone deacetylases, like HDAC3, typically enhances long-term memory formation. In contrast, disrupting nucleosome remodeling by blocking the neuron-specific…

Electrolytic lesions of the bilateral ventrolateral orbital cortex inhibit methamphetamine-associated contextual memory formation in rats.

PubMed

Zhao, Yan; Liu, Peng; Chu, Zheng; Liu, Fei; Han, Wei; Xun, Xi; Dang, Yong-Hui

2015-10-22

The memories that are formed between rewarding and drug-associated contextual cues have been suggested to contribute to drug addiction relapse. Recent evidence has indicated that the ventrolateral orbital cortex (VLO) plays important roles in reward-based learning and reversal learning. However, whether the VLO is required for methamphetamine-induced contextual memory formation is not well understood. In the present study, a three-phase methamphetamine-induced conditioned place preference (CPP) model was used to investigate the effects of VLO lesions on the formation of drug-associated contextual memories in rats. We found that the VLO lesions themselves elicited no observable effects on place preferences. However, the VLO lesions delayed the acquisition and extinction phases of CPP without affecting the expression level. Furthermore, the VLO lesions did not have an obvious influence on CPP reinstatement. These results indicate that electrolytic lesions of the bilateral ventrolateral orbital cortex can inhibit the formation of methamphetamine-induced contextual memories in rats. Moreover, VLO may not be critically involved in memory storage and retrieval. Copyright © 2015 Elsevier B.V. All rights reserved.

Formation of model-free motor memories during motor adaptation depends on perturbation schedule

PubMed Central

Lefèvre, Philippe

2015-01-01

Motor adaptation to an external perturbation relies on several mechanisms such as model-based, model-free, strategic, or repetition-dependent learning. Depending on the experimental conditions, each of these mechanisms has more or less weight in the final adaptation state. Here we focused on the conditions that lead to the formation of a model-free motor memory (Huang VS, Haith AM, Mazzoni P, Krakauer JW. Neuron 70: 787–801, 2011), i.e., a memory that does not depend on an internal model or on the size or direction of the errors experienced during the learning. The formation of such model-free motor memory was hypothesized to depend on the schedule of the perturbation (Orban de Xivry JJ, Ahmadi-Pajouh MA, Harran MD, Salimpour Y, Shadmehr R. J Neurophysiol 109: 124–136, 2013). Here we built on this observation by directly testing the nature of the motor memory after abrupt or gradual introduction of a visuomotor rotation, in an experimental paradigm where the presence of model-free motor memory can be identified (Huang VS, Haith AM, Mazzoni P, Krakauer JW. Neuron 70: 787–801, 2011). We found that relearning was faster after abrupt than gradual perturbation, which suggests that model-free learning is reduced during gradual adaptation to a visuomotor rotation. In addition, the presence of savings after abrupt introduction of the perturbation but gradual extinction of the motor memory suggests that unexpected errors are necessary to induce a model-free motor memory. Overall, these data support the hypothesis that different perturbation schedules do not lead to a more or less stabilized motor memory but to distinct motor memories with different attributes and neural representations. PMID:25673736

Caffeine in floral nectar enhances a pollinator’s memory of reward

PubMed Central

Wright, G. A.; Baker, D. D.; Palmer, M. J.; Stabler, D.; Mustard, J. A.; Power, E. F.; Borland, A. M.; Stevenson, P. C.

2015-01-01

Plant defence compounds occur in floral nectar, but their ecological role is not well-understood. We provide the first evidence that plant compounds pharmacologically alter pollinator behaviour by enhancing their memory of reward. Honeybees rewarded with caffeine, which occurs naturally in nectar of Coffea and Citrus species, were three times more likely to remember a learned floral scent than those rewarded with sucrose alone. Caffeine potentiated responses of mushroom body neurons involved in olfactory learning and memory by acting as an adenosine receptor antagonist. Caffeine concentrations in nectar never exceeded the bees’ bitter taste threshold, implying that pollinators impose selection for nectar that is pharmacologically active but not repellent. By using a drug to enhance memories of reward, plants secure pollinator fidelity and improve reproductive success. PMID:23471406

A single bout of resistance exercise can enhance episodic memory performance.

PubMed

Weinberg, Lisa; Hasni, Anita; Shinohara, Minoru; Duarte, Audrey

2014-11-01

Acute aerobic exercise can be beneficial to episodic memory. This benefit may occur because exercise produces a similar physiological response as physical stressors. When administered during consolidation, acute stress, both physical and psychological, consistently enhances episodic memory, particularly memory for emotional materials. Here we investigated whether a single bout of resistance exercise performed during consolidation can produce episodic memory benefits 48 h later. We used a one-leg knee extension/flexion task for the resistance exercise. To assess the physiological response to the exercise, we measured salivary alpha amylase (a biomarker of central norepinephrine), heart rate, and blood pressure. To test emotional episodic memory, we used a remember-know recognition memory paradigm with equal numbers of positive, negative, and neutral IAPS images as stimuli. The group that performed the exercise, the active group, had higher overall recognition accuracy than the group that did not exercise, the passive group. We found a robust effect of valence across groups, with better performance on emotional items as compared to neutral items and no difference between positive and negative items. This effect changed based on the physiological response to the exercise. Within the active group, participants with a high physiological response to the exercise were impaired for neutral items as compared to participants with a low physiological response to the exercise. Our results demonstrate that a single bout of resistance exercise performed during consolidation can enhance episodic memory and that the effect of valence on memory depends on the physiological response to the exercise. Copyright © 2014 Elsevier B.V. All rights reserved.

Trial-by-Trial Modulation of Associative Memory Formation by Reward Prediction Error and Reward Anticipation as Revealed by a Biologically Plausible Computational Model.

PubMed

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

Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: evidence for a dual-process memory model.

PubMed

Sanderson, David J; Good, Mark A; Skelton, Kathryn; Sprengel, Rolf; Seeburg, Peter H; Rawlins, J Nicholas P; Bannerman, David M

2009-06-01

The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of GluA1-dependent synaptic plasticity for short-term memory of recently visited places, but not for the ability to form long-term associations between a particular spatial location and an outcome. This hypothesis is in concordance with the theory that short-term and long-term memory depend on dissociable psychological processes. In this study we tested GluA1-/- mice on both short-term and long-term spatial memory using a simple novelty preference task. Mice were given a series of repeated exposures to a particular spatial location (the arm of a Y-maze) before their preference for a novel spatial location (the unvisited arm of the maze) over the familiar spatial location was assessed. GluA1-/- mice were impaired if the interval between the trials was short (1 min), but showed enhanced spatial memory if the interval between the trials was long (24 h). This enhancement was caused by the interval between the exposure trials rather than the interval prior to the test, thus demonstrating enhanced learning and not simply enhanced performance or expression of memory. This seemingly paradoxical enhancement of hippocampus-dependent spatial learning may be caused by GluA1 gene deletion reducing the detrimental effects of short-term memory on subsequent long-term learning. Thus, these results support a dual-process model of memory in which short-term and long-term memory are separate and sometimes competitive processes.

The Role of Lactate-Mediated Metabolic Coupling between Astrocytes and Neurons in Long-Term Memory Formation

PubMed Central

Steinman, Michael Q.; Gao, Virginia; Alberini, Cristina M.

2016-01-01

Long-term memory formation, the ability to retain information over time about an experience, is a complex function that affects multiple behaviors, and is an integral part of an individual’s identity. In the last 50 years many scientists have focused their work on understanding the biological mechanisms underlying memory formation and processing. Molecular studies over the last three decades have mostly investigated, or given attention to, neuronal mechanisms. However, the brain is composed of different cell types that, by concerted actions, cooperate to mediate brain functions. Here, we consider some new insights that emerged from recent studies implicating astrocytic glycogen and glucose metabolisms, and particularly their coupling to neuronal functions via lactate, as an essential mechanism for long-term memory formation. PMID:26973477

Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval

PubMed Central

Ishikawa, Rie; Fukushima, Hotaka; Frankland, Paul W; Kida, Satoshi

2016-01-01

Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re-exposures. Importantly, we find that long, but not short re-exposures activate gene expression in the hippocampus and induce hippocampus-dependent reconsolidation of remote contextual fear memory. Furthermore, remote memory retrieval becomes hippocampus-dependent after the long-time recall, suggesting that remote fear memory returns to a hippocampus dependent state after the long-time recall, thereby allowing enhanced forgetting by increased hippocampal neurogenesis. Forgetting of traumatic memory may contribute to the development of PTSD treatment. DOI: http://dx.doi.org/10.7554/eLife.17464.001 PMID:27669409

Post-learning arousal enhances veridical memory and reduces false memory in the Deese-Roediger-McDermott paradigm.

PubMed

Nielson, Kristy A; Correro, Anthony N

2017-10-01

The Deese-Roediger-McDermott (DRM) paradigm examines false memory by introducing words associated with a non-presented 'critical lure' as memoranda, which typically causes the lures to be remembered as frequently as studied words. Our prior work has shown enhanced veridical memory and reduced misinformation effects when arousal is induced after learning (i.e., during memory consolidation). These effects have not been examined in the DRM task, or with signal detection analysis, which can elucidate the mechanisms underlying memory alterations. Thus, 130 subjects studied and then immediately recalled six DRM lists, one after another, and then watched a 3-min arousing (n=61) or neutral (n=69) video. Recognition tested 70min later showed that arousal induced after learning led to better delayed discrimination of studied words from (a) critical lures, and (b) other non-presented 'weak associates.' Furthermore, arousal reduced liberal response bias (i.e., the tendency toward accepting dubious information) for studied words relative to all foils, including critical lures and 'weak associates.' Thus, arousal induced after learning effectively increased the distinction between signal and noise by enhancing access to verbatim information and reducing endorsement of dubious information. These findings provide important insights into the cognitive mechanisms by which arousal modulates early memory consolidation processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Formation of model-free motor memories during motor adaptation depends on perturbation schedule.

PubMed

Orban de Xivry, Jean-Jacques; Lefèvre, Philippe

2015-04-01

Motor adaptation to an external perturbation relies on several mechanisms such as model-based, model-free, strategic, or repetition-dependent learning. Depending on the experimental conditions, each of these mechanisms has more or less weight in the final adaptation state. Here we focused on the conditions that lead to the formation of a model-free motor memory (Huang VS, Haith AM, Mazzoni P, Krakauer JW. Neuron 70: 787-801, 2011), i.e., a memory that does not depend on an internal model or on the size or direction of the errors experienced during the learning. The formation of such model-free motor memory was hypothesized to depend on the schedule of the perturbation (Orban de Xivry JJ, Ahmadi-Pajouh MA, Harran MD, Salimpour Y, Shadmehr R. J Neurophysiol 109: 124-136, 2013). Here we built on this observation by directly testing the nature of the motor memory after abrupt or gradual introduction of a visuomotor rotation, in an experimental paradigm where the presence of model-free motor memory can be identified (Huang VS, Haith AM, Mazzoni P, Krakauer JW. Neuron 70: 787-801, 2011). We found that relearning was faster after abrupt than gradual perturbation, which suggests that model-free learning is reduced during gradual adaptation to a visuomotor rotation. In addition, the presence of savings after abrupt introduction of the perturbation but gradual extinction of the motor memory suggests that unexpected errors are necessary to induce a model-free motor memory. Overall, these data support the hypothesis that different perturbation schedules do not lead to a more or less stabilized motor memory but to distinct motor memories with different attributes and neural representations. Copyright © 2015 the American Physiological Society.

Can Survival Processing Enhance Story Memory? Testing the Generalizability of the Adaptive Memory Framework

ERIC Educational Resources Information Center

Seamon, John G.; Bohn, Justin M.; Coddington, Inslee E.; Ebling, Maritza C.; Grund, Ethan M.; Haring, Catherine T.; Jang, Sue-Jung; Kim, Daniel; Liong, Christopher; Paley, Frances M.; Pang, Luke K.; Siddique, Ashik H.

2012-01-01

Research from the adaptive memory framework shows that thinking about words in terms of their survival value in an incidental learning task enhances their free recall relative to other semantic encoding strategies and intentional learning (Nairne, Pandeirada, & Thompson, 2008). We found similar results. When participants used incidental…

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

PubMed

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

2015-04-07

Metabolic homeostasis is regulated by the brain, but 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 in 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 lipid levels. Importantly, this function of metabolic learning requires not only the mushroom body but also 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 that 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 that the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis.

Face format at encoding affects the other-race effect in face memory.

PubMed

Zhao, Mintao; Hayward, William G; Bülthoff, Isabelle

2014-08-07

Memory of own-race faces is generally better than memory of other-races faces. This other-race effect (ORE) in face memory has been attributed to differences in contact, holistic processing, and motivation to individuate faces. Since most studies demonstrate the ORE with participants learning and recognizing static, single-view faces, it remains unclear whether the ORE can be generalized to different face learning conditions. Using an old/new recognition task, we tested whether face format at encoding modulates the ORE. The results showed a significant ORE when participants learned static, single-view faces (Experiment 1). In contrast, the ORE disappeared when participants learned rigidly moving faces (Experiment 2). Moreover, learning faces displayed from four discrete views produced the same results as learning rigidly moving faces (Experiment 3). Contact with other-race faces was correlated with the magnitude of the ORE. Nonetheless, the absence of the ORE in Experiments 2 and 3 cannot be readily explained by either more frequent contact with other-race faces or stronger motivation to individuate them. These results demonstrate that the ORE is sensitive to face format at encoding, supporting the hypothesis that relative involvement of holistic and featural processing at encoding mediates the ORE observed in face memory. © 2014 ARVO.

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

PubMed Central

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

In sync: gamma oscillations and emotional memory

PubMed Central

Headley, Drew B.; Paré, Denis

2013-01-01

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. PMID:24319416

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

PubMed

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.

Designer Receptors Enhance Memory in a Mouse Model of Down Syndrome

PubMed Central

Fortress, Ashley M.; Hamlett, Eric D.; Vazey, Elena M.; Aston-Jones, Gary; Cass, Wayne A.; Boger, Heather A.

2015-01-01

Designer receptors exclusively activated by designer drugs (DREADDs) are novel and powerful tools to investigate discrete neuronal populations in the brain. We have used DREADDs to stimulate degenerating neurons in a Down syndrome (DS) model, Ts65Dn mice. Individuals with DS develop Alzheimer's disease (AD) neuropathology and have elevated risk for dementia starting in their 30s and 40s. Individuals with DS often exhibit working memory deficits coupled with degeneration of the locus coeruleus (LC) norepinephrine (NE) neurons. It is thought that LC degeneration precedes other AD-related neuronal loss, and LC noradrenergic integrity is important for executive function, working memory, and attention. Previous studies have shown that LC-enhancing drugs can slow the progression of AD pathology, including amyloid aggregation, oxidative stress, and inflammation. We have shown that LC degeneration in Ts65Dn mice leads to exaggerated memory loss and neuronal degeneration. We used a DREADD, hM3Dq, administered via adeno-associated virus into the LC under a synthetic promoter, PRSx8, to selectively stimulate LC neurons by exogenous administration of the inert DREADD ligand clozapine-N-oxide. DREADD stimulation of LC-NE enhanced performance in a novel object recognition task and reduced hyperactivity in Ts65Dn mice, without significant behavioral effects in controls. To confirm that the noradrenergic transmitter system was responsible for the enhanced memory function, the NE prodrug l-threo-dihydroxyphenylserine was administered in Ts65Dn and normosomic littermate control mice, and produced similar behavioral results. Thus, NE stimulation may prevent memory loss in Ts65Dn mice, and may hold promise for treatment in individuals with DS and dementia. PMID:25632113

System level mechanisms of adaptation, learning, memory formation and evolvability: the role of chaperone and other networks.

PubMed

Gyurko, David M; Soti, Csaba; Stetak, Attila; Csermely, Peter

2014-05-01

During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here, we describe first the protein structure networks of molecular chaperones, then characterize chaperone containing sub-networks of interactomes called as chaperone-networks or chaperomes. We review the role of molecular chaperones in short-term adaptation of cellular networks in response to stress, and in long-term adaptation discussing their putative functions in the regulation of evolvability. We provide a general overview of possible network mechanisms of adaptation, learning and memory formation. We propose that changes of network rigidity play a key role in learning and memory formation processes. Flexible network topology provides ' learning-competent' state. Here, networks may have much less modular boundaries than locally rigid, highly modular networks, where the learnt information has already been consolidated in a memory formation process. Since modular boundaries are efficient filters of information, in the 'learning-competent' state information filtering may be much smaller, than after memory formation. This mechanism restricts high information transfer to the 'learning competent' state. After memory formation, modular boundary-induced segregation and information filtering protect the stored information. The flexible networks of young organisms are generally in a 'learning competent' state. On the contrary, locally rigid networks of old organisms have lost their 'learning competent' state, but store and protect their learnt information efficiently. We anticipate that the above mechanism may operate at the level of both protein-protein interaction and neuronal networks.

Interaction of Inhibitory and Facilitatory Effects of Conditioning Trials on Long-Term Memory Formation

ERIC Educational Resources Information Center

Hosono, Shouhei; Matsumoto, Yukihisa; Mizunami, Makoto

2016-01-01

Animals learn through experience and consolidate the memories into long-time storage. Conditioning parameters to induce protein synthesis-dependent long-term memory (LTM) have been the subject of extensive studies in many animals. Here we found a case in which a conditioning trial inhibits or facilitates LTM formation depending on the intervals…

Brain computer interface to enhance episodic memory in human participants

PubMed Central

Burke, John F.; Merkow, Maxwell B.; Jacobs, Joshua; Kahana, Michael J.

2015-01-01

Recent research has revealed that neural oscillations in the theta (4–8 Hz) and alpha (9–14 Hz) bands are predictive of future success in memory encoding. Because these signals occur before the presentation of an upcoming stimulus, they are considered stimulus-independent in that they correlate with enhanced memory encoding independent of the item being encoded. Thus, such stimulus-independent activity has important implications for the neural mechanisms underlying episodic memory as well as the development of cognitive neural prosthetics. Here, we developed a brain computer interface (BCI) to test the ability of such pre-stimulus activity to modulate subsequent memory encoding. We recorded intracranial electroencephalography (iEEG) in neurosurgical patients as they performed a free recall memory task, and detected iEEG theta and alpha oscillations that correlated with optimal memory encoding. We then used these detected oscillatory changes to trigger the presentation of items in the free recall task. We found that item presentation contingent upon the presence of pre-stimulus theta and alpha oscillations modulated memory performance in more sessions than expected by chance. Our results suggest that an electrophysiological signal may be causally linked to a specific behavioral condition, and contingent stimulus presentation has the potential to modulate human memory encoding. PMID:25653605

Motivational valence alters memory formation without altering exploration of a real-life spatial environment.

PubMed

Chiew, Kimberly S; Hashemi, Jordan; Gans, Lee K; Lerebours, Laura; Clement, Nathaniel J; Vu, Mai-Anh T; Sapiro, Guillermo; Heller, Nicole E; Adcock, R Alison

2018-01-01

Volitional exploration and learning are key to adaptive behavior, yet their characterization remains a complex problem for cognitive science. Exploration has been posited as a mechanism by which motivation promotes memory, but this relationship is not well-understood, in part because novel stimuli that motivate exploration also reliably elicit changes in neuromodulatory brain systems that directly alter memory formation, via effects on neural plasticity. To deconfound interrelationships between motivation, exploration, and memory formation we manipulated motivational state prior to entering a spatial context, measured exploratory responses to the context and novel stimuli within it, and then examined motivation and exploration as predictors of memory outcomes. To elicit spontaneous exploration, we used the physical space of an art exhibit with affectively rich content; we expected motivated exploration and memory to reflect multiple factors, including not only motivational valence, but also individual differences. Motivation was manipulated via an introductory statement framing exhibit themes in terms of Promotion- or Prevention-oriented goals. Participants explored the exhibit while being tracked by video. They returned 24 hours later for recall and spatial memory tests, followed by measures of motivation, personality, and relevant attitude variables. Promotion and Prevention condition participants did not differ in terms of group-level exploration time or memory metrics, suggesting similar motivation to explore under both framing contexts. However, exploratory behavior and memory outcomes were significantly more closely related under Promotion than Prevention, indicating that Prevention framing disrupted expected depth-of-encoding effects. Additionally, while trait measures predicted exploration similarly across framing conditions, traits interacted with motivational framing context and facial affect to predict memory outcomes. This novel characterization of

Motivational valence alters memory formation without altering exploration of a real-life spatial environment

PubMed Central

Hashemi, Jordan; Gans, Lee K.; Lerebours, Laura; Clement, Nathaniel J.; Vu, Mai-Anh T.; Sapiro, Guillermo; Heller, Nicole E.; Adcock, R. Alison

2018-01-01

Volitional exploration and learning are key to adaptive behavior, yet their characterization remains a complex problem for cognitive science. Exploration has been posited as a mechanism by which motivation promotes memory, but this relationship is not well-understood, in part because novel stimuli that motivate exploration also reliably elicit changes in neuromodulatory brain systems that directly alter memory formation, via effects on neural plasticity. To deconfound interrelationships between motivation, exploration, and memory formation we manipulated motivational state prior to entering a spatial context, measured exploratory responses to the context and novel stimuli within it, and then examined motivation and exploration as predictors of memory outcomes. To elicit spontaneous exploration, we used the physical space of an art exhibit with affectively rich content; we expected motivated exploration and memory to reflect multiple factors, including not only motivational valence, but also individual differences. Motivation was manipulated via an introductory statement framing exhibit themes in terms of Promotion- or Prevention-oriented goals. Participants explored the exhibit while being tracked by video. They returned 24 hours later for recall and spatial memory tests, followed by measures of motivation, personality, and relevant attitude variables. Promotion and Prevention condition participants did not differ in terms of group-level exploration time or memory metrics, suggesting similar motivation to explore under both framing contexts. However, exploratory behavior and memory outcomes were significantly more closely related under Promotion than Prevention, indicating that Prevention framing disrupted expected depth-of-encoding effects. Additionally, while trait measures predicted exploration similarly across framing conditions, traits interacted with motivational framing context and facial affect to predict memory outcomes. This novel characterization of

Significantly enhanced memory effect in metallic glass by multistep training

NASA Astrophysics Data System (ADS)

Li, M. X.; Luo, P.; Sun, Y. T.; Wen, P.; Bai, H. Y.; Liu, Y. H.; Wang, W. H.

2017-11-01

The state of metastable equilibrium glass can carry an imprint of the past and exhibit memory effect. As a hallmark of glassy dynamics, memory effect can affect glassy behavior as it evolves further upon time. Even though the physical picture of the memory effect has been well studied, it is unclear whether a glass can recall as many pieces of information as possible, and if so, how the glass will accordingly behave. We report that by fractionizing temperature interval, inserting multistep aging protocols, and optimizing the time of each temperature step, i.e., by imposing a multistep "training" on a prototypical P d40N i10C u30P20 metallic glass, the memory of the trained glass can be significantly strengthened, marked by a pronounced augment in potential energy. These findings provide a new guide for regulating the energy state of glass by enhancing the nonequilibrium behaviors of the memory effect and offer an opportunity to develop a clearer physical picture of glassy dynamics.

Distinct circuits for the formation and retrieval of an imprinted olfactory memory

PubMed Central

Jin, Xin; Pokala, Navin; Bargmann, Cornelia I.

2016-01-01

Summary Memories formed early in life are particularly stable and influential, representing privileged experiences that shape enduring behaviors. Here we show that exposing newly-hatched C. elegans to pathogenic bacteria results in persistent aversion to those bacterial odors, whereas adult exposure generates only transient aversive memory. Long-lasting imprinted aversion has a critical period in the first larval stage, and is specific to the experienced pathogen. Distinct groups of neurons are required during formation (AIB, RIM) and retrieval (AIY, RIA) of the imprinted memory. RIM synthesizes the neuromodulator tyramine, which is required in the L1 stage for learning. AIY memory retrieval neurons sense tyramine via the SER-2 receptor, which is essential for imprinted but not for adult-learned aversion. Odor responses in several neurons, most notably RIA, are altered in imprinted animals. These findings provide insight into neuronal substrates of different forms of memory, and lay a foundation for further understanding of early learning. PMID:26871629

The specificity of memory enhancement during interaction with a virtual environment.

PubMed

Brooks, B M; Attree, E A; Rose, F D; Clifford, B R; Leadbetter, A G

1999-01-01

Two experiments investigated differences between active and passive participation in a computer-generated virtual environment in terms of spatial memory, object memory, and object location memory. It was found that active participants, who controlled their movements in the virtual environment using a joystick, recalled the spatial layout of the virtual environment better than passive participants, who merely watched the active participants' progress. Conversely, there were no significant differences between the active and passive participants' recall or recognition of the virtual objects, nor in their recall of the correct locations of objects in the virtual environment. These findings are discussed in terms of subject-performed task research and the specificity of memory enhancement in virtual environments.

Gift from statistical learning: Visual statistical learning enhances memory for sequence elements and impairs memory for items that disrupt regularities.

PubMed

Otsuka, Sachio; Saiki, Jun

2016-02-01

Prior studies have shown that visual statistical learning (VSL) enhances familiarity (a type of memory) of sequences. How do statistical regularities influence the processing of each triplet element and inserted distractors that disrupt the regularity? Given that increased attention to triplets induced by VSL and inhibition of unattended triplets, we predicted that VSL would promote memory for each triplet constituent, and degrade memory for inserted stimuli. Across the first two experiments, we found that objects from structured sequences were more likely to be remembered than objects from random sequences, and that letters (Experiment 1) or objects (Experiment 2) inserted into structured sequences were less likely to be remembered than those inserted into random sequences. In the subsequent two experiments, we examined an alternative account for our results, whereby the difference in memory for inserted items between structured and random conditions is due to individuation of items within random sequences. Our findings replicated even when control letters (Experiment 3A) or objects (Experiment 3B) were presented before or after, rather than inserted into, random sequences. Our findings suggest that statistical learning enhances memory for each item in a regular set and impairs memory for items that disrupt the regularity. Copyright © 2015 Elsevier B.V. All rights reserved.

Semantic processes leading to true and false memory formation in schizophrenia.

PubMed

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. Copyright © 2013 Elsevier B.V. All rights reserved.

Adaptive memory: young children show enhanced retention of fitness-related information.

PubMed

Aslan, Alp; Bäuml, Karl-Heinz T

2012-01-01

Evolutionary psychologists propose that human cognition evolved through natural selection to solve adaptive problems related to survival and reproduction, with its ultimate function being the enhancement of reproductive fitness. Following this proposal and the evolutionary-developmental view that ancestral selection pressures operated not only on reproductive adults, but also on pre-reproductive children, the present study examined whether young children show superior memory for information that is processed in terms of its survival value. In two experiments, we found such survival processing to enhance retention in 4- to 10-year-old children, relative to various control conditions that also required deep, meaningful processing but were not related to survival. These results suggest that, already in very young children, survival processing is a special and extraordinarily effective form of memory encoding. The results support the functional-evolutionary proposal that young children's memory is "tuned" to process and retain fitness-related information. Copyright © 2011 Elsevier B.V. All rights reserved.

Reconciling findings of emotion-induced memory enhancement and impairment of preceding items

PubMed Central

Knight, Marisa; Mather, Mara

2009-01-01

A large body of work reveals that people remember emotionally arousing information better than neutral information. However, previous research reveals contradictory effects of emotional events on memory for neutral events that precede or follow them: in some studies emotionally arousing items impair memory for immediately preceding or following items and in others arousing items enhance memory for preceding items. By demonstrating both emotion-induced enhancement and impairment, Experiments 1 and 2 clarified the conditions under which these effects are likely to occur. The results suggest that emotion-induced enhancement is most likely to occur for neutral items that: (1) precede (and so are poised to predict the onset of) emotionally arousing items, (2) have high attentional weights at encoding, and (3) are tested after a delay period of a week rather than within the same experiment session. In contrast, emotion-induced impairment is most likely to occur for neutral items near the onset of emotional arousal that are overshadowed by highly activated competing items during encoding. PMID:20001121

Two Components of Aversive Memory in Drosophila, Anesthesia-Sensitive and Anesthesia-Resistant Memory, Require Distinct Domains Within the Rgk1 Small GTPase.

PubMed

Murakami, Satoshi; Minami-Ohtsubo, Maki; Nakato, Ryuichiro; Shirahige, Katsuhiko; Tabata, Tetsuya

2017-05-31

Multiple components have been identified that exhibit different stabilities for aversive olfactory memory in Drosophila These components have been defined by behavioral and genetic studies and genes specifically required for a specific component have also been identified. Intermediate-term memory generated after single cycle conditioning is divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We determined that the ASM and ARM pathways converged on the Rgk1 small GTPase and that the N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Rgk1 is specifically accumulated at the synaptic site of the Kenyon cells (KCs), the intrinsic neurons of the mushroom bodies, which play a pivotal role in olfactory memory formation. A higher than normal Rgk1 level enhanced memory retention, which is consistent with the result that Rgk1 suppressed Rac-dependent memory decay; these findings suggest that rgk1 bolsters ASM via the suppression of forgetting. We propose that Rgk1 plays a pivotal role in the regulation of memory stabilization by serving as a molecular node that resides at KC synapses, where the ASM and ARM pathway may interact. SIGNIFICANCE STATEMENT Memory consists of multiple components. Drosophila olfactory memory serves as a fundamental model with which to investigate the mechanisms that underlie memory formation and has provided genetic and molecular means to identify the components of memory, namely short-term, intermediate-term, and long-term memory, depending on how long the memory lasts. Intermediate memory is further divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We have identified a small GTPase in Drosophila , Rgk1, which plays a pivotal role in the regulation of olfactory memory stability. Rgk1 is required for both ASM and ARM. Moreover, N

TRPC3 channels critically regulate hippocampal excitability and contextual fear memory.

PubMed

Neuner, Sarah M; Wilmott, Lynda A; Hope, Kevin A; Hoffmann, Brian; Chong, Jayhong A; Abramowitz, Joel; Birnbaumer, Lutz; O'Connell, Kristen M; Tryba, Andrew K; Greene, Andrew S; Savio Chan, C; Kaczorowski, Catherine C

2015-03-15

Memory formation requires de novo protein synthesis, and memory disorders may result from misregulated synthesis of critical proteins that remain largely unidentified. Plasma membrane ion channels and receptors are likely candidates given their role in regulating neuron excitability, a candidate memory mechanism. Here we conduct targeted molecular monitoring and quantitation of hippocampal plasma membrane proteins from mice with intact or impaired contextual fear memory to identify putative candidates. Here we report contextual fear memory deficits correspond to increased Trpc3 gene and protein expression, and demonstrate TRPC3 regulates hippocampal neuron excitability associated with memory function. These data provide a mechanistic explanation for enhanced contextual fear memory reported herein following knockdown of TRPC3 in hippocampus. Collectively, TRPC3 modulates memory and may be a feasible target to enhance memory and treat memory disorders. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Gaming is related to enhanced working memory performance and task-related cortical activity.

PubMed

Moisala, M; Salmela, V; Hietajärvi, L; Carlson, S; Vuontela, V; Lonka, K; Hakkarainen, K; Salmela-Aro, K; Alho, K

2017-01-15

Gaming experience has been suggested to lead to performance enhancements in a wide variety of working memory tasks. Previous studies have, however, mostly focused on adult expert gamers and have not included measurements of both behavioral performance and brain activity. In the current study, 167 adolescents and young adults (aged 13-24 years) with different amounts of gaming experience performed an n-back working memory task with vowels, with the sensory modality of the vowel stream switching between audition and vision at random intervals. We studied the relationship between self-reported daily gaming activity, working memory (n-back) task performance and related brain activity measured using functional magnetic resonance imaging (fMRI). The results revealed that the extent of daily gaming activity was related to enhancements in both performance accuracy and speed during the most demanding (2-back) level of the working memory task. This improved working memory performance was accompanied by enhanced recruitment of a fronto-parietal cortical network, especially the dorsolateral prefrontal cortex. In contrast, during the less demanding (1-back) level of the task, gaming was associated with decreased activity in the same cortical regions. Our results suggest that a greater degree of daily gaming experience is associated with better working memory functioning and task difficulty-dependent modulation in fronto-parietal brain activity already in adolescence and even when non-expert gamers are studied. The direction of causality within this association cannot be inferred with certainty due to the correlational nature of the current study. Copyright © 2016 Elsevier B.V. All rights reserved.

Consolidation power of extrinsic rewards: reward cues enhance long-term memory for irrelevant past events.

PubMed

Murayama, Kou; Kitagami, Shinji

2014-02-01

Recent research suggests that extrinsic rewards promote memory consolidation through dopaminergic modulation processes. However, no conclusive behavioral evidence exists given that the influence of extrinsic reward on attention and motivation during encoding and consolidation processes are inherently confounded. The present study provides behavioral evidence that extrinsic rewards (i.e., monetary incentives) enhance human memory consolidation independently of attention and motivation. Participants saw neutral pictures, followed by a reward or control cue in an unrelated context. Our results (and a direct replication study) demonstrated that the reward cue predicted a retrograde enhancement of memory for the preceding neutral pictures. This retrograde effect was observed only after a delay, not immediately upon testing. An additional experiment showed that emotional arousal or unconscious resource mobilization cannot explain the retrograde enhancement effect. These results provide support for the notion that the dopaminergic memory consolidation effect can result from extrinsic reward.

Training Working Memory in Childhood Enhances Coupling between Frontoparietal Control Network and Task-Related Regions.

PubMed

Barnes, Jessica J; Nobre, Anna Christina; Woolrich, Mark W; Baker, Kate; Astle, Duncan E

2016-08-24

Working memory is a capacity upon which many everyday tasks depend and which constrains a child's educational progress. We show that a child's working memory can be significantly enhanced by intensive computer-based training, relative to a placebo control intervention, in terms of both standardized assessments of working memory and performance on a working memory task performed in a magnetoencephalography scanner. Neurophysiologically, we identified significantly increased cross-frequency phase amplitude coupling in children who completed training. Following training, the coupling between the upper alpha rhythm (at 16 Hz), recorded in superior frontal and parietal cortex, became significantly coupled with high gamma activity (at ∼90 Hz) in inferior temporal cortex. This altered neural network activity associated with cognitive skill enhancement is consistent with a framework in which slower cortical rhythms enable the dynamic regulation of higher-frequency oscillatory activity related to task-related cognitive processes. Whether we can enhance cognitive abilities through intensive training is one of the most controversial topics of cognitive psychology in recent years. This is particularly controversial in childhood, where aspects of cognition, such as working memory, are closely related to school success and are implicated in numerous developmental disorders. We provide the first neurophysiological account of how working memory training may enhance ability in childhood, using a brain recording technique called magnetoencephalography. We borrowed an analysis approach previously used with intracranial recordings in adults, or more typically in other animal models, called "phase amplitude coupling." Copyright © 2016 Barnes et al.

Training Working Memory in Childhood Enhances Coupling between Frontoparietal Control Network and Task-Related Regions

PubMed Central

Barnes, Jessica J.; Nobre, Anna Christina; Woolrich, Mark W.; Baker, Kate

2016-01-01

Working memory is a capacity upon which many everyday tasks depend and which constrains a child's educational progress. We show that a child's working memory can be significantly enhanced by intensive computer-based training, relative to a placebo control intervention, in terms of both standardized assessments of working memory and performance on a working memory task performed in a magnetoencephalography scanner. Neurophysiologically, we identified significantly increased cross-frequency phase amplitude coupling in children who completed training. Following training, the coupling between the upper alpha rhythm (at 16 Hz), recorded in superior frontal and parietal cortex, became significantly coupled with high gamma activity (at ∼90 Hz) in inferior temporal cortex. This altered neural network activity associated with cognitive skill enhancement is consistent with a framework in which slower cortical rhythms enable the dynamic regulation of higher-frequency oscillatory activity related to task-related cognitive processes. SIGNIFICANCE STATEMENT Whether we can enhance cognitive abilities through intensive training is one of the most controversial topics of cognitive psychology in recent years. This is particularly controversial in childhood, where aspects of cognition, such as working memory, are closely related to school success and are implicated in numerous developmental disorders. We provide the first neurophysiological account of how working memory training may enhance ability in childhood, using a brain recording technique called magnetoencephalography. We borrowed an analysis approach previously used with intracranial recordings in adults, or more typically in other animal models, called “phase amplitude coupling.” PMID:27559180

Enhanced recognition memory following glycine transporter 1 deletion in forebrain neurons.

PubMed

Singer, Philipp; Boison, Detlev; Möhler, Hanns; Feldon, Joram; Yee, Benjamin K

2007-10-01

Selective deletion of glycine transporter 1 (GlyT1) in forebrain neurons enhances N-methyl-D-aspartate receptor (NMDAR)-dependent neurotransmission and facilitates associative learning. These effects are attributable to increases in extracellular glycine availability in forebrain neurons due to reduced glycine re-uptake. Using a forebrain- and neuron-specific GlyT1-knockout mouse line (CamKIIalphaCre; GlyT1tm1.2fl/fI), the authors investigated whether this molecular intervention can affect recognition memory. In a spontaneous object recognition memory test, enhanced preference for a novel object was demonstrated in mutant mice relative to littermate control subjects at a retention interval of 2 hr, but not at 2 min. Furthermore, mutants were responsive to a switch in the relative spatial positions of objects, whereas control subjects were not. These potential procognitive effects were demonstrated against a lack of difference in contextual novelty detection: Mutant and control subjects showed equivalent preference for a novel over a familiar context. Results therefore extend the possible range of potential promnesic effects of specific forebrain neuronal GlyT1 deletion from associative learning to recognition memory and further support the possibility that mnemonic functions can be enhanced by reducing GlyT1 function. (PsycINFO Database Record (c) 2007 APA, all rights reserved).

Dynorphins regulate the strength of social memory.

PubMed

Bilkei-Gorzo, A; Mauer, D; Michel, K; Zimmer, A

2014-02-01

Emotionally arousing events like encounter with an unfamiliar con-species produce strong and vivid memories, whereby the hippocampus and amygdala play a crucial role. It is less understood, however, which neurotransmitter systems regulate the strength of social memories, which have a strong emotional component. It was shown previously that dynorphin signalling is involved in the formation and extinction of fear memories, therefore we asked if it influences social memories as well. Mice with a genetic deletion of the prodynorphin gene Pdyn (Pdyn(-/-)) showed a superior partner recognition ability, whereas their performance in the object recognition test was identical as in wild-type mice. Pharmacological blockade of kappa opioid receptors (KORs) led to an enhanced social memory in wild-type animals, whereas activation of KORs reduced the recognition ability of Pdyn(-/-) mice. Partner recognition test situation induced higher elevation in dynorphin A levels in the central and basolateral amygdala as well as in the hippocampus, and also higher dynorphin B levels in the hippocampus than the object recognition test situation. Our result suggests that dynorphin system activity is increased in emotionally arousing situation and it decreases the formation of social memories. Thus, dynorphin signalling is involved in the formation of social memories by diminishing the emotional component of the experience. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed Central

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. PMID:25136297

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

ERIC Educational Resources Information Center

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,…

How color enhances visual memory for natural scenes.

PubMed

Spence, Ian; Wong, Patrick; Rusan, Maria; Rastegar, Naghmeh

2006-01-01

We offer a framework for understanding how color operates to improve visual memory for images of the natural environment, and we present an extensive data set that quantifies the contribution of color in the encoding and recognition phases. Using a continuous recognition task with colored and monochrome gray-scale images of natural scenes at short exposure durations, we found that color enhances recognition memory by conferring an advantage during encoding and by strengthening the encoding-specificity effect. Furthermore, because the pattern of performance was similar at all exposure durations, and because form and color are processed in different areas of cortex, the results imply that color must be bound as an integral part of the representation at the earliest stages of processing.

Selective Attention to Auditory Memory Neurally Enhances Perceptual Precision.

PubMed

Lim, Sung-Joo; Wöstmann, Malte; Obleser, Jonas

2015-12-09

Selective attention to a task-relevant stimulus facilitates encoding of that stimulus into a working memory representation. It is less clear whether selective attention also improves the precision of a stimulus already represented in memory. Here, we investigate the behavioral and neural dynamics of selective attention to representations in auditory working memory (i.e., auditory objects) using psychophysical modeling and model-based analysis of electroencephalographic signals. Human listeners performed a syllable pitch discrimination task where two syllables served as to-be-encoded auditory objects. Valid (vs neutral) retroactive cues were presented during retention to allow listeners to selectively attend to the to-be-probed auditory object in memory. Behaviorally, listeners represented auditory objects in memory more precisely (expressed by steeper slopes of a psychometric curve) and made faster perceptual decisions when valid compared to neutral retrocues were presented. Neurally, valid compared to neutral retrocues elicited a larger frontocentral sustained negativity in the evoked potential as well as enhanced parietal alpha/low-beta oscillatory power (9-18 Hz) during memory retention. Critically, individual magnitudes of alpha oscillatory power (7-11 Hz) modulation predicted the degree to which valid retrocues benefitted individuals' behavior. Our results indicate that selective attention to a specific object in auditory memory does benefit human performance not by simply reducing memory load, but by actively engaging complementary neural resources to sharpen the precision of the task-relevant object in memory. Can selective attention improve the representational precision with which objects are held in memory? And if so, what are the neural mechanisms that support such improvement? These issues have been rarely examined within the auditory modality, in which acoustic signals change and vanish on a milliseconds time scale. Introducing a new auditory memory

Negative emotion enhances mnemonic precision and subjective feelings of remembering in visual long-term memory.

PubMed

Xie, Weizhen; Zhang, Weiwei

2017-09-01

Negative emotion sometimes enhances memory (higher accuracy and/or vividness, e.g., flashbulb memories). The present study investigates whether it is the qualitative (precision) or quantitative (the probability of successful retrieval) aspect of memory that drives these effects. In a visual long-term memory task, observers memorized colors (Experiment 1a) or orientations (Experiment 1b) of sequentially presented everyday objects under negative, neutral, or positive emotions induced with International Affective Picture System images. In a subsequent test phase, observers reconstructed objects' colors or orientations using the method of adjustment. We found that mnemonic precision was enhanced under the negative condition relative to the neutral and positive conditions. In contrast, the probability of successful retrieval was comparable across the emotion conditions. Furthermore, the boost in memory precision was associated with elevated subjective feelings of remembering (vividness and confidence) and metacognitive sensitivity in Experiment 2. Altogether, these findings suggest a novel precision-based account for emotional memories. Copyright © 2017 Elsevier B.V. All rights reserved.

RNG105/caprin1, an RNA granule protein for dendritic mRNA localization, is essential for long-term memory formation.

PubMed

Nakayama, Kei; Ohashi, Rie; Shinoda, Yo; Yamazaki, Maya; Abe, Manabu; Fujikawa, Akihiro; Shigenobu, Shuji; Futatsugi, Akira; Noda, Masaharu; Mikoshiba, Katsuhiko; Furuichi, Teiichi; Sakimura, Kenji; Shiina, Nobuyuki

2017-11-21

Local regulation of synaptic efficacy is thought to be important for proper networking of neurons and memory formation. Dysregulation of global translation influences long-term memory in mice, but the relevance of the regulation specific for local translation by RNA granules remains elusive. Here, we demonstrate roles of RNG105/caprin1 in long-term memory formation. RNG105 deletion in mice impaired synaptic strength and structural plasticity in hippocampal neurons. Furthermore, RNG105-deficient mice displayed unprecedentedly severe defects in long-term memory formation in spatial and contextual learning tasks. Genome-wide profiling of mRNA distribution in the hippocampus revealed an underlying mechanism: RNG105 deficiency impaired the asymmetric somato-dendritic localization of mRNAs. Particularly, RNG105 deficiency reduced the dendritic localization of mRNAs encoding regulators of AMPAR surface expression, which was consistent with attenuated homeostatic AMPAR scaling in dendrites and reduced synaptic strength. Thus, RNG105 has an essential role, as a key regulator of dendritic mRNA localization, in long-term memory formation.

Chronic transcranial focal stimulation from tripolar concentric ring electrodes does not disrupt memory formation in rats.

PubMed

Luby, Matthew D; Makeyev, Oleksandr; Besio, Walter G

2014-01-01

Non-invasive electrical brain stimulation has shown potential utility as a treatment for seizures in epilepsy patients. Transcranial focal stimulation (TFS) via tripolar concentric ring electrodes (TCREs) has been effective in reducing seizure severity in acute rodent models, but it has yet to be determined whether or not it will serve as a viable long-term treatment strategy. Prior experiments indicate that a single dose of TFS via TCRE does not impact short- or long-term memory formation. The present study investigated if five daily doses of TFS via a TCRE on the scalp affected the memory. The spontaneous object recognition (SOR) test was used to evaluate the memory. Sham and TFS-treated groups were evaluated and both showed comparable levels of preference for novel objects, indicating successful memory formation. More work on repeated dosage strategies is important for establishing the safety and efficacy of TFS as a putative treatment.

Activation of Gαq Signaling Enhances Memory Consolidation and Slows Cognitive Decline.

PubMed

Arey, Rachel N; Stein, Geneva M; Kaletsky, Rachel; Kauffman, Amanda; Murphy, Coleen T

2018-05-02

Perhaps the most devastating decline with age is the loss of memory. Therefore, identifying mechanisms to restore memory function with age is critical. Using C. elegans associative learning and memory assays, we identified a gain-of-function G αq signaling pathway mutant that forms a long-term (cAMP response element binding protein [CREB]-dependent) memory following one conditioned stimulus-unconditioned stimulus (CS-US) pairing, which usually requires seven CS-US pairings. Increased CREB activity in AIM interneurons reduces the threshold for memory consolidation through transcription of a set of previously identified "long-term memory" genes. Enhanced G αq signaling in the AWC sensory neuron is both necessary and sufficient for improved memory and increased AIM CREB activity, and activation of G αq specifically in aged animals rescues the ability to form memory. Activation of G αq in AWC sensory neurons non-cell autonomously induces consolidation after one CS-US pairing, enabling both cognitive function maintenance with age and restoration of memory function in animals with impaired memory performance without decreased longevity. Copyright © 2018 Elsevier Inc. All rights reserved.

Central Nervous Insulin Signaling in Sleep-Associated Memory Formation and Neuroendocrine Regulation.

PubMed

Feld, Gordon B; Wilhem, Ines; Benedict, Christian; Rüdel, Benjamin; Klameth, Corinna; Born, Jan; Hallschmid, Manfred

2016-05-01

The neurochemical underpinnings of sleep's contribution to the establishment and maintenance of memory traces are largely unexplored. Considering that intranasal insulin administration to the CNS improves memory functions in healthy and memory-impaired humans, we tested whether brain insulin signaling and sleep interact to enhance memory consolidation in healthy participants. We investigated the effect of intranasal insulin on sleep-associated neurophysiological and neuroendocrine parameters and memory consolidation in 16 men and 16 women (aged 18-30 years), who learned a declarative word-pair task and a procedural finger sequence tapping task in the evening before intranasal insulin (160 IU) or placebo administration and 8 h of nocturnal sleep. On the subsequent evening, they learned interfering word-pairs and a new finger sequence before retrieving the original memories. Insulin increased growth hormone concentrations in the first night-half and EEG delta power during the second 90 min of non-rapid-eye-movement sleep. Insulin treatment impaired the acquisition of new contents in both the declarative and procedural memory systems on the next day, whereas retrieval of original memories was unchanged. Results indicate that sleep-associated memory consolidation is not a primary mediator of insulin's acute memory-improving effect, but that the peptide acts on mechanisms that diminish the subsequent encoding of novel information. Thus, by inhibiting processes of active forgetting during sleep, central nervous insulin might reduce the interfering influence of encoding new information.

Adult-Onset Hypothyroidism Enhances Fear Memory and Upregulates Mineralocorticoid and Glucocorticoid Receptors in the Amygdala

PubMed Central

Montero-Pedrazuela, Ana; Fernández-Lamo, Iván; Alieva, María; Pereda-Pérez, Inmaculada; Venero, César; Guadaño-Ferraz, Ana

2011-01-01

Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment. PMID:22039511

Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala.

PubMed

Montero-Pedrazuela, Ana; Fernández-Lamo, Iván; Alieva, María; Pereda-Pérez, Inmaculada; Venero, César; Guadaño-Ferraz, Ana

2011-01-01

Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment.

S-Adenosylmethionine Prevents Mallory Denk Body Formation in Drug-Primed Mice by Inhibiting the Epigenetic Memory

PubMed Central

Li, Jun; Bardag-Gorce, Fawzia; Dedes, Jennifer; French, Barbara Alan; Amidi, Fataneh; Oliva, Joan; French, Samuel William

2010-01-01

In previous studies, microarray analysis of livers from mice fed diethyl-1,4-dihydro-2,4,6-trimethyl-3,5-pyridine decarboxylate (DDC) for 10 weeks followed by 1 month of drug withdrawal (drug-primed mice) and then 7 days of drug refeeding showed an increase in the expression of numerous genes referred to here as the molecular cellular memory. This memory predisposes the liver to Mallory Denk body formation in response to drug refeeding. In the current study, drug-primed mice were refed DDC with or without a daily dose of S-adenosylmethionine (SAMe; 4 g/kg of body weight). The livers were studied for evidence of oxidative stress and changes in gene expression with microarray analysis. SAMe prevented Mallory Denk body formation in vivo. The molecular cellular memory induced by DDC refeeding lasted for 4 months after drug withdrawal and was not manifest when SAMe was added to the diet in the in vivo experiment. Liver cells from drug-primed mice spontaneously formed Mallory Denk bodies in primary tissue cultures. SAMe prevented Mallory Denk bodies when it was added to the culture medium. Conclusion SAMe treatment prevented Mallory Denk body formation in vivo and in vitro by preventing the expression of a molecular cellular memory induced by prior DDC feeding. No evidence for the involvement of oxidative stress in induction of the memory was found. The molecular memory included the up-regulation of the expression of genes associated with the development of liver cell preneoplasia. PMID:18098314

Neuroscience of learning and memory for addiction medicine: from habit formation to memory reconsolidation.

PubMed

Torregrossa, Mary M; Taylor, Jane R

2016-01-01

Identifying effective pharmacological treatments for addictive disorders has remained an elusive goal. Many different classes of drugs have shown some efficacy in preclinical models, but the number of effective clinical therapeutics has remained stubbornly low. The persistence of drug use and the high frequency of relapse is at least partly attributable to the enduring ability of environmental stimuli associated with drug use to maintain behavioral patterns of drug use and induce craving during abstinence. We propose that stimuli associated with drug use exert such powerful control over behavior through the development of abnormally strong memories, and their ability to initiate subconscious sequences of motor actions (habits) that promote uncontrolled drug use. In this chapter, we will review the evidence suggesting that drugs of abuse strengthen associations with cues in the environment and facilitate habit formation. We will also discuss potential mechanisms for disrupting memories associated with drug use to help improve treatments for addiction. © 2016 Elsevier B.V. All rights reserved.

Enhanced tactile encoding and memory recognition in congenital blindness.

PubMed

D'Angiulli, Amedeo; Waraich, Paul

2002-06-01

Several behavioural studies have shown that early-blind persons possess superior tactile skills. Since neurophysiological data show that early-blind persons recruit visual as well as somatosensory cortex to carry out tactile processing (cross-modal plasticity), blind persons' sharper tactile skills may be related to cortical re-organisation resulting from loss of vision early in their life. To examine the nature of blind individuals' tactile superiority and its implications for cross-modal plasticity, we compared the tactile performance of congenitally totally blind, low-vision and sighted children on raised-line picture identification test and re-test, assessing effects of task familiarity, exploratory strategy and memory recognition. What distinguished the blind from the other children was higher memory recognition and higher tactile encoding associated with efficient exploration. These results suggest that enhanced perceptual encoding and recognition memory may be two cognitive correlates of cross-modal plasticity in congenital blindness.

Prior perceptual processing enhances the effect of emotional arousal on the neural correlates of memory retrieval

PubMed Central

Dew, Ilana T. Z.; Ritchey, Maureen; LaBar, Kevin S.; Cabeza, Roberto

2014-01-01

A fundamental idea in memory research is that items are more likely to be remembered if encoded with a semantic, rather than perceptual, processing strategy. Interestingly, this effect has been shown to reverse for emotionally arousing materials, such that perceptual processing enhances memory for emotional information or events. The current fMRI study investigated the neural mechanisms of this effect by testing how neural activations during emotional memory retrieval are influenced by the prior encoding strategy. Participants incidentally encoded emotional and neutral pictures under instructions to attend to either semantic or perceptual properties of each picture. Recognition memory was tested two days later. fMRI analyses yielded three main findings. First, right amygdalar activity associated with emotional memory strength was enhanced by prior perceptual processing. Second, prior perceptual processing of emotional pictures produced a stronger effect on recollection- than familiarity-related activations in the right amygdala and left hippocampus. Finally, prior perceptual processing enhanced amygdalar connectivity with regions strongly associated with retrieval success, including hippocampal/parahippocampal regions, visual cortex, and ventral parietal cortex. Taken together, the results specify how encoding orientations yield alterations in brain systems that retrieve emotional memories. PMID:24380867

Does computerized working memory training with game elements enhance motivation and training efficacy in children with ADHD?

PubMed

Prins, Pier J M; Dovis, Sebastiaan; Ponsioen, Albert; ten Brink, Esther; van der Oord, Saskia

2011-03-01

This study examined the benefits of adding game elements to standard computerized working memory (WM) training. Specifically, it examined whether game elements would enhance motivation and training performance of children with ADHD, and whether it would improve training efficacy. A total of 51 children with ADHD aged between 7 and 12 years were randomly assigned to WM training in a gaming format or to regular WM training that was not in a gaming format. Both groups completed three weekly sessions of WM training. Children using the game version of the WM training showed greater motivation (i.e., more time training), better training performance (i.e., more sequences reproduced and fewer errors), and better WM (i.e., higher scores on a WM task) at post-training than children using the regular WM training. Results are discussed in terms of executive functions and reinforcement models of ADHD. It is concluded that WM training with game elements significantly improves the motivation, training performance, and working memory of children with ADHD. The findings of this study are encouraging and may have wide-reaching practical implications in terms of the role of game elements in the design and implementation of new intervention efforts for children with ADHD.

Olfactory memory formation and the influence of reward pathway during appetitive learning by honey bees.

PubMed

Wright, Geraldine A; Mustard, Julie A; Kottcamp, Sonya M; Smith, Brian H

2007-11-01

Animals possess the ability to assess food quality via taste and via changes in state that occur after ingestion. Here, we investigate the extent to which a honey bee's ability to assess food quality affected the formation of association with an odor stimulus and the retention of olfactory memories associated with reward. We used three different conditioning protocols in which the unconditioned stimulus (food) was delivered as sucrose stimulation to the proboscis (mouthparts), the antennae or to both proboscis and antennae. All means of delivery of the unconditioned stimulus produced robust associative conditioning with an odor. However, the memory of a conditioned odor decayed at a significantly greater rate for subjects experiencing antennal-only stimulation after either multiple- or single-trial conditioning. Finally, to test whether the act of feeding on a reward containing sucrose during conditioning affected olfactory memory formation, we conditioned honey bees to associate an odor with antennal stimulation with sucrose followed by feeding on a water droplet. We observed that a honey bee's ability to recall the conditioned odor was not significantly different from that of subjects conditioned with an antennal-only sucrose stimulus. Our results show that stimulation of the sensory receptors on the proboscis and/or ingestion of the sucrose reward during appetitive olfactory conditioning are necessary for long-term memory formation.

Intrinsic functional connectivity between amygdala and hippocampus during rest predicts enhanced memory under stress.

PubMed

de Voogd, Lycia D; Klumpers, Floris; Fernández, Guillén; Hermans, Erno J

2017-01-01

Declarative memories of stressful events are less prone to forgetting than mundane events. Animal research has demonstrated that such stress effects on consolidation of hippocampal-dependent memories require the amygdala. In humans, it has been shown that during learning, increased amygdala-hippocampal interactions are related to more efficient memory encoding. Animal models predict that following learning, amygdala-hippocampal interactions are instrumental to strengthening the consolidation of such declarative memories. Whether this is the case in humans is unknown and remains to be empirically verified. To test this, we analyzed data from a sample of 120 healthy male participants who performed an incidental encoding task and subsequently underwent resting-state functional MRI in a stressful and a neutral context. Stress was assessed by measures of salivary cortisol, blood pressure, heart rate, and subjective ratings. Memory was tested afterwards outside of the scanner. Our data show that memory was stronger in the stress context compared to the neutral context and that stress-induced cortisol responses were associated with this memory enhancement. Interestingly, amygdala-hippocampal connectivity during post-encoding awake rest regardless of context (stress or neutral) was associated with the enhanced memory performance under stress. Thus, our findings are in line with a role for intrinsic functional connectivity during rest between the amygdala and the hippocampus in the state effects of stress on strengthening memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hippocampal SSTR4 somatostatin receptors control the selection of memory strategies.

PubMed

Gastambide, François; Viollet, Cécile; Lepousez, Gabriel; Epelbaum, Jacques; Guillou, Jean-Louis

2009-01-01

Somatostatin (SS14) has been implicated in various cognitive disorders, and converging evidence from animal studies suggests that SS14 neurons differentially regulate hippocampal- and striatal-dependent memory formation. Four SS14 receptor subtypes (SSTR1-4) are expressed in the hippocampus, but their respective roles in memory processes remain to be determined. In the present study, effects of selective SSTR1-4 agonists on memory formation were assessed in a water-maze task which can engage either hippocampus-dependent "place" and/or striatum-dependent "cue" memory formation. Mice received an intrahippocampal injection of one of each of the selective agonists and were then trained to locate an escape platform based on either distal cues (place memory) or a visible proximal cue (cue memory). Retention was tested 24 h later on probe trials aimed at identifying which memory strategy was preferentially retained. Both SS14 and the SSTR4 agonist (L-803,087) dramatically impaired place memory formation in a dose-dependent manner, whereas SSTR1 (L-797,591), SSTR2 (L-779,976), or SSTR3 (L-796,778) agonists did not yield any behavioral effects. However, unlike SS14, the SSTR4 agonist also dose-dependently enhanced cue-based memory formation. This effect was confirmed in another striatal-dependent memory task, the bar-pressing task, where L-803,087 improved memory of the instrumental response, whereas SS14 was once again ineffective. These data suggest that hippocampal SSTR4 are selectively involved in the selection of memory strategies by switching from the use of hippocampus-based multiple associations to the use of simple dorsal striatum-based behavioral responses. Possible neural mechanisms and functional implications are discussed.

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

ERIC Educational Resources Information Center

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…

A mouse model of Rubinstein-Taybi syndrome: Defective long-term memory is ameliorated by inhibitors of phosphodiesterase 4

PubMed Central

Bourtchouladze, Rusiko; Lidge, Regina; Catapano, Ray; Stanley, Jennifer; Gossweiler, Scott; Romashko, Darlene; Scott, Rod; Tully, Tim

2003-01-01

Mice carrying a truncated form of cAMP-responsive element binding protein (CREB)-binding protein (CBP) show several developmental abnormalities similar to patients with Rubinstein-Taybi syndrome (RTS). RTS patients suffer from mental retardation, whereas long-term memory formation is defective in mutant CBP mice. A critical role for cAMP signaling during CREB-dependent long-term memory formation appears to be evolutionarily conserved. From this observation, we reasoned that drugs that modulate CREB function by enhancing cAMP signaling might yield an effective treatment for the memory defect(s) of CBP+/− mice. To this end, we designed a cell-based drug screen and discovered inhibitors of phosphodiesterase 4 (PDE4) to be particularly effective enhancers of CREB function. We extend previous behavioral observations by showing that CBP+/− mutants have impaired long-term memory but normal learning and short-term memory in an object recognition task. We demonstrate that the prototypical PDE4 inhibitor, rolipram, and a novel one (HT0712) abolish the long-term memory defect of CBP+/− mice. Importantly, the genetic lesion in CBP acts specifically to shift the dose sensitivity for HT0712 to enhance memory formation, which conveys molecular specificity on the drug's mechanism of action. Our results suggest that PDE4 inhibitors may be used to treat the cognitive dysfunction of RTS patients. PMID:12930888

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

ERIC Educational Resources Information Center

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…

Lesions affecting the right hippocampal formation differentially impair short-term memory of spatial and nonspatial associations.

PubMed

Braun, Mischa; Weinrich, Christiane; Finke, Carsten; Ostendorf, Florian; Lehmann, Thomas-Nicolas; Ploner, Christoph J

2011-03-01

Converging evidence from behavioral and imaging studies suggests that within the human medial temporal lobe (MTL) the hippocampal formation may be particularly involved in recognition memory of associative information. However, it is unclear whether the hippocampal formation processes all types of associations or whether there is a specialization for processing of associations involving spatial information. Here, we investigated this issue in six patients with postsurgical lesions of the right MTL affecting the hippocampal formation and in ten healthy controls. Subjects performed a battery of delayed match-to-sample tasks with two delays (900/5,000 ms) and three set sizes. Subjects were requested to remember either single features (colors, locations, shapes, letters) or feature associations (color-location, color-shape, color-letter). In the single-feature conditions, performance of patients did not differ from controls. In the association conditions, a significant delay-dependent deficit in memory of color-location associations was found. This deficit was largely independent of set size. By contrast, performance in the color-shape and color-letter conditions was normal. These findings support the hypothesis that a region within the right MTL, presumably the hippocampal formation, does not equally support all kinds of visual memory but rather has a bias for processing of associations involving spatial information. Recruitment of this region during memory tasks appears to depend both on processing type (associative/nonassociative) and to-be-remembered material (spatial/nonspatial). Copyright © 2010 Wiley-Liss, Inc.

Sensory and short-term memory formations observed in a Ag2S gap-type atomic switch

NASA Astrophysics Data System (ADS)

Ohno, Takeo; Hasegawa, Tsuyoshi; Nayak, Alpana; Tsuruoka, Tohru; Gimzewski, James K.; Aono, Masakazu

2011-11-01

Memorization caused by the change in conductance in a Ag2S gap-type atomic switch was investigated as a function of the amplitude and width of input voltage pulses (Vin). The conductance changed little for the first few Vin, but the information of the input was stored as a redistribution of Ag-ions in the Ag2S, indicating the formation of sensory memory. After a certain number of Vin, the conductance increased abruptly followed by a gradual decrease, indicating the formation of short-term memory (STM). We found that the probability of STM formation depends strongly on the amplitude and width of Vin, which resembles the learning behavior of the human brain.

Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation

PubMed Central

Phan, Mimi L.; Bieszczad, Kasia M.

2016-01-01

Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded. PMID:26881129

Short theta burst stimulation to left frontal cortex prior to encoding enhances subsequent recognition memory

PubMed Central

Demeter, Elise; Mirdamadi, Jasmine L.; Meehan, Sean K.; Taylor, Stephan F.

2016-01-01

Deep semantic encoding of verbal stimuli can aid in later successful retrieval of those stimuli from long-term episodic memory. Evidence from numerous neuropsychological and neuroimaging experiments demonstrate regions in left prefrontal cortex, including left dorsolateral prefrontal cortex (DLPFC), are important for processes related to encoding. Here, we investigated the relationship between left DLPFC activity during encoding and successful subsequent memory with transcranial magnetic stimulation (TMS). In a pair of experiments using a 2-session within-subjects design, we stimulated either left DLPFC or a control region (Vertex) with a single 2-s train of short theta burst stimulation (sTBS) during a semantic encoding task and then gave participants a recognition memory test. We found that subsequent memory was enhanced on the day left DLPFC was stimulated, relative to the day Vertex was stimulated, and that DLPFC stimulation also increased participants’ confidence in their decisions during the recognition task. We also explored the time course of how long the effects of sTBS persisted. Our data suggest 2 s of sTBS to left DLPFC is capable of enhancing subsequent memory for items encoded up to 15 s following stimulation. Collectively, these data demonstrate sTBS is capable of enhancing long-term memory and provide evidence that TBS protocols are a potentially powerful tool for modulating cognitive function. PMID:27098772

Enhancing Mobile Working Memory Training by Using Affective Feedback

ERIC Educational Resources Information Center

Schaaff, Kristina

2013-01-01

The objective of this paper is to propose a novel approach to enhance working memory (WM) training for mobile devices by using information about the arousal level of a person. By the example of an adaptive n-back task, we combine methodologies from different disciplines to tackle this challenge: mobile learning, affective computing and cognitive…

Picturing survival memories: enhanced memory after fitness-relevant processing occurs for verbal and visual stimuli.

PubMed

Otgaar, Henry; Smeets, Tom; van Bergen, Saskia

2010-01-01

Recent studies have shown that processing words according to a survival scenario leads to superior retention relative to control conditions. Here, we examined whether a survival recall advantage could be elicited by using pictures. Furthermore, in Experiment 1, we were interested in whether survival processing also results in improved memory for details. Undergraduates rated the relevance of pictures in a survival, moving, or pleasantness scenario and were subsequently given a surprise free recall test. We found that survival processing yielded superior retention. We also found that distortions occurred more often in the survival condition than in the pleasantness condition. In Experiment 2, we directly compared the survival recall effect between pictures and words. A comparable survival recall advantage was found for pictures and words. The present findings support the idea that memory is enhanced by processing information in terms of fitness value, yet at the same time, the present results suggest that this may increase the risk for memory distortions.

Importance of the GluN2B Carboxy-Terminal Domain for Enhancement of Social Memories

ERIC Educational Resources Information Center

Jacobs, Stephanie; Wei, Wei; Wang, Deheng; Tsien, Joe Z.

2015-01-01

The N-methyl-D-aspartate (NMDA) receptor is known to be necessary for many forms of learning and memory, including social recognition memory. Additionally, the GluN2 subunits are known to modulate multiple forms of memory, with a high GluN2A:GluN2B ratio leading to impairments in long-term memory, while a low GluN2A:GluN2B ratio enhances some…

CB2 Cannabinoid Receptor Knockout in Mice Impairs Contextual Long-Term Memory and Enhances Spatial Working Memory

PubMed Central

Li, Yong; Kim, Jimok

2016-01-01

Neurocognitive effects of cannabinoids have been extensively studied with a focus on CB1 cannabinoid receptors because CB1 receptors have been considered the major cannabinoid receptor in the nervous system. However, recent discoveries of CB2 cannabinoid receptors in the brain demand accurate determination of whether and how CB2 receptors are involved in the cognitive effects of cannabinoids. CB2 cannabinoid receptors are primarily involved in immune functions, but also implicated in psychiatric disorders such as schizophrenia and depression. Here, we examined the effects of CB2 receptor knockout in mice on memory to determine the roles of CB2 receptors in modulating cognitive function. Behavioral assays revealed that hippocampus-dependent, long-term contextual fear memory was impaired whereas hippocampus-independent, cued fear memory was normal in CB2 receptor knockout mice. These mice also displayed enhanced spatial working memory when tested in a Y-maze. Motor activity and anxiety of CB2 receptor knockout mice were intact when assessed in an open field arena and an elevated zero maze. In contrast to the knockout of CB2 receptors, acute blockade of CB2 receptors by AM603 in C57BL/6J mice had no effect on memory, motor activity, or anxiety. Our results suggest that CB2 cannabinoid receptors play diverse roles in regulating memory depending on memory types and/or brain areas. PMID:26819779

Retrospective attention enhances visual working memory in the young but not the old: an ERP study

PubMed Central

Duarte, Audrey; Hearons, Patricia; Jiang, Yashu; Delvin, Mary Courtney; Newsome, Rachel N.; Verhaeghen, Paul

2013-01-01

Behavioral evidence from the young suggests spatial cues that orient attention toward task relevant items in visual working memory (VWM) enhance memory capacity. Whether older adults can also use retrospective cues (“retro-cues”) to enhance VWM capacity is unknown. In the current event-related potential (ERP) study, young and old adults performed a VWM task in which spatially informative retro-cues were presented during maintenance. Young but not older adults’ VWM capacity benefitted from retro-cueing. The contralateral delay activity (CDA) ERP index of VWM maintenance was attenuated after the retro-cue, which effectively reduced the impact of memory load. CDA amplitudes were reduced prior to retro-cue onset in the old only. Despite a preserved ability to delete items from VWM, older adults may be less able to use retrospective attention to enhance memory capacity when expectancy of impending spatial cues disrupts effective VWM maintenance. PMID:23445536

Stochastic memory: Memory enhancement due to noise

NASA Astrophysics Data System (ADS)

Stotland, Alexander; di Ventra, Massimiliano

2012-01-01

There are certain classes of resistors, capacitors, and inductors that, when subject to a periodic input of appropriate frequency, develop hysteresis loops in their characteristic response. Here we show that the hysteresis of such memory elements can also be induced by white noise of appropriate intensity even at very low frequencies of the external driving field. We illustrate this phenomenon using a physical model of memory resistor realized by TiO2 thin films sandwiched between metallic electrodes and discuss under which conditions this effect can be observed experimentally. We also discuss its implications on existing memory systems described in the literature and the role of colored noise.

Is emotional memory enhancement preserved in amnestic mild cognitive impairment? Evidence from separating recollection and familiarity.

PubMed

Wang, Pengyun; Li, Juan; Li, Huijie; Li, Bing; Jiang, Yang; Bao, Feng; Zhang, Shouzi

2013-11-01

This study investigated whether the observed absence of emotional memory enhancement in recognition tasks in patients with amnestic mild cognitive impairment (aMCI) could be related to their greater proportion of familiarity-based responses for all stimuli, and whether recognition tests with emotional items had better discriminative power for aMCI patients than those with neutral items. In total, 31 aMCI patients and 30 healthy older adults participated in a recognition test followed by remember/know judgments. Positive, neutral, and negative faces were used as stimuli. For overall recognition performance, emotional memory enhancement was found only in healthy controls; they remembered more negative and positive stimuli than neutral ones. For "remember" responses, we found equivalent emotional memory enhancement in both groups, though a greater proportion of "remember" responses was observed in normal controls. For "know" responses, aMCI patients presented a larger proportion than normal controls did, and their "know" responses were not affected by emotion. A negative correlation was found between emotional enhancement effect and the memory performance related to "know" responses. In addition, receiver operating characteristic curve analysis revealed higher diagnostic accuracy for recognition test with emotional stimuli than with neutral stimuli. The present results implied that the absence of the emotional memory enhancement effect in aMCI patients might be related to their tendency to rely more on familiarity-based "know" responses for all stimuli. Furthermore, recognition memory tests using emotional stimuli may be better able than neutral stimuli to differentiate people with aMCI from cognitively normal older adults. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Exploring the influence of encoding format on subsequent memory.

PubMed

Turney, Indira C; Dennis, Nancy A; Maillet, David; Rajah, M Natasha

2017-05-01

Distinctive encoding is greatly influenced by gist-based processes and has been shown to suffer when highly similar items are presented in close succession. Thus, elucidating the mechanisms underlying how presentation format affects gist processing is essential in determining the factors that influence these encoding processes. The current study utilised multivariate partial least squares (PLS) analysis to identify encoding networks directly associated with retrieval performance in a blocked and intermixed presentation condition. Subsequent memory analysis for successfully encoded items indicated no significant differences between reaction time and retrieval performance and presentation format. Despite no significant behavioural differences, behaviour PLS revealed differences in brain-behaviour correlations and mean condition activity in brain regions associated with gist-based vs. distinctive encoding. Specifically, the intermixed format encouraged more distinctive encoding, showing increased activation of regions associated with strategy use and visual processing (e.g., frontal and visual cortices, respectively). Alternatively, the blocked format exhibited increased gist-based processes, accompanied by increased activity in the right inferior frontal gyrus. Together, results suggest that the sequence that information is presented during encoding affects the degree to which distinctive encoding is engaged. These findings extend our understanding of the Fuzzy Trace Theory and the role of presentation format on encoding processes.

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

PubMed

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.

Rapid, experience-dependent translation of neurogranin enables memory encoding.

PubMed

Jones, Kendrick J; Templet, Sebastian; Zemoura, Khaled; Kuzniewska, Bozena; Pena, Franciso X; Hwang, Hongik; Lei, Ding J; Haensgen, Henny; Nguyen, Shannon; Saenz, Christopher; Lewis, Michael; Dziembowska, Magdalena; Xu, Weifeng

2018-06-19

Experience induces de novo protein synthesis in the brain and protein synthesis is required for long-term memory. It is important to define the critical temporal window of protein synthesis and identify newly synthesized proteins required for memory formation. Using a behavioral paradigm that temporally separates the contextual exposure from the association with fear, we found that protein synthesis during the transient window of context exposure is required for contextual memory formation. Among an array of putative activity-dependent translational neuronal targets tested, we identified one candidate, a schizophrenia-associated candidate mRNA, neurogranin (Ng, encoded by the Nrgn gene) responding to novel-context exposure. The Ng mRNA was recruited to the actively translating mRNA pool upon novel-context exposure, and its protein levels were rapidly increased in the hippocampus. By specifically blocking activity-dependent translation of Ng using virus-mediated molecular perturbation, we show that experience-dependent translation of Ng in the hippocampus is required for contextual memory formation. We further interrogated the molecular mechanism underlying the experience-dependent translation of Ng, and found that fragile-X mental retardation protein (FMRP) interacts with the 3'UTR of the Nrgn mRNA and is required for activity-dependent translation of Ng in the synaptic compartment and contextual memory formation. Our results reveal that FMRP-mediated, experience-dependent, rapid enhancement of Ng translation in the hippocampus during the memory acquisition enables durable context memory encoding. Copyright © 2018 the Author(s). Published by PNAS.

Rapid, experience-dependent translation of neurogranin enables memory encoding

PubMed Central

Jones, Kendrick J.; Templet, Sebastian; Zemoura, Khaled; Pena, Franciso X.; Hwang, Hongik; Lei, Ding J.; Haensgen, Henny; Nguyen, Shannon; Saenz, Christopher; Lewis, Michael; Dziembowska, Magdalena

2018-01-01

Experience induces de novo protein synthesis in the brain and protein synthesis is required for long-term memory. It is important to define the critical temporal window of protein synthesis and identify newly synthesized proteins required for memory formation. Using a behavioral paradigm that temporally separates the contextual exposure from the association with fear, we found that protein synthesis during the transient window of context exposure is required for contextual memory formation. Among an array of putative activity-dependent translational neuronal targets tested, we identified one candidate, a schizophrenia-associated candidate mRNA, neurogranin (Ng, encoded by the Nrgn gene) responding to novel-context exposure. The Ng mRNA was recruited to the actively translating mRNA pool upon novel-context exposure, and its protein levels were rapidly increased in the hippocampus. By specifically blocking activity-dependent translation of Ng using virus-mediated molecular perturbation, we show that experience-dependent translation of Ng in the hippocampus is required for contextual memory formation. We further interrogated the molecular mechanism underlying the experience-dependent translation of Ng, and found that fragile-X mental retardation protein (FMRP) interacts with the 3′UTR of the Nrgn mRNA and is required for activity-dependent translation of Ng in the synaptic compartment and contextual memory formation. Our results reveal that FMRP-mediated, experience-dependent, rapid enhancement of Ng translation in the hippocampus during the memory acquisition enables durable context memory encoding. PMID:29880715

Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory

PubMed Central

Maher, Pamela; Akaishi, Tatsuhiro; Abe, Kazuho

2006-01-01

Small molecules that activate signaling pathways used by neurotrophic factors could be useful for treating CNS disorders. Here we show that the flavonoid fisetin activates ERK and induces cAMP response element-binding protein (CREB) phosphorylation in rat hippocampal slices, facilitates long-term potentiation in rat hippocampal slices, and enhances object recognition in mice. Together, these data demonstrate that the natural product fisetin can facilitate long-term memory, and therefore it may be useful for treating patients with memory disorders. PMID:17050681

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

ERIC Educational Resources Information Center

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…

Changes in blood glucose and salivary cortisol are not necessary for arousal to enhance memory in young or older adults.

PubMed

Gore, Jane B; Krebs, Desiree L; Parent, Marise B

2006-06-01

Emotional arousal enhances memory, and this memory-enhancing effect may involve neurochemicals released by arousal, such as glucose and cortisol. Physiological consequences of arousal change with age, and these changes may contribute to age-related memory decline. The present study examined whether emotionally arousing pictures would affect glucose and cortisol levels and enhance memory in young and older adults. Blood glucose and salivary cortisol were measured once before and six times after young and old adults viewed either 60 highly arousing or 60 relatively neutral pictures. Recall for the stimuli was measured 75 min later. The results indicated that recall was impaired in older adults. Arousal as measured by self-report enhanced recall in both young and older adults. However, arousal did not affect glucose or cortisol levels in either group. These findings demonstrate that changes in blood glucose or salivary cortisol levels are not necessary for arousal to enhance memory.

Drosophila SLC22A transporter is a memory suppressor gene that influences cholinergic neurotransmission to the mushroom bodies

PubMed Central

Gai, Yunchao; Liu, Ze; Cervantes-Sandoval, Isaac; Davis, Ronald L.

2016-01-01

SUMMARY The mechanisms that constrain memory formation are of special interest because they provide insights into the brain’s memory management systems and potential avenues for correcting cognitive disorders. RNAi knockdown in the Drosophila mushroom body neurons (MBn) of a newly discovered memory suppressor gene, Solute Carrier DmSLC22A, a member of the organic cation transporter family, enhances olfactory memory expression, while overexpression inhibits it. The protein localizes to the dendrites of the MBn, surrounding the presynaptic terminals of cholinergic afferent fibers from projection neurons (Pn). Cell-based expression assays show that this plasma membrane protein transports cholinergic compounds with the highest affinity among several in vitro substrates. Feeding flies choline or inhibiting acetylcholinesterase in Pn enhances memory; an effect blocked by overexpression of the transporter in the MBn. The data argue that DmSLC22A is a memory suppressor protein that limits memory formation by helping to terminate cholinergic neurotransmission at the Pn:MBn synapse. PMID:27146270

The role of attention and relatedness in emotionally enhanced memory.

PubMed

Talmi, Deborah; Schimmack, Ulrich; Paterson, Theone; Moscovitch, Morris

2007-02-01

Examining the positive and negative pictures separately revealed that emotionally enhanced memory (EEM) for positive pictures was mediated by attention, with no significant influence of emotional arousal, whereas the reverse was true of negative pictures. Consistent with this finding, in Experiment 2 EEM for negative pictures was found even when task emphasis was manipulated so that equivalent attention was allocated to negative and neutral pictures. The results show that attention and semantic relatedness contribute to EEM, with the extent varying with emotional valence. Negative emotion can influence memory independently of these 2 factors. (c) 2007 APA, all rights reserved.

The infamous among us: Enhanced reputational memory for uncooperative ingroup members.

PubMed

Hechler, Stefanie; Neyer, Franz J; Kessler, Thomas

2016-12-01

People remember uncooperative individuals better than cooperative ones. We hypothesize that this is particularly true when uncooperative individuals belong to one's ingroup, as their behavior violates positive expectations. Two studies examined the effect of minimal group categorization on reputational memory of the social behavior of particular ingroup and outgroup members. We manipulated uncooperative behavior as the unfair sharing of resources with ingroup members (Study 1), or as descriptions of cheating (Study 2). Participants evaluated several uncooperative and cooperative (and neutral) ingroup and outgroup members. In a surprise memory test, they had to recognize target faces and recall their behavior. We disentangled face recognition, reputational memory, and guessing biases with multinomial models of source monitoring. The results show enhanced reputational memory for uncooperative ingroup members, but not uncooperative outgroup members. In contrast, guessing behavior indicated that participants assumed more ingroup cooperation than outgroup cooperation. Our findings integrate prior research on memory for uncooperative person behavior and person memory in group contexts. We suggest that the ability to remember the uncooperative amidst the supposedly cooperative ingroup could stabilize intragroup cooperation. Copyright © 2016 Elsevier B.V. All rights reserved.

Sex, cheating, and disgust: enhanced source memory for trait information that violates gender stereotypes.

PubMed

Kroneisen, Meike; Bell, Raoul

2013-01-01

The present study examines memory for social-exchange-relevant information. In Experiment 1 male and female faces were shown together with behaviour descriptions of cheating, altruistic, and neutral behaviour. Previous results have led to the hypothesis that people preferentially remember schema-atypical information. Given the common gender stereotype that women are kinder and less egoistic than men, this atypicality account would predict that source memory (that is, memory for the type of context to which a face was associated) should be enhanced for female cheaters in comparison to male cheaters. The results of Experiment 1 confirmed this hypothesis. Experiment 2 reveals that source memory for female faces associated with disgusting behaviours is enhanced in comparison to male faces associated with disgusting behaviours. Thus the atypicality effect generalises beyond social-exchange-relevant information, a result which is inconsistent with the assumption that the findings can be ascribed to a highly specific cheater detection module.

Learning at different satiation levels reveals parallel functions for the cAMP-protein kinase A cascade in formation of long-term memory.

PubMed

Friedrich, Anke; Thomas, Ulf; Müller, Uli

2004-05-05

Learning and memory formation in intact animals is generally studied under defined parameters, including the control of feeding. We used associative olfactory conditioning of the proboscis extension response in honeybees to address effects of feeding status on processes of learning and memory formation. Comparing groups of animals with different but defined feeding status at the time of conditioning reveals new and characteristic features in memory formation. In animals fed 18 hr earlier, three-trial conditioning induces a stable memory that consists of different phases: a mid-term memory (MTM), translation-dependent early long-term memory (eLTM; 1-2 d), and a transcription-dependent late LTM (lLTM; > or =3 d). Additional feeding of a small amount of sucrose 4 hr before conditioning leads to a loss of all of these memory phases. Interestingly, the basal activity of the cAMP-dependent protein kinase A (PKA), a key player in LTM formation, differs in animals with different satiation levels. Pharmacological rescue of the low basal PKA activity in animals fed 4 hr before conditioning points to a specific function of cAMP-PKA cascade in mediating satiation-dependent memory formation. An increase in PKA activity during conditioning rescues only transcription-dependent lLTM; acquisition, MTM, and eLTM are still impaired. Thus, during conditioning, the cAMP-PKA cascade mediates the induction of the transcription-dependent lLTM, depending on the satiation level. This result provides the first evidence for a central and distinct function of the cAMP-PKA cascade connecting satiation level with learning.

Glucose Administration Enhances fMRI Brain Activation and Connectivity Related to Episodic Memory Encoding for Neutral and Emotional Stimuli

ERIC Educational Resources Information Center

Parent, Marise B.; Krebs-Kraft, Desiree L.; Ryan, John P.; Wilson, Jennifer S.; Harenski, Carla; Hamann, Stephan

2011-01-01

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with…

Pharmacologic inhibition of phospholipase C in the brain attenuates early memory formation in the honeybee (Apis mellifera L.)

PubMed Central

Iino, Shiori; Kubo, Takeo

2018-01-01

ABSTRACT Although the molecular mechanisms involved in learning and memory in insects have been studied intensively, the intracellular signaling mechanisms involved in early memory formation are not fully understood. We previously demonstrated that phospholipase C epsilon (PLCe), whose product is involved in calcium signaling, is almost selectively expressed in the mushroom bodies, a brain structure important for learning and memory in the honeybee. Here, we pharmacologically examined the role of phospholipase C (PLC) in learning and memory in the honeybee. First, we identified four genes for PLC subtypes in the honeybee genome database. Quantitative reverse transcription-polymerase chain reaction revealed that, among these four genes, three, including PLCe, were expressed higher in the brain than in sensory organs in worker honeybees, suggesting their main roles in the brain. Edelfosine and neomycin, pan-PLC inhibitors, significantly decreased PLC activities in homogenates of the brain tissues. These drugs injected into the head of foragers significantly attenuated memory acquisition in comparison with the control groups, whereas memory retention was not affected. These findings suggest that PLC in the brain is involved in early memory formation in the honeybee. To our knowledge, this is the first report of a role for PLC in learning and memory in an insect. PMID:29330349

Regulators of Long-Term Memory Revealed by Mushroom Body-Specific Gene Expression Profiling in Drosophila melanogaster.

PubMed

Widmer, Yves F; Bilican, Adem; Bruggmann, Rémy; Sprecher, Simon G

2018-06-20

Memory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short-term memory traces rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory formation. With Drosophila melanogaster as a model system we profiled transcriptomic changes in the mushroom body, a memory center in the fly brain, at distinct time intervals during appetitive olfactory long-term memory formation using the targeted DamID technique. We describe the gene expression profiles during these phases and tested 33 selected candidate genes for deficits in long-term memory formation using RNAi knockdown. We identified 10 genes that enhance or decrease memory when knocked-down in the mushroom body. For vajk-1 and hacd1 , the two strongest hits, we gained further support for their crucial role in appetitive learning and forgetting. These findings show that profiling gene expression changes in specific cell-types harboring memory traces provides a powerful entry point to identify new genes involved in learning and memory. The presented transcriptomic data may further be used as resource to study genes acting at different memory phases. Copyright © 2018, Genetics.

Learning Induces Sonic Hedgehog Signaling in the Amygdala which Promotes Neurogenesis and Long-Term Memory Formation

PubMed Central

Hung, Hui-Chi; Hsiao, Ya-Hsin

2015-01-01

Background: It is known that neurogenesis occurs throughout the life mostly in the subgranular zone of the hippocampus and the subventricular zone of the lateral ventricle. We investigated whether neurogenesis occurred in the amygdala and its function in fear memory formation. Methods: For detection of newborn neurons, mice were injected intraperitoneally with 5-bromo-2’-deoxyuridine (BrdU) 2h before receiving 15 tone–footshock pairings, and newborn neurons were analyzed 14 and 42 days after training. To determine the relationship between neurogenesis and memory formation, mice were given a proliferation inhibitor methylazoxymethanol (MAM) or a DNA synthesis inhibitor cytosine arabinoside (Ara-C). To test whether sonic hedgehog (Shh) signaling was required for neurogenesis, Shh-small hairpin–interfering RNA (shRNA) was inserted into a retroviral vector (Retro-Shh-shRNA). Results: The number of BrdU+/Neuronal nuclei (NeuN)+ cells was significantly higher in the conditioned mice, suggesting that association of tone with footshock induced neurogenesis. MAM and Ara-C markedly reduced neurogenesis and impaired fear memory formation. Shh, its receptor patched 1 (Ptc1), and transcription factor Gli1 protein levels increased at 1 day and returned to baseline at 7 days after fear conditioning. Retro-Shh-shRNA, which knocked down Shh specifically in the mitotic neurons, reduced the number of BrdU+/NeuN+ cells and decreased freezing responses. Conclusions: These results suggest that fear learning induces Shh signaling activation in the amygdala, which promotes neurogenesis and fear memory formation. PMID:25522410

A kinase-dependent feedforward loop affects CREBB stability and long term memory formation.

PubMed

Lee, Pei-Tseng; Lin, Guang; Lin, Wen-Wen; Diao, Fengqiu; White, Benjamin H; Bellen, Hugo J

2018-02-23

In Drosophila , long-term memory (LTM) requires the cAMP-dependent transcription factor CREBB, expressed in the mushroom bodies (MB) and phosphorylated by PKA. To identify other kinases required for memory formation, we integrated Trojan exons encoding T2A-GAL4 into genes encoding putative kinases and selected for genes expressed in MB. These lines were screened for learning/memory deficits using UAS-RNAi knockdown based on an olfactory aversive conditioning assay. We identified a novel, conserved kinase, Meng-Po ( MP , CG11221 , SBK1 in human), the loss of which severely affects 3 hr memory and 24 hr LTM, but not learning. Remarkably, memory is lost upon removal of the MP protein in adult MB but restored upon its reintroduction. Overexpression of MP in MB significantly increases LTM in wild-type flies showing that MP is a limiting factor for LTM. We show that PKA phosphorylates MP and that both proteins synergize in a feedforward loop to control CREBB levels and LTM. key words: Drosophila, Mushroom bodies, SBK1, deGradFP, T2A-GAL4, MiMIC.

Spaced Learning Enhances Subsequent Recognition Memory by Reducing Neural Repetition Suppression

PubMed Central

Xue, Gui; Mei, Leilei; Chen, Chuansheng; Lu, Zhong-Lin; Poldrack, Russell; Dong, Qi

2012-01-01

Spaced learning usually leads to better recognition memory as compared with massed learning, yet the underlying neural mechanisms remain elusive. One open question is whether the spacing effect is achieved by reducing neural repetition suppression. In this fMRI study, participants were scanned while intentionally memorizing 120 novel faces, half under the massed learning condition (i.e., four consecutive repetitions with jittered interstimulus interval) and the other half under the spaced learning condition (i.e., the four repetitions were interleaved). Recognition memory tests afterward revealed a significant spacing effect: Participants recognized more items learned under the spaced learning condition than under the massed learning condition. Successful face memory encoding was associated with stronger activation in the bilateral fusiform gyrus, which showed a significant repetition suppression effect modulated by subsequent memory status and spaced learning. Specifically, remembered faces showed smaller repetition suppression than forgotten faces under both learning conditions, and spaced learning significantly reduced repetition suppression. These results suggest that spaced learning enhances recognition memory by reducing neural repetition suppression. PMID:20617892

Spaced learning enhances subsequent recognition memory by reducing neural repetition suppression.

PubMed

Xue, Gui; Mei, Leilei; Chen, Chuansheng; Lu, Zhong-Lin; Poldrack, Russell; Dong, Qi

2011-07-01

Spaced learning usually leads to better recognition memory as compared with massed learning, yet the underlying neural mechanisms remain elusive. One open question is whether the spacing effect is achieved by reducing neural repetition suppression. In this fMRI study, participants were scanned while intentionally memorizing 120 novel faces, half under the massed learning condition (i.e., four consecutive repetitions with jittered interstimulus interval) and the other half under the spaced learning condition (i.e., the four repetitions were interleaved). Recognition memory tests afterward revealed a significant spacing effect: Participants recognized more items learned under the spaced learning condition than under the massed learning condition. Successful face memory encoding was associated with stronger activation in the bilateral fusiform gyrus, which showed a significant repetition suppression effect modulated by subsequent memory status and spaced learning. Specifically, remembered faces showed smaller repetition suppression than forgotten faces under both learning conditions, and spaced learning significantly reduced repetition suppression. These results suggest that spaced learning enhances recognition memory by reducing neural repetition suppression.

Acute stress enhances learning and memory by activating acid-sensing ion channels in rats.

PubMed

Ye, Shunjie; Yang, Rong; Xiong, Qiuju; Yang, Youhua; Zhou, Lianying; Gong, Yeli; Li, Changlei; Ding, Zhenhan; Ye, Guohai; Xiong, Zhe

2018-04-15

Acute stress has been shown to enhance learning and memory ability, predominantly through the action of corticosteroid stress hormones. However, the valuable targets for promoting learning and memory induced by acute stress and the underlying molecular mechanisms remain unclear. Acid-sensing ion channels (ASICs) play an important role in central neuronal systems and involves in depression, synaptic plasticity and learning and memory. In the current study, we used a combination of electrophysiological and behavioral approaches in an effort to explore the effects of acute stress on ASICs. We found that corticosterone (CORT) induced by acute stress caused a potentiation of ASICs current via glucocorticoid receptors (GRs) not mineralocorticoid receptors (MRs). Meanwhile, CORT did not produce an increase of ASICs current by pretreated with GF109203X, an antagonist of protein kinase C (PKC), whereas CORT did result in a markedly enhancement of ASICs current by bryostatin 1, an agonist of PKC, suggesting that potentiation of ASICs function may be depended on PKC activating. More importantly, an antagonist of ASICs, amiloride (10 μM) reduced the performance of learning and memory induced by acute stress, which is further suggesting that ASICs as the key components involves in cognitive processes induced by acute stress. These results indicate that acute stress causes the enhancement of ASICs function by activating PKC signaling pathway, which leads to potentiated learning and memory. Copyright © 2018 Elsevier Inc. All rights reserved.

Impact of exogenous cortisol on the formation of intrusive memories in healthy women.

PubMed

Rombold, Felicitas; Wingenfeld, Katja; Renneberg, Babette; Schwarzkopf, Friederike; Hellmann-Regen, Julian; Otte, Christian; Roepke, Stefan

2016-12-01

Stress hormones such as cortisol are involved in modulating emotional memory. However, little is known about the influence of cortisol on the formation of intrusive memories after a traumatic event. The aim of this study was to examine whether cortisol levels during encoding and consolidation of an intrusion-inducing trauma film paradigm would influence subsequent intrusion formation. In an experimental, double-blind, placebo-controlled study a trauma film paradigm was used to induce intrusions in 60 healthy women. Participants received a single dose of either 20 mg hydrocortisone or placebo before watching a trauma film. Salivary cortisol and alpha-amylase as well as blood pressure were measured during the experiment. The consecutive number of intrusions, the vividness of intrusions, and the degree of distress evoked by the intrusions resulting from the trauma film were assessed throughout the following seven days. Hydrocortisone administration before the trauma film resulted in increased salivary cortisol levels but did not affect the consecutive number of intrusions, the vividness of intrusions, and the degree of distress evoked by the intrusions throughout the following week. These results indicate that pharmacologically increased cortisol levels during an experimental trauma film paradigm do not influence consecutive intrusive memories. Current data do not support a prominent role of exogenous cortisol on intrusive memories, at least in healthy young women after a relatively mild trauma equivalent. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novelty-Sensitive Dopaminergic Neurons in the Human Substantia Nigra Predict Success of Declarative Memory Formation.

PubMed

Kamiński, Jan; Mamelak, Adam N; Birch, Kurtis; Mosher, Clayton P; Tagliati, Michele; Rutishauser, Ueli

2018-05-07

The encoding of information into long-term declarative memory is facilitated by dopamine. This process depends on hippocampal novelty signals, but it remains unknown how midbrain dopaminergic neurons are modulated by declarative-memory-based information. We recorded individual substantia nigra (SN) neurons and cortical field potentials in human patients performing a recognition memory task. We found that 25% of SN neurons were modulated by stimulus novelty. Extracellular waveform shape and anatomical location indicated that these memory-selective neurons were putatively dopaminergic. The responses of memory-selective neurons appeared 527 ms after stimulus onset, changed after a single trial, and were indicative of recognition accuracy. SN neurons phase locked to frontal cortical theta-frequency oscillations, and the extent of this coordination predicted successful memory formation. These data reveal that dopaminergic neurons in the human SN are modulated by memory signals and demonstrate a progression of information flow in the hippocampal-basal ganglia-frontal cortex loop for memory encoding. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Verapamil enhances acute stress or glucocorticoid-induced deficits in retrieval of long-term memory in rats.

PubMed

Rashidy-Pour, Ali; Vafaei, Abbas Ali; Taherian, Abbas Ali; Miladi-Gorji, Hossein; Sadeghi, Hassan; Fathollahi, Yaghoub; Bandegi, Ahmad Reza

2009-10-12

This study was designed to investigate an interaction between acute restraint stress and corticosterone with verapamil, a blocker of L-type voltage-dependent calcium (VDC) channels on retrieval of long-term memory. Young adult male rats were trained in one trial inhibitory avoidance task (0.5 mA, 3 s footshock). On retention test given 48 h after training, the latency to re-enter dark compartment of the apparatus was recorded. In Experiment 1, verapamil pretreatment (5, 10, or 20 mg/kg) enhanced the impairing effects of acute stress (which was applied for 10 min in a Plexiglass tube 30 min before the retention test) on memory retrieval. The applied stress increased circulating corticosterone levels as assessed immediately after the retention test, indicating that stress-induced impairment of memory retrieval is mediated, in part, by increased plasma levels of glucocorticoids. Verapamil did not change this response. In Experiment 2, pretreatment of an intermediate dose of verapamil also enhanced corticosterone-induced impairment of memory retrieval. In Experiments 3 and 4, acute stress or corticosterone did not change motor activity with or without prior treatment of verapamil, suggesting that stress or glucocorticoid-induced impairment of memory retrieval is not due to any gross disturbances in motor performance of animals. These findings indicate that blockade of L-type VDC channels enhances stress or glucocorticoid-induced impairment of memory retrieval, and provide evidence for the existence of an interaction between glucocorticoids and L-type VDC channels on memory retrieval.

Cytokine-Induced Memory-Like Differentiation Enhances Unlicensed Natural Killer Cell Antileukemia and FcγRIIIa-Triggered Responses.

PubMed

Wagner, Julia A; Berrien-Elliott, Melissa M; Rosario, Maximillian; Leong, Jeffrey W; Jewell, Brea A; Schappe, Timothy; Abdel-Latif, Sara; Fehniger, Todd A

2017-03-01

Cytokine-induced memory-like natural killer (NK) cells differentiate after short-term preactivation with IL-12, IL-15, and IL-18 and display enhanced effector function in response to cytokines or tumor targets for weeks after the initial preactivation. Conventional NK cell function depends on a licensing signal, classically delivered by an inhibitory receptor engaging its cognate MHC class I ligand. How licensing status integrates with cytokine-induced memory-like NK cell responses is unknown. We investigated this interaction using killer cell immunoglobulin-like receptor- and HLA-genotyped primary human NK cells. Memory-like differentiation resulted in enhanced IFN-γ production triggered by leukemia targets or FcγRIIIa ligation within licensed NK cells, which exhibited the highest functionality of the NK cell subsets interrogated. IFN-γ production by unlicensed memory-like NK cells was also enhanced to a level comparable with that of licensed control NK cells. Mechanistically, differences in responses to FcγRIIIa-based triggering were not explained by alterations in key signaling intermediates, indicating that the underlying biology of memory-like NK cells is distinct from that of adaptive NK cells in human cytomegalovirus-positive individuals. Additionally, memory-like NK cells responded robustly to cytokine receptor restimulation with no impact of licensing status. These results demonstrate that both licensed and unlicensed memory-like NK cell populations have enhanced functionality, which may be translated to improve leukemia immunotherapy. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Failure of Working Memory Training to Enhance Cognition or Intelligence

PubMed Central

Thompson, Todd W.; Waskom, Michael L.; Garel, Keri-Lee A.; Cardenas-Iniguez, Carlos; Reynolds, Gretchen O.; Winter, Rebecca; Chang, Patricia; Pollard, Kiersten; Lala, Nupur; Alvarez, George A.; Gabrieli, John D. E.

2013-01-01

Fluid intelligence is important for successful functioning in the modern world, but much evidence suggests that fluid intelligence is largely immutable after childhood. Recently, however, researchers have reported gains in fluid intelligence after multiple sessions of adaptive working memory training in adults. The current study attempted to replicate and expand those results by administering a broad assessment of cognitive abilities and personality traits to young adults who underwent 20 sessions of an adaptive dual n-back working memory training program and comparing their post-training performance on those tests to a matched set of young adults who underwent 20 sessions of an adaptive attentional tracking program. Pre- and post-training measurements of fluid intelligence, standardized intelligence tests, speed of processing, reading skills, and other tests of working memory were assessed. Both training groups exhibited substantial and specific improvements on the trained tasks that persisted for at least 6 months post-training, but no transfer of improvement was observed to any of the non-trained measurements when compared to a third untrained group serving as a passive control. These findings fail to support the idea that adaptive working memory training in healthy young adults enhances working memory capacity in non-trained tasks, fluid intelligence, or other measures of cognitive abilities. PMID:23717453

How memory of direct animal interactions can lead to territorial pattern formation.

PubMed

Potts, Jonathan R; Lewis, Mark A

2016-05-01

Mechanistic home range analysis (MHRA) is a highly effective tool for understanding spacing patterns of animal populations. It has hitherto focused on populations where animals defend their territories by communicating indirectly, e.g. via scent marks. However, many animal populations defend their territories using direct interactions, such as ritualized aggression. To enable application of MHRA to such populations, we construct a model of direct territorial interactions, using linear stability analysis and energy methods to understand when territorial patterns may form. We show that spatial memory of past interactions is vital for pattern formation, as is memory of 'safe' places, where the animal has visited but not suffered recent territorial encounters. Additionally, the spatial range over which animals make decisions to move is key to understanding the size and shape of their resulting territories. Analysis using energy methods, on a simplified version of our system, shows that stability in the nonlinear system corresponds well to predictions of linear analysis. We also uncover a hysteresis in the process of territory formation, so that formation may depend crucially on initial space-use. Our analysis, in one dimension and two dimensions, provides mathematical groundwork required for extending MHRA to situations where territories are defended by direct encounters. © 2016 The Author(s).

The Histone Deacetylase HDAC4 Regulates Long-Term Memory in Drosophila

PubMed Central

Fitzsimons, Helen L.; Schwartz, Silvia; Given, Fiona M.; Scott, Maxwell J.

2013-01-01

A growing body of research indicates that pharmacological inhibition of histone deacetylases (HDACs) correlates with enhancement of long-term memory and current research is concentrated on determining the roles that individual HDACs play in cognitive function. Here, we investigate the role of HDAC4 in long-term memory formation in Drosophila. We show that overexpression of HDAC4 in the adult mushroom body, an important structure for memory formation, resulted in a specific impairment in long-term courtship memory, but had no affect on short-term memory. Overexpression of an HDAC4 catalytic mutant also abolished LTM, suggesting a mode of action independent of catalytic activity. We found that overexpression of HDAC4 resulted in a redistribution of the transcription factor MEF2 from a relatively uniform distribution through the nucleus into punctate nuclear bodies, where it colocalized with HDAC4. As MEF2 has also been implicated in regulation of long-term memory, these data suggest that the repressive effects of HDAC4 on long-term memory may be through interaction with MEF2. In the same genetic background, we also found that RNAi-mediated knockdown of HDAC4 impairs long-term memory, therefore we demonstrate that HDAC4 is not only a repressor of long-term memory, but also modulates normal memory formation. PMID:24349558

Both mineralocorticoid and glucocorticoid receptors regulate emotional memory in mice.

PubMed

Zhou, Ming; Bakker, Eveline H M; Velzing, Els H; Berger, Stefan; Oitzl, Melly; Joëls, Marian; Krugers, Harm J

2010-11-01

Corticosteroid hormones are thought to promote optimal behavioral adaptation under fearful conditions, primarily via glucocorticoid receptors (GRs). Here, we examined - using pharmacological and genetic approaches in mice - if mineralocorticoid receptors (MRs) also play a role in fearful memory formation. As expected, administration of the GR-antagonist RU38486 prior to training in a fear conditioning paradigm impaired contextual memory when tested 24 (but not when tested 3) h after training. Tone-cue memory was enhanced by RU38486 when tested at 4 (but not 25) h after training. Interestingly, pre (but not post)-training administration of MR antagonist spironolactone impaired contextual memory, both at 3 and 24h after training. Similar effects were also found in forebrain-specific MR knockout mice. Spironolactone also impaired tone-cue memory, but only at 4h after training. These results reveal that - in addition to GRs - MRs also play a critical role in establishing fear memories, particularly in the early phase of memory formation. Copyright © 2010 Elsevier Inc. All rights reserved.