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Sample records for fear memory consolidation

  1. Sleep supports cued fear extinction memory consolidation independent of circadian phase.

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    Melo, Irene; Ehrlich, Ingrid

    2016-07-01

    Sleep promotes memory, particularly for declarative learning. However, its role in non-declarative, emotional memories is less well understood. Some studies suggest that sleep may influence fear-related memories, and thus may be an important factor determining the outcome of treatments for emotional disorders such as post-traumatic stress disorder. Here, we investigated the effect of sleep deprivation and time of day on fear extinction memory consolidation. Mice were subjected to a cued Pavlovian fear and extinction paradigm at the beginning of their resting or active phase. Immediate post-extinction learning sleep deprivation for 5h compromised extinction memory when tested 24h after learning. Context-dependent extinction memory recall was completely prevented by sleep-manipulation during the resting phase, while impairment was milder during the active phase and extinction memory retained its context-specificity. Importantly, control experiments excluded confounding factors such as differences in baseline locomotion, fear generalization and stress hormone levels. Together, our findings indicate that post-learning sleep supports cued fear extinction memory consolidation in both circadian phases. The lack of correlation between memory efficacy and sleep time suggests that extinction memory may be influenced by specific sleep events in the early consolidation period. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Fear memory consolidation in sleep requires protein kinase A.

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    Cho, Jiyeon; Sypniewski, Krzysztof A; Arai, Shoko; Yamada, Kazuo; Ogawa, Sonoko; Pavlides, Constantine

    2018-05-01

    It is well established that protein kinase A (PKA) is involved in hippocampal dependent memory consolidation. Sleep is also known to play an important role in this process. However, whether sleep-dependent memory consolidation involves PKA activation has not been clearly determined. Using behavioral observation, animals were categorized into sleep and awake groups. We show that intrahippocampal injections of the PKA inhibitor Rp-cAMPs in post-contextual fear conditioning sleep produced a suppression of long-term fear memory, while injections of Rp-cAMPs during an awake state, at a similar time point, had no effect. In contrast, injections of the PKA activator Sp-cAMPs in awake state, rescued sleep deprivation-induced memory impairments. These results suggest that following learning, PKA activation specifically in sleep is required for the consolidation of long-term memory. © 2018 Cho et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep

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    Datta, Subimal; O'Malley, Matthew W .

    2013-01-01

    Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction. PMID:23467372

  4. The role of sleep and sleep deprivation in consolidating fear memories.

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    Menz, M M; Rihm, J S; Salari, N; Born, J; Kalisch, R; Pape, H C; Marshall, L; Büchel, C

    2013-07-15

    Sleep, in particular REM sleep, has been shown to improve the consolidation of emotional memories. Here, we investigated the role of sleep and sleep deprivation on the consolidation of fear memories and underlying neuronal mechanisms. We employed a Pavlovian fear conditioning paradigm either followed by a night of polysomnographically monitored sleep, or wakefulness in forty healthy participants. Recall of learned fear was better after sleep, as indicated by stronger explicitly perceived anxiety and autonomous nervous responses. These effects were positively correlated with the preceding time spent in REM sleep and paralleled by activation of the basolateral amygdala. These findings suggest REM sleep-associated consolidation of fear memory in the human amygdala. In view of the critical participation of fear learning mechanisms in the etiology of anxiety and post-traumatic stress disorder, deprivation of REM sleep after exposure to distressing events is an interesting target for further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Differential Recruitment of Auditory Cortices in the Consolidation of Recent Auditory Fearful Memories.

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    Cambiaghi, Marco; Grosso, Anna; Renna, Annamaria; Sacchetti, Benedetto

    2016-08-17

    Memories of frightening events require a protracted consolidation process. Sensory cortex, such as the auditory cortex, is involved in the formation of fearful memories with a more complex sensory stimulus pattern. It remains controversial, however, whether the auditory cortex is also required for fearful memories related to simple sensory stimuli. In the present study, we found that, 1 d after training, the temporary inactivation of either the most anterior region of the auditory cortex, including the primary (Te1) cortex, or the most posterior region, which included the secondary (Te2) component, did not affect the retention of recent memories, which is consistent with the current literature. However, at this time point, the inactivation of the entire auditory cortices completely prevented the formation of new memories. Amnesia was site specific and was not due to auditory stimuli perception or processing and strictly related to the interference with memory consolidation processes. Strikingly, at a late time interval 4 d after training, blocking the posterior part (encompassing the Te2) alone impaired memory retention, whereas the inactivation of the anterior part (encompassing the Te1) left memory unaffected. Together, these data show that the auditory cortex is necessary for the consolidation of auditory fearful memories related to simple tones in rats. Moreover, these results suggest that, at early time intervals, memory information is processed in a distributed network composed of both the anterior and the posterior auditory cortical regions, whereas, at late time intervals, memory processing is concentrated in the most posterior part containing the Te2 region. Memories of threatening experiences undergo a prolonged process of "consolidation" to be maintained for a long time. The dynamic of fearful memory consolidation is poorly understood. Here, we show that 1 d after learning, memory is processed in a distributed network composed of both primary Te1 and

  6. Reversible Inactivation of the Higher Order Auditory Cortex during Fear Memory Consolidation Prevents Memory-Related Activity in the Basolateral Amygdala during Remote Memory Retrieval.

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    Cambiaghi, Marco; Renna, Annamaria; Milano, Luisella; Sacchetti, Benedetto

    2017-01-01

    Recent findings have shown that the auditory cortex, and specifically the higher order Te2 area, is necessary for the consolidation of long-term fearful memories and that it interacts with the amygdala during the retrieval of long-term fearful memories. Here, we tested whether the reversible blockade of Te2 during memory consolidation may affect the activity changes occurring in the amygdala during the retrieval of fearful memories. To address this issue, we blocked Te2 in a reversible manner during memory consolidation processes. After 4 weeks, we assessed the activity of Te2 and individual nuclei of the amygdala during the retrieval of long-term memories. Rats in which Te2 was inactivated upon memory encoding showed a decreased freezing and failed to show Te2-to-basolateral amygdala (BLA) synchrony during memory retrieval. In addition, the expression of the immediate early gene zif268 in the lateral, basal and central amygdala nuclei did not show memory-related enhancement. As all sites were intact upon memory retrieval, we propose that the auditory cortex represents a key node in the consolidation of fear memories and it is essential for amygdala nuclei to support memory retrieval process.

  7. Effects of the swimming exercise on the consolidation and persistence of auditory and contextual fear memory.

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    Faria, Rodolfo Souza; Gutierres, Luís Felipe Soares; Sobrinho, Fernando César Faria; Miranda, Iris do Vale; Reis, Júlia Dos; Dias, Elayne Vieira; Sartori, Cesar Renato; Moreira, Dalmo Antonio Ribeiro

    2016-08-15

    Exposure to negative environmental events triggers defensive behavior and leads to the formation of aversive associative memory. Cellular and molecular changes in the central nervous system underlie this memory formation, as well as the associated behavioral changes. In general, memory process is established in distinct phases such as acquisition, consolidation, evocation, persistence, and extinction of the acquired information. After exposure to a particular event, early changes in involved neural circuits support the memory consolidation, which corresponds to the short-term memory. Re-exposure to previously memorized events evokes the original memory, a process that is considered essential for the reactivation and consequent persistence of memory, ensuring that long-term memory is established. Different environmental stimuli may modulate the memory formation process, as well as their distinct phases. Among the different environmental stimuli able of modulating memory formation is the physical exercise which is a potent modulator of neuronal activity. There are many studies showing that physical exercise modulates learning and memory processes, mainly in the consolidation phase of the explicit memory. However, there are few reports in the literature regarding the role of physical exercise in implicit aversive associative memory, especially at the persistence phase. Thus, the present study aimed to investigate the relationship between swimming exercise and the consolidation and persistence of contextual and auditory-cued fear memory. Male Wistar rats were submitted to sessions of swimming exercise five times a week, over six weeks. After that, the rats were submitted to classical aversive conditioning training by a pairing tone/foot shock paradigm. Finally, rats were evaluated for consolidation and persistence of fear memory to both auditory and contextual cues. Our results demonstrate that classical aversive conditioning with tone/foot shock pairing induced

  8. Hippocampal Administration of Levothyroxine Impairs Contextual Fear Memory Consolidation in Rats.

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    Yu, Dafu; Zhou, Heng; Zou, Lin; Jiang, Yong; Wu, Xiaoqun; Jiang, Lizhu; Zhou, Qixin; Yang, Yuexiong; Xu, Lin; Mao, Rongrong

    2017-01-01

    Thyroid hormone (TH) receptors are highly distributed in the hippocampus, which plays a vital role in memory processes. However, how THs are involved in the different stages of memory process is little known. Herein, we used hippocampus dependent contextual fear conditioning to address the effects of hippocampal THs on the different stages of fear memory. First, we found that a single systemic levothyroxine (LT 4 ) administration increased the level of free triiodothyronine (FT 3 ) and free tetraiodothyroxine (FT 4 ) not only in serum but also in hippocampus. In addition, a single systemic LT 4 administration immediately after fear conditioning significantly impaired fear memory. These results indicated the important role of hippocampal THs in fear memory process. To further confirm the effects of hippocampal THs on the different stages of fear memory, LT 4 (0.4 μg/μl, 1 μl/side) was injected bilaterally into hippocampus. Rats given LT 4 into hippocampus before training or tests had no effect on the acquisition or retrieval of fear memory, however rats given LT 4 into hippocampus either immediately or 2 h after training showed being significantly impaired fear memory, which demonstrated LT 4 administration into hippocampus impairs the consolidation but has no effect on the acquisition and retrieval of fear memory. Furthermore, hippocampal injection of LT 4 did not affect rats' locomotor activity, thigmotaxis and THs level in prefrontal cortex (PFC) and serum. These findings may have important implications for understanding mechanisms underlying contribution of THs to memory disorders.

  9. Oxytocin receptor antagonist atosiban impairs consolidation, but not reconsolidation of contextual fear memory in rats.

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    Abdullahi, Payman Rasise; Eskandarian, Sharaf; Ghanbari, Ali; Rashidy-Pour, Ali

    2018-05-23

    There is increasing evidence that oxytocin is involved in learning and memory process. This study investigated the effects of blockade of oxytocin receptors using the selective oxytocin receptor antagonist atosiban (ATO) on contextual fear memory consolidation and reconsolidation in male rats. Post-training injections of different doses of ATO (1, 10, 100 or 1000 µg/kg) impaired the 48 h retention performance in a dose-dependent manner. The same doses of ATO following memory reactivation did not impair subsequent expression of contextual fear memories which formed under low or high shock intensities and tested 24 h or one week following memory reactivation. Also, no effect was found when ATO was administrated in the absence of memory reactivation. Our finding is the first report that indicates endogenous oxytocin released during training play an important role in the consolidation, but not reconsolidation of contextual fear memory in rats. Copyright © 2018. Published by Elsevier B.V.

  10. Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala.

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    Melissa S Monsey

    Full Text Available Epigenetic mechanisms, including histone acetylation and DNA methylation, have been widely implicated in hippocampal-dependent learning paradigms. Here, we have examined the role of epigenetic alterations in amygdala-dependent auditory Pavlovian fear conditioning and associated synaptic plasticity in the lateral nucleus of the amygdala (LA in the rat. Using Western blotting, we first show that auditory fear conditioning is associated with an increase in histone H3 acetylation and DNMT3A expression in the LA, and that training-related alterations in histone acetylation and DNMT3A expression in the LA are downstream of ERK/MAPK signaling. Next, we show that intra-LA infusion of the histone deacetylase (HDAC inhibitor TSA increases H3 acetylation and enhances fear memory consolidation; that is, long-term memory (LTM is enhanced, while short-term memory (STM is unaffected. Conversely, intra-LA infusion of the DNA methyltransferase (DNMT inhibitor 5-AZA impairs fear memory consolidation. Further, intra-LA infusion of 5-AZA was observed to impair training-related increases in H3 acetylation, and pre-treatment with TSA was observed to rescue the memory consolidation deficit induced by 5-AZA. In our final series of experiments, we show that bath application of either 5-AZA or TSA to amygdala slices results in significant impairment or enhancement, respectively, of long-term potentiation (LTP at both thalamic and cortical inputs to the LA. Further, the deficit in LTP following treatment with 5-AZA was observed to be rescued at both inputs by co-application of TSA. Collectively, these findings provide strong support that histone acetylation and DNA methylation work in concert to regulate memory consolidation of auditory fear conditioning and associated synaptic plasticity in the LA.

  11. Reduced Consolidation, Reinstatement, and Renewal of Conditioned Fear Memory by Repetitive Treatment of Radix Polygalae in Mice

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    Jung-Won Shin

    2017-05-01

    Full Text Available The therapeutic goal for the treatment of posttraumatic stress disorder (PTSD is to promote extinction and to prevent the relapse of fearful memories. Research has identified pharmacological treatments that may regulate the formation and extinction of fear memories, but not many reagents that block the relapse of extinguished fear are known. Radix Polygalae (RP is an Asian herb used for sedation, and its ingredients have anxiolytic and antidepressant properties. As various neurological effects have been identified, we tested whether RP affects the relapse of fear. Freezing in response to a conditioned context and cues was used to measure the effects of RP in mice. In cohort 1 (n = 30, consolidation, extinction, and reinstatement were tested during the course of 18 days of treatment. In cohort 2 (n = 30, consolidation, extinction, and renewal were tested during 10 days of treatment. The consolidation, extinction, reinstatement, and possibly the renewal of context-induced freezing were inhibited due to the administration of RP in animal subjects. However, the effects of RP on the freezing responses of subjects elicited by conditioned auditory cues were less obvious. Because it effectively suppresses the consolidation of fear memories, RP may be used for primary and secondary prevention of symptoms in PTSD patients. Additionally, because it effectively suppresses the reinstatement and renewal of fear memories, RP may be applied for the prevention of fear relapse in PTSD patients who have undergone exposure therapy.

  12. Stress Enables Reinforcement-Elicited Serotonergic Consolidation of Fear Memory.

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    Baratta, Michael V; Kodandaramaiah, Suhasa B; Monahan, Patrick E; Yao, Junmei; Weber, Michael D; Lin, Pei-Ann; Gisabella, Barbara; Petrossian, Natalie; Amat, Jose; Kim, Kyungman; Yang, Aimei; Forest, Craig R; Boyden, Edward S; Goosens, Ki A

    2016-05-15

    Prior exposure to stress is a risk factor for developing posttraumatic stress disorder (PTSD) in response to trauma, yet the mechanisms by which this occurs are unclear. Using a rodent model of stress-based susceptibility to PTSD, we investigated the role of serotonin in this phenomenon. Adult mice were exposed to repeated immobilization stress or handling, and the role of serotonin in subsequent fear learning was assessed using pharmacologic manipulation and western blot detection of serotonin receptors, measurements of serotonin, high-speed optogenetic silencing, and behavior. Both dorsal raphe serotonergic activity during aversive reinforcement and amygdala serotonin 2C receptor (5-HT2CR) activity during memory consolidation were necessary for stress enhancement of fear memory, but neither process affected fear memory in unstressed mice. Additionally, prior stress increased amygdala sensitivity to serotonin by promoting surface expression of 5-HT2CR without affecting tissue levels of serotonin in the amygdala. We also showed that the serotonin that drives stress enhancement of associative cued fear memory can arise from paired or unpaired footshock, an effect not predicted by theoretical models of associative learning. Stress bolsters the consequences of aversive reinforcement, not by simply enhancing the neurobiological signals used to encode fear in unstressed animals, but rather by engaging distinct mechanistic pathways. These results reveal that predictions from classical associative learning models do not always hold for stressed animals and suggest that 5-HT2CR blockade may represent a promising therapeutic target for psychiatric disorders characterized by excessive fear responses such as that observed in PTSD. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Impairment of fear memory consolidation in maternally stressed male mouse offspring: evidence for nongenomic glucocorticoid action on the amygdala.

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    Lee, Eun Jeong; Son, Gi Hoon; Chung, Sooyoung; Lee, Sukwon; Kim, Jeongyeon; Choi, Sukwoo; Kim, Kyungjin

    2011-05-11

    The environment in early life elicits profound effects on fetal brain development that can extend into adulthood. However, the long-lasting impact of maternal stress on emotional learning remains largely unknown. Here, we focus on amygdala-related learning processes in maternally stressed mice. In these mice, fear memory consolidation and certain related signaling cascades were significantly impaired, though innate fear, fear memory acquisition, and synaptic NMDA receptor expression in the amygdala were unaltered. In accordance with these findings, maintenance of long-term potentiation (LTP) at amygdala synapses, but not its induction, was significantly impaired in the maternally stressed animals. Interestingly, amygdala glucocorticoid receptor expression was reduced in the maternally stressed mice, and administration of glucocorticoids (GCs) immediately after fear conditioning and LTP induction restored memory consolidation and LTP maintenance, respectively, suggesting that a weakening of GC signaling was responsible for the observed impairment. Furthermore, microinfusion of a membrane-impermeable form of GC (BSA-conjugated GC) into the amygdala mimicked the restorative effects of GC, indicating that a nongenomic activity of GC mediates the restorative effect. Together, these findings suggest that prenatal stress induces long-term dysregulation of nongenomic GC action in the amygdala of adult offspring, resulting in the impairment of fear memory consolidation. Since modulation of amygdala activity is known to alter the consolidation of emotionally influenced memories allocated in other brain regions, the nongenomic action of GC on the amygdala shown herein may also participate in the amygdala-dependent modulation of memory consolidation.

  14. Systemic inhibition of mTOR kinase via rapamycin disrupts consolidation and reconsolidation of auditory fear memory.

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    Mac Callum, Phillip E; Hebert, Mark; Adamec, Robert E; Blundell, Jacqueline

    2014-07-01

    The mammalian target of rapamycin (mTOR) kinase is a critical regulator of mRNA translation and is known to be involved in various long lasting forms of synaptic and behavioural plasticity. However, information concerning the temporal pattern of mTOR activation and susceptibility to pharmacological intervention during both consolidation and reconsolidation of long-term memory (LTM) remains scant. Male C57BL/6 mice were injected systemically with rapamycin at various time points following conditioning or retrieval in an auditory fear conditioning paradigm, and compared to vehicle (and/or anisomycin) controls for subsequent memory recall. Systemic blockade of mTOR with rapamycin immediately or 12h after training or reactivation impairs both consolidation and reconsolidation of an auditory fear memory. Further behavioural analysis revealed that the enduring effects of rapamycin on reconsolidation are dependent upon reactivation of the memory trace. Rapamycin, however, has no effect on short-term memory or the ability to retrieve an established fear memory. Collectively, our data suggest that biphasic mTOR signalling is essential for both consolidation and reconsolidation-like activities that contribute to the formation, re-stabilization, and persistence of long term auditory-fear memories, while not influencing other aspects of the memory trace. These findings also provide evidence for a cogent treatment model for reducing the emotional strength of established, traumatic memories analogous to those observed in acquired anxiety disorders such as posttraumatic stress disorder (PTSD) and specific phobias, through pharmacologic blockade of mTOR using systemic rapamycin following reactivation. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. A role for nitric oxide-driven retrograde signaling in the consolidation of a fear memory

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    Kathie A Overeem

    2010-02-01

    Full Text Available In both invertebrate and vertebrate models of synaptic plasticity, signaling via the putative “retrograde messenger” nitric oxide (NO has been hypothesized to serve as a critical link between functional and structural alterations at pre- and postsynaptic sites. However, while in vitro models of synaptic plasticity have consistently implicated NO signaling in linking postsynaptic induction mechanisms with accompanying presynaptic changes, a convincing role of such “retrograde signaling” in mammalian memory formation has remained elusive. Using auditory Pavlovian fear conditioning, we show that synaptic plasticity and NO signaling in the lateral nucleus of the amygdala (LA regulate the expression of the ERK-driven immediate early gene early growth response gene I (EGR-1 in regions of the auditory thalamus that are presynaptic to the LA. Further, antisense knockdown of EGR-1 in the auditory thalamus impairs both fear memory consolidation and the training-induced elevation of two presynaptically localized proteins in the LA. These findings indicate that synaptic plasticity and NO signaling in the LA during auditory fear conditioning promote alterations in ERK-driven gene expression in auditory thalamic neurons that are required for both fear memory consolidation as well as presynaptic correlates of fear memory formation in the LA, and provide general support for a role of NO as a “retrograde signal” in mammalian memory formation.

  16. Effects of sleep on memory for conditioned fear and fear extinction

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    Pace-Schott, Edward F.; Germain, Anne; Milad, Mohammed R.

    2015-01-01

    Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and neural circuitry associated with fear conditioning, extinction learning and extinction memory in the rodent and human, interactions of sleep with th...

  17. Sleep deprivation affects fear memory consolidation: bi-stable amygdala connectivity with insula and ventromedial prefrontal cortex.

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    Feng, Pan; Becker, Benjamin; Zheng, Yong; Feng, Tingyong

    2018-02-01

    Sleep plays an important role for successful fear memory consolidation. Growing evidence suggests that sleep disturbances might contribute to the development and the maintenance of posttraumatic stress disorder (PTSD), a disorders characterized by dysregulations in fear learning mechanisms, as well as exaggerated arousal and salience processing. Against this background, the present study examined the effects of sleep deprivation (SD) on the acquisition of fear and the subsequent neural consolidation. To this end, the present study assessed fear acquisition and associated changes in fMRI-based amygdala-functional connectivity following 24 h of SD. Relative to non-sleep deprived controls, SD subjects demonstrated increased fear ratings and skin conductance responses (SCR) during fear acquisition. During fear consolidation SD inhibited increased amygdala-ventromendial prefrontal cortex (vmPFC) connectivity and concomitantly increased changes in amygdala-insula connectivity. Importantly, whereas in controls fear indices during acquisition were negatively associated with amygdala-vmPFC connectivity during consolidation, fear indices were positively associated with amygdala-insula coupling following SD. Together the findings suggest that SD may interfere with vmPFC control of the amygdala and increase bottom-up arousal signaling in the amygdala-insula pathway during fear consolidation, which might mediate the negative impact of sleep disturbances on PSTD symptomatology.

  18. Chronic corticosterone exposure persistently elevates the expression of memory-related genes in the lateral amygdala and enhances the consolidation of a Pavlovian fear memory.

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    Melissa S Monsey

    Full Text Available Chronic exposure to stress has been widely implicated in the development of anxiety disorders, yet relatively little is known about the long-term effects of chronic stress on amygdala-dependent memory formation. Here, we examined the effects of a history of chronic exposure to the stress-associated adrenal steroid corticosterone (CORT on the consolidation of a fear memory and the expression of memory-related immediate early genes (IEGs in the lateral nucleus of the amygdala (LA. Rats received chronic exposure to CORT (50 μg/ml in their drinking water for 2 weeks and were then titrated off the CORT for an additional 6 days followed by a 2 week 'wash-out' period consisting of access to plain water. Rats were then either sacrificed to examine the expression of memory-related IEG expression in the LA or given auditory Pavlovian fear conditioning. We show that chronic exposure to CORT leads to a persistent elevation in the expression of the IEGs Arc/Arg3.1 and Egr-1 in the LA. Further, we show that rats with a history of chronic CORT exposure exhibit enhanced consolidation of a fear memory; short-term memory (STM is not affected, while long-term memory (LTM is significantly enhanced. Treatment with the selective serotonin reuptake inhibitor (SSRI fluoxetine following the chronic CORT exposure period was observed to effectively reverse both the persistent CORT-related increases in memory-related IEG expression in the LA and the CORT-related enhancement in fear memory consolidation. Our findings suggest that chronic exposure to CORT can regulate memory-related IEG expression and fear memory consolidation processes in the LA in a long-lasting manner and that treatment with fluoxetine can reverse these effects.

  19. Chronic corticosterone exposure persistently elevates the expression of memory-related genes in the lateral amygdala and enhances the consolidation of a Pavlovian fear memory.

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    Monsey, Melissa S; Boyle, Lara M; Zhang, Melinda L; Nguyen, Caroline P; Kronman, Hope G; Ota, Kristie T; Duman, Ronald S; Taylor, Jane R; Schafe, Glenn E

    2014-01-01

    Chronic exposure to stress has been widely implicated in the development of anxiety disorders, yet relatively little is known about the long-term effects of chronic stress on amygdala-dependent memory formation. Here, we examined the effects of a history of chronic exposure to the stress-associated adrenal steroid corticosterone (CORT) on the consolidation of a fear memory and the expression of memory-related immediate early genes (IEGs) in the lateral nucleus of the amygdala (LA). Rats received chronic exposure to CORT (50 μg/ml) in their drinking water for 2 weeks and were then titrated off the CORT for an additional 6 days followed by a 2 week 'wash-out' period consisting of access to plain water. Rats were then either sacrificed to examine the expression of memory-related IEG expression in the LA or given auditory Pavlovian fear conditioning. We show that chronic exposure to CORT leads to a persistent elevation in the expression of the IEGs Arc/Arg3.1 and Egr-1 in the LA. Further, we show that rats with a history of chronic CORT exposure exhibit enhanced consolidation of a fear memory; short-term memory (STM) is not affected, while long-term memory (LTM) is significantly enhanced. Treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine following the chronic CORT exposure period was observed to effectively reverse both the persistent CORT-related increases in memory-related IEG expression in the LA and the CORT-related enhancement in fear memory consolidation. Our findings suggest that chronic exposure to CORT can regulate memory-related IEG expression and fear memory consolidation processes in the LA in a long-lasting manner and that treatment with fluoxetine can reverse these effects.

  20. Acute nicotine disrupts consolidation of contextual fear extinction and alters long-term memory-associated hippocampal kinase activity.

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    Kutlu, Munir Gunes; Garrett, Brendan; Gadiwalla, Sana; Tumolo, Jessica M; Gould, Thomas J

    2017-11-01

    Previous research has shown that acute nicotine, an agonist of nAChRs, impaired fear extinction. However, the effects of acute nicotine on consolidation of contextual fear extinction memories and associated cell signaling cascades are unknown. Therefore, we examined the effects of acute nicotine injections before (pre-extinction) and after (post-extinction) contextual fear extinction on behavior and the phosphorylation of dorsal and ventral hippocampal ERK1/2 and JNK1 and protein levels on the 1st and 3rd day of extinction. Our results showed that acute nicotine administered prior to extinction sessions downregulated the phosphorylated forms of ERK1/2 in the ventral hippocampus, but not dorsal hippocampus, and JNK1 in both dorsal and ventral hippocampus on the 3rd extinction day. These effects were absent on the 1st day of extinction. We also showed that acute nicotine administered immediately and 30 min, but not 6 h, following extinction impaired contextual fear extinction suggesting that acute nicotine disrupts consolidation of contextual fear extinction memories. Finally, acute nicotine injections immediately after extinction sessions upregulated the phosphorylated forms of ERK1/2 in the ventral hippocampus, but did not affect JNK1. These results show that acute nicotine impairs contextual fear extinction potentially by altering molecular processes responsible for the consolidation of extinction memories. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Functional Integrity of the Retrosplenial Cortex Is Essential for Rapid Consolidation and Recall of Fear Memory

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    Katche, Cynthia; Dorman, Guido; Slipczuk, Leandro; Cammarota, Martin; Medina, Jorge H.

    2013-01-01

    Memory storage is a temporally graded process involving different phases and different structures in the mammalian brain. Cortical plasticity is essential to store stable memories, but little is known regarding its involvement in memory processing. Here we show that fear memory consolidation requires early post-training macromolecular synthesis in…

  2. Effects of sleep on memory for conditioned fear and fear extinction

    Science.gov (United States)

    Pace-Schott, Edward F.; Germain, Anne; Milad, Mohammed R.

    2015-01-01

    Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and neural circuitry associated with fear conditioning, extinction learning and extinction memory in the rodent and human, interactions of sleep with these processes will be examined. Animal and human studies suggest that sleep can serve to consolidate both fear and extinction memory. In humans, sleep also promotes generalization of extinction memory. Time-of-day effects on extinction learning and generalization are also seen. REM may be a sleep stage of particular importance for the consolidation of both fear and extinction memory as evidenced by selective REM deprivation experiments. REM sleep is accompanied by selective activation of the same limbic structures implicated in the learning and memory of fear and extinction. Preliminary evidence also suggests extinction learning can take place during slow wave sleep. Study of low-level processes such as conditioning, extinction and habituation may allow sleep effects on emotional memory to be identified and inform study of sleep’s effects on more complex, emotionally salient declarative memories. Anxiety disorders are marked by impairments of both sleep and extinction memory. Improving sleep quality may ameliorate anxiety disorders by strengthening naturally acquired extinction. Strategically timed sleep may be used to enhance treatment of anxiety by strengthening therapeutic extinction learned via exposure therapy. PMID:25894546

  3. Effects of sleep on memory for conditioned fear and fear extinction.

    Science.gov (United States)

    Pace-Schott, Edward F; Germain, Anne; Milad, Mohammed R

    2015-07-01

    Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and neural circuitry associated with fear conditioning, extinction learning, and extinction memory in the rodent and human, interactions of sleep with these processes will be examined. Animal and human studies suggest that sleep can serve to consolidate both fear and extinction memory. In humans, sleep also promotes generalization of extinction memory. Time-of-day effects on extinction learning and generalization are also seen. Rapid eye movement (REM) may be a sleep stage of particular importance for the consolidation of both fear and extinction memory as evidenced by selective REM deprivation experiments. REM sleep is accompanied by selective activation of the same limbic structures implicated in the learning and memory of fear and extinction. Preliminary evidence also suggests extinction learning can take place during slow wave sleep. Study of low-level processes such as conditioning, extinction, and habituation may allow sleep effects on emotional memory to be identified and inform study of sleep's effects on more complex, emotionally salient declarative memories. Anxiety disorders are marked by impairments of both sleep and extinction memory. Improving sleep quality may ameliorate anxiety disorders by strengthening naturally acquired extinction. Strategically timed sleep may be used to enhance treatment of anxiety by strengthening therapeutic extinction learned via exposure therapy. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  4. Memory suppression trades prolonged fear and sleep-dependent fear plasticity for the avoidance of current fear

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    Kuriyama, Kenichi; Honma, Motoyasu; Yoshiike, Takuya; Kim, Yoshiharu

    2013-07-01

    Sleep deprivation immediately following an aversive event reduces fear by preventing memory consolidation during homeostatic sleep. This suggests that acute insomnia might act prophylactically against the development of posttraumatic stress disorder (PTSD) even though it is also a possible risk factor for PTSD. We examined total sleep deprivation and memory suppression to evaluate the effects of these interventions on subsequent aversive memory formation and fear conditioning. Active suppression of aversive memory impaired retention of event memory. However, although the remembered fear was more reduced in sleep-deprived than sleep-control subjects, suppressed fear increased, and seemed to abandon the sleep-dependent plasticity of fear. Active memory suppression, which provides a psychological model for Freud's ego defense mechanism, enhances fear and casts doubt on the potential of acute insomnia as a prophylactic measure against PTSD. Our findings bring into question the role of sleep in aversive-memory consolidation in clinical PTSD pathophysiology.

  5. Fragmentation of Rapid Eye Movement and Nonrapid Eye Movement Sleep without Total Sleep Loss Impairs Hippocampus-Dependent Fear Memory Consolidation.

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    Lee, Michael L; Katsuyama, Ângela M; Duge, Leanne S; Sriram, Chaitra; Krushelnytskyy, Mykhaylo; Kim, Jeansok J; de la Iglesia, Horacio O

    2016-11-01

    Sleep is important for consolidation of hippocampus-dependent memories. It is hypothesized that the temporal sequence of nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep is critical for the weakening of nonadaptive memories and the subsequent transfer of memories temporarily stored in the hippocampus to more permanent memories in the neocortex. A great body of evidence supporting this hypothesis relies on behavioral, pharmacological, neural, and/or genetic manipulations that induce sleep deprivation or stage-specific sleep deprivation. We exploit an experimental model of circadian desynchrony in which intact animals are not deprived of any sleep stage but show fragmentation of REM and NREM sleep within nonfragmented sleep bouts. We test the hypothesis that the shortening of NREM and REM sleep durations post-training will impair memory consolidation irrespective of total sleep duration. When circadian-desynchronized animals are trained in a hippocampus-dependent contextual fear-conditioning task they show normal short-term memory but impaired long-term memory consolidation. This impairment in memory consolidation is positively associated with the post-training fragmentation of REM and NREM sleep but is not significantly associated with the fragmentation of total sleep or the total amount of delta activity. We also show that the sleep stage fragmentation resulting from circadian desynchrony has no effect on hippocampus-dependent spatial memory and no effect on hippocampus-independent cued fear-conditioning memory. Our findings in an intact animal model, in which sleep deprivation is not a confounding factor, support the hypothesis that the stereotypic sequence and duration of sleep stages play a specific role in long-term hippocampus-dependent fear memory consolidation. © 2016 Associated Professional Sleep Societies, LLC.

  6. Modulation of the consolidation and reconsolidation of fear memory by three different serotonin receptors in hippocampus.

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    Schmidt, S D; Furini, C R G; Zinn, C G; Cavalcante, L E; Ferreira, F F; Behling, J A K; Myskiw, J C; Izquierdo, I

    2017-07-01

    The process of memory formation is complex and highly dynamic. During learning, the newly acquired information is found in a fragile and labile state. Through a process known as consolidation, which requires specific mechanisms such as protein synthesis, the memory trace is stored and stabilized. It is known that when a consolidated memory is recalled, it again becomes labile and sensitive to disruption. To be maintained, this memory must undergo an additional process of restabilization called reconsolidation, which requires another phase of protein synthesis. Memory consolidation has been studied for more than a century, while the molecular mechanisms underlying the memory reconsolidation are starting to be elucidated. For this, is essential compare the participation of important neurotransmitters and its receptors in both processes in brain regions that play a central role in the fear response learning. With focus on serotonin (5-HT), a well characterized neurotransmitter that has been strongly implicated in learning and memory, we investigated, in the CA1 region of the dorsal hippocampus, whether the latest discovered serotonergic receptors, 5-HT 5A , 5-HT 6 and 5-HT 7 , are involved in the consolidation and reconsolidation of contextual fear conditioning (CFC) memory. For this, male rats with cannulae implanted in the CA1 region received immediately after the training or reactivation session, or 3h post-reactivation of the CFC, infusions of agonists or antagonists of the 5-HT 5A , 5-HT 6 and 5-HT 7 receptors. After 24h, animals were subjected to a 3-min retention test. The results indicated that in the CA1 region of the hippocampus the 5-HT 5A , 5-HT 6 and 5-HT 7 serotonin receptors participate in the reconsolidation of the CFC memory 3h post-reactivation. Additionally, the results suggest that the 5-HT 6 and 5-HT 7 receptors also participate in the consolidation of the CFC memory. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Facilitating influence of stress on the consolidation of fear memory induced by a weak training: reversal by midazolam pretreatment.

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    Maldonado, Noelia Martina; Martijena, Irene Delia; Molina, Víctor Alejandro

    2011-11-20

    It is well known that an emotionally arousing experience usually results in a robust and persistent memory trace. The present study explored the potential mechanisms involved in the influence of stress on the consolidation of a contextual fear memory in animals subjected to a weak fear training protocol, and whether pretreatment with intra-basolateral amygdala or systemic administration of midazolam (MDZ) prevents the potential stress-induced influence on fear memory formation. A previous restraint session facilitated fear retention, this effect was not due to a sensitized effect of restraint on the footshock experience. MDZ, both systemically or intra-basolateral amygdala infusion prior to the restraint, attenuated the stress-induced promoting influence on fear memory formation. In addition, stress exposure activated the ERK1/2 pathway in basolateral amygdala (BLA) after the weak training procedure but not after the immediate footshock protocol. Similar to our behavioral findings, MDZ attenuated stress-induced elevation of phospho-ERK2 (p-ERK2) in BLA following the acquisition session. Given that the activation of ERK1/2 pathway is essential for associative learning, we propose that stress-induced facilitation of p-ERK2 in BLA is an important mechanism for the promoting influence of stress on the consolidation of contextual fear memory. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation within the Amygdala.

    Science.gov (United States)

    Aubry, Antonio V; Serrano, Peter A; Burghardt, Nesha S

    2016-01-01

    Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by which stress affects the amygdala and amygdala-dependent fear memories remain unclear. Here we review the literature on the enhancing effects of acute and chronic stress on the acquisition and/or consolidation of a fear memory, as measured by auditory Pavlovian fear conditioning, and discuss potential mechanisms by which these changes occur in the amygdala. We hypothesize that stress-mediated activation of glucocorticoid receptors (GR) and norepinephrine release within the amygdala leads to the mobilization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors to the synapse, which underlies stress-induced increases in fear memory. We discuss the implications of this hypothesis for evaluating the effects of stress on extinction and for developing treatments for anxiety disorders. Understanding how stress-induced changes in glucocorticoid and norepinephrine signaling might converge to affect emotional learning by increasing the trafficking of AMPA receptors and enhancing amygdala excitability is a promising area for future research.

  9. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation Within the Amygdala

    Directory of Open Access Journals (Sweden)

    Antonio Aubry

    2016-10-01

    Full Text Available Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by which stress affects the amygdala and amygdala-dependent fear memories remain unclear. Here we review the literature on the enhancing effects of acute and chronic stress on the acquisition and/or consolidation of a fear memory, as measured by auditory Pavlovian fear conditioning, and discuss potential mechanisms by which these changes occur in the amygdala. We hypothesize that stress-mediated activation of glucocorticoid receptors (GR and norepinephrine release within the amygdala leads to the mobilization of AMPA receptors to the synapse, which underlies stress-induced increases in fear memory. We discuss the implications of this hypothesis for evaluating the effects of stress on extinction and for developing treatments for anxiety disorders. Understanding how stress-induced changes in glucocorticoid and norepinephrine signaling might converge to affect emotional learning by increasing the trafficking of AMPA receptors and enhancing amygdala excitability is a promising area for future research.

  10. Rethinking the fear circuit: the central nucleus of the amygdala is required for the acquisition, consolidation, and expression of Pavlovian fear conditioning

    DEFF Research Database (Denmark)

    Wilensky, Ann E; Schafe, Glenn E; Kristensen, Morten Pilgaard

    2006-01-01

    of the amygdala (CE), which serves as the principal output nucleus for the expression of conditioned fear responses. In the present study, we reexamined the roles of LA and CE. Specifically, we asked whether CE, like LA, might also be involved in fear learning and memory consolidation. Using functional...... inactivation methods, we first show that CE is involved not only in the expression but also the acquisition of fear conditioning. Next, we show that inhibition of protein synthesis in CE after training impairs fear memory consolidation. These findings indicate that CE is not only involved in fear expression...... but, like LA, is also involved in the learning and consolidation of pavlovian fear conditioning....

  11. Postreactivation glucocorticoids impair recall of established fear memory.

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    Cai, Wen-Hui; Blundell, Jacqueline; Han, Jie; Greene, Robert W; Powell, Craig M

    2006-09-13

    Pavlovian fear conditioning provides one of the best rodent models of acquired anxiety disorders, including posttraumatic stress disorder. Injection of a variety of drugs after training in fear-conditioning paradigms can impair consolidation of fear memories. Indeed, early clinical trials suggest that immediate administration of such drugs after a traumatic event may decrease the risk of developing posttraumatic stress disorder in humans (Pitman et al., 2002; Vaiva et al., 2003). The use of such a treatment is limited by the difficulty of treating every patient at risk and by the difficulty in predicting which patients will experience chronic adverse consequences. Recent clinical trials suggest that administration of glucocorticoids may have a beneficial effect on established posttraumatic stress disorder (Aerni et al., 2004) and specific phobia (Soravia et al., 2006). Conversely, glucocorticoid administration after training is known to enhance memory consolidation (McGaugh and Roozendaal, 2002; Roozendaal, 2002). From a clinical perspective, enhancement of a fear memory or a reactivated fear memory would not be desirable. We report here that when glucocorticoids are administered immediately after reactivation of a contextual fear memory, subsequent recall is significantly diminished. Additional experiments support the interpretation that glucocorticoids not only decrease fear memory retrieval but, in addition, augment consolidation of fear memory extinction rather than decreasing reconsolidation. These findings provide a rodent model for a potential treatment of established acquired anxiety disorders in humans, as suggested by others (Aerni et al., 2004; Schelling et al., 2004), based on a mechanism of enhanced extinction.

  12. The influence of stress on fear memory processes

    Directory of Open Access Journals (Sweden)

    I.D. Martijena

    2012-04-01

    Full Text Available It is well recognized that stressful experiences promote robust emotional memories, which are well remembered. The amygdaloid complex, principally the basolateral complex (BLA, plays a pivotal role in fear memory and in the modulation of stress-induced emotional responses. A large number of reports have revealed that GABAergic interneurons provide a powerful inhibitory control of the activity of projecting glutamatergic neurons in the BLA. Indeed, a reduced GABAergic control in the BLA is essential for the stress-induced influence on the emergence of associative fear memory and on the generation of long-term potentiation (LTP in BLA neurons. The extracellular signal-regulated kinase (ERK subfamily of the mitogen-activated protein kinase (MAPK signaling pathway in the BLA plays a central role in the consolidation process and synaptic plasticity. In support of the view that stress facilitates long-term fear memory, stressed animals exhibited a phospho-ERK2 (pERK2 increase in the BLA, suggesting the involvement of this mechanism in the promoting influence of threatening stimuli on the consolidation fear memory. Moreover, the occurrence of reactivation-induced lability is prevented when fear memory is encoded under intense stressful conditions since the memory trace remains immune to disruption after recall in previously stressed animals. Thus, the underlying mechanism in retrieval-induced instability seems not to be functional in memories formed under stress. All these findings are indicative that stress influences both the consolidation and reconsolidation fear memory processes. Thus, it seems reasonable to propose that the emotional state generated by an environmental challenge critically modulates the formation and maintenance of long-term fear memory.

  13. Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala.

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    Stehberg, Jimmy; Moraga-Amaro, Rodrigo; Salazar, Christian; Becerra, Alvaro; Echeverría, Cesar; Orellana, Juan A; Bultynck, Geert; Ponsaerts, Raf; Leybaert, Luc; Simon, Felipe; Sáez, Juan C; Retamal, Mauricio A

    2012-09-01

    Recent in vitro evidence indicates that astrocytes can modulate synaptic plasticity by releasing neuroactive substances (gliotransmitters). However, whether gliotransmitter release from astrocytes is necessary for higher brain function in vivo, particularly for memory, as well as the contribution of connexin (Cx) hemichannels to gliotransmitter release, remain elusive. Here, we microinfused into the rat basolateral amygdala (BLA) TAT-Cx43L2, a peptide that selectively inhibits Cx43-hemichannel opening while maintaining synaptic transmission or interastrocyte gap junctional communication. In vivo blockade of Cx43 hemichannels during memory consolidation induced amnesia for auditory fear conditioning, as assessed 24 h after training, without affecting short-term memory, locomotion, or shock reactivity. The amnesic effect was transitory, specific for memory consolidation, and was confirmed after microinfusion of Gap27, another Cx43-hemichannel blocker. Learning capacity was recovered after coinfusion of TAT-Cx43L2 and a mixture of putative gliotransmitters (glutamate, glutamine, lactate, d-serine, glycine, and ATP). We propose that gliotransmitter release from astrocytes through Cx43 hemichannels is necessary for fear memory consolidation at the BLA. Thus, the present study is the first to demonstrate a physiological role for astroglial Cx43 hemichannels in brain function, making these channels a novel pharmacological target for the treatment of psychiatric disorders, including post-traumatic stress disorder.

  14. The effect of left frontal transcranial direct-current stimulation on propranolol-induced fear memory acquisition and consolidation deficits.

    Science.gov (United States)

    Nasehi, Mohammad; Khani-Abyaneh, Mozhgan; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2017-07-28

    Accumulating evidence supports the efficacy of transcranial direct current stimulation (tDCS) in modulating numerous cognitive functions. Despite the fact that tDCS has been used for the enhancement of memory and cognition, very few animal studies have addressed its impact on the modulation of fear memory. This study was designed to determine whether pre/post-training frontal tDCS application would alter fear memory acquisition and/or consolidation deficits induced by propranolol in NMRI mice. Results indicated that administration of β1-adrenoceptor blocker propranolol (0.1mg/kg) impaired fear memory retrieval. Pre/post-training application of anodal tDCS when propranolol was administered prior to training reversed contextual memory retrieval whereas only the anodal application prior to training could induce the same result in the auditory test. Meanwhile, anodal stimulation had no effect on fear memories by itself. Moreover, regardless of when cathode was applied and propranolol administered, their combination restored contextual memory retrieval, while only cathodal stimulation prior to training facilitated the contextual memory retrieval. Also, auditory memory retrieval was restored when cathodal stimulation and propranolol occurred prior to training but it was abolished when stimulation occurred after training and propranolol was administered prior to training. Collectively, our findings show that tDCS applied on the left frontal cortex of mice affects fear memory performance. This alteration seems to be task-dependent and varies depending on the nature and timing of the stimulation. In certain conditions, tDCS reverses the effect of propranolol. These results provide initial evidence to support the timely use of tDCS for the modulation of fear-related memories. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. A NMDA receptor antagonist, MK-801 impairs consolidating extinction of auditory conditioned fear responses in a Pavlovian model.

    Directory of Open Access Journals (Sweden)

    Jun-Li Liu

    Full Text Available BACKGROUND: In auditory fear conditioning, repeated presentation of the tone in the absence of shock leads to extinction of the acquired fear responses. The glutamate N-methyl-D-aspartate receptor (NMDAR is thought to be involved in the extinction of the conditioned fear responses, but its detailed role in initiating and consolidating or maintaining the fear extinction memory is unclear. Here we investigated this issue by using a NMDAR antagonist, MK-801. METHODS/MAIN FINDINGS: The effects of immediate (beginning at 10 min after the conditioning and delayed (beginning at 24 h after conditioning extinctions were first compared with the finding that delayed extinction caused a better and long-lasting (still significant on the 20(th day after extinction depression on the conditioned fear responses. In a second experiment, MK-801 was intraperitoneally (i.p. injected at 40 min before, 4 h or 12 h after the delayed extinction, corresponding to critical time points for initiating, consolidating or maintaining the fear extinction memory. i.p. injection of MK-801 at either 40 min before or 4 h after delayed extinction resulted in an impairment of initiating and consolidating fear extinction memory, which caused a long lasting increased freezing score that was still significant on the 7th day after extinction, compared with extinction group. However, MK-801 administered at 12 h after the delayed extinction, when robust consolidation has been occurred and stabilized, did not affect the established extinction memory. Furthermore, the changed freezing behaviors was not due to an alteration in general anxiety levels, since MK-801 treatment had no effect on the percentage of open-arm time or open-arm entries in an Elevated Plus Maze (EPM task. CONCLUSIONS/SIGNIFICANCE: Our data suggested that the activation of NMDARs plays important role in initiation and consolidation but not maintenance of fear extinction memory. Together with the fact that NMDA receptor is

  16. Central Ghrelin Resistance Permits the Overconsolidation of Fear Memory.

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    Harmatz, Elia S; Stone, Lauren; Lim, Seh Hong; Lee, Graham; McGrath, Anna; Gisabella, Barbara; Peng, Xiaoyu; Kosoy, Eliza; Yao, Junmei; Liu, Elizabeth; Machado, Nuno J; Weiner, Veronica S; Slocum, Warren; Cunha, Rodrigo A; Goosens, Ki A

    2017-06-15

    There are many contradictory findings about the role of the hormone ghrelin in aversive processing, with studies suggesting that ghrelin signaling can both inhibit and enhance aversion. Here, we characterize and reconcile the paradoxical role of ghrelin in the acquisition of fearful memories. We used enzyme-linked immunosorbent assay to measure endogenous acyl-ghrelin and corticosterone at time points surrounding auditory fear learning. We used pharmacological (systemic and intra-amygdala) manipulations of ghrelin signaling and examined several aversive and appetitive behaviors. We also used biotin-labeled ghrelin to visualize ghrelin binding sites in coronal brain sections of amygdala. All work was performed in rats. In unstressed rodents, endogenous peripheral acyl-ghrelin robustly inhibits fear memory consolidation through actions in the amygdala and accounts for virtually all interindividual variability in long-term fear memory strength. Higher levels of endogenous ghrelin after fear learning were associated with weaker long-term fear memories, and pharmacological agonism of the ghrelin receptor during the memory consolidation period reduced fear memory strength. These fear-inhibitory effects cannot be explained by changes in appetitive behavior. In contrast, we show that chronic stress, which increases both circulating endogenous acyl-ghrelin and fear memory formation, promotes profound loss of ghrelin binding sites in the amygdala and behavioral insensitivity to ghrelin receptor agonism. These studies provide a new link between stress, a novel type of metabolic resistance, and vulnerability to excessive fear memory formation and reveal that ghrelin can regulate negative emotionality in unstressed animals without altering appetite. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

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

    2015-01-01

    Using the single prolonged stress (SPS) animal model of post-traumatic stress disorder (PTSD), previous studies suggest that enhanced glucocorticoid receptor (GR) expression leads to cued fear extinction retention deficits. However, it is unknown how the endogenous ligand of GRs, corticosterone (CORT), may contribute to extinction retention deficits in the SPS model. Given that CORT synthesis during fear learning is critical for fear memory consolidation and SPS enhances GR expression, CORT synthesis during fear memory formation could strengthen fear memory in SPS rats by enhancing GR activation during fear learning. In turn, this could lead to cued fear extinction retention deficits. We tested the hypothesis that CORT synthesis during fear learning leads to cued fear extinction retention deficits in SPS rats by administering the CORT synthesis inhibitor metyrapone to SPS and control rats prior to fear conditioning, and observed the effect this had on extinction memory. Inhibiting CORT synthesis during fear memory formation in control rats tended to decrease cued freezing, though this effect never reached statistical significance. Contrary to our hypothesis, inhibiting CORT synthesis during fear memory formation disrupted extinction retention in SPS rats. This finding suggests that even though SPS exposure leads to cued fear extinction memory deficits, CORT synthesis during fear memory formation enhances extinction retention in SPS rats. This suggests that stress-induced CORT synthesis in previously stressed rats can be beneficial. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Aversive Memory Reactivation Engages in the Amygdala Only Some Neurotransmitters Involved in Consolidation

    Science.gov (United States)

    Bucherelli, Corrado; Baldi, Elisabetta; Mariottini, Chiara; Passani, Maria Beatrice; Blandina, Patrizio

    2006-01-01

    Consolidation refers to item stabilization in long-term memory. Retrieval renders a consolidated memory sensitive, and a "reconsolidation" process has been hypothesized to keep the original memory persistent. Some authors could not detect this phenomenon. Here we show that retrieved contextual fear memory is vulnerable to amnesic treatments and…

  19. Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala.

    Science.gov (United States)

    Ihara, Fumiaki; Nishimura, Maki; Muroi, Yoshikage; Mahmoud, Motamed Elsayed; Yokoyama, Naoaki; Nagamune, Kisaburo; Nishikawa, Yoshifumi

    2016-10-01

    Chronic infection with Toxoplasma gondii becomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found that T. gondii infection impairs consolidation of conditioned fear memory. To examine the brain pathology induced by T. gondii infection, we analyzed the parasite load and histopathological changes. T. gondii infects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest that T. gondii infection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen during T. gondii infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  20. The hypocretin/orexin system mediates the extinction of fear memories.

    Science.gov (United States)

    Flores, África; Valls-Comamala, Victòria; Costa, Giulia; Saravia, Rocío; Maldonado, Rafael; Berrendero, Fernando

    2014-11-01

    Anxiety disorders are often associated with an inability to extinguish learned fear responses. The hypocretin/orexin system is involved in the regulation of emotional states and could also participate in the consolidation and extinction of aversive memories. Using hypocretin receptor-1 and hypocretin receptor-2 antagonists, hypocretin-1 and hypocretin-2 peptides, and hypocretin receptor-1 knockout mice, we investigated the role of the hypocretin system in cue- and context-dependent fear conditioning and extinction. Hypocretins were crucial for the consolidation of fear conditioning, and this effect was mainly observed in memories with a high emotional component. Notably, after the acquisition of fear memory, hypocretin receptor-1 blockade facilitated fear extinction, whereas hypocretin-1 administration impaired this extinction process. The extinction-facilitating effects of the hypocretin receptor-1 antagonist SB334867 were associated with increased expression of cFos in the basolateral amygdala and the infralimbic cortex. Intra-amygdala, but neither intra-infralimbic prefrontal cortex nor intra-dorsohippocampal infusion of SB334867 enhanced fear extinction. These results reveal a key role for hypocretins in the extinction of aversive memories and suggest that hypocretin receptor-1 blockade could represent a novel therapeutic target for the treatment of diseases associated with inappropriate retention of fear, such as post-traumatic stress disorder and phobias.

  1. The Hypocretin/Orexin System Mediates the Extinction of Fear Memories

    Science.gov (United States)

    Flores, África; Valls-Comamala, Victòria; Costa, Giulia; Saravia, Rocío; Maldonado, Rafael; Berrendero, Fernando

    2014-01-01

    Anxiety disorders are often associated with an inability to extinguish learned fear responses. The hypocretin/orexin system is involved in the regulation of emotional states and could also participate in the consolidation and extinction of aversive memories. Using hypocretin receptor-1 and hypocretin receptor-2 antagonists, hypocretin-1 and hypocretin-2 peptides, and hypocretin receptor-1 knockout mice, we investigated the role of the hypocretin system in cue- and context-dependent fear conditioning and extinction. Hypocretins were crucial for the consolidation of fear conditioning, and this effect was mainly observed in memories with a high emotional component. Notably, after the acquisition of fear memory, hypocretin receptor-1 blockade facilitated fear extinction, whereas hypocretin-1 administration impaired this extinction process. The extinction-facilitating effects of the hypocretin receptor-1 antagonist SB334867 were associated with increased expression of cFos in the basolateral amygdala and the infralimbic cortex. Intra-amygdala, but neither intra-infralimbic prefrontal cortex nor intra-dorsohippocampal infusion of SB334867 enhanced fear extinction. These results reveal a key role for hypocretins in the extinction of aversive memories and suggest that hypocretin receptor-1 blockade could represent a novel therapeutic target for the treatment of diseases associated with inappropriate retention of fear, such as post-traumatic stress disorder and phobias. PMID:24930888

  2. Direct dorsal hippocampal-prelimbic cortex connections strengthen fear memories.

    Science.gov (United States)

    Ye, Xiaojing; Kapeller-Libermann, Dana; Travaglia, Alessio; Inda, M Carmen; Alberini, Cristina M

    2017-01-01

    The ability to regulate the consolidation and strengthening of memories for threatening experiences is critical for mental health, and its dysregulation may lead to psychopathologies. Re-exposure to the context in which the threat was experienced can either increase or decrease fear response through distinct processes known, respectively, as reconsolidation or extinction. Using a context retrieval-dependent memory-enhancement model in rats, we report that memory strengthens through activation of direct projections from dorsal hippocampus to prelimbic (PL) cortex and activation of critical PL molecular mechanisms that are not required for extinction. Furthermore, while sustained PL brain-derived neurotrophic factor (BDNF) expression is required for memory consolidation, retrieval engages PL BDNF to regulate excitatory and inhibitory synaptic proteins neuroligin 1 and neuroligin 2, which promote memory strengthening while inhibiting extinction. Thus, context retrieval-mediated fear-memory enhancement results from a concerted action of mechanisms that strengthen memory through reconsolidation while suppressing extinction.

  3. Beta-adrenergic receptors in the lateral nucleus of the amygdala contribute to the acquisition but not the consolidation of auditory fear conditioning.

    Science.gov (United States)

    Bush, David E A; Caparosa, Ellen M; Gekker, Anna; Ledoux, Joseph

    2010-01-01

    Beta-adrenergic receptors (βARs) have long been associated with fear disorders and with learning and memory. However, the contribution of these receptors to Pavlovian fear conditioning, a leading behavioral model for studying fear learning and memory, is still poorly understood. The aim of this study was to investigate the involvement of βAR activation in the acquisition, consolidation and expression of fear conditioning. We focused on manipulations of βARs in the lateral nucleus of the amygdala (LA) because of the well-established contribution of this area to fear conditioning. Specifically, we tested the effects of intra-LA microinfusions of the βAR antagonist, propranolol, on learning and memory for auditory Pavlovian fear conditioning in rats. Pre-training propranolol infusions disrupted the initial acquisition, short-term memory (STM), and long-term memory (LTM) for fear conditioning, but infusions immediately after training had no effect. Further, infusion of propranolol prior to testing fear responses did not affect fear memory expression. These findings indicate that amygdala βARs are important for the acquisition but not the consolidation of fear conditioning.

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

    Science.gov (United States)

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

    2017-03-29

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

  5. Hypobaric hypoxia impairs cued and contextual fear memory in rats.

    Science.gov (United States)

    Kumari, Punita; Kauser, Hina; Wadhwa, Meetu; Roy, Koustav; Alam, Shahnawaz; Sahu, Surajit; Kishore, Krishna; Ray, Koushik; Panjwani, Usha

    2018-04-26

    Fear memory is essential for survival, and its dysregulation leads to disorders. High altitude hypobaric hypoxia (HH) is known to induce cognitive decline. However, its effect on fear memory is still an enigma. We aimed to investigate the temporal effect of HH on fear conditioning and the underlying mechanism. Adult male Sprague-Dawley rats were trained for fear conditioning and exposed to simulated HH equivalent to 25,000 ft for different durations (1, 3, 7, 14 and 21 days). Subsequently, rats were tested for cued and contextual fear conditioning. Neuronal morphology, apoptosis and DNA fragmentation were studied in the medial prefrontal cortex (mPFC), hippocampus and basolateral amygdala (BLA). We observed significant deficit in cued and contextual fear acquisition (at 1, 3 and 7 days) and consolidation (cued at 1 and 3 days and contextual fear at 1, 3 and 7 days) under HH. HH exposure with retraining showed the earlier restoration of contextual fear memory. Further, we found a gradual increase in the number of pyknotic and apoptotic neurons together with the increase in DNA fragmentation in mPFC, hippocampus, and BLA up to 7 days of HH exposure. The present study concludes that HH exposure equivalent to 25000 ft induced cued and contextual fear memory deficit (acquisition and consolidation) which is found to be correlated with the neurodegenerative changes in the limbic brain regions. Copyright © 2018. Published by Elsevier B.V.

  6. Vicarious extinction learning during reconsolidation neutralizes fear memory.

    Science.gov (United States)

    Golkar, Armita; Tjaden, Cathelijn; Kindt, Merel

    2017-05-01

    Previous studies have suggested that fear memories can be updated when recalled, a process referred to as reconsolidation. Given the beneficial effects of model-based safety learning (i.e. vicarious extinction) in preventing the recovery of short-term fear memory, we examined whether consolidated long-term fear memories could be updated with safety learning accomplished through vicarious extinction learning initiated within the reconsolidation time-window. We assessed this in a final sample of 19 participants that underwent a three-day within-subject fear-conditioning design, using fear-potentiated startle as our primary index of fear learning. On day 1, two fear-relevant stimuli (reinforced CSs) were paired with shock (US) and a third stimulus served as a control (CS). On day 2, one of the two previously reinforced stimuli (the reminded CS) was presented once in order to reactivate the fear memory 10 min before vicarious extinction training was initiated for all CSs. The recovery of the fear memory was tested 24 h later. Vicarious extinction training conducted within the reconsolidation time window specifically prevented the recovery of the reactivated fear memory (p = 0.03), while leaving fear-potentiated startle responses to the non-reactivated cue intact (p = 0.62). These findings are relevant to both basic and clinical research, suggesting that a safe, non-invasive model-based exposure technique has the potential to enhance the efficiency and durability of anxiolytic therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation.

    Science.gov (United States)

    Wang, Dong V; Yau, Hau-Jie; Broker, Carl J; Tsou, Jen-Hui; Bonci, Antonello; Ikemoto, Satoshi

    2015-05-01

    Sharp wave-associated field oscillations (∼200 Hz) of the hippocampus, referred to as ripples, are believed to be important for consolidation of explicit memory. Little is known about how ripples are regulated by other brain regions. We found that the median raphe region (MnR) is important for regulating hippocampal ripple activity and memory consolidation. We performed in vivo simultaneous recording in the MnR and hippocampus of mice and found that, when a group of MnR neurons was active, ripples were absent. Consistently, optogenetic stimulation of MnR neurons suppressed ripple activity and inhibition of these neurons increased ripple activity. Notably, using a fear conditioning procedure, we found that photostimulation of MnR neurons interfered with memory consolidation. Our results demonstrate a critical role of the MnR in regulating ripples and memory consolidation.

  8. MOLECULAR MECHANISMS OF FEAR LEARNING AND MEMORY

    Science.gov (United States)

    Johansen, Joshua P.; Cain, Christopher K.; Ostroff, Linnaea E.; LeDoux, Joseph E.

    2011-01-01

    Pavlovian fear conditioning is a useful behavioral paradigm for exploring the molecular mechanisms of learning and memory because a well-defined response to a specific environmental stimulus is produced through associative learning processes. Synaptic plasticity in the lateral nucleus of the amygdala (LA) underlies this form of associative learning. Here we summarize the molecular mechanisms that contribute to this synaptic plasticity in the context of auditory fear conditioning, the form of fear conditioning best understood at the molecular level. We discuss the neurotransmitter systems and signaling cascades that contribute to three phases of auditory fear conditioning: acquisition, consolidation, and reconsolidation. These studies suggest that multiple intracellular signaling pathways, including those triggered by activation of Hebbian processes and neuromodulatory receptors, interact to produce neural plasticity in the LA and behavioral fear conditioning. Together, this research illustrates the power of fear conditioning as a model system for characterizing the mechanisms of learning and memory in mammals, and potentially for understanding fear related disorders, such as PTSD and phobias. PMID:22036561

  9. Molecular mechanisms of fear learning and memory.

    Science.gov (United States)

    Johansen, Joshua P; Cain, Christopher K; Ostroff, Linnaea E; LeDoux, Joseph E

    2011-10-28

    Pavlovian fear conditioning is a particularly useful behavioral paradigm for exploring the molecular mechanisms of learning and memory because a well-defined response to a specific environmental stimulus is produced through associative learning processes. Synaptic plasticity in the lateral nucleus of the amygdala (LA) underlies this form of associative learning. Here, we summarize the molecular mechanisms that contribute to this synaptic plasticity in the context of auditory fear conditioning, the form of fear conditioning best understood at the molecular level. We discuss the neurotransmitter systems and signaling cascades that contribute to three phases of auditory fear conditioning: acquisition, consolidation, and reconsolidation. These studies suggest that multiple intracellular signaling pathways, including those triggered by activation of Hebbian processes and neuromodulatory receptors, interact to produce neural plasticity in the LA and behavioral fear conditioning. Collectively, this body of research illustrates the power of fear conditioning as a model system for characterizing the mechanisms of learning and memory in mammals and potentially for understanding fear-related disorders, such as PTSD and phobias. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Light exposure before learning improves memory consolidation at night

    Science.gov (United States)

    Shan, Li-Li; Guo, Hao; Song, Ning-Ning; Jia, Zheng-Ping; Hu, Xin-Tian; Huang, Jing-Fei; Ding, Yu-Qiang; Richter-Levine, Gal; Zhou, Qi-Xin; Xu, Lin

    2015-01-01

    Light is recently recognized as a modulator able to activate the hippocampus and modulate memory processing, but little is known about the molecular mechanisms. Here, we report that in mice, a short pulse of white light before learning dramatically improves consolidation of contextual fear memory during the night. The light exposure increases hippocampal active p21-activated kinase 1 (PAK1) and CA1 long-term potentiation (LTP). These light effects are abolished in PAK1 knockout and dominant-negative transgenic mice, but preserved by expression of constitutively active PAK1 in the hippocampus. Our results indicate that light can act as a switch of PAK1 activity that modulate CA1 LTP and thereby memory consolidation without affecting learning and short-term memory. PMID:26493375

  11. Memory formation for trace fear conditioning requires ubiquitin-proteasome mediated protein degradation in the prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    David S Reis

    2013-10-01

    Full Text Available The cellular mechanisms supporting plasticity during memory consolidation have been a subject of considerable interest. De novo protein and mRNA synthesis in several brain areas are critical, and more recently protein degradation, mediated by the ubiquitin-proteasome system (UPS, has been shown to be important. Previous work clearly establishes a relationship between protein synthesis and protein degradation in the amygdala, but it is unclear whether cortical mechanisms of memory consolidation are similar to those in the amygdala. Recent work demonstrating a critical role for prefrontal cortex (PFC in the acquisition and consolidation of fear memory allows us to address this question. Here we use a PFC-dependent fear conditioning protocol to determine whether UPS mediated protein degradation is necessary for memory consolidation in PFC. Groups of rats were trained with auditory delay or trace fear conditioning and sacrificed 60 min after training. PFC tissue was then analyzed to quantify the amount of polyubiquinated protein. Other animals were trained with similar procedures but were infused with either a proteasome inhibitor (clasto-lactacystin β-lactone or a translation inhibitor (anisomycin in the PFC immediately after training. Our results show increased UPS-mediated protein degradation in the PFC following trace but not delay fear conditioning. Additionally, post-training proteasome or translation inhibition significantly impaired trace but not delay fear memory when tested the next day. Our results further support the idea that the PFC is critical for trace but not delay fear conditioning highlight the role of UPS-mediated degradation as critical for synaptic plasticity.

  12. Phosphodiesterase 10A inhibition attenuates sleep deprivation-induced deficits in long-term fear memory.

    Science.gov (United States)

    Guo, Lengqiu; Guo, Zhuangli; Luo, Xiaoqing; Liang, Rui; Yang, Shui; Ren, Haigang; Wang, Guanghui; Zhen, Xuechu

    2016-12-02

    Sleep, particularly rapid eye movement (REM) sleep, is implicated in the consolidation of emotional memories. In the present study, we investigated the protective effects of a phosphodiesterase 10A (PDE10A) inhibitor MP-10 on deficits in long-term fear memory induced by REM sleep deprivation (REM-SD). REM-SD caused deficits in long-term fear memory, however, MP-10 administration ameliorated the deleterious effects of REM-SD on long term fear memory. Brain-derived neurotropic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) were altered in specific brain regions associated with learning and memory in REM-SD rats. Accordingly, REM-SD caused a significant decrease of pCREB in hippocampus and striatum and a significant decrease of BDNF in the hippocampus, striatum and amygdala, however, MP-10 reversed the effects of REM-SD in a dose-dependent manner. Our findings suggest that REM-SD disrupts the consolidation of long-term fear memory and that administration of MP-10 protects the REM-SD-induced deficits in fear memory, which may be due to the MP-10-induced expression of BDNF in the hippocampus, striatum and amygdala, and phosphorylation of CREB in the hippocampus and striatum. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Stress, glucocorticoids and memory: implications for treating fear-related disorders.

    Science.gov (United States)

    de Quervain, Dominique; Schwabe, Lars; Roozendaal, Benno

    2017-01-01

    Glucocorticoid stress hormones are crucially involved in modulating mnemonic processing of emotionally arousing experiences. They enhance the consolidation of new memories, including those that extinguish older memories, but impair the retrieval of information stored in long-term memory. As strong aversive memories lie at the core of several fear-related disorders, including post-traumatic stress disorder and phobias, the memory-modulating properties of glucocorticoids have recently become of considerable translational interest. Clinical trials have provided the first evidence that glucocorticoid-based pharmacotherapies aimed at attenuating aversive memories might be helpful in the treatment of fear-related disorders. Here, we review important advances in the understanding of how glucocorticoids mediate stress effects on memory processes, and discuss the translational potential of these new conceptual insights.

  14. Effects of Mineralocorticoid Receptors Blockade on FearMemory Reconsolidation in Rats

    Directory of Open Access Journals (Sweden)

    Abbas Ali Vafaei

    2011-08-01

    Full Text Available Reconsolidation memory is defined as a process in which the retrieval of a previously consolidated memory returns to a labile state which is then subject to stabilization. Previous studies have shown that mineralocorticoid receptors (MRs modulate distinct phases of learning and memory, which display a high concentration and distinct distribution in the hippocampus. Moreover, we found no studies that examined the role of hippocampal MRs in fear memory reconsolidation. Here, we investigated the effect of MRs blockade on fear memory reconsolidation in rats. Additionally, to test whether blockade of protein synthesis would disrupt fear memory reconsolidation in our paradigm, we tested the effect of cycloheximide, an inhibitor of protein synthesis after memory reactivation. Results indicated that systemic as well as intra-hippocampal administrations of the MR antagonist spironolactone immediately following memory reactivation did not affect on post-retrieval long-term memory. Cycloheximide given after the reactivation treatment produced a strong impairment that persisted over test sessions. These findings indicate that MRs are not required for reconsolidation of fear-based memory.

  15. Exploring epigenetic regulation of fear memory and biomarkers associated with Post-traumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Stephanie A. Maddox

    2013-07-01

    Full Text Available This review examines recent work on epigenetic mechanisms underlying animal models of fear learning as well as its translational implications in disorders of fear regulation, such as Posttraumatic Stress Disorder (PTSD. Specifically, we will examine work outlining roles of differential histone acetylation and DNA methylation associated with consolidation, reconsolidation and extinction in Pavlovian fear paradigms. We then focus on the numerous studies examining the epigenetic modifications of the Brain-derived neurotrophin factor (BDNF pathway and the extension of these findings from animal models to recent work in human clinical populations. We will also review recently published data on FKBP5 regulation of glucocorticoid receptor function, and how this is modulated in animal models of PTSD and in human clinical populations via epigenetic mechanisms. As glucocorticoid regulation of memory consolidation is well established in fear models, we examine how these recent data contribute to our broader understanding of fear memory formation. The combined recent progress in epigenetic modulation of memory with the advances in fear neurobiology suggest that this area may be critical to progress in our understanding of fear-related disorders with implications for new approaches to treatment and prevention.

  16. The Class I HDAC Inhibitor RGFP963 Enhances Consolidation of Cued Fear Extinction

    Science.gov (United States)

    Bowers, Mallory E.; Xia, Bing; Carreiro, Samantha; Ressler, Kerry J.

    2015-01-01

    Evidence indicates that broad, nonspecific histone deacetylase (HDAC) inhibition enhances learning and memory, however, the contribution of the various HDACs to specific forms of learning is incompletely understood. Here, we show that the Class I HDAC inhibitor, RGFP963, enhances consolidation of cued fear extinction. However, RGFP966, a strong…

  17. Induction and requirement of gene expression in the anterior cingulate cortex and medial prefrontal cortex for the consolidation of inhibitory avoidance memory

    Directory of Open Access Journals (Sweden)

    Zhang Yue

    2011-01-01

    Full Text Available Abstract Background Memory consolidation is a process to stabilize short-term memory, generating long-term memory. A critical biochemical feature of memory consolidation is a requirement for gene expression. Previous studies have shown that fear memories are consolidated through the activation of gene expression in the amygdala and hippocampus, indicating essential roles of these brain regions in memory formation. However, it is still poorly understood whether gene expression in brain regions other than the amygdala/hippocampus is required for the consolidation of fear memory; however, several brain regions are known to play modulatory roles in fear memory formation. Results To further understand the mechanisms underlying the formation of fear memory, we first identified brain regions where gene expression is activated after learning inhibitory avoidance (IA by analyzing the expression of the immediately early genes c-fos and Arc as markers. Similarly with previous findings, the induction of c-fos and Arc expression was observed in the amygdala and hippocampus. Interestingly, we also observed the induction of c-fos and Arc expression in the medial prefrontal cortex (mPFC: prelimbic (PL and infralimbic (IL regions and Arc expression in the anterior cingulate cortex (ACC. We next examined the roles of these brain regions in the consolidation of IA memory. Consistent with previous findings, inhibiting protein synthesis in the hippocampus blocked the consolidation of IA memory. More importantly, inhibition in the mPFC or ACC also blocked the formation of IA memory. Conclusion Our observations indicated that the formation of IA memory requires gene expression in the ACC and mPFC as well as in the amygdala and hippocampus, suggesting essential roles of the ACC and mPFC in IA memory formation.

  18. Systems reconsolidation reveals a selective role for the anterior cingulate cortex in generalized contextual fear memory expression.

    Science.gov (United States)

    Einarsson, Einar Ö; Pors, Jennifer; Nader, Karim

    2015-01-01

    After acquisition, hippocampus-dependent memories undergo a systems consolidation process, during which they become independent of the hippocampus and dependent on the anterior cingulate cortex (ACC) for memory expression. However, consolidated remote memories can become transiently hippocampus-dependent again following memory reactivation. How this systems reconsolidation affects the role of the ACC in remote memory expression is not known. Using contextual fear conditioning, we show that the expression of 30-day-old remote memory can transiently be supported by either the ACC or the dorsal hippocampus following memory reactivation, and that the ACC specifically mediates expression of remote generalized contextual fear memory. We found that suppression of neural activity in the ACC with the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) impaired the expression of remote, but not recent, contextual fear memory. Fear expression was not affected by this treatment if preceded by memory reactivation 6 h earlier, nor was it affected by suppression of neural activity in the dorsal hippocampus with the GABA-receptor agonist muscimol. However, simultaneous targeting of both the ACC and the dorsal hippocampus 6 h after memory reactivation disrupted contextual fear memory expression. Second, we observed that expression of a 30-day-old generalized contextual fear memory in a novel context was not affected by memory reactivation 6 h earlier. However, intra-ACC CNQX infusion before testing impaired contextual fear expression in the novel context, but not the original training context. Together, these data suggest that although the dorsal hippocampus may be recruited during systems reconsolidation, the ACC remains necessary for the expression of generalized contextual fear memory.

  19. A naturally-occurring histone acetyltransferase inhibitor derived from Garcinia indica impairs newly acquired and reactivated fear memories.

    Directory of Open Access Journals (Sweden)

    Stephanie A Maddox

    Full Text Available The study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has progressed rapidly in recent years, yet few compounds have emerged that are readily useful in a clinical setting for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD. Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically investigate the ability of garcinol, a naturally-occurring histone acetyltransferase (HAT inhibitor derived from the rind of the fruit of the Kokum tree (Garcina indica, to disrupt the consolidation and reconsolidation of Pavlovian fear conditioning, a widely studied rodent model of PTSD. We show that local infusion of garcinol into the rat lateral amygdala (LA impairs the training and retrieval-related acetylation of histone H3 in the LA. Further, we show that either intra-LA or systemic administration of garcinol within a narrow window after either fear conditioning or fear memory retrieval significantly impairs the consolidation and reconsolidation of a Pavlovian fear memory and associated neural plasticity in the LA. Our findings suggest that a naturally-occurring compound derived from the diet that regulates chromatin function may be useful in the treatment of newly acquired or recently reactivated traumatic memories.

  20. A Naturally-Occurring Histone Acetyltransferase Inhibitor Derived from Garcinia indica Impairs Newly Acquired and Reactivated Fear Memories

    Science.gov (United States)

    Maddox, Stephanie A.; Watts, Casey S.; Doyère, Valérie; Schafe, Glenn E.

    2013-01-01

    The study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has progressed rapidly in recent years, yet few compounds have emerged that are readily useful in a clinical setting for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD). Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically investigate the ability of garcinol, a naturally-occurring histone acetyltransferase (HAT) inhibitor derived from the rind of the fruit of the Kokum tree (Garcina indica), to disrupt the consolidation and reconsolidation of Pavlovian fear conditioning, a widely studied rodent model of PTSD. We show that local infusion of garcinol into the rat lateral amygdala (LA) impairs the training and retrieval-related acetylation of histone H3 in the LA. Further, we show that either intra-LA or systemic administration of garcinol within a narrow window after either fear conditioning or fear memory retrieval significantly impairs the consolidation and reconsolidation of a Pavlovian fear memory and associated neural plasticity in the LA. Our findings suggest that a naturally-occurring compound derived from the diet that regulates chromatin function may be useful in the treatment of newly acquired or recently reactivated traumatic memories. PMID:23349897

  1. Short-Term Total Sleep-Deprivation Impairs Contextual Fear Memory, and Contextual Fear-Conditioning Reduces REM Sleep in Moderately Anxious Swiss Mice

    Directory of Open Access Journals (Sweden)

    Munazah F. Qureshi

    2017-11-01

    Full Text Available The conditioning tasks have been widely used to model fear and anxiety and to study their association with sleep. Many reports suggest that sleep plays a vital role in the consolidation of fear memory. Studies have also demonstrated that fear-conditioning influences sleep differently in mice strains having a low or high anxiety level. It is, therefore, necessary to know, how sleep influences fear-conditioning and how fear-conditioning induces changes in sleep architecture in moderate anxious strains. We have used Swiss mice, a moderate anxious strain, to study the effects of: (i sleep deprivation on contextual fear conditioned memory, and also (ii contextual fear conditioning on sleep architecture. Animals were divided into three groups: (a non-sleep deprived (NSD; (b stress control (SC; and (c sleep-deprived (SD groups. The SD animals were SD for 5 h soon after training. We found that the NSD and SC animals showed 60.57% and 58.12% freezing on the testing day, while SD animals showed significantly less freezing (17.13% only; p < 0.001 on the testing day. Further, we observed that contextual fear-conditioning did not alter the total amount of wakefulness and non-rapid eye movement (NREM sleep. REM sleep, however, significantly decreased in NSD and SC animals on the training and testing days. Interestingly, REM sleep did not decrease in the SD animals on the testing day. Our results suggest that short-term sleep deprivation impairs fear memory in moderate anxious mice. It also suggests that NREM sleep, but not REM sleep, may have an obligatory role in memory consolidation.

  2. The Hypocretin/Orexin System Mediates the Extinction of Fear Memories

    OpenAIRE

    Flores, África; Valls-Comamala, Victòria; Costa, Giulia; Saravia, Rocío; Maldonado, Rafael; Berrendero, Fernando

    2014-01-01

    Anxiety disorders are often associated with an inability to extinguish learned fear responses. The hypocretin/orexin system is involved in the regulation of emotional states and could also participate in the consolidation and extinction of aversive memories. Using hypocretin receptor-1 and hypocretin receptor-2 antagonists, hypocretin-1 and hypocretin-2 peptides, and hypocretin receptor-1 knockout mice, we investigated the role of the hypocretin system in cue- and context-dependent fear condi...

  3. Posttraining handling facilitates memory for auditory-cue fear conditioning in rats.

    Science.gov (United States)

    Hui, Isabel R; Hui, Gabriel K; Roozendaal, Benno; McGaugh, James L; Weinberger, Norman M

    2006-09-01

    A large number of studies have indicated that stress exposure or the administration of stress hormones and other neuroactive drugs immediately after a learning experience modulates the consolidation of long-term memory. However, there has been little investigation into how arousal induced by handling of the animals in order to administer these drugs affects memory. Therefore, the present study examined whether the posttraining injection or handling procedure per se affects memory of auditory-cue classical fear conditioning. Male Sprague-Dawley rats, which had been pre-handled on three days for 1 min each prior to conditioning, received three pairings of a single-frequency auditory stimulus and footshock, followed immediately by either a subcutaneous injection of a vehicle solution or brief handling without injection. A control group was placed back into their home cages without receiving any posttraining treatment. Retention was tested 24 h later in a novel chamber and suppression of ongoing motor behavior during a 10-s presentation of the auditory-cue served as the measure of conditioned fear. Animals that received posttraining injection or handling did not differ from each other but showed significantly less stimulus-induced movement compared to the non-handled control group. These findings thus indicate that the posttraining injection or handling procedure is sufficiently arousing or stressful to facilitate memory consolidation of auditory-cue classical fear conditioning.

  4. Differential role of Rac in the basolateral amygdala and cornu ammonis 1 in the reconsolidation of auditory and contextual Pavlovian fear memory in rats.

    Science.gov (United States)

    Wu, Ping; Ding, Zeng-Bo; Meng, Shi-Qiu; Shen, Hao-Wei; Sun, Shi-Chao; Luo, Yi-Xiao; Liu, Jian-Feng; Lu, Lin; Zhu, Wei-Li; Shi, Jie

    2014-08-01

    A conditioned stimulus (CS) is associated with a fearful unconditioned stimulus (US) in the traditional fear conditioning model. After fear conditioning, the CS-US association memory undergoes the consolidation process to become stable. Consolidated memory enters an unstable state after retrieval and requires the reconsolidation process to stabilize again. Evidence indicates the important role of Rac (Ras-related C3 botulinum toxin substrate) in the acquisition and extinction of fear memory. In the present study, we hypothesized that Rac in the amygdala is crucial for the reconsolidation of auditory and contextual Pavlovian fear memory. Auditory and contextual fear conditioning and microinjections of the Rac inhibitor NSC23766 were used to explore the role of Rac in the reconsolidation of auditory and contextual Pavlovian fear memory in rats. A microinjection of NSC23766 into the basolateral amygdala (BLA) but not central amygdala (CeA) or cornu ammonis 1 (CA1) immediately after memory retrieval disrupted the reconsolidation of auditory Pavlovian fear memory. A microinjection of NSC23766 into the CA1 but not BLA or CeA after memory retrieval disrupted the reconsolidation of contextual Pavlovian fear memory. Our experiments demonstrate that Rac in the BLA is crucial for the reconsolidation of auditory Pavlovian fear memory, whereas Rac in the CA1 is critical for the reconsolidation of contextual Pavlovian fear memory.

  5. Infusion of methylphenidate into the basolateral nucleus of amygdala or anterior cingulate cortex enhances fear memory consolidation in rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The psychostimulant methylphenidate (MPD; also called Ritalin) is a blocker of dopamine and norepi-nephrine transporter. It has been clinically used for treatment of Attention Deficit and Hyperactivity Disorder (ADHD). There have been inconsistent reports regarding the effects of systemically adminis-tered MPD on learning and memory, either in animals or humans. In the present study, we investigated the effect of direct infusion of MPD into the basolateral nucleus of amygdala (BLA) or the anterior cin-gulate cortex (ACC) on conditioned fear memory. Rats were trained on a one-trial step-through inhibi-tory avoidance task. MPD was infused bilaterally into the BLA or the ACC, either at ‘0’ or 6 h post-training. Saline was administered as control. Memory retention was tested 48 h post-training. In-tra-BLA or intra-ACC infusion of MPD ‘0’ h but not 6 h post-training significantly improved 48-h memory retention: the MPD-treated rats had significant longer step-through latency than controls. The present results indicate that action of MPD in the BLA or the ACC produces a beneficial effect on the consoli-dation of inhibitory avoidance memory.

  6. Influence of cued-fear conditioning and its impairment on NREM sleep.

    Science.gov (United States)

    Kumar, Tankesh; Jha, Sushil K

    2017-10-01

    Many studies suggest that fear conditioning influences sleep. It is, however, not known if the changes in sleep architecture after fear conditioning are essentially associated with the consolidation of fearful memory or with fear itself. Here, we have observed that within sleep, NREM sleep consistently remained augmented after the consolidation of cued fear-conditioned memory. But a similar change did not occur after impairing memory consolidation by blocking new protein synthesis and glutamate transmission between glial-neuronal loop in the lateral amygdala (LA). Anisomycin (a protein synthesis inhibitor) and DL-α-amino-adipic acid (DL- α -AA) (a glial glutamine synthetase enzyme inhibitor) were microinjected into the LA soon after cued fear-conditioning to induce memory impairment. On the post-conditioning day, animals in both the groups exhibited significantly less freezing. In memory-consolidated groups (vehicle groups), NREM sleep significantly increased during 2nd to 5th hours after training compared to their baseline days. However, in memory impaired groups (anisomycin and DL- α -AA microinjected groups), similar changes were not observed. Our results thus suggest that changes in sleep architecture after cued fear-conditioning are indeed a consolidation dependent event. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Corticosterone facilitates extinction of fear memory in BALB/c mice but strengthens cue related fear in C57BL/6 mice.

    Science.gov (United States)

    Brinks, V; de Kloet, E R; Oitzl, M S

    2009-04-01

    Corticosterone, the naturally occurring glucocorticoid of rodents is secreted in response to stressors and is known for its facilitating and detrimental effects on emotional learning and memory. The large variability in the action of corticosterone on processing of emotional memories is postulated to depend on genetic background and the spatio-temporal domain in which the hormone operates. To address this hypothesis, mice of two strains with distinct corticosterone secretory patterns and behavioural phenotype (BALB/c and C57BL/6J) were treated with corticosterone (250 microg/kg, i.p.), either 5 min before or directly after acquisition in a fear conditioning task. As the paradigm allowed assessing in one experimental procedure both context- and cue-related fear behaviour, we were able to detect generalization and specificity of fear. BALB/c showed generalized strong fear memory, while C57BL/6J mice discriminated between freezing during context- and cue episodes. Corticosterone had opposite effects on fear memory depending on the strain and time of injection. Corticosterone after acquisition did not affect C57BL/6J mice, but destabilized consolidation and facilitated extinction in BALB/c. Corticosterone 5 min before acquisition strengthened stress-associated signals: BALB/c no longer showed lower fear memory, while C57BL/6J mice displayed increased fear memory and impaired extinction in cue episodes. We propose that corticosterone-induced facilitation of fear memory in C57BL/6J mice can be used to study the development of fear memories, corticosterone administration in BALB/c mice presents a model to examine treatment. We conclude that genetic background and time of corticosterone action are modifiers of fear memory with interesting translational implications for anxiety-related diseases.

  8. Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation

    KAUST Repository

    Gao, Virginia; Suzuki, Akinobu; Magistretti, Pierre J.; Lengacher, Sylvain; Pollonini, Gabriella; Steinman, Michael Q.; Alberini, Cristina M.

    2016-01-01

    Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which β2- Adrenergic receptors (βARs) are of particular importance. The differential anatomical and cellular distribution of βAR subtypes in the brain suggests that they play distinct roles in memory processing, although much about their specific contributions and mechanisms of action remains to be understood. Here we show that astrocytic rather than neuronal β2ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal β2ARs, but not β1ARs, are coupled to the training-dependent release of lactate from astrocytes, which is necessary for long- Term memory formation and for underlying molecular changes. This key metabolic role of astrocytic β2ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration.

  9. Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation

    KAUST Repository

    Gao, Virginia

    2016-07-12

    Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which β2- Adrenergic receptors (βARs) are of particular importance. The differential anatomical and cellular distribution of βAR subtypes in the brain suggests that they play distinct roles in memory processing, although much about their specific contributions and mechanisms of action remains to be understood. Here we show that astrocytic rather than neuronal β2ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal β2ARs, but not β1ARs, are coupled to the training-dependent release of lactate from astrocytes, which is necessary for long- Term memory formation and for underlying molecular changes. This key metabolic role of astrocytic β2ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration.

  10. Schemas and memory consolidation.

    Science.gov (United States)

    Tse, Dorothy; Langston, Rosamund F; Kakeyama, Masaki; Bethus, Ingrid; Spooner, Patrick A; Wood, Emma R; Witter, Menno P; Morris, Richard G M

    2007-04-06

    Memory encoding occurs rapidly, but the consolidation of memory in the neocortex has long been held to be a more gradual process. We now report, however, that systems consolidation can occur extremely quickly if an associative "schema" into which new information is incorporated has previously been created. In experiments using a hippocampal-dependent paired-associate task for rats, the memory of flavor-place associations became persistent over time as a putative neocortical schema gradually developed. New traces, trained for only one trial, then became assimilated and rapidly hippocampal-independent. Schemas also played a causal role in the creation of lasting associative memory representations during one-trial learning. The concept of neocortical schemas may unite psychological accounts of knowledge structures with neurobiological theories of systems memory consolidation.

  11. Retrieval per se is not sufficient to trigger reconsolidation of human fear memory.

    Science.gov (United States)

    Sevenster, Dieuwke; Beckers, Tom; Kindt, Merel

    2012-03-01

    Ample evidence suggests that consolidated memories, upon their retrieval, enter a labile state, in which they might be susceptible to change. It has been proposed that memory labilization allows for the integration of relevant information in the established memory trace (memory updating). Memory labilization and reconsolidation do not necessarily occur when a memory is being reactivated, but only when there is something to be learned during memory retrieval (prediction error). Thus, updating of a fear memory trace should not occur under retrieval conditions in which the outcome is fully predictable (no prediction error). Here, we addressed this issue, using a human differential fear conditioning procedure, by eliminating the very possibility of reinforcement of the reminder cue. A previously established fear memory (picture-shock pairings) was reactivated with shock-electrodes attached (Propranolol group, n=18) or unattached (Propranolol No-Shock Expectation group, n=19). We additionally tested a placebo-control group with the shock-electrodes attached (Placebo group, n=18). Reconsolidation was not triggered when nothing could be learned during the reminder trial, as noradrenergic blockade did not affect expression of the fear memory 24h later in the Propranolol No-Shock Expectation group. Only when the outcome of the retrieval cue was not fully predictable, propranolol, contrary to placebo, reduced the startle fear response and prevented the return of fear (reinstatement) the following day. In line with previous studies, skin conductance response and shock expectancies were not affected by propranolol. Remarkably, a double dissociation emerged between the emotional (startle response) and more cognitive expression (expectancies, SCR) of the fear memory. Our findings have important implications for reconsolidation blockade as treatment strategy for emotional disorders. First, fear reducing procedures that target the emotional component of fear memory do not

  12. Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: Reduced dopaminergic modulation and immediate gene expression in limbic circuits.

    Science.gov (United States)

    Rossignoli, Matheus Teixeira; Lopes-Aguiar, Cleiton; Ruggiero, Rafael Naime; Do Val da Silva, Raquel Araujo; Bueno-Junior, Lezio Soares; Kandratavicius, Ludmyla; Peixoto-Santos, José Eduardo; Crippa, José Alexandre; Cecilio Hallak, Jaime Eduardo; Zuardi, Antonio Waldo; Szawka, Raphael Escorsim; Anselmo-Franci, Janete; Leite, João Pereira; Romcy-Pereira, Rodrigo Neves

    2017-05-14

    The prefrontal cortex (PFC), amygdala and hippocampus display a coordinated activity during acquisition of associative fear memories. Evidence indicates that PFC engagement in aversive memory formation does not progress linearly as previously thought. Instead, it seems to be recruited at specific time windows after memory acquisition, which has implications for the treatment of post-traumatic stress disorders. Cannabidiol (CBD), the major non-psychotomimetic phytocannabinoid of the Cannabis sativa plant, is known to modulate contextual fear memory acquisition in rodents. However, it is still not clear how CBD interferes with PFC-dependent processes during post-training memory consolidation. Here, we tested whether intra-PFC infusions of CBD immediately after or 5h following contextual fear conditioning was able to interfere with memory consolidation. Neurochemical and cellular correlates of the CBD treatment were evaluated by the quantification of extracellular levels of dopamine (DA), serotonin, and their metabolites in the PFC and by measuring the cellular expression of activity-dependent transcription factors in cortical and limbic regions. Our results indicate that bilateral intra-PFC CBD infusion impaired contextual fear memory consolidation when applied 5h after conditioning, but had no effect when applied immediately after it. This effect was associated with a reduction in DA turnover in the PFC following retrieval 5days after training. We also observed that post-conditioning infusion of CBD reduced c-fos and zif-268 protein expression in the hippocampus, PFC, and thalamus. Our findings support that CBD interferes with contextual fear memory consolidation by reducing PFC influence on cortico-limbic circuits. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation.

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    Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-03-01

    Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured spatial learning and memory, the time of normal rats was shortened by GEN treatment compared to the vehicle group, but only in the early stages of testing. In the glucose-loaded group, GEN treatment improved performance as mazes were advanced. In the open-field test, GEN treatment delayed habituation to the new environment in normal rats, and increased the exploratory behaviors of glucose-loaded rats. There were no significant differences observed for emotionality or fear-motivated learning and memory. Together, these results indicate that GEN treatment improved spatial learning and memory only in the early stages of testing in the normal state, but improved spatial learning and memory when glucose levels increased during memory consolidation. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Serotonergic Modulation of Conditioned Fear

    Directory of Open Access Journals (Sweden)

    Judith R. Homberg

    2012-01-01

    Full Text Available Conditioned fear plays a key role in anxiety disorders as well as depression and other neuropsychiatric conditions. Understanding how neuromodulators drive the associated learning and memory processes, including memory consolidation, retrieval/expression, and extinction (recall, is essential in the understanding of (individual differences in vulnerability to these disorders and their treatment. The human and rodent studies I review here together reveal, amongst others, that acute selective serotonin reuptake inhibitor (SSRI treatment facilitates fear conditioning, reduces contextual fear, and increases cued fear, chronic SSRI treatment reduces both contextual and cued fear, 5-HT1A receptors inhibit the acquisition and expression of contextual fear, 5-HT2A receptors facilitates the consolidation of cued and contextual fear, inactivation of 5-HT2C receptors facilitate the retrieval of cued fear memory, the 5-HT3 receptor mediates contextual fear, genetically induced increases in serotonin levels are associated with increased fear conditioning, impaired cued fear extinction, or impaired extinction recall, and that genetically induced 5-HT depletion increases fear conditioning and contextual fear. Several explanations are presented to reconcile seemingly paradoxical relationships between serotonin levels and conditioned fear.

  15. Influence of stress on fear memory processes in an aversive differential conditioning paradigm in humans.

    Science.gov (United States)

    Bentz, Dorothée; Michael, Tanja; Wilhelm, Frank H; Hartmann, Francina R; Kunz, Sabrina; von Rohr, Isabelle R Rudolf; de Quervain, Dominique J-F

    2013-07-01

    It is widely assumed that learning and memory processes play an important role in the pathogenesis, expression, maintenance and therapy of anxiety disorders, such as phobias or post-traumatic stress disorder (PTSD). Memory retrieval is involved in symptom expression and maintenance of these disorders, while memory extinction is believed to be the underlying mechanism of behavioral exposure therapy of anxiety disorders. There is abundant evidence that stress and stress hormones can reduce memory retrieval of emotional information, whereas they enhance memory consolidation of extinction training. In this study we aimed at investigating if stress affects these memory processes in a fear conditioning paradigm in healthy human subjects. On day 1, fear memory was acquired through a standard differential fear conditioning procedure. On day 2 (24h after fear acquisition), participants either underwent a stressful cold pressor test (CPT) or a control condition, 20 min before memory retrieval testing and extinction training. Possible prolonged effects of the stress manipulation were investigated on day 3 (48 h after fear acquisition), when memory retrieval and extinction were tested again. On day 2, men in the stress group showed a robust cortisol response to stress and showed lower unconditioned stimulus (US) expectancy ratings than men in the control group. This reduction in fear memory retrieval was maintained on day 3. In women, who showed a significantly smaller cortisol response to stress than men, no stress effects on fear memory retrieval were observed. No group differences were observed with respect to extinction. In conclusion, the present study provides evidence that stress can reduce memory retrieval of conditioned fear in men. Our findings may contribute to the understanding of the effects of stress and glucocorticoids on fear symptoms in anxiety disorders and suggest that such effects may be sex-specific. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Durable fear memories require PSD-95

    Science.gov (United States)

    Fitzgerald, Paul J.; Pinard, Courtney R.; Camp, Marguerite C.; Feyder, Michael; Sah, Anupam; Bergstrom, Hadley; Graybeal, Carolyn; Liu, Yan; Schlüter, Oliver; Grant, Seth G.N.; Singewald, Nicolas; Xu, Weifeng; Holmes, Andrew

    2014-01-01

    Traumatic fear memories are highly durable but also dynamic, undergoing repeated reactivation and rehearsal over time. While overly persistent fear memories underlie anxiety disorders such as posttraumatic stress disorder, the key neural and molecular mechanisms underlying fear memory durability remain unclear. Post-synaptic density 95 (PSD-95) is a synaptic protein regulating glutamate receptor anchoring, synaptic stability and certain types of memory. Employing a loss-of-function mutant mouse lacking the guanylate kinase domain of PSD-95 (PSD-95GK), we analyzed the contribution of PSD-95 to fear memory formation and retrieval, and sought to identify the neural basis of PSD-95-mediated memory maintenance using ex vivo immediate-early gene mapping, in vivo neuronal recordings and viral-mediated knockdown approaches. We show that PSD-95 is dispensable for the formation and expression of recent fear memories, but essential for the formation of precise and flexible fear memories and for the maintenance of memories at remote time points. The failure of PSD-95GK mice to retrieve remote cued fear memories was associated with hypoactivation of the infralimbic cortex (IL) (not anterior cingulate (ACC) or prelimbic cortex), reduced IL single-unit firing and bursting, and attenuated IL gamma and theta oscillations. Adeno-associated PSD-95 virus-mediated knockdown in the IL, not ACC, was sufficient to impair recent fear extinction and remote fear memory, and remodel IL dendritic spines. Collectively, these data identify PSD-95 in the IL as a critical mechanism supporting the durability of fear memories over time. These preclinical findings have implications for developing novel approaches to treating trauma-based anxiety disorders that target the weakening of overly persistent fear memories. PMID:25510511

  17. Inhaled Lavandula angustifolia essential oil inhibits consolidation of contextual- but not tone-fear conditioning in rats.

    Science.gov (United States)

    Coelho, Laura Segismundo; Correa-Netto, Nelson Francisco; Masukawa, Marcia Yuriko; Lima, Ariadiny Caetano; Maluf, Samia; Linardi, Alessandra; Santos-Junior, Jair Guilherme

    2018-04-06

    Although the current treatment for anxiety is effective, it promotes a number of adverse reactions and medical interactions. Inhaled essential oils have a prominent action on the central nervous system, with minimal systemic effects, primarily because of reduced systemic bioavailability. The effects of drugs on the consolidation of fear conditioning reflects its clinical efficacy in preventing a vicious cycle of anticipatory anxiety leading to fearful cognition and anxiety symptoms. In this study, we investigated the effects of inhaled Lavandula angustifolia essential oil on the consolidation of aversive memories and its influence on c-Fos expression. Adult male Wistar rats were subjected to a fear conditioning protocol. Immediately after the training session, the rats were exposed to vaporized water or essential oil (1%, 2.5% and 5% solutions) for 4h. The next day, the rats underwent contextual- or tone-fear tests and 90min after the test they were euthanized and their brains processed for c-Fos immunohistochemistry. In the contextual-fear test, essential oil at 2.5% and 5% (but not 1%) reduced the freezing response and its respective c-Fos expression in the ventral hippocampus and amygdala. In the tone-fear test, essential oil did not reduce the freezing response during tone presentation. However, rats that inhaled essential oil at 2.5% and 5% (but not 1%) showed decreased freezing in the three minutes after tone presentation, as well as reduced c-Fos expression in the prefrontal cortex and amygdala. These results show that the inhalation of L. angustifolia essential oil inhibited the consolidation of contextual- but not tone-fear conditioning and had an anxiolytic effect in a conditioned animal model of anxiety. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Dysfunctional overnight memory consolidation in ecstasy users.

    Science.gov (United States)

    Smithies, Vanessa; Broadbear, Jillian; Verdejo-Garcia, Antonio; Conduit, Russell

    2014-08-01

    Sleep plays an important role in the consolidation and integration of memory in a process called overnight memory consolidation. Previous studies indicate that ecstasy users have marked and persistent neurocognitive and sleep-related impairments. We extend past research by examining overnight memory consolidation among regular ecstasy users (n=12) and drug naïve healthy controls (n=26). Memory recall of word pairs was evaluated before and after a period of sleep, with and without interference prior to testing. In addition, we assessed neurocognitive performances across tasks of learning, memory and executive functioning. Ecstasy users demonstrated impaired overnight memory consolidation, a finding that was more pronounced following associative interference. Additionally, ecstasy users demonstrated impairments on tasks recruiting frontostriatal and hippocampal neural circuitry, in the domains of proactive interference memory, long-term memory, encoding, working memory and complex planning. We suggest that ecstasy-associated dysfunction in fronto-temporal circuitry may underlie overnight consolidation memory impairments in regular ecstasy users. © The Author(s) 2014.

  19. Role of NPY Y1 receptor on acquisition, consolidation and extinction on contextual fear conditioning: dissociation between anxiety, locomotion and non-emotional memory behavior.

    Science.gov (United States)

    Lach, Gilliard; de Lima, Thereza Christina Monteiro

    2013-07-01

    Neuropeptide Y (NPY) is the most abundant peptide in the central nervous system (CNS) and is densely localized in the brain regions involved in stress, memory, fear and anxiety. Although previous research supports a role for NPY in the mediation of rodent and human emotional behavior, there is currently a lack of information on the effects of low doses of NPY that could have a potential therapeutic advantage, minimizing side-effects such as cognition impairment or sedation. Herein, we assessed the effects of intracerebroventricular (i.c.v.) administration of low doses of NPY, and of the Y1-agonist Leu31Pro34-NPY (LP-NPY) on contextual fear conditioning (CFC), as they have no effect on unconditioned anxiety-like, locomotor activity and non-emotional memory. NPY (3 pmol) and LP-NPY (1 pmol) inhibited freezing behavior when administered in the acquisition or consolidation stages, indicating a reduction of fear. When injected in the extinction phase, only NPY inhibited freezing behavior on CFC. Pre-treatment with the Y1-antagonist BIBO3304 before NPY and LP-NPY was able to prevent the inhibition of fear responses induced by both NPY agonists. Taken together, our results demonstrate robust fear-inhibiting effects of i.c.v. injection of NPY on contextual fear conditioning in rats, a response that is mediated, at least in part, by the Y1 receptor. Moreover, these treatments were unable to change locomotor activity or to show an anxiolytic-like effect, as evaluated in an open-field and an elevated plus-maze. This specific fear reduction effect may underlie resilience systems in the CNS and has potential therapeutic relevance in PTSD. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Distributed learning enhances relational memory consolidation.

    Science.gov (United States)

    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.

  1. Sensory-specific associations stored in the lateral amygdala allow for selective alteration of fear memories.

    Science.gov (United States)

    Díaz-Mataix, Lorenzo; Debiec, Jacek; LeDoux, Joseph E; Doyère, Valérie

    2011-06-29

    Consolidated long-term fear memories become labile and can be disrupted after being reactivated by the presentation of the unconditioned stimulus (US). Whether this is due to an alteration of the conditioned stimulus (CS) representation in the lateral amygdala (LA) is not known. Here, we show in rats that fear memory reactivation through presentation of the aversive US, like CS presentation, triggers a process which, when disrupted, results in a selective depotentiation of CS-evoked neural responses in the LA in correlation with a selective suppression of CS-elicited fear memory. Thus, an aversive US triggers the reconsolidation of its associated predictor representation in LA. This new finding suggests that sensory-specific associations are stored in the lateral amygdala, allowing for their selective alteration by either element of the association.

  2. Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model

    Science.gov (United States)

    Li, Yuzhe; Nakae, Ken; Ishii, Shin; Naoki, Honda

    2016-01-01

    Uncertainty of fear conditioning is crucial for the acquisition and extinction of fear memory. Fear memory acquired through partial pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) is more resistant to extinction than that acquired through full pairings; this effect is known as the partial reinforcement extinction effect (PREE). Although the PREE has been explained by psychological theories, the neural mechanisms underlying the PREE remain largely unclear. Here, we developed a neural circuit model based on three distinct types of neurons (fear, persistent and extinction neurons) in the amygdala and medial prefrontal cortex (mPFC). In the model, the fear, persistent and extinction neurons encode predictions of net severity, of unconditioned stimulus (US) intensity, and of net safety, respectively. Our simulation successfully reproduces the PREE. We revealed that unpredictability of the US during extinction was represented by the combined responses of the three types of neurons, which are critical for the PREE. In addition, we extended the model to include amygdala subregions and the mPFC to address a recent finding that the ventral mPFC (vmPFC) is required for consolidating extinction memory but not for memory retrieval. Furthermore, model simulations led us to propose a novel procedure to enhance extinction learning through re-conditioning with a stronger US; strengthened fear memory up-regulates the extinction neuron, which, in turn, further inhibits the fear neuron during re-extinction. Thus, our models increased the understanding of the functional roles of the amygdala and vmPFC in the processing of uncertainty in fear conditioning and extinction. PMID:27617747

  3. Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model.

    Science.gov (United States)

    Li, Yuzhe; Nakae, Ken; Ishii, Shin; Naoki, Honda

    2016-09-01

    Uncertainty of fear conditioning is crucial for the acquisition and extinction of fear memory. Fear memory acquired through partial pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) is more resistant to extinction than that acquired through full pairings; this effect is known as the partial reinforcement extinction effect (PREE). Although the PREE has been explained by psychological theories, the neural mechanisms underlying the PREE remain largely unclear. Here, we developed a neural circuit model based on three distinct types of neurons (fear, persistent and extinction neurons) in the amygdala and medial prefrontal cortex (mPFC). In the model, the fear, persistent and extinction neurons encode predictions of net severity, of unconditioned stimulus (US) intensity, and of net safety, respectively. Our simulation successfully reproduces the PREE. We revealed that unpredictability of the US during extinction was represented by the combined responses of the three types of neurons, which are critical for the PREE. In addition, we extended the model to include amygdala subregions and the mPFC to address a recent finding that the ventral mPFC (vmPFC) is required for consolidating extinction memory but not for memory retrieval. Furthermore, model simulations led us to propose a novel procedure to enhance extinction learning through re-conditioning with a stronger US; strengthened fear memory up-regulates the extinction neuron, which, in turn, further inhibits the fear neuron during re-extinction. Thus, our models increased the understanding of the functional roles of the amygdala and vmPFC in the processing of uncertainty in fear conditioning and extinction.

  4. Effects of Stress and Sex on Acquisition and Consolidation of Human Fear Conditioning

    Science.gov (United States)

    Kuhn, Cynthia M.; LaBar, Kevin S.; Zorawski, Michael; Blanding, Nineequa Q.

    2006-01-01

    We examined the relationship between stress hormone (cortisol) release and acquisition and consolidation of conditioned fear learning in healthy adults. Participants underwent acquisition of differential fear conditioning, and consolidation was assessed in a 24-h delayed extinction test. The acquisition phase was immediately followed by an 11-min…

  5. Reward value determines memory consolidation in parasitic wasps.

    Science.gov (United States)

    Kruidhof, H Marjolein; Pashalidou, Foteini G; Fatouros, Nina E; Figueroa, Ilich A; Vet, Louise E M; Smid, Hans M; Huigens, Martinus E

    2012-01-01

    Animals can store learned information in their brains through a series of distinct memory forms. Short-lasting memory forms can be followed by longer-lasting, consolidated memory forms. However, the factors determining variation in memory consolidation encountered in nature have thus far not been fully elucidated. Here, we show that two parasitic wasp species belonging to different families, Cotesia glomerata (Hymenoptera: Braconidae) and Trichogramma evanescens (Hymenoptera; Trichogrammatidae), similarly adjust the memory form they consolidate to a fitness-determining reward: egg-laying into a host-insect that serves as food for their offspring. Protein synthesis-dependent long-term memory (LTM) was consolidated after single-trial conditioning with a high-value host. However, single-trial conditioning with a low-value host induced consolidation of a shorter-lasting memory form. For Cotesia glomerata, we subsequently identified this shorter-lasting memory form as anesthesia-resistant memory (ARM) because it was not sensitive to protein synthesis inhibitors or anesthesia. Associative conditioning using a single reward of different value thus induced a physiologically different mechanism of memory formation in this species. We conclude that the memory form that is consolidated does not only change in response to relatively large differences in conditioning, such as the number and type of conditioning trials, but is also sensitive to more subtle differences, such as reward value. Reward-dependent consolidation of exclusive ARM or LTM provides excellent opportunities for within-species comparison of mechanisms underlying memory consolidation.

  6. Orexin receptor-1 in the locus coeruleus plays an important role in cue-dependent fear memory consolidation.

    Science.gov (United States)

    Soya, Shingo; Shoji, Hirotaka; Hasegawa, Emi; Hondo, Mari; Miyakawa, Tsuyoshi; Yanagisawa, Masashi; Mieda, Michihiro; Sakurai, Takeshi

    2013-09-04

    The noradrenergic (NA) projections arising from the locus ceruleus (LC) to the amygdala and bed nucleus of the stria terminalis have been implicated in the formation of emotional memory. Since NA neurons in the LC (LC-NA neurons) abundantly express orexin receptor-1 (OX1R) and receive prominent innervation by orexin-producing neurons, we hypothesized that an OX1R-mediated pathway is involved in the physiological fear learning process via regulation of LC-NA neurons. To evaluate this hypothesis, we examined the phenotype of Ox1r(-/-) mice in the classic cued and contextual fear-conditioning test. We found that Ox1r(-/-) mice showed impaired freezing responses in both cued and contextual fear-conditioning paradigms. In contrast, Ox2r(-/-) mice showed normal freezing behavior in the cued fear-conditioning test, while they exhibited shorter freezing time in the contextual fear-conditioning test. Double immunolabeling of Fos and tyrosine hydroxylase showed that double-positive LC-NA neurons after test sessions of both cued and contextual stimuli were significantly fewer in Ox1r(-/-) mice. AAV-mediated expression of OX1R in LC-NA neurons in Ox1r(-/-) mice restored the freezing behavior to the auditory cue to a comparable level to that in wild-type mice in the test session. Decreased freezing time during the contextual fear test was not affected by restoring OX1R expression in LC-NA neurons. These observations support the hypothesis that the orexin system modulates the formation and expression of fear memory via OX1R in multiple pathways. Especially, OX1R in LC-NA neurons plays an important role in cue-dependent fear memory formation and/or retrieval.

  7. Sleep-related memory consolidation in primary insomnia.

    Science.gov (United States)

    Nissen, Christoph; Kloepfer, Corinna; Feige, Bernd; Piosczyk, Hannah; Spiegelhalder, Kai; Voderholzer, Ulrich; Riemann, Dieter

    2011-03-01

    It has been suggested that healthy sleep facilitates the consolidation of newly acquired memories and underlying brain plasticity. The authors tested the hypothesis that patients with primary insomnia (PI) would show deficits in sleep-related memory consolidation compared to good sleeper controls (GSC). The study used a four-group parallel design (n=86) to investigate the effects of 12 h of night-time, including polysomnographically monitored sleep ('sleep condition' in PI and GSC), versus 12 h of daytime wakefulness ('wake condition' in PI and GSC) on procedural (mirror tracing task) and declarative memory consolidation (visual and verbal learning task). Demographic characteristics and memory encoding did not differ between the groups at baseline. Polysomnography revealed a significantly disturbed sleep profile in PI compared to GSC in the sleep condition. Night-time periods including sleep in GSC were associated with (i) a significantly enhanced procedural and declarative verbal memory consolidation compared to equal periods of daytime wakefulness in GSC and (ii) a significantly enhanced procedural memory consolidation compared to equal periods of daytime wakefulness and night-time sleep in PI. Across retention intervals of daytime wakefulness, no differences between the experimental groups were observed. This pattern of results suggests that healthy sleep fosters the consolidation of new memories, and that this process is impaired for procedural memories in patients with PI. Future work is needed to investigate the impact of treatment on improving sleep and memory. © 2010 European Sleep Research Society.

  8. Dreaming and offline memory consolidation.

    Science.gov (United States)

    Wamsley, Erin J

    2014-03-01

    Converging evidence suggests that dreaming is influenced by the consolidation of memory during sleep. Following encoding, recently formed memory traces are gradually stabilized and reorganized into a more permanent form of long-term storage. Sleep provides an optimal neurophysiological state to facilitate this process, allowing memory networks to be repeatedly reactivated in the absence of new sensory input. The process of memory reactivation and consolidation in the sleeping brain appears to influence conscious experience during sleep, contributing to dream content recalled on awakening. This article outlines several lines of evidence in support of this hypothesis, and responds to some common objections.

  9. Encoding of contextual fear memory requires de novo proteins in the prelimbic cortex

    Science.gov (United States)

    Rizzo, Valerio; Touzani, Khalid; Raveendra, Bindu L.; Swarnkar, Supriya; Lora, Joan; Kadakkuzha, Beena M.; Liu, Xin-An; Zhang, Chao; Betel, Doron; Stackman, Robert W.; Puthanveettil, Sathyanarayanan V.

    2016-01-01

    Background Despite our understanding of the significance of the prefrontal cortex in the consolidation of long-term memories (LTM), its role in the encoding of LTM remains elusive. Here we investigated the role of new protein synthesis in the mouse medial prefrontal cortex (mPFC) in encoding contextual fear memory. Methods Because a change in the association of mRNAs to polyribosomes is an indicator of new protein synthesis, we assessed the changes in polyribosome-associated mRNAs in the mPFC following contextual fear conditioning (CFC) in the mouse. Differential gene expression in mPFC was identified by polyribosome profiling (n = 18). The role of new protein synthesis in mPFC was determined by focal inhibition of protein synthesis (n = 131) and by intra-prelimbic cortex manipulation (n = 56) of Homer 3, a candidate identified from polyribosome profiling. Results We identified several mRNAs that are differentially and temporally recruited to polyribosomes in the mPFC following CFC. Inhibition of protein synthesis in the prelimbic (PL), but not in the anterior cingulate cortex (ACC) region of the mPFC immediately after CFC disrupted encoding of contextual fear memory. Intriguingly, inhibition of new protein synthesis in the PL 6 hours after CFC did not impair encoding. Furthermore, expression of Homer 3, an mRNA enriched in polyribosomes following CFC, in the PL constrained encoding of contextual fear memory. Conclusions Our studies identify several molecular substrates of new protein synthesis in the mPFC and establish that encoding of contextual fear memories require new protein synthesis in PL subregion of mPFC. PMID:28503670

  10. [The consolidation of memory, one century on].

    Science.gov (United States)

    Prado-Alcala, R A; Quirarte, G L

    The theory of memory consolidation, based on the work published by Georg Elias Muller and Alfons Pilzecker over a century ago, continues to guide research into the neurobiology of memory, either directly or indirectly. In their classic monographic work, they concluded that fixing memory requires the passage of time (consolidation) and that memory is vulnerable during this period of consolidation, as symptoms of amnesia appear when brain functioning is interfered with before the consolidation process is completed. Most of the experimental data concerning this phenomenon strongly support the theory. In this article we present a review of experiments that have made it possible to put forward a model that explains the amnesia produced in conventional learning conditions, as well as another model related to the protection of memory when the same instances of learning are submitted to a situation involving intensive training. Findings from relatively recent studies have shown that treatments that typically produce amnesia when they are administered immediately after a learning experience (during the period in which the memory would be consolidating itself) no longer have any effect when the instances of learning involve a relatively large number of trials or training sessions, or relatively high intensity aversive events. These results are not congruent with the prevailing theories about consolidation.

  11. Dissociating response systems: erasing fear from memory.

    Science.gov (United States)

    Soeter, Marieke; Kindt, Merel

    2010-07-01

    In addition to the extensive evidence in animals, we previously showed that disrupting reconsolidation by noradrenergic blockade produced amnesia for the original fear response in humans. Interestingly, the declarative memory for the fear association remained intact. These results asked for a solid replication. Moreover, given the constructive nature of memories, the intact recollection of the fear association could eventually 'rebuild' the fear memory, resulting in the spontaneous recovery of the fear response. Yet, perseverance of the amnesic effects would have substantial clinical implications, as even the most effective treatments for psychiatric disorders display high percentages of relapse. Using a differential fear conditioning procedure in humans, we replicated our previous findings by showing that administering propranolol (40mg) prior to memory reactivation eliminated the startle fear response 24h later. But most importantly, this effect persisted at one month follow-up. Notably, the propranolol manipulation not only left the declarative memory for the acquired contingency untouched, but also skin conductance discrimination. In addition, a close association between declarative knowledge and skin conductance responses was found. These findings are in line with the supposed double dissociation of fear conditioning and declarative knowledge relative to the amygdala and hippocampus in humans. They support the view that skin conductance conditioning primarily reflects contingency learning, whereas the startle response is a rather specific measure of fear. Furthermore, the results indicate the absence of a causal link between the actual knowledge of a fear association and its fear response, even though they often operate in parallel. Interventions targeting the amygdalar fear memory may be essential in specifically and persistently dampening the emotional impact of fear. From a clinical and ethical perspective, disrupting reconsolidation points to promising

  12. Enhanced Noradrenergic Activity Potentiates Fear Memory Consolidation and Reconsolidation by Differentially Recruiting alpha1- and beta-Adrenergic Receptors

    Science.gov (United States)

    Gazarini, Lucas; Stern, Cristina A. Jark; Carobrez, Antonio P.; Bertoglio, Leandro J.

    2013-01-01

    Consolidation and reconsolidation are phases of memory stabilization that diverge slightly. Noradrenaline is known to influence both processes, but the relative contribution of alpha1- and beta-adrenoceptors is unclear. The present study sought to investigate this matter by comparing their recruitment to consolidate and/or reconsolidate a…

  13. Resting state EEG correlates of memory consolidation.

    Science.gov (United States)

    Brokaw, Kate; Tishler, Ward; Manceor, Stephanie; Hamilton, Kelly; Gaulden, Andrew; Parr, Elaine; Wamsley, Erin J

    2016-04-01

    Numerous studies demonstrate that post-training sleep benefits human memory. At the same time, emerging data suggest that other resting states may similarly facilitate consolidation. In order to identify the conditions under which non-sleep resting states benefit memory, we conducted an EEG (electroencephalographic) study of verbal memory retention across 15min of eyes-closed rest. Participants (n=26) listened to a short story and then either rested with their eyes closed, or else completed a distractor task for 15min. A delayed recall test was administered immediately following the rest period. We found, first, that quiet rest enhanced memory for the short story. Improved memory was associated with a particular EEG signature of increased slow oscillatory activity (rest can facilitate memory, and that this may occur via an active process of consolidation supported by slow oscillatory EEG activity and characterized by decreased attention to the external environment. Slow oscillatory EEG rhythms are proposed to facilitate memory consolidation during sleep by promoting hippocampal-cortical communication. Our findings suggest that EEG slow oscillations could play a significant role in memory consolidation during other resting states as well. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Consolidation and restoration of memory traces in working memory.

    Science.gov (United States)

    De Schrijver, Sébastien; Barrouillet, Pierre

    2017-10-01

    Consolidation is the process through which ephemeral sensory traces are transformed into more stable short-term memory traces. It has been shown that consolidation plays a crucial role in working memory (WM) performance, by strengthening memory traces that then better resist interference and decay. In a recent study, Bayliss, Bogdanovs, and Jarrold (Journal of Memory and Language, 81, 34-50, 2015) argued that this process is separate from the processes known to restore WM traces after degradation, such as attentional refreshing and verbal rehearsal. In the present study, we investigated the relationship between the two types of processes in the context of WM span tasks. Participants were presented with series of letters for serial recall, each letter being followed by four digits for parity judgment. Consolidation opportunity was manipulated by varying the delay between each letter and the first digit to be processed, while opportunities for restoration were manipulated by varying the pace at which the parity task had to be performed (i.e., its cognitive load, or CL). Increasing the time available for either consolidation or restoration resulted in higher WM spans, with some substitutability between the two processes. Accordingly, when consolidation time was added to restoration time in the calculation of CL, the new resulting index, called extended CL, proved a very good predictor of recall performance, a finding also observed when verbal rehearsal was prevented by articulatory suppression. This substitutability between consolidation and restoration suggests that both processes may rely on the same mechanisms.

  15. Reward Value Determines Memory Consolidation in Parasitic Wasps

    NARCIS (Netherlands)

    Kruidhof, H.M.; Pashalidou, F.G.; Fatouros, N.E.; Figueroa, I.A.; Vet, L.E.M.; Smid, H.M.; Huigens, M.E.

    2012-01-01

    Animals can store learned information in their brains through a series of distinct memory forms. Short-lasting memory forms can be followed by longer-lasting, consolidated memory forms. However, the factors determining variation in memory consolidation encountered in nature have thus far not been

  16. The neural dynamics of fear memory

    NARCIS (Netherlands)

    Visser, R.M.

    2016-01-01

    While much of what we learn will be forgotten over time, fear memory appears to be particularly resilient to forgetting. Our understanding of how fearful events are transformed into durable memory, and how this memory subsequently influences the processing of (novel) stimuli, is limited. Studying

  17. How aging affects sleep-dependent memory consolidation?

    Directory of Open Access Journals (Sweden)

    Caroline eHarand

    2012-02-01

    Full Text Available Sleep plays multiple functions among which energy conservation or recuperative processes. Besides, growing evidence indicate that sleep plays also a major role in memory consolidation, a process by which recently acquired and labile memory traces are progressively strengthened into more permanent and/or enhanced forms. Indeed, memories are not stored as they were initially encoded but rather undergo a gradual reorganization process, which is favoured by the neurochemical environment and the electrophysiological activity observed during sleep. Two putative, probably not exclusive, models (hippocampo-neocortical dialogue and synaptic homeostasis hypothesis have been proposed to explain the beneficial effect of sleep on memory processes. It is worth noting that all data gathered until now emerged from studies conducted in young subjects. The investigation of the relationships between sleep and memory in older adults has sparked off little interest until recently. Though, aging is characterized by memory impairment, changes in sleep architecture, as well as brain and neurochemical alterations. All these elements suggest that sleep-dependent memory consolidation may be impaired or occurs differently in older adults.Here, we give an overview of the mechanisms governing sleep-dependent memory consolidation, and the crucial points of this complex process that may dysfunction and result in impaired memory consolidation in aging.

  18. Sleep enhances memory consolidation in children.

    Science.gov (United States)

    Ashworth, Anna; Hill, Catherine M; Karmiloff-Smith, Annette; Dimitriou, Dagmara

    2014-06-01

    Sleep is an active state that plays an important role in the consolidation of memory. It has been found to enhance explicit memories in both adults and children. However, in contrast to adults, children do not always show a sleep-related improvement in implicit learning. The majority of research on sleep-dependent memory consolidation focuses on adults; hence, the current study examined sleep-related effects on two tasks in children. Thirty-three typically developing children aged 6-12 years took part in the study. Actigraphy was used to monitor sleep. Sleep-dependent memory consolidation was assessed using a novel non-word learning task and the Tower of Hanoi cognitive puzzle, which involves discovering an underlying rule to aid completion. Children were trained on the two tasks and retested following approximately equal retention intervals of both wake and sleep. After sleep, children showed significant improvements in performance of 14% on the non-word learning task and 25% on the Tower of Hanoi task, but no significant change in score following the wake retention interval. Improved performance on the Tower of Hanoi may have been due to children consolidating explicit aspects of the task, for example rule-learning or memory of previous sequences; thus, we propose that sleep is necessary for consolidation of explicit memory in children. Sleep quality and duration were not related to children's task performance. If such experimental sleep-related learning enhancement is generalizable to everyday life, then it is clear that sleep plays a vital role in children's educational attainment. © 2013 European Sleep Research Society.

  19. Retrieving fear memories, as time goes by…

    Science.gov (United States)

    Do Monte, Fabricio H.; Quirk, Gregory J.; Li, Bo; Penzo, Mario A.

    2016-01-01

    Fear conditioning researches have led to a comprehensive picture of the neuronal circuit underlying the formation of fear memories. In contrast, knowledge about the retrieval of fear memories is much more limited. This disparity may stem from the fact that fear memories are not rigid, but reorganize over time. To bring clarity and raise awareness on the time-dependent dynamics of retrieval circuits, we review current evidence on the neuronal circuitry participating in fear memory retrieval at both early and late time points after conditioning. We focus on the temporal recruitment of the paraventricular nucleus of the thalamus, and its BDNFergic efferents to the central nucleus of the amygdala, for the retrieval and maintenance of fear memories. Finally, we speculate as to why retrieval circuits change across time, and the functional benefits of recruiting structures such as the paraventricular nucleus into the retrieval circuit. PMID:27217148

  20. Chronic fluoxetine dissociates contextual from auditory fear memory.

    Science.gov (United States)

    Sanders, Jeff; Mayford, Mark

    2016-10-06

    Fluoxetine is a medication used to treat Major Depressive Disorder and other psychiatric conditions. These experiments studied the effects of chronic fluoxetine treatment on the contextual versus auditory fear memory of mice. We found that chronic fluoxetine treatment of adult mice impaired their contextual fear memory, but spared auditory fear memory. Hippocampal perineuronal nets, which are involved in contextual fear memory plasticity, were unaltered by fluoxetine treatment. These data point to a selective inability to form contextual fear memory as a result of fluoxetine treatment, and they suggest that a blunting of hippocampal-mediated aversive memory may be a therapeutic action for this medication. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Role of adult neurogenesis in hippocampal-cortical memory consolidation

    Science.gov (United States)

    2014-01-01

    Acquired memory is initially dependent on the hippocampus (HPC) for permanent memory formation. This hippocampal dependency of memory recall progressively decays with time, a process that is associated with a gradual increase in dependency upon cortical structures. This process is commonly referred to as systems consolidation theory. In this paper, we first review how memory becomes hippocampal dependent to cortical dependent with an emphasis on the interactions that occur between the HPC and cortex during systems consolidation. We also review the mechanisms underlying the gradual decay of HPC dependency during systems consolidation from the perspective of memory erasures by adult hippocampal neurogenesis. Finally, we discuss the relationship between systems consolidation and memory precision. PMID:24552281

  2. The nature of short-term consolidation in visual working memory.

    Science.gov (United States)

    Ricker, Timothy J; Hardman, Kyle O

    2017-11-01

    Short-term consolidation is the process by which stable working memory representations are created. This process is fundamental to cognition yet poorly understood. The present work examines short-term consolidation using a Bayesian hierarchical model of visual working memory recall to determine the underlying processes at work. Our results show that consolidation functions largely through changing the proportion of memory items successfully maintained until test. Although there was some evidence that consolidation affects representational precision, this change was modest and could not account for the bulk of the consolidation effect on memory performance. The time course of the consolidation function and selective influence of consolidation on specific serial positions strongly indicates that short-term consolidation induces an attentional blink. The blink leads to deficits in memory for the immediately following item when time pressure is introduced. Temporal distinctiveness accounts of the consolidation process are tested and ruled out. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. Kinase activity in the olfactory bulb is required for odor memory consolidation.

    Science.gov (United States)

    Tong, Michelle T; Kim, Tae-Young P; Cleland, Thomas A

    2018-05-01

    Long-term fear memory formation in the hippocampus and neocortex depends upon brain-derived neurotrophic factor (BDNF) signaling after acquisition. Incremental, appetitive odor discrimination learning is thought to depend substantially on the differentiation of adult-born neurons within the olfactory bulb (OB)-a process that is closely associated with BDNF signaling. We sought to elucidate the role of neurotrophin signaling within the OB on odor memory consolidation. Male mice were trained on odor-reward associative discriminations after bilateral infusion of the kinase inhibitor K252a, or vehicle control, into the OB. K252a is a partially selective inhibitor of tyrosine kinase (Trk) receptors, including the TrkB receptor for BDNF, though it also inhibits other plasticity-related kinases such as PKC and CaMKII/IV. K252a infusion into the OB did not impair odor acquisition or short-term (2 h) memory for the learned discriminations, but significantly impaired long-term (48 h) odor memory (LTM). This LTM deficit also was associated with reduced selectivity for the conditioned odorant in a reward-seeking digging task. Infusions of K252a immediately prior to testing did not impair LTM recall. These results indicate that kinase activation in the OB is required for the consolidation of odor memory of incrementally acquired information. © 2018 Tong et al.; Published by Cold Spring Harbor Laboratory Press.

  4. Does abnormal sleep impair memory consolidation in schizophrenia?

    Directory of Open Access Journals (Sweden)

    Dara S Manoach

    2009-09-01

    Full Text Available Although disturbed sleep is a prominent feature of schizophrenia, its relation to the pathophysiology, signs, and symptoms of schizophrenia remains poorly understood. Sleep disturbances are well known to impair cognition in healthy individuals. Yet, in spite of its ubiquity in schizophrenia, abnormal sleep has generally been overlooked as a potential contributor to cognitive deficits. Amelioration of cognitive deficits is a current priority of the schizophrenia research community, but most efforts to define, characterize, and quantify cognitive deficits focus on cross-sectional measures. While this approach provides a valid snapshot of function, there is now overwhelming evidence that critical aspects of learning and memory consolidation happen offline, both over time and with sleep. Initial memory encoding is followed by a prolonged period of consolidation, integration, and reorganization, that continues over days or even years. Much of this evolution of memories is mediated by sleep. This article briefly reviews (i abnormal sleep in schizophrenia, (ii sleep-dependent memory consolidation in healthy individuals, (iii recent findings of impaired sleep-dependent memory consolidation in schizophrenia, and (iv implications of impaired sleep-dependent memory consolidation in schizophrenia. This literature suggests that abnormal sleep in schizophrenia disrupts attention and impairs sleep-dependent memory consolidation and task automation. We conclude that these sleep-dependent impairments may contribute substantially to generalized cognitive deficits in schizophrenia. Understanding this contribution may open new avenues to ameliorating cognitive dysfunction and thereby improve outcome in schizophrenia.

  5. Enhancement of striatum-dependent memory by conditioned fear is mediated by beta-adrenergic receptors in the basolateral amygdala

    Directory of Open Access Journals (Sweden)

    Travis D. Goode

    2016-06-01

    Full Text Available Emotional arousal can have a profound impact on various learning and memory processes. For example, unconditioned emotional stimuli (e.g., predator odor or anxiogenic drugs enhance dorsolateral striatum (DLS-dependent habit memory. These effects critically depend on a modulatory role of the basolateral complex of the amygdala (BLA. Recent work indicates that, like unconditioned emotional stimuli, exposure to an aversive conditioned stimulus (CS (i.e., a tone previously paired with shock can also enhance consolidation of DLS-dependent habit memory. The present experiments examined whether noradrenergic activity, particularly within the BLA, is required for a fear CS to enhance habit memory consolidation. First, rats underwent a fear conditioning procedure in which a tone CS was paired with an aversive unconditioned stimulus. Over the course of the next five days, rats received training in a DLS-dependent water plus-maze task, in which rats were reinforced to make a consistent body-turn response to reach a hidden escape platform. Immediately after training on days 1–3, rats received post-training systemic (Experiment 1 or intra-BLA (Experiment 2 administration of the β-adrenoreceptor antagonist, propranolol. Immediately after drug administration, half of the rats were re-exposed to the tone CS in the conditioning context (without shock. Post-training CS exposure enhanced consolidation of habit memory in vehicle-treated rats, and this effect was blocked by peripheral (Experiment 1 or intra-BLA (Experiment 2 propranolol administration. The present findings reveal that noradrenergic activity within the BLA is critical for the enhancement of DLS-dependent habit memory as a result of exposure to conditioned emotional stimuli.

  6. Slow oscillations orchestrating fast oscillations and memory consolidation.

    Science.gov (United States)

    Mölle, Matthias; Born, Jan

    2011-01-01

    Slow-wave sleep (SWS) facilitates the consolidation of hippocampus-dependent declarative memory. Based on the standard two-stage memory model, we propose that memory consolidation during SWS represents a process of system consolidation which is orchestrated by the neocortical memory. The slow oscillations temporally group neuronal activity into up-states of strongly enhanced neuronal activity and down-states of neuronal silence. In a feed-forward efferent action, this grouping is induced not only in the neocortex but also in other structures relevant to consolidation, namely the thalamus generating 10-15Hz spindles, and the hippocampus generating sharp wave-ripples, with the latter well known to accompany a replay of newly encoded memories taking place in hippocampal circuitries. The feed-forward synchronizing effect of the slow oscillation enables the formation of spindle-ripple events where ripples and accompanying reactivated hippocampal memory information become nested into the single troughs of spindles. Spindle-ripple events thus enable reactivated memory-related hippocampal information to be fed back to neocortical networks in the excitable slow oscillation up-state where they can induce enduring plastic synaptic changes underlying the effective formation of long-term memories. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Consolidation of long-term memory: evidence and alternatives.

    Science.gov (United States)

    Meeter, Martijn; Murre, Jaap M J

    2004-11-01

    Memory loss in retrograde amnesia has long been held to be larger for recent periods than for remote periods, a pattern usually referred to as the Ribot gradient. One explanation for this gradient is consolidation of long-term memories. Several computational models of such a process have shown how consolidation can explain characteristics of amnesia, but they have not elucidated how consolidation must be envisaged. Here findings are reviewed that shed light on how consolidation may be implemented in the brain. Moreover, consolidation is contrasted with alternative theories of the Ribot gradient. Consolidation theory, multiple trace theory, and semantization can all handle some findings well but not others. Conclusive evidence for or against consolidation thus remains to be found.

  8. Consolidation of long-term memory: Evidence and alternatives.

    OpenAIRE

    Meeter, M.; Murre, J.M.J.

    2004-01-01

    Memory loss in retrograde amnesia has long been held to be larger for recent periods than for remote periods, a pattern usually referred to as the Ribot gradient. One explanation for this gradient is consolidation of long-term memories. Several computational models of such a process have shown how consolidation can explain characteristics of amnesia, but they have not elucidated how consolidation must be envisaged. Here findings are reviewed that shed light on how consolidation may be impleme...

  9. The CB1 receptor antagonist AM251 impairs reconsolidation of pavlovian fear memory in the rat basolateral amygdala.

    Science.gov (United States)

    Ratano, Patrizia; Everitt, Barry J; Milton, Amy L

    2014-10-01

    We have investigated the requirement for signaling at CB1 receptors in the reconsolidation of a previously consolidated auditory fear memory, by infusing the CB1 receptor antagonist AM251, or the FAAH inhibitor URB597, directly into the basolateral amygdala (BLA) in conjunction with memory reactivation. AM251 disrupted memory restabilization, but only when administered after reactivation. URB597 produced a small, transient enhancement of memory restabilization when administered after reactivation. The amnestic effect of AM251 was rescued by coadministration of the GABAA receptor antagonist bicuculline at reactivation, indicating that the disruption of reconsolidation was mediated by altered GABAergic transmission in the BLA. These data show that the endocannabinoid system in the BLA is an important modulator of fear memory reconsolidation and that its effects on memory are mediated by an interaction with the GABAergic system. Thus, targeting the endocannabinoid system may have therapeutic potential to reduce the impact of maladaptive memories in neuropsychiatric disorders such as posttraumatic stress disorder.

  10. Behavioural memory reconsolidation of food and fear memories.

    Science.gov (United States)

    Flavell, Charlotte R; Barber, David J; Lee, Jonathan L C

    2011-10-18

    The reactivation of a memory through retrieval can render it subject to disruption or modification through the process of memory reconsolidation. In both humans and rodents, briefly reactivating a fear memory results in effective erasure by subsequent extinction training. Here we show that a similar strategy is equally effective in the disruption of appetitive pavlovian cue-food memories. However, systemic administration of the NMDA receptor partial agonist D-cycloserine, under the same behavioural conditions, did not potentiate appetitive memory extinction, suggesting that reactivation does not enhance subsequent extinction learning. To confirm that reactivation followed by extinction reflects a behavioural analogue of memory reconsolidation, we show that prevention of contextual fear memory reactivation by the L-type voltage-gated calcium channel blocker nimodipine interferes with the amnestic outcome. Therefore, the reconsolidation process can be manipulated behaviourally to disrupt both aversive and appetitive memories. © 2011 Macmillan Publishers Limited. All rights reserved.

  11. Differential effects of non-REM and REM sleep on memory consolidation?

    Science.gov (United States)

    Ackermann, Sandra; Rasch, Björn

    2014-02-01

    Sleep benefits memory consolidation. Previous theoretical accounts have proposed a differential role of slow-wave sleep (SWS), rapid-eye-movement (REM) sleep, and stage N2 sleep for different types of memories. For example the dual process hypothesis proposes that SWS is beneficial for declarative memories, whereas REM sleep is important for consolidation of non-declarative, procedural and emotional memories. In fact, numerous recent studies do provide further support for the crucial role of SWS (or non-REM sleep) in declarative memory consolidation. However, recent evidence for the benefit of REM sleep for non-declarative memories is rather scarce. In contrast, several recent studies have related consolidation of procedural memories (and some also emotional memories) to SWS (or non-REM sleep)-dependent consolidation processes. We will review this recent evidence, and propose future research questions to advance our understanding of the role of different sleep stages for memory consolidation.

  12. The roles of the actin cytoskeleton in fear memory formation

    Directory of Open Access Journals (Sweden)

    Raphael eLamprecht

    2011-07-01

    Full Text Available The formation and storage of fear memory is needed to adapt behavior and avoid danger during subsequent fearful events. However, fear memory may also play a significant role in stress and anxiety disorders. When fear becomes disproportionate to that necessary to cope with a given stimulus, or begins to occur in inappropriate situations, a fear or anxiety disorder exists. Thus, the study of cellular and molecular mechanisms underpinning fear memory may shed light on the formation of memory and on anxiety and stress related disorders. Evidence indicates that fear learning leads to changes in neuronal synaptic transmission and morphology in brain areas underlying fear memory formation including the amygdala and hippocampus. The actin cytoskeleton has been shown to participate in these key neuronal processes. Recent findings show that the actin cytoskeleton is needed for fear memory formation and extinction. Moreover, the actin cytoskeleton is involved in synaptic plasticity and in neuronal morphogenesis in brain areas that mediate fear memory. The actin cytoskeleton may therefore mediate between synaptic transmission during fear learning and long-term cellular alterations mandatory for fear memory formation.

  13. Susceptibility of memory consolidation during lapses in recall

    Science.gov (United States)

    Marra, Vincenzo; O’Shea, Michael; Benjamin, Paul R.; Kemenes, Ildikó

    2013-01-01

    Memories that can be recalled several hours after learning may paradoxically become inaccessible for brief periods after their formation. This raises major questions about the function of these early memory lapses in the structure of memory consolidation. These questions are difficult to investigate because of the lack of information on the precise timing of lapses. However, the use of a single-trial conditioning paradigm in Lymnaea solves this problem. Here we use electrophysiological and behavioural experiments to reveal lapses in memory recall at 30 min and 2 h post conditioning. We show that only during these lapses is consolidation of long-term memory susceptible to interruption by external disturbance. These shared time points of memory lapse and susceptibility correspond to transitions between different phases of memory that have different molecular requirements. We propose that during periods of molecular transition memory recall is weakened, allowing novel sensory cues to block the consolidation of long-term memory. PMID:23481386

  14. Susceptibility of memory consolidation during lapses in recall.

    Science.gov (United States)

    Marra, Vincenzo; O'Shea, Michael; Benjamin, Paul R; Kemenes, Ildikó

    2013-01-01

    Memories that can be recalled several hours after learning may paradoxically become inaccessible for brief periods after their formation. This raises major questions about the function of these early memory lapses in the structure of memory consolidation. These questions are difficult to investigate because of the lack of information on the precise timing of lapses. However, the use of a single-trial conditioning paradigm in Lymnaea solves this problem. Here we use electrophysiological and behavioural experiments to reveal lapses in memory recall at 30 min and 2 h post conditioning. We show that only during these lapses is consolidation of long-term memory susceptible to interruption by external disturbance. These shared time points of memory lapse and susceptibility correspond to transitions between different phases of memory that have different molecular requirements. We propose that during periods of molecular transition memory recall is weakened, allowing novel sensory cues to block the consolidation of long-term memory.

  15. A unified theory for systems and cellular memory consolidation.

    Science.gov (United States)

    Dash, Pramod K; Hebert, April E; Runyan, Jason D

    2004-04-01

    The time-limited role of the hippocampus for explicit memory storage has been referred to as systems consolidation where learning-related changes occur first in the hippocampus followed by the gradual development of a more distributed memory trace in the neocortex. Recent experiments are beginning to show that learning induces plasticity-related molecular changes in the neocortex as well as in the hippocampus and with a similar time course. Present memory consolidation theories do not account for these findings. In this report, we present a theory (the C theory) that incorporates these new findings, provides an explanation for the length of time for hippocampal dependency, and that can account for the apparent longer consolidation periods in species with larger brains. This theory proposes that a process of cellular consolidation occurs in the hippocampus and in areas of the neocortex during and shortly after learning resulting in long-term memory storage in both areas. For a limited time, the hippocampus is necessary for memory retrieval, a process involving the coordinated reactivation of these areas. This reactivation is later mediated by longer extrahippocampal connectivity between areas. The delay in hippocampal-independent memory retrieval is the time it takes for gene products in these longer extrahippocampal projections to be transported from the soma to tagged synapses by slow axonal transport. This cellular transport event defines the period of hippocampal dependency and, thus, the duration of memory consolidation. The theoretical description for memory consolidation presented in this review provides alternative explanations for several experimental observations and presents a unification of the concepts of systems and cellular memory consolidation.

  16. Fear Conditioning Downregulates Rac1 Activity in the Basolateral Amygdala Astrocytes to Facilitate the Formation of Fear Memory.

    Science.gov (United States)

    Liao, Zhaohui; Tao, Yezheng; Guo, Xiaomu; Cheng, Deqin; Wang, Feifei; Liu, Xing; Ma, Lan

    2017-01-01

    Astrocytes are well known to scale synaptic structural and functional plasticity, while the role in learning and memory, such as conditioned fear memory, is poorly elucidated. Here, using pharmacological approach, we find that fluorocitrate (FC) significantly inhibits the acquisition of fear memory, suggesting that astrocyte activity is required for fear memory formation. We further demonstrate that fear conditioning downregulates astrocytic Rac1 activity in basolateral amygdala (BLA) in mice and promotes astrocyte structural plasticity. Ablation of astrocytic Rac1 in BLA promotes fear memory acquisition, while overexpression or constitutive activation of astrocytic Rac1 attenuates fear memory acquisition. Furthermore, temporal activation of Rac1 by photoactivatable Rac1 (Rac1-PA) induces structural alterations in astrocytes and in vivo activation of Rac1 in BLA astrocytes during fear conditioning attenuates the formation of fear memory. Taken together, our study demonstrates that fear conditioning-induced suppression of BLA astrocytic Rac1 activity, associated with astrocyte structural plasticity, is required for the formation of conditioned fear memory.

  17. Zinc supplementation in rats impairs hippocampal-dependent memory consolidation and dampens post-traumatic recollection of stressful event.

    Science.gov (United States)

    Contestabile, Antonio; Peña-Altamira, Emiliano; Virgili, Marco; Monti, Barbara

    2016-06-01

    Zinc is a trace element important for synaptic plasticity, learning and memory. Zinc deficiency, both during pregnancy and after birth, impairs cognitive performance and, in addition to memory deficits, also results in alterations of attention, activity, neuropsychological behavior and motor development. The effects of zinc supplementation on cognition, particularly in the adult, are less clear. We demonstrate here in adult rats, that 4 week-long zinc supplementation given by drinking water, and approximately doubling normal daily intake, strongly impairs consolidation of hippocampal-dependent memory, tested through contextual fear conditioning and inhibitory avoidance. Furthermore, the same treatment started after memory consolidation of training for the same behavioral tests, substantially dampens the recall of the stressful event occurred 4 weeks before. A molecular correlate of the amnesic effect of zinc supplementation is represented by a dysregulated function of GSK-3ß in the hippocampus, a kinase that participates in memory processes. The possible relevance of these data for humans, in particular regarding post-traumatic stress disorders, is discussed in view of future investigation. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  18. Hippocampal structural plasticity accompanies the resulting contextual fear memory following stress and fear conditioning.

    Science.gov (United States)

    Giachero, Marcelo; Calfa, Gaston D; Molina, Victor A

    2013-10-15

    The present research investigated the resulting contextual fear memory and structural plasticity changes in the dorsal hippocampus (DH) following stress and fear conditioning. This combination enhanced fear retention and increased the number of total and mature dendritic spines in DH. Intra-basolateral amygdala (BLA) infusion of midazolam prior to stress prevented both the enhancement of fear retention and an increase in the density of total and mature dendritic spines in DH. These findings emphasize the role of the stress-induced attenuation of GABAergic neurotransmission in BLA in the promoting influence of stress on fear memory and on synaptic remodeling in DH. In conclusion, the structural remodeling in DH accompanied the facilitated fear memory following a combination of fear conditioning and stressful stimulation.

  19. A BDNF sensitive mechanism is involved in the fear memory resulting from the interaction between stress and the retrieval of an established trace.

    Science.gov (United States)

    Giachero, Marcelo; Bustos, Silvia G; Calfa, Gaston; Molina, Victor A

    2013-04-15

    The present study investigates the fear memory resulting from the interaction of a stressful experience and the retrieval of an established fear memory trace. Such a combination enhanced both fear expression and fear retention in adult Wistar rats. Likewise, midazolam intra-basolateral amygdala (BLA) infusion prior to stress attenuated the enhancement of fear memory thus suggesting the involvement of a stress-induced reduction of the GABAergic transmission in BLA in the stress-induced enhancing effect. It has been suggested that, unlike the immediate-early gene Zif268 which is related to the reconsolidation process, the expression of hippocampal brain-derived neurotrophic factor (BDNF) is highly correlated with consolidation. We therefore evaluate the relative contribution of these two neurobiological processes to the fear memory resulting from the above-mentioned interaction. Intra-dorsal hippocampus (DH) infusions of either the antisense Zif268 or the inhibitor of the protein degradation (Clasto-Lactacystin β-Lactone), suggested to be involved in the retrieval-dependent destabilization process, did not affect the resulting contextual memory. In contrast, the knockdown of hippocampal BDNF mitigated the stress-induced facilitating influence on fear retention. In addition, the retrieval experience elevated BDNF level in DH at 60 min after recall exclusively in stressed animals. These findings suggest the involvement of a hippocampal BDNF sensitive mechanism in the stress-promoting influence on the fear memory following retrieval.

  20. Resting-state functional connectivity between amygdala and the ventromedial prefrontal cortex following fear reminder predicts fear extinction

    Science.gov (United States)

    Feng, Pan; Zheng, Yong

    2016-01-01

    Investigations of fear conditioning have elucidated the neural mechanisms of fear acquisition, consolidation and extinction, but it is not clear how the neural activation following fear reminder influence the following extinction. To address this question, we measured human brain activity following fear reminder using resting-state functional magnetic resonance imaging, and investigated whether the extinction effect can be predicted by resting-state functional connectivity (RSFC). Behaviorally, we found no significant differences of fear ratings between the reminder group and the no reminder group at the fear acquisition and extinction stages, but spontaneous recovery during re-extinction stage appeared only in the no reminder group. Imaging data showed that functional connectivity between ventromedial prefrontal cortex (vmPFC) and amygdala in the reminder group was greater than that in the no reminder group after fear memory reactivation. More importantly, the functional connectivity between amygdala and vmPFC of the reminder group after fear memory reactivation was positively correlated with extinction effect. These results suggest RSFC between amygdala and the vmPFC following fear reminder can predict fear extinction, which provide important insight into the neural mechanisms of fear memory after fear memory reactivation. PMID:27013104

  1. Post-study caffeine administration enhances memory consolidation in humans.

    Science.gov (United States)

    Borota, Daniel; Murray, Elizabeth; Keceli, Gizem; Chang, Allen; Watabe, Joseph M; Ly, Maria; Toscano, John P; Yassa, Michael A

    2014-02-01

    It is currently not known whether caffeine has an enhancing effect on long-term memory in humans. We used post-study caffeine administration to test its effect on memory consolidation using a behavioral discrimination task. Caffeine enhanced performance 24 h after administration according to an inverted U-shaped dose-response curve; this effect was specific to consolidation and not retrieval. We conclude that caffeine enhanced consolidation of long-term memories in humans.

  2. Interacting Brain Systems Modulate Memory Consolidation

    Science.gov (United States)

    McIntyre, Christa K.; McGaugh, James L.; Williams, Cedric L.

    2011-01-01

    Emotional arousal influences the consolidation of long-term memory. This review discusses experimental approaches and relevant findings that provide the foundation for current understanding of coordinated interactions between arousal activated peripheral hormones and the brain processes that modulate memory formation. Rewarding or aversive experiences release the stress hormones epinephrine (adrenalin) and glucocorticoids from the adrenal glands into the bloodstream. The effect of these hormones on memory consolidation depends upon binding of norepinephrine to beta-adrenergic receptors in the basolateral complex of the amygdala (BLA). Much evidence indicates that the stress hormones influence release of norepinephrine in the BLA through peripheral actions on the vagus nerve which stimulates, through polysynaptic connections, cells of the locus coeruleus to release norepinephrine. The BLA influences memory storage by actions on synapses, distributed throughout the brain, that are engaged in sensory and cognitive processing at the time of amygdala activation. The implications of the activation of these stress-activated memory processes are discussed in relation to stress-related memory disorders. PMID:22085800

  3. Memory processes during sleep: beyond the standard consolidation theory.

    Science.gov (United States)

    Axmacher, Nikolai; Draguhn, Andreas; Elger, Christian E; Fell, Juergen

    2009-07-01

    Two-step theories of memory formation suggest that an initial encoding stage, during which transient neural assemblies are formed in the hippocampus, is followed by a second step called consolidation, which involves re-processing of activity patterns and is associated with an increasing involvement of the neocortex. Several studies in human subjects as well as in animals suggest that memory consolidation occurs predominantly during sleep (standard consolidation model). Alternatively, it has been suggested that consolidation may occur during waking state as well and that the role of sleep is rather to restore encoding capabilities of synaptic connections (synaptic downscaling theory). Here, we review the experimental evidence favoring and challenging these two views and suggest an integrative model of memory consolidation.

  4. User Preference-Based Dual-Memory Neural Model With Memory Consolidation Approach.

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    Nasir, Jauwairia; Yoo, Yong-Ho; Kim, Deok-Hwa; Kim, Jong-Hwan; Nasir, Jauwairia; Yong-Ho Yoo; Deok-Hwa Kim; Jong-Hwan Kim; Nasir, Jauwairia; Yoo, Yong-Ho; Kim, Deok-Hwa; Kim, Jong-Hwan

    2018-06-01

    Memory modeling has been a popular topic of research for improving the performance of autonomous agents in cognition related problems. Apart from learning distinct experiences correctly, significant or recurring experiences are expected to be learned better and be retrieved easier. In order to achieve this objective, this paper proposes a user preference-based dual-memory adaptive resonance theory network model, which makes use of a user preference to encode memories with various strengths and to learn and forget at various rates. Over a period of time, memories undergo a consolidation-like process at a rate proportional to the user preference at the time of encoding and the frequency of recall of a particular memory. Consolidated memories are easier to recall and are more stable. This dual-memory neural model generates distinct episodic memories and a flexible semantic-like memory component. This leads to an enhanced retrieval mechanism of experiences through two routes. The simulation results are presented to evaluate the proposed memory model based on various kinds of cues over a number of trials. The experimental results on Mybot are also presented. The results verify that not only are distinct experiences learned correctly but also that experiences associated with higher user preference and recall frequency are consolidated earlier. Thus, these experiences are recalled more easily relative to the unconsolidated experiences.

  5. The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation.

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    Miyamoto, Daisuke; Hirai, Daichi; Murayama, Masanori

    2017-01-01

    Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5-4 Hz) are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow waves can enhance or impair memory consolidation. During slow wave sleep, inter-areal interactions between the cortex and hippocampus (HC) have been proposed to consolidate declarative memory; however, interactions for non-declarative (HC-independent) memory remain largely uninvestigated. We recently showed that the directional influence in a slow-wave range through a top-down cortical long-range circuit is involved in the consolidation of non-declarative memory. At the synaptic level, the average cortical synaptic strength is known to be potentiated during wakefulness and depressed during sleep. Moreover, learning causes plasticity in a subset of synapses, allocating memory to them. Sleep may help to differentiate synaptic strength between allocated and non-allocated synapses (i.e., improving the signal-to-noise ratio, which may facilitate memory consolidation). Herein, we offer perspectives on inter-areal interactions and synaptic plasticity for memory consolidation during sleep.

  6. The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation

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    Daisuke Miyamoto

    2017-11-01

    Full Text Available Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5–4 Hz are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow waves can enhance or impair memory consolidation. During slow wave sleep, inter-areal interactions between the cortex and hippocampus (HC have been proposed to consolidate declarative memory; however, interactions for non-declarative (HC-independent memory remain largely uninvestigated. We recently showed that the directional influence in a slow-wave range through a top-down cortical long-range circuit is involved in the consolidation of non-declarative memory. At the synaptic level, the average cortical synaptic strength is known to be potentiated during wakefulness and depressed during sleep. Moreover, learning causes plasticity in a subset of synapses, allocating memory to them. Sleep may help to differentiate synaptic strength between allocated and non-allocated synapses (i.e., improving the signal-to-noise ratio, which may facilitate memory consolidation. Herein, we offer perspectives on inter-areal interactions and synaptic plasticity for memory consolidation during sleep.

  7. Memory Consolidation and Gene Expression in "Periplaneta Americana"

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    Strausfeld, Nicholas J.; Pinter, Marianna; Lent, David D.

    2005-01-01

    A unique behavioral paradigm has been developed for "Periplaneta americana" that assesses the timing and success of memory consolidation leading to long-term memory of visual-olfactory associations. The brains of trained and control animals, removed at the critical consolidation period, were screened by two-directional suppression subtractive…

  8. Sleep-dependent memory consolidation--what can be learnt from children?

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    Wilhelm, I; Prehn-Kristensen, A; Born, J

    2012-08-01

    Extensive research has been accumulated demonstrating that sleep is essential for processes of memory consolidation in adults. In children and infants, a great capacity to learn and to memorize coincides with longer and more intense sleep. Here, we review the available data on the influence of sleep on memory consolidation in healthy children and infants, as well as in children with attention-deficit/hyperactivity disorder (ADHD) as a model of prefrontal impairment, and consider possible mechanisms underlying age-dependent differences. Findings indicate a major role of slow wave sleep (SWS) for processes of memory consolidation during early development. Importantly, longer and deeper SWS during childhood appears to produce a distinctly superior strengthening of hippocampus-dependent declarative memories, but concurrently prevents an immediate benefit from sleep for procedural memories, as typically observed in adults. Studies of ADHD children point toward an essential contribution of prefrontal cortex to the preferential consolidation of declarative memory during SWS. Developmental studies of sleep represent a particularly promising approach for characterizing the supra-ordinate control of memory consolidation during sleep by prefrontal-hippocampal circuitry underlying the encoding of declarative memory. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Negative Reinforcement Impairs Overnight Memory Consolidation

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    Stamm, Andrew W.; Nguyen, Nam D.; Seicol, Benjamin J.; Fagan, Abigail; Oh, Angela; Drumm, Michael; Lundt, Maureen; Stickgold, Robert; Wamsley, Erin J.

    2014-01-01

    Post-learning sleep is beneficial for human memory. However, it may be that not all memories benefit equally from sleep. Here, we manipulated a spatial learning task using monetary reward and performance feedback, asking whether enhancing the salience of the task would augment overnight memory consolidation and alter its incorporation into…

  10. Extinction training during the reconsolidation window prevents recovery of fear.

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    Schiller, Daniela; Raio, Candace M; Phelps, Elizabeth A

    2012-08-24

    Fear is maladaptive when it persists long after circumstances have become safe. It is therefore crucial to develop an approach that persistently prevents the return of fear. Pavlovian fear-conditioning paradigms are commonly employed to create a controlled, novel fear association in the laboratory. After pairing an innocuous stimulus (conditioned stimulus, CS) with an aversive outcome (unconditioned stimulus, US) we can elicit a fear response (conditioned response, or CR) by presenting just the stimulus alone. Once fear is acquired, it can be diminished using extinction training, whereby the conditioned stimulus is repeatedly presented without the aversive outcome until fear is no longer expressed. This inhibitory learning creates a new, safe representation for the CS, which competes for expression with the original fear memory. Although extinction is effective at inhibiting fear, it is not permanent. Fear can spontaneously recover with the passage of time. Exposure to stress or returning to the context of initial learning can also cause fear to resurface. Our protocol addresses the transient nature of extinction by targeting the reconsolidation window to modify emotional memory in a more permanent manner. Ample evidence suggests that reactivating a consolidated memory returns it to a labile state, during which the memory is again susceptible to interference. This window of opportunity appears to open shortly after reactivation and close approximately 6 hrs later, although this may vary depending on the strength and age of the memory. By allowing new information to incorporate into the original memory trace, this memory may be updated as it reconsolidates. Studies involving non-human animals have successfully blocked the expression of fear memory by introducing pharmacological manipulations within the reconsolidation window, however, most agents used are either toxic to humans or show equivocal effects when used in human studies. Our protocol addresses these

  11. High trait anxiety: a challenge for disrupting fear memory reconsolidation.

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    Soeter, Marieke; Kindt, Merel

    2013-01-01

    Disrupting reconsolidation may be promising in the treatment of anxiety disorders but the fear-reducing effects are thus far solely demonstrated in the average organism. A relevant question is whether disrupting fear memory reconsolidation is less effective in individuals who are vulnerable to develop an anxiety disorder. By collapsing data from six previous human fear conditioning studies we tested whether trait anxiety was related to the fear-reducing effects of a pharmacological agent targeting the process of memory reconsolidation--n = 107. Testing included different phases across three consecutive days each separated by 24 h. Fear responding was measured by the eye-blink startle reflex. Disrupting the process of fear memory reconsolidation was manipulated by administering the β-adrenergic receptor antagonist propranolol HCl either before or after memory retrieval. Trait anxiety uniquely predicted the fear-reducing effects of disrupting memory reconsolidation: the higher the trait anxiety, the less fear reduction. Vulnerable individuals with the propensity to develop anxiety disorders may need higher dosages of propranolol HCl or more retrieval trials for targeting and changing fear memory. Our finding clearly demonstrates that we cannot simply translate observations from fundamental research on fear reduction in the average organism to clinical practice.

  12. Impaired memory consolidation in children with obstructive sleep disordered breathing.

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    Kiran Maski

    Full Text Available Memory consolidation is stabilized and even enhanced by sleep (and particularly by 12-15 Hz sleep spindles in NREM stage 2 sleep in healthy children but it is unclear what happens to these processes when sleep is disturbed by obstructive sleep disordered breathing. This cross-sectional study investigates differences in declarative memory consolidation among children with primary snoring (PS and obstructive sleep apnea (OSA compared to controls. We further investigate whether memory consolidation group differences are associated with NREM stage 2 (N2 sigma (12-15 Hz or NREM slow oscillation (0.5-1 Hz spectral power bands. In this study, we trained and tested participants on a spatial declarative memory task with cued recall. Retest occurred after a period of daytime wake (Wake or a night of sleep (Sleep with in-lab polysomnography. 36 participants ages 5-9 years completed the protocol: 14 with OSA as defined by respiratory disturbance index (RDI > 1/hour, 12 with primary snoring (PS and 10 controls. OSA participants had poorer overall memory consolidation than controls across Wake and Sleep conditions [OSA: mean = -18.7% (5.8, controls: mean = 1.9% (7.2, t = -2.20, P = 0.04]. In contrast, PS participants and controls had comparable memory consolidation across conditions (t = 0.41; P = 0.38. We did not detect a main effect for condition (Sleep, Wake or group x condition interaction on memory consolidation. OSA participants had lower N2 sigma power than PS (P = 0.03 and controls (P = 0.004 and N2 sigma power inversely correlated with percentage of time snoring on the study night (r = -0.33, P<0.05. Across all participants, N2 sigma power modestly correlated with memory consolidation in both Sleep (r = 0.37, P = 0.03 and Wake conditions (r = 0.44, P = 0.009. Further observed variable path analysis showed that N2 sigma power mediated the relationship between group and mean memory consolidation across Sleep and Wake states [Bindirect = 6.76(3.5, z = 2

  13. Propranolol's effects on the consolidation and reconsolidation of long-term emotional memory in healthy participants: a meta-analysis.

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    Lonergan, Michelle H; Olivera-Figueroa, Lening A; Pitman, Roger K; Brunet, Alain

    2013-07-01

    Considering the pivotal role of negative emotional experiences in the development and persistence of mental disorders, interfering with the consolidation/reconsolidation of such experiences would open the door to a novel treatment approach in psychiatry. We conducted a meta-analysis on the experimental evidence regarding the capacity of the ß-blocker propranolol to block the consolidation/reconsolidation of emotional memories in healthy adults. Selected studies consisted of randomized, double-blind experiments assessing long-term memory for emotional material in healthy adults and involved at least 1 propranolol and 1 placebo condition. We searched PsycInfo, PubMed, Web of Science, Cochrane Central, PILOTS, Google Scholar and clinicaltrials.org for eligible studies from the period 1995-2012. Ten consolidation (n = 259) and 8 reconsolidation (n = 308) experiments met the inclusion criteria. We calculated effect sizes (Hedges g) using a random effects model. Compared with placebo, propranolol given before memory consolidation reduced subsequent recall for negatively valenced stories, pictures and word lists (Hedges g = 0.44, 95% confidence interval [CI] 0.14-0.74). Propranolol before reconsolidation also reduced subsequent recall for negatively valenced emotional words and the expression of cue-elicited fear responses (Hedges g = 0.56, 95% CI 0.13-1.00). Limitations include the moderate number of studies examining the influence of propranolol on emotional memory consolidation and reconsolidation in healthy adults and the fact that most samples consisted entirely of young adults, which may limit the ecological validity of results. Propranolol shows promise in reducing subsequent memory for new or recalled emotional material in healthy adults. However, future studies will need to investigate whether more powerful idiosyncratic emotional memories can also be weakened and whether this weakening can bring about long-lasting symptomatic relief in clinical populations

  14. Blocking mineralocorticoid receptors prior to retrieval reduces contextual fear memory in mice.

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    Ming Zhou

    Full Text Available BACKGROUND: Corticosteroid hormones regulate appraisal and consolidation of information via mineralocorticoid receptors (MRs and glucocorticoid receptors (GRs respectively. How activation of these receptors modulates retrieval of fearful information and the subsequent expression of fear is largely unknown. We tested here whether blockade of MRs or GRs during retrieval also affects subsequent expression of fear memory. METHODOLOGY/PRINCIPAL FINDINGS: Mice were trained in contextual or tone cue fear conditioning paradigms, by pairing mild foot shocks with a particular context or tone respectively. Twenty-four hours after training, context-conditioned animals were re-exposed to the context for 3 or 30 minutes (day 2; tone-conditioned animals were placed in a different context and re-exposed to one or six tones. Twenty-four hours (day 3 and one month later, freezing behavior to the aversive context/tone was scored again. MR or GR blockade was achieved by giving spironolactone or RU486 subcutaneously one hour before retrieval on day 2. Spironolactone administered prior to brief context re-exposure reduced freezing behavior during retrieval and 24 hours later, but not one month later. Administration of spironolactone without retrieval of the context or immediately after retrieval on day 2 did not reduce freezing on day 3. Re-exposure to the context for 30 minutes on day 2 significantly reduced freezing on day 3 and one month later, but freezing was not further reduced by spironolactone. Administration of spironolactone prior to tone-cue re-exposure on day 2 did not affect freezing behavior. Treatment with RU486 prior to re-exposure did not affect context or tone-cue fear memories at any time point. CONCLUSIONS/SIGNIFICANCE: We conclude that MR blockade prior to retrieval strongly reduces the expression of contextual fear, implying that MRs, rather than GRs, play an important role in retrieval of emotional information and subsequent fear expression.

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

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    Saravana R K Murthy

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

  16. Changes in heart rate variability are associated with expression of short-term and long-term contextual and cued fear memories.

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    Jun Liu

    Full Text Available Heart physiology is a highly useful indicator for measuring not only physical states, but also emotional changes in animals. Yet changes of heart rate variability during fear conditioning have not been systematically studied in mice. Here, we investigated changes in heart rate and heart rate variability in both short-term and long-term contextual and cued fear conditioning. We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I and a more variable phase (stage-II. We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories. Moreover, it could also detect fear extinction effect during the repeated tone recall. These results suggest that heart rate variability is a valuable physiological indicator for sensitively measuring the consolidation and expression of fear memories in mice.

  17. Autobiographical thinking interferes with episodic memory consolidation.

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    Michael Craig

    Full Text Available New episodic memories are retained better if learning is followed by a few minutes of wakeful rest than by the encoding of novel external information. Novel encoding is said to interfere with the consolidation of recently acquired episodic memories. Here we report four experiments in which we examined whether autobiographical thinking, i.e. an 'internal' memory activity, also interferes with episodic memory consolidation. Participants were presented with three wordlists consisting of common nouns; one list was followed by wakeful rest, one by novel picture encoding and one by autobiographical retrieval/future imagination, cued by concrete sounds. Both novel encoding and autobiographical retrieval/future imagination lowered wordlist retention significantly. Follow-up experiments demonstrated that the interference by our cued autobiographical retrieval/future imagination delay condition could not be accounted for by the sound cues alone or by executive retrieval processes. Moreover, our results demonstrated evidence of a temporal gradient of interference across experiments. Thus, we propose that rich autobiographical retrieval/future imagination hampers the consolidation of recently acquired episodic memories and that such interference is particularly likely in the presence of external concrete cues.

  18. High trait anxiety: a challenge for disrupting fear memory reconsolidation.

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    Marieke Soeter

    Full Text Available Disrupting reconsolidation may be promising in the treatment of anxiety disorders but the fear-reducing effects are thus far solely demonstrated in the average organism. A relevant question is whether disrupting fear memory reconsolidation is less effective in individuals who are vulnerable to develop an anxiety disorder. By collapsing data from six previous human fear conditioning studies we tested whether trait anxiety was related to the fear-reducing effects of a pharmacological agent targeting the process of memory reconsolidation--n = 107. Testing included different phases across three consecutive days each separated by 24 h. Fear responding was measured by the eye-blink startle reflex. Disrupting the process of fear memory reconsolidation was manipulated by administering the β-adrenergic receptor antagonist propranolol HCl either before or after memory retrieval. Trait anxiety uniquely predicted the fear-reducing effects of disrupting memory reconsolidation: the higher the trait anxiety, the less fear reduction. Vulnerable individuals with the propensity to develop anxiety disorders may need higher dosages of propranolol HCl or more retrieval trials for targeting and changing fear memory. Our finding clearly demonstrates that we cannot simply translate observations from fundamental research on fear reduction in the average organism to clinical practice.

  19. β-Adrenergic Receptors Regulate the Acquisition and Consolidation Phases of Aversive Memory Formation Through Distinct, Temporally Regulated Signaling Pathways.

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    Schiff, Hillary C; Johansen, Joshua P; Hou, Mian; Bush, David E A; Smith, Emily K; Klein, JoAnna E; LeDoux, Joseph E; Sears, Robert M

    2017-03-01

    Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on β-adrenergic receptors (βARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms. Specifically, using behavioral pharmacology and biochemistry in adult rats, we determined that βAR activity during, but not after PTC training initiates the activation of two plasticity-related targets: AMPA receptors (AMPARs) for memory acquisition and short-term memory and extracellular regulated kinase (ERK) for consolidating the learned association into a long-term memory. These findings reveal that βAR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations.

  20. The Limited Capacity of Sleep-Dependent Memory Consolidation

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    Gordon B Feld

    2016-09-01

    Full Text Available Sleep supports memory consolidation. However, the conceptually important influence of the amount of items encoded in a memory test on this effect has not been investigated. In two experiments, participants (n=101 learned lists of word-pairs varying in length (40, 160, 320 word-pairs in the evening before a night of sleep (sleep group or of sleep deprivation (wake group. After 36 h (including a night allowing recovery sleep retrieval was tested. Compared with wakefulness, post-learning sleep enhanced retention for the 160 word-pair condition (p < 0.01, importantly, this effect completely vanished for the 320 word-pair condition. This result indicates a limited capacity for sleep-dependent memory consolidation, which is consistent with an active system consolidation view on sleep’s role for memory, if it is complemented by processes of active forgetting and/or gist abstraction. Whereas the absolute benefit from sleep should have increased with increasing amounts of successfully encoded items, if sleep only passively protected memory from interference. Moreover, the finding that retention performance was significantly diminished for the 320 word-pair condition compared to the 160 word-pair condition in the sleep group, makes it tempting to speculate that with increasing loads of information encoded during wakefulness, sleep might favour processes of forgetting over consolidation.

  1. Differential effect of an anticholinergic antidepressant on sleep-dependent memory consolidation.

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    Goerke, Monique; Cohrs, Stefan; Rodenbeck, Andrea; Kunz, Dieter

    2014-05-01

    Rapid eye movement (REM) sleep is considered critical to the consolidation of procedural memory - the memory of skills and habits. Many antidepressants strongly suppress REM sleep, however, and procedural memory consolidation has been shown to be impaired in depressed patients on antidepressant therapy. As a result, it is important to determine whether antidepressive therapy can lead to amnestic impairment. We thus investigated the effects of the anticholinergic antidepressant amitriptyline on sleep-dependent memory consolidation. Double-blind, placebo-controlled, randomized, parallel-group study. Sleep laboratory. Twenty-five healthy men (mean age: 26.8 ± 5.6 y). 75 mg amitriptyline versus placebo. To test memory consolidation, a visual discrimination task, a finger-tapping task, the Rey-Osterrieth Complex Figure Test, and the Rey Auditory-Verbal Learning Test were performed. Sleep was measured using polysomnography. Our findings show that amitriptyline profoundly suppressed REM sleep and impaired perceptual skill learning, but not motor skill or declarative learning. Our study is the first to demonstrate that an antidepressant can affect procedural memory consolidation in healthy subjects. Moreover, considering the results of a recent study, in which selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors were shown not to impair procedural memory consolidation, our findings suggest that procedural memory consolidation is not facilitated by the characteristics of REM sleep captured by visual sleep scoring, but rather by the high cholinergic tone associated with REM sleep. Our study contributes to the understanding of potentially undesirable behavioral effects of amitriptyline.

  2. Better than sleep: theta neurofeedback training accelerates memory consolidation.

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    Reiner, Miriam; Rozengurt, Roman; Barnea, Anat

    2014-01-01

    Consistent empirical results showed that both night and day sleep enhanced memory consolidation. In this study we explore processes of consolidation of memory during awake hours. Since theta oscillations have been shown to play a central role in exchange of information, we hypothesized that elevated theta during awake hours will enhance memory consolidation. We used a neurofeedback protocol, to enhance the relative power of theta or beta oscillations. Participants trained on a tapping task, were divided into three groups: neurofeedback theta; neurofeedback beta; control. We found a significant improvement in performance in the theta group, relative to the beta and control groups, immediately after neurofeedback. Performance was further improved after night sleep in all groups, with a significant advantage favoring the theta group. Theta power during training was correlated with the level of improvement, indicating a clear relationship between memory consolidation, and theta neurofeedback. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. The Roles of Protein Expression in Synaptic Plasticity and Memory Consolidation

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    Tali eRosenberg

    2014-11-01

    Full Text Available The amount and availability of proteins are regulated by their synthesis, degradation, and transport. These processes can specifically, locally, and temporally regulate a protein or a population of proteins, thus affecting numerous biological processes in health and disease states. Accordingly, malfunction in the processes of protein turnover and localization underlies different neuronal diseases. However, as early as a century ago, it was recognized that there is a specific need for normal macromolecular synthesis in a specific fragment of the learning process, memory consolidation, which takes place minutes to hours following acquisition. Memory consolidation is the process by which fragile short-term memory is converted into stable long-term memory. It is accepted today that synaptic plasticity is a cellular mechanism of learning and memory processes. Interestingly, similar molecular mechanisms subserve both memory and synaptic plasticity consolidation. In this review, we survey the current view on the connection between memory consolidation processes and proteostasis, i.e., maintaining the protein contents at the neuron and the synapse. In addition, we describe the technical obstacles and possible new methods to determine neuronal proteostasis of synaptic function and better explain the process of memory and synaptic plasticity consolidation.

  4. Delayed working memory consolidation during the attentional blink.

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    Vogel, Edward K; Luck, Steven J

    2002-12-01

    After the detection of a target (T1) in a rapid stream of visual stimuli, there is a period of 400-600 msec during which a subsequent target (T2) is missed. This impairment in performance has been labeled the attentional blink. Recent theories propose that the attentional blink reflects a bottleneck in working memory consolidation such that T2 cannot be consolidated until after T1 is consolidated, and T2 is therefore masked by subsequent stimuli if it is presented while T1 is being consolidated. In support of this explanation, Giesbrecht & Di Lollo (1998) found that when T2 is the final item in the stimulus stream, no attentional blink is observed, because there are no subsequent stimuli that might mask T2. To provide a direct test of this explanation of the attentional blink, in the present study we used the P3 component of the event-related potential waveform to track the processing of T2. When T2 was followed by a masking item, we found that the P3 wave was completely suppressed during the attentional blink period, indicating that T2 was not consolidated in working memory. When T2 was the last item in the stimulus stream, however, we found that the P3 wave was delayed but not suppressed, indicating that T2 consolidation was not eliminated but simply delayed. These results are consistent with a fundamental limit on the consolidation of information in working memory.

  5. Signaling through cGMP-dependent protein kinase I in the amygdala is critical for auditory-cued fear memory and long-term potentiation.

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    Paul, Cindy; Schöberl, Florian; Weinmeister, Pascal; Micale, Vincenzo; Wotjak, Carsten T; Hofmann, Franz; Kleppisch, Thomas

    2008-12-24

    Long-term potentiation (LTP) of inputs relaying sensory information from cortical and thalamic neurons to principal neurons in the lateral amygdala (LA) is thought to serve as a cellular mechanism for associative fear learning. Nitric oxide (NO), a messenger molecule widely implicated in synaptic plasticity and behavior, has been shown to enhance LTP in the LA as well as consolidation of associative fear memory. Additional evidence suggests that NO-induced enhancement of LTP and amygdala-dependent learning requires signaling through soluble guanylyl cyclase (sGC) and cGMP-dependent protein kinase (cGK). Mammals possess two genes for cGK: the prkg1 gene gives rise to the cGK type I isoforms, cGKIalpha and cGKIbeta, and the prkg2 gene encodes the cGK type II. Reportedly, both cGKI and cGKII are expressed in the amygdala, and cGKII is involved in controlling anxiety-like behavior. Because selective pharmacological tools for individual cGK isoforms are lacking, we used different knock-out mouse models to examine the function of cGKI and cGKII for LTP in the LA and pavlovian fear conditioning. We found robust expression of the cGKI specifically in the LA with cGKIbeta as the prevailing isoform. We further show a marked reduction of LTP at both thalamic and cortical inputs to the LA and a selective impairment of auditory-cued fear memory in cGKI-deficient mutants. In contrast, cGKII null mutants lack these phenotypes. Our data suggest a function of cGKI, likely the beta isoform, in the LA, supporting synaptic plasticity and consolidation of fear memory.

  6. Morphine administration during low ovarian hormone stage results in transient over expression of fear memories in females

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    Emily M Perez-Torres

    2015-05-01

    Full Text Available Acute exposure to morphine after a traumatic event reduces trauma related symptoms in humans and conditioned fear expression in male rats. We aimed to determine whether acute administration of morphine alters consolidation of fear learning and extinction. Male and female rats in proestrus and metaestrus (high and low ovarian hormones respectively underwent fear conditioning and received saline or morphine (2.5 mg/kg s.c.. The next day they underwent extinction. Results showed increased freezing during extinction only in the morphine metaestrus group while morphine did not affect males or proestrus females. Recall of extinction was similar on all groups. On a second experiment, a subset of rats conditioned during metaestrus was administered morphine prior to extinction producing no effects. We then measured mu opioid receptor (MOR expression in the amygdala and periaqueductal gray (PAG at the end of extinction (day 2. In males and proestrus females, morphine caused an increase in MOR in the amygdala but no in the PAG. In metaestrus females, morphine did not change MOR expression in either structure. These data suggests that ovarian hormones may interact with MORs in the amygdala to transiently alter memory consolidation. Morphine given after trauma to females with low ovarian hormones might increase the recall of fear responses, making recovery harder.

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

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    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.

  8. The dynamic nature of systems consolidation: Stress during learning as a switch guiding the rate of the hippocampal dependency and memory quality.

    Science.gov (United States)

    Pedraza, Lizeth K; Sierra, Rodrigo O; Boos, Flávia Z; Haubrich, Josué; Quillfeldt, Jorge A; Alvares, Lucas de Oliveira

    2016-03-01

    Memory fades over time, becoming more schematic or abstract. The loss of contextual detail in memory may reflect a time-dependent change in the brain structures supporting memory. It has been well established that contextual fear memory relies on the hippocampus for expression shortly after learning, but it becomes hippocampus-independent at a later time point, a process called systems consolidation. This time-dependent process correlates with the loss of memory precision. Here, we investigated whether training intensity predicts the gradual decay of hippocampal dependency to retrieve memory, and the quality of the contextual memory representation over time. We have found that training intensity modulates the progressive decay of hippocampal dependency and memory precision. Strong training intensity accelerates systems consolidation and memory generalization in a remarkable timeframe match. The mechanisms underpinning such process are triggered by glucocorticoid and noradrenaline released during training. These results suggest that the stress levels during emotional learning act as a switch, determining the fate of memory quality. Moderate stress will create a detailed memory, whereas a highly stressful training will develop a generic gist-like memory. © 2015 Wiley Periodicals, Inc.

  9. Neuromodulation: acetylcholine and memory consolidation.

    Science.gov (United States)

    Hasselmo

    1999-09-01

    Clinical and experimental evidence suggests that hippocampal damage causes more severe disruption of episodic memories if those memories were encoded in the recent rather than the more distant past. This decrease in sensitivity to damage over time might reflect the formation of multiple traces within the hippocampus itself, or the formation of additional associative links in entorhinal and association cortices. Physiological evidence also supports a two-stage model of the encoding process in which the initial encoding occurs during active waking and deeper consolidation occurs via the formation of additional memory traces during quiet waking or slow-wave sleep. In this article I will describe the changes in cholinergic tone within the hippocampus in different stages of the sleep-wake cycle and will propose that these changes modulate different stages of memory formation. In particular, I will suggest that the high levels of acetylcholine that are present during active waking might set the appropriate dynamics for encoding new information in the hippocampus, by partially suppressing excitatory feedback connections and so facilitating encoding without interference from previously stored information. By contrast, the lower levels of acetylcholine that are present during quiet waking and slow-wave sleep might release this suppression and thereby allow a stronger spread of activity within the hippocampus itself and from the hippocampus to the entorhinal cortex, thus facilitating the process of consolidation of separate memory traces.

  10. Vicarious extinction learning during reconsolidation neutralizes fear memory

    NARCIS (Netherlands)

    Golkar, A.; Tjaden, C.; Kindt, M.

    Background: Previous studies have suggested that fear memories can be updated when recalled, a process referred to as reconsolidation. Given the beneficial effects of model-based safety learning (i.e. vicarious extinction) in preventing the recovery of short-term fear memory, we examined whether

  11. Memory consolidation in human sleep depends on inhibition of glucocorticoid release.

    Science.gov (United States)

    Plihal, W; Born, J

    1999-09-09

    Early sleep dominated by slow-wave sleep has been found to be particularly relevant for declarative memory formation via hippocampo-neocortical networks. Concurrently, early nocturnal sleep is characterized by an inhibition of glucocorticoid release from the adrenals. Here, we show in healthy humans that this inhibition serves to support declarative memory consolidation during sleep. Elevating plasma glucocorticoid concentration during early sleep by administration of cortisol impaired consolidation of paired associate words, but not of non-declarative memory of visuomotor skills. Since glucocorticoid concentration was enhanced only during retention sleep, but not during acquisition or retrieval, a specific effect on the consolidation process is indicated. Blocking mineralocorticoid receptors by canrenoate did not affect memory, suggesting inactivation of glucocorticoid receptors to be the essential prerequisite for memory consolidation during early sleep.

  12. Optogenetic stimulation of a hippocampal engram activates fear memory recall.

    Science.gov (United States)

    Liu, Xu; Ramirez, Steve; Pang, Petti T; Puryear, Corey B; Govindarajan, Arvind; Deisseroth, Karl; Tonegawa, Susumu

    2012-03-22

    A specific memory is thought to be encoded by a sparse population of neurons. These neurons can be tagged during learning for subsequent identification and manipulation. Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. We labelled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear-conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear-conditioned mice with cells labelled by enhanced yellow fluorescent protein instead of ChR2. Finally, activation of cells labelled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.

  13. Post-learning molecular reactivation underlies taste memory consolidation

    Directory of Open Access Journals (Sweden)

    Kioko eGuzman-Ramos

    2011-09-01

    Full Text Available It is considered that memory consolidation is a progressive process that requires post-trial stabilization of the information. In this regard, it has been speculated that waves of receptors activation, expression of immediate early genes and replenishment of receptor subunit pools occur to induce functional or morphological changes to maintain the information for longer periods. In this paper, we will review data related to neuronal changes in the post-acquisition stage of taste aversion learning that could be involved in further stabilization of the memory trace. In order to achieve such stabilization, evidence suggests that the functional integrity of the insular cortex (IC and the amygdala (AMY is required. Particularly the increase of extracellular levels of glutamate and activation of N-methyl-D-aspartate (NMDA receptors within the IC shows a main role in the consolidation process. Additionally the modulatory actions of the dopaminergic system in the IC appear to be involved in the mechanisms that lead to taste aversion memory consolidation through the activation of pathways related to enhancement of protein synthesis such as the Protein Kinase A pathway. In summary, we suggest that post-acquisition molecular and neuronal changes underlying memory consolidation are dependent on the interactions between the AMY and the IC.

  14. The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation

    OpenAIRE

    Miyamoto, Daisuke; Hirai, Daichi; Murayama, Masanori

    2017-01-01

    Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5–4 Hz) are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow...

  15. Nicotine facilitates memory consolidation in perceptual learning.

    Science.gov (United States)

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

    2013-01-01

    Perceptual learning is a special type of non-declarative learning that involves experience-dependent plasticity in sensory cortices. The cholinergic system is known to modulate declarative learning. In particular, reduced levels or efficacy of the neurotransmitter acetylcholine were found to facilitate declarative memory consolidation. However, little is known about the role of the cholinergic system in memory consolidation of non-declarative learning. Here we compared two groups of non-smoking men who learned a visual texture discrimination task (TDT). One group received chewing tobacco containing nicotine for 1 h directly following the TDT training. The other group received a similar tasting control substance without nicotine. Electroencephalographic recordings during substance consumption showed reduced alpha activity and P300 latencies in the nicotine group compared to the control group. When re-tested on the TDT the following day, both groups responded more accurately and more rapidly than during training. These improvements were specific to the retinal location and orientation of the texture elements of the TDT suggesting that learning involved early visual cortex. A group comparison showed that learning effects were more pronounced in the nicotine group than in the control group. These findings suggest that oral consumption of nicotine enhances the efficacy of nicotinic acetylcholine receptors. Our findings further suggest that enhanced efficacy of the cholinergic system facilitates memory consolidation in perceptual learning (and possibly other types of non-declarative learning). In that regard acetylcholine seems to affect consolidation processes in perceptual learning in a different manner than in declarative learning. Alternatively, our findings might reflect dose-dependent cholinergic modulation of memory consolidation. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Activation of ERK2 in basolateral amygdala underlies the promoting influence of stress on fear memory and anxiety: influence of midazolam pretreatment.

    Science.gov (United States)

    Maldonado, N M; Espejo, P J; Martijena, I D; Molina, V A

    2014-02-01

    Exposure to emotionally arousing experiences elicits a robust and persistent memory and enhances anxiety. The amygdala complex plays a key role in stress-induced emotional processing and in the fear memory formation. It is well known that ERK activation in the amygdala is a prerequisite for fear memory consolidation. Moreover, stress elevates p-ERK2 levels in several areas of the brain stress circuitry. Therefore, given that the ERK1/2 cascade is activated following stress and that the role of this cascade is critical in the formation of fear memory, the present study investigated the potential involvement of p-ERK2 in amygdala subnuclei in the promoting influence of stress on fear memory formation and on anxiety-like behavior. A robust and persistent ERK2 activation was noted in the Basolateral amygdala (BLA), which was evident at 5min after restraint and lasted at least one day after the stressful experience. Midazolam, a short-acting benzodiazepine ligand, administered prior to stress prevented the increase in the p-ERK2 level in the BLA. Pretreatment with intra-BLA infusion of U0126 (MEK inhibitor), but not into the adjacent central nucleus of the amygdala, attenuated the stress-induced promoting influence on fear memory formation. Finally, U0126 intra-BLA infusion prevented the enhancement of anxiety-like behavior in stressed animals. These findings suggest that the selective ERK2 activation in BLA following stress exposure is an important mechanism for the occurrence of the promoting influence of stress on fear memory and on anxiety-like behavior. © 2013 Published by Elsevier B.V. and ECNP.

  17. The role of sleep in declarative memory consolidation--direct evidence by intracranial EEG.

    NARCIS (Netherlands)

    Axmacher, N.; Haupt, S.; Fernandez, G.S.E.; Elger, C.E.; Fell, J.

    2008-01-01

    Two step theories of memory formation assume that an initial learning phase is followed by a consolidation stage. Memory consolidation has been suggested to occur predominantly during sleep. Very recent findings, however, suggest that important steps in memory consolidation occur also during waking

  18. Unilateral hippocampal inactivation or lesion selectively impairs remote contextual fear memory.

    Science.gov (United States)

    Zhou, Heng; Zhou, Qixin; Xu, Lin

    2016-10-01

    Contextual fear memory depends on the hippocampus, but the role of unilateral hippocampus in this type of memory remains unclear. Herein, pharmacological inactivation or excitotoxic lesions were used to study the role of unilateral hippocampus in the stages of contextual fear memory. The pharmacological experiments revealed that compared with the control groups, unilateral hippocampal blockade did not impair 1-day recent memory following learning, whereas bilateral hippocampal blockade significantly impaired this memory. The lesion experiments showed that compared with the control groups, the formed contextual fear memory was retained for 7 days and that 30-day remote memory was markedly reduced in unilateral hippocampal lesion groups. These results indicate that an intact bilateral hippocampus is required for the formation of remote memory and that unilateral hippocampus is sufficient for recent contextual fear memory.

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

    Science.gov (United States)

    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

  20. Time-Dependent Expression of Arc and Zif268 after Acquisition of Fear Conditioning

    Directory of Open Access Journals (Sweden)

    Mary E. Lonergan

    2010-01-01

    Full Text Available Memory consolidation requires transcription and translation of new protein. Arc, an effector immediate early gene, and zif268, a regulatory transcription factor, have been implicated in synaptic plasticity underlying learning and memory. This study explored the temporal expression profiles of these proteins in the rat hippocampus following fear conditioning. We observed a time-dependent increase of Arc protein in the dorsal hippocampus 30-to-90-minute post training, returning to basal levels at 4 h. Zif268 protein levels, however, gradually increased at 30-minute post training before peaking in expression at 60 minute. The timing of hippocampal Arc and zif268 expression coincides with the critical period for protein synthesis-dependent memory consolidation following fear conditioning. However, the expression of Arc protein appears to be driven by context exploration, whereas, zif268 expression may be more specifically related to associative learning. These findings suggest that altered Arc and zif268 expression are related to neural plasticity during the formation of fear memory.

  1. Targeting memory reconsolidation to prevent the return of fear in patients with fear of flying.

    Science.gov (United States)

    Maples-Keller, Jessica L; Price, Matthew; Jovanovic, Tanja; Norrholm, Seth D; Odenat, Lydia; Post, Loren; Zwiebach, Liza; Breazeale, Kathryn; Gross, Robin; Kim, Sae-Jin; Rothbaum, Barbara Olasov

    2017-07-01

    When a memory is recalled, it may again exist in a labile state and stored information becomes amenable to change, a psychobiological process known as reconsolidation. Exposure therapy for anxiety disorders involves accessing a fear memory and modifying it with less fearful information. A preclinical study reported that providing a reminder of a fear memory 10 min prior to extinction training in humans decreased fear up to 1 year later (Schiller et al., 2010). For this pilot clinical study, we used virtual reality exposure therapy (VRE) for fear of flying (FoF) to determine if using a cue to reactivate the memory of the feared stimulus 10 min prior to exposure sessions leads to fewer anxiety-related behaviors and a more durable response compared to a neutral cue. FoF participants (N = 89) received four sessions of anxiety management training followed by four sessions of VRE. Participants were randomly assigned to receive an FoF cue (reactivation group) or a neutral cue (control group) prior to the VRE sessions. Heart rate (HR) and skin conductance levels (SCLs) were collected during posttreatment and 3-month follow-up assessments as objective markers of fear responding. Treatment was effective and all clinical measures improved equally between groups at posttreatment with maintained gains through follow-ups. Significant differences were identified with regard to HR and SCL indices. These results suggest that memory reactivation prior to exposure therapy did not have an impact on clinical measures but may enhance the effect of exposure therapy at the physiological level. © 2017 Wiley Periodicals, Inc.

  2. Disruption of Memory Reconsolidation Erases a Fear Memory Trace in the Human Amygdala: An 18-Month Follow-Up.

    Directory of Open Access Journals (Sweden)

    Johannes Björkstrand

    Full Text Available Fear memories can be attenuated by reactivation followed by disrupted reconsolidation. Using functional magnetic resonance imaging we recently showed that reactivation and reconsolidation of a conditioned fear memory trace in the basolateral amygdala predicts subsequent fear expression over two days, while reactivation followed by disrupted reconsolidation abolishes the memory trace and suppresses fear. In this follow-up study we demonstrate that the behavioral effect persists over 18 months reflected in superior reacquisition after undisrupted, as compared to disrupted reconsolidation, and that neural activity in the basolateral amygdala representing the initial fear memory predicts return of fear. We conclude that disrupting reconsolidation have long lasting behavioral effects and may permanently erase the fear component of an amygdala-dependent memory.

  3. The role of sleep in cognitive processing: focusing on memory consolidation.

    Science.gov (United States)

    Chambers, Alexis M

    2017-05-01

    Research indicates that sleep promotes various cognitive functions, such as decision-making, language, categorization, and memory. Of these, most work has focused on the influence of sleep on memory, with ample work showing that sleep enhances memory consolidation, a process that stores new memories in the brain over time. Recent psychological and neurophysiological research has vastly increased understanding of this process. Such work not only suggests that consolidation relies on plasticity-related mechanisms that reactivate and stabilize memory representations, but also that this process may be experimentally manipulated by methods that target which memory traces are reactivated during sleep. Furthermore, aside from memory storage capabilities, memory consolidation also appears to reorganize and integrate memories with preexisting knowledge, which may facilitate the discovery of underlying rules and associations that benefit other cognitive functioning, including problem solving and creativity. WIREs Cogn Sci 2017, 8:e1433. doi: 10.1002/wcs.1433 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

  4. Working-memory consolidation : Insights from studies on attention and working memory

    NARCIS (Netherlands)

    Ricker, Timothy; Nieuwenstein, Mark; Bayliss, Donna; Barrouillet, Pierre

    2018-01-01

    Working memory, the system that maintains a limited set of representations for immediate use in cognition, is a central part of human cognition. Three processes have recently been proposed to govern information storage in working memory: Consolidation, refreshing and removal. Here we discuss in

  5. The effect of mild acute stress during memory consolidation on emotional recognition memory

    Science.gov (United States)

    Corbett, Brittany; Weinberg, Lisa; Duarte, Audrey

    2018-01-01

    Stress during consolidation improves recognition memory performance. Generally, this memory benefit is greater for emotionally arousing stimuli than neutral stimuli. The strength of the stressor also plays a role in memory performance, with memory performance improving up to a moderate level of stress and thereafter worsening. As our daily stressors are generally minimal in strength, we chose to induce mild acute stress to determine its effect on memory performance. In the current study, we investigated if mild acute stress during consolidation improves memory performance for emotionally arousing images. To investigate this, we had participants encode highly arousing negative, minimally arousing negative, and neutral images. We induced stress using the Montreal Imaging Stress Task (MIST) in half of the participants and a control task to the other half of the participants directly after encoding (i.e. during consolidation) and tested recognition 48 h later. We found no difference in memory performance between the stress and control group. We found a graded pattern among confidence, with responders in the stress group having the least amount of confidence in their hits and controls having the most. Across groups, we found highly arousing negative images were better remembered than minimally arousing negative or neutral images. Although stress did not affect memory accuracy, responders, as defined by cortisol reactivity, were less confident in their decisions. Our results suggest that the daily stressors humans experience, regardless of their emotional affect, do not have adverse effects on memory. PMID:28838881

  6. Heart rate response to post-learning stress predicts memory consolidation.

    Science.gov (United States)

    Larra, Mauro F; Schulz, André; Schilling, Thomas M; Ferreira de Sá, Diana S; Best, Daniel; Kozik, Bartlomiej; Schächinger, Hartmut

    2014-03-01

    Stressful experiences are often well remembered, an effect that has been explained by beta-adrenergic influences on memory consolidation. Here, we studied the impact of stress induced heart rate (HR) responses on memory consolidation in a post-learning stress paradigm. 206 male and female participants saw 52 happy and angry faces immediately before being exposed to the Cold Pressor Test or a non-stressful control procedure. Memory for the faces and their respective expression was tested twice, after 30 min and on the next day. High HR responders (in comparison to low HR responders as well as to the non-stressful control group) showed enhanced recognition memory one day after learning. Our results show that beta-adrenergic activation elicited shortly after learning enhances memory consolidation and that the stress induced HR response is a predictor for this effect. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Relief memory consolidation requires protein synthesis within the nucleus accumbens.

    Science.gov (United States)

    Bruning, Johann E A; Breitfeld, Tino; Kahl, Evelyn; Bergado-Acosta, Jorge R; Fendt, Markus

    2016-06-01

    Relief learning refers to the association of a stimulus with the relief from an aversive event. The thus-learned relief stimulus then can induce, e.g., an attenuation of the startle response or approach behavior, indicating positive valence. Previous studies revealed that the nucleus accumbens is essential for the acquisition and retrieval of relief memory. Here, we ask whether the nucleus accumbens is also the brain site for consolidation of relief memory into a long-term form. In rats, we blocked local protein synthesis within the nucleus accumbens by local infusions of anisomycin at different time points during a relief conditioning experiment. Accumbal anisomycin injections immediately after the relief conditioning session, but not 4 h later, prevented the consolidation into long-term relief memory. The retention of already consolidated relief memory was not affected by anisomycin injections. This identifies a time window and site for relief memory consolidation. These findings should complement our understanding of the full range of effects of adverse experiences, including cases of their distortion in humans such as post-traumatic stress disorder and/or phobias. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Linking new information to a reactivated memory requires consolidation and not reconsolidation mechanisms.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available A new memory is initially labile and becomes stabilized through a process of consolidation, which depends on gene expression. Stable memories, however, can again become labile if reactivated by recall and require another phase of protein synthesis in order to be maintained. This process is known as reconsolidation. The functional significance of the labile phase of reconsolidation is unknown; one hypothesis proposes that it is required to link new information with reactivated memories. Reconsolidation is distinct from the initial consolidation, and one distinction is that the requirement for specific proteins or general protein synthesis during the two processes occurs in different brain areas. Here, we identified an anatomically distinctive molecular requirement that doubly dissociates consolidation from reconsolidation of an inhibitory avoidance memory. We then used this requirement to investigate whether reconsolidation and consolidation are involved in linking new information with reactivated memories. In contrast to what the hypothesis predicted, we found that reconsolidation does not contribute to the formation of an association between new and reactivated information. Instead, it recruits mechanisms similar to those underlying consolidation of a new memory. Thus, linking new information to a reactivated memory is mediated by consolidation and not reconsolidation mechanisms.

  9. Long-term consolidation of declarative memory: insight from temporal lobe epilepsy.

    Science.gov (United States)

    Tramoni, Eve; Felician, Olivier; Barbeau, Emmanuel J; Guedj, Eric; Guye, Maxime; Bartolomei, Fabrice; Ceccaldi, Mathieu

    2011-03-01

    Several experiments carried out with a subset of patients with temporal lobe epilepsy have demonstrated normal memory performance at standard delays of recall (i.e. minutes to hours) but impaired performance over longer delays (i.e. days or weeks), suggesting altered long-term consolidation mechanisms. These mechanisms were specifically investigated in a group of five adult-onset pharmaco-sensitive patients with temporal lobe epilepsy, exhibiting severe episodic memory complaints despite normal performance at standardized memory assessment. In a first experiment, the magnitude of autobiographical memory loss was evaluated using retrograde personal memory tasks based on verbal and visual cues. In both conditions, results showed an unusual U-shaped pattern of personal memory impairment, encompassing most of the patients' life, sparing however, periods of the childhood, early adulthood and past several weeks. This profile was suggestive of a long-term consolidation impairment of personal episodes, adequately consolidated over 'short-term' delays but gradually forgotten thereafter. Therefore, in a subsequent experiment, patients were submitted to a protocol specifically devised to investigate short and long-term consolidation of contextually-bound experiences (episodic memory) and context-free information (semantic knowledge and single-items). In the short term (1 h), performance at both contextually-free and contextually-bound memory tasks was intact. After a 6-week delay, however, contextually-bound memory performance was impaired while contextually-free memory performance remained preserved. This effect was independent of task difficulty and the modality of retrieval (recall and recognition). Neuroimaging studies revealed the presence of mild metabolic changes within medial temporal lobe structures. Taken together, these results show the existence of different consolidation systems within declarative memory. They suggest that mild medial temporal lobe dysfunction

  10. Sleep-dependent memory consolidation in patients with sleep disorders.

    Science.gov (United States)

    Cipolli, Carlo; Mazzetti, Michela; Plazzi, Giuseppe

    2013-04-01

    Sleep can improve the off-line memory consolidation of new items of declarative and non-declarative information in healthy subjects, whereas acute sleep loss, as well as sleep restriction and fragmentation, impair consolidation. This suggests that, by modifying the amount and/or architecture of sleep, chronic sleep disorders may also lead to a lower gain in off-line consolidation, which in turn may be responsible for the varying levels of impaired performance at memory tasks usually observed in sleep-disordered patients. The experimental studies conducted to date have shown specific impairments of sleep-dependent consolidation overall for verbal and visual declarative information in patients with primary insomnia, for verbal declarative information in patients with obstructive sleep apnoeas, and for visual procedural skills in patients with narcolepsy-cataplexy. These findings corroborate the hypothesis that impaired consolidation is a consequence of the chronically altered organization of sleep. Moreover, they raise several novel questions as to: a) the reversibility of consolidation impairment in the case of effective treatment, b) the possible negative influence of altered prior sleep also on the encoding of new information, and c) the relationships between altered sleep and memory impairment in patients with other (medical, psychiatric or neurological) diseases associated with quantitative and/or qualitative changes of sleep architecture. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Individual variation in working memory is associated with fear extinction performance.

    Science.gov (United States)

    Stout, Daniel M; Acheson, Dean T; Moore, Tyler M; Gur, Ruben C; Baker, Dewleen G; Geyer, Mark A; Risbrough, Victoria B

    2018-03-01

    PTSD has been associated consistently with abnormalities in fear acquisition and extinction learning and retention. Fear acquisition refers to learning to discriminate between threat and safety cues. Extinction learning reflects the formation of a new inhibitory-memory that competes with a previously learned threat-related memory. Adjudicating the competition between threat memory and the new inhibitory memory during extinction may rely, in part, on cognitive processes such as working memory (WM). Despite significant shared neural circuits and signaling pathways the relationship between WM, fear acquisition, and extinction is poorly understood. Here, we analyzed data from a large sample of healthy Marines who underwent an assessment battery including tests of fear acquisition, extinction learning, and WM (N-back). Fear potentiated startle (FPS), fear expectancy ratings, and self-reported anxiety served as the primary dependent variables. High WM ability (N = 192) was associated with greater CS + fear inhibition during the late block of extinction and greater US expectancy change during extinction learning compared to individuals with low WM ability (N = 204). WM ability was not associated with magnitude of fear conditioning/expression. Attention ability was unrelated to fear acquisition or extinction supporting specificity of WM associations with extinction. These results support the conclusion that individual differences in WM may contribute to regulating fear responses. Copyright © 2018. Published by Elsevier Ltd.

  12. Consolidation differentially modulates schema effects on memory for items and associations.

    Science.gov (United States)

    van Kesteren, Marlieke T R; Rijpkema, Mark; Ruiter, Dirk J; Fernández, Guillén

    2013-01-01

    Newly learned information that is congruent with a preexisting schema is often better remembered than information that is incongruent. This schema effect on memory has previously been associated to more efficient encoding and consolidation mechanisms. However, this effect is not always consistently supported in the literature, with differential schema effects reported for different types of memory, different retrieval cues, and the possibility of time-dependent effects related to consolidation processes. To examine these effects more directly, we tested participants on two different types of memory (item recognition and associative memory) for newly encoded visuo-tactile associations at different study-test intervals, thus probing memory retrieval accuracy for schema-congruent and schema-incongruent items and associations at different time points (t = 0, t = 20, and t = 48 hours) after encoding. Results show that the schema effect on visual item recognition only arises after consolidation, while the schema effect on associative memory is already apparent immediately after encoding, persisting, but getting smaller over time. These findings give further insight into different factors influencing the schema effect on memory, and can inform future schema experiments by illustrating the value of considering effects of memory type and consolidation on schema-modulated retrieval.

  13. Consolidation differentially modulates schema effects on memory for items and associations.

    Directory of Open Access Journals (Sweden)

    Marlieke T R van Kesteren

    Full Text Available Newly learned information that is congruent with a preexisting schema is often better remembered than information that is incongruent. This schema effect on memory has previously been associated to more efficient encoding and consolidation mechanisms. However, this effect is not always consistently supported in the literature, with differential schema effects reported for different types of memory, different retrieval cues, and the possibility of time-dependent effects related to consolidation processes. To examine these effects more directly, we tested participants on two different types of memory (item recognition and associative memory for newly encoded visuo-tactile associations at different study-test intervals, thus probing memory retrieval accuracy for schema-congruent and schema-incongruent items and associations at different time points (t = 0, t = 20, and t = 48 hours after encoding. Results show that the schema effect on visual item recognition only arises after consolidation, while the schema effect on associative memory is already apparent immediately after encoding, persisting, but getting smaller over time. These findings give further insight into different factors influencing the schema effect on memory, and can inform future schema experiments by illustrating the value of considering effects of memory type and consolidation on schema-modulated retrieval.

  14. Sleep Spindle Density Predicts the Effect of Prior Knowledge on Memory Consolidation

    Science.gov (United States)

    Lambon Ralph, Matthew A.; Kempkes, Marleen; Cousins, James N.; Lewis, Penelope A.

    2016-01-01

    Information that relates to a prior knowledge schema is remembered better and consolidates more rapidly than information that does not. Another factor that influences memory consolidation is sleep and growing evidence suggests that sleep-related processing is important for integration with existing knowledge. Here, we perform an examination of how sleep-related mechanisms interact with schema-dependent memory advantage. Participants first established a schema over 2 weeks. Next, they encoded new facts, which were either related to the schema or completely unrelated. After a 24 h retention interval, including a night of sleep, which we monitored with polysomnography, participants encoded a second set of facts. Finally, memory for all facts was tested in a functional magnetic resonance imaging scanner. Behaviorally, sleep spindle density predicted an increase of the schema benefit to memory across the retention interval. Higher spindle densities were associated with reduced decay of schema-related memories. Functionally, spindle density predicted increased disengagement of the hippocampus across 24 h for schema-related memories only. Together, these results suggest that sleep spindle activity is associated with the effect of prior knowledge on memory consolidation. SIGNIFICANCE STATEMENT Episodic memories are gradually assimilated into long-term memory and this process is strongly influenced by sleep. The consolidation of new information is also influenced by its relationship to existing knowledge structures, or schemas, but the role of sleep in such schema-related consolidation is unknown. We show that sleep spindle density predicts the extent to which schemas influence the consolidation of related facts. This is the first evidence that sleep is associated with the interaction between prior knowledge and long-term memory formation. PMID:27030764

  15. Targeted memory reactivation during slow wave sleep facilitates emotional memory consolidation.

    Science.gov (United States)

    Cairney, Scott A; Durrant, Simon J; Hulleman, Johan; Lewis, Penelope A

    2014-04-01

    To investigate the mechanisms by which auditory targeted memory reactivation (TMR) during slow wave sleep (SWS) influences the consolidation of emotionally negative and neutral memories. Each of 72 (36 negative, 36 neutral) picture-location associations were encoded with a semantically related sound. During a subsequent nap, half of the sounds were replayed in SWS, before picture-location recall was examined in a final test. Manchester Sleep Laboratory, University of Manchester. 15 adults (3 male) mean age = 20.40 (standard deviation ± 3.07). TMR with auditory cues during SWS. Performance was assessed by memory accuracy and recall response times (RTs). Data were analyzed with a 2 (sound: replayed/not replayed) × 2 (emotion: negative/neutral) repeated measures analysis of covariance with SWS duration, and then SWS spindles, as the mean-centered covariate. Both analyses revealed a significant three-way interaction for RTs but not memory accuracy. Critically, SWS duration and SWS spindles predicted faster memory judgments for negative, relative to neutral, picture locations that were cued with TMR. TMR initiates an enhanced consolidation process during subsequent SWS, wherein sleep spindles mediate the selective enhancement of reactivated emotional memories.

  16. Familiarity speeds up visual short-term memory consolidation.

    Science.gov (United States)

    Xie, Weizhen; Zhang, Weiwei

    2017-06-01

    Existing long-term memory (LTM) can boost the number of retained representations over a short delay in visual short-term memory (VSTM). However, it is unclear whether and how prior LTM affects the initial process of transforming fragile sensory inputs into durable VSTM representations (i.e., VSTM consolidation). The consolidation speed hypothesis predicts faster consolidation for familiar relative to unfamiliar stimuli. Alternatively, the perceptual boost hypothesis predicts that the advantage in perceptual processing of familiar stimuli should add a constant boost for familiar stimuli during VSTM consolidation. To test these competing hypotheses, the present study examined how the large variance in participants' prior multimedia experience with Pokémon affected VSTM for Pokémon. In Experiment 1, the amount of time allowed for VSTM consolidation was manipulated by presenting consolidation masks at different intervals after the onset of to-be-remembered Pokémon characters. First-generation Pokémon characters that participants were more familiar with were consolidated faster into VSTM as compared with recent-generation Pokémon characters that participants were less familiar with. These effects were absent in participants who were unfamiliar with both generations of Pokémon. Although familiarity also increased the number of retained Pokémon characters when consolidation was uninterrupted but still incomplete due to insufficient encoding time in Experiment 1, this capacity effect was absent in Experiment 2 when consolidation was allowed to complete with sufficient encoding time. Together, these results support the consolidation speed hypothesis over the perceptual boost hypothesis and highlight the importance of assessing experimental effects on both processing and representation aspects of VSTM. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. The role of negative and positive memories in fear of dental treatment.

    Science.gov (United States)

    Risløv Staugaard, Søren; Jøssing, Marit; Krohn, Christina

    2017-12-01

    Most young adults transition from childhood dental care to adult dental care without problems. However, a substantial minority leaves childhood dental care with considerable fear of dental treatment. In the present study, we hypothesized that fear of dental treatment in the young adult is influenced by memories of positive and negative childhood experiences with dental care. More specifically, we predicted that the emotional impact, sense of reliving, rehearsal, and belief in the accuracy of a negative treatment memory would be associated with increased dental fear, while positive treatment memories would show the opposite relation. One hundred thirty-six young adults leaving childhood dental care responded to a online measures of dental fear, the most negative and most positive memory of dental treatment, and symptoms of posttraumatic stress disorder. Negative memories of events that involved pain and dentist behaviors such as impatience or scolding were frequently described and significantly associated with dental fear and symptoms of posttraumatic stress. Positive memories were more frequent, but did not show a consistent relationship with dental fear. The importance of negative memories suggests an avenue for intervention against dental fear that focuses on restructuring those memories to emphasize positive aspects. © 2016 American Association of Public Health Dentistry.

  18. Acute immobilization stress following contextual fear conditioning reduces fear memory: timing is essential.

    Science.gov (United States)

    Uwaya, Akemi; Lee, Hyunjin; Park, Jonghyuk; Lee, Hosung; Muto, Junko; Nakajima, Sanae; Ohta, Shigeo; Mikami, Toshio

    2016-02-24

    Histone acetylation is regulated in response to stress and plays an important role in learning and memory. Chronic stress is known to deteriorate cognition, whereas acute stress facilitates memory formation. However, whether acute stress facilitates memory formation when it is applied after fear stimulation is not yet known. Therefore, this study aimed to investigate the effect of acute stress applied after fear training on memory formation, mRNA expression of brain-derived neurotrophic factor (BDNF), epigenetic regulation of BDNF expression, and corticosterone level in mice in vivo. Mice were subjected to acute immobilization stress for 30 min at 60 or 90 min after contextual fear conditioning training, and acetylation of histone 3 at lysine 14 (H3K14) and level of corticosterone were measured using western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. A freezing behavior test was performed 24 h after training, and mRNA expression of BDNF was measured using real-time polymerase chain reactions. Different groups of mice were used for each test. Freezing behavior significantly decreased with the down-regulation of BDNF mRNA expression caused by acute immobilization stress at 60 min after fear conditioning training owing to the reduction of H3K14 acetylation. However, BDNF mRNA expression and H3K14 acetylation were not reduced in animals subjected to immobilization stress at 90 min after the training. Further, the corticosterone level was significantly high in mice subjected to immobilization stress at 60 min after the training. Acute immobilization stress for 30 min at 60 min after fear conditioning training impaired memory formation and reduced BDNF mRNA expression and H3K14 acetylation in the hippocampus of mice owing to the high level of corticosterone.

  19. Multimodal assessment of long-term memory recall and reinstatement in a combined cue and context fear conditioning and extinction paradigm in humans.

    Directory of Open Access Journals (Sweden)

    Jan Haaker

    Full Text Available Learning to predict danger via associative learning processes is critical for adaptive behaviour. After successful extinction, persisting fear memories often emerge as returning fear. Investigation of return of fear phenomena, e.g. reinstatement, have only recently began and to date, many critical questions with respect to reinstatement in human populations remain unresolved. Few studies have separated experimental phases in time even though increasing evidence shows that allowing for passage of time (and consolidation between experimental phases has a major impact on the results. In addition, studies have relied on a single psychophysiological dimension only (SCRs/SCL or FPS which hampers comparability between different studies that showed both differential or generalized return of fear following a reinstatement manipulation. In 93 participants, we used a multimodal approach (fear-potentiated startle, skin conductance responses, fear ratings to asses fear conditioning (day 1, extinction (day 2 as well as delayed memory recall and reinstatement (day 8 in a paradigm that probed contextual and cued fear intra-individually. Our findings show persistence of conditioning and extinction memory over time and demonstrate that reinstated fear responses were qualitatively different between dependent variables (subjective fear ratings, FPS, SCRs as well as between cued and contextual CSs. While only the arousal-related measurement (SCRs showed increasing reactions following reinstatement to the cued CSs, no evidence of reinstatement was observed for the subjective ratings and fear-related measurement (FPS. In contrast, for contextual CSs, reinstatement was evident as differential and generalized reinstatement in fear ratings as well as generally elevated physiological fear (FPS and arousal (SCRs related measurements to all contextual CSs (generalized non-differential reinstatement. Returning fear after reinstatement likely depends on a variety of variables

  20. The effect of mild acute stress during memory consolidation on emotional recognition memory.

    Science.gov (United States)

    Corbett, Brittany; Weinberg, Lisa; Duarte, Audrey

    2017-11-01

    Stress during consolidation improves recognition memory performance. Generally, this memory benefit is greater for emotionally arousing stimuli than neutral stimuli. The strength of the stressor also plays a role in memory performance, with memory performance improving up to a moderate level of stress and thereafter worsening. As our daily stressors are generally minimal in strength, we chose to induce mild acute stress to determine its effect on memory performance. In the current study, we investigated if mild acute stress during consolidation improves memory performance for emotionally arousing images. To investigate this, we had participants encode highly arousing negative, minimally arousing negative, and neutral images. We induced stress using the Montreal Imaging Stress Task (MIST) in half of the participants and a control task to the other half of the participants directly after encoding (i.e. during consolidation) and tested recognition 48h later. We found no difference in memory performance between the stress and control group. We found a graded pattern among confidence, with responders in the stress group having the least amount of confidence in their hits and controls having the most. Across groups, we found highly arousing negative images were better remembered than minimally arousing negative or neutral images. Although stress did not affect memory accuracy, responders, as defined by cortisol reactivity, were less confident in their decisions. Our results suggest that the daily stressors humans experience, regardless of their emotional affect, do not have adverse effects on memory. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Hippocampal Structural Plasticity Accompanies the Resulting Contextual Fear Memory Following Stress and Fear Conditioning

    Science.gov (United States)

    Giachero, Marcelo; Calfa, Gaston D.; Molina, Victor A.

    2013-01-01

    The present research investigated the resulting contextual fear memory and structural plasticity changes in the dorsal hippocampus (DH) following stress and fear conditioning. This combination enhanced fear retention and increased the number of total and mature dendritic spines in DH. Intra-basolateral amygdala (BLA) infusion of midazolam prior to…

  2. Effects of daytime food intake on memory consolidation during sleep or sleep deprivation.

    Directory of Open Access Journals (Sweden)

    Nina Herzog

    Full Text Available Sleep enhances memory consolidation. Bearing in mind that food intake produces many metabolic signals that can influence memory processing in humans (e.g., insulin, the present study addressed the question as to whether the enhancing effect of sleep on memory consolidation is affected by the amount of energy consumed during the preceding daytime. Compared to sleep, nocturnal wakefulness has been shown to impair memory consolidation in humans. Thus, a second question was to examine whether the impaired memory consolidation associated with sleep deprivation (SD could be compensated by increased daytime energy consumption. To these aims, 14 healthy normal-weight men learned a finger tapping sequence (procedural memory and a list of semantically associated word pairs (declarative memory. After the learning period, standardized meals were administered, equaling either ∼50% or ∼150% of the estimated daily energy expenditure. In the morning, after sleep or wakefulness, memory consolidation was tested. Plasma glucose was measured both before learning and retrieval. Polysomnographic sleep recordings were performed by electroencephalography (EEG. Independent of energy intake, subjects recalled significantly more word pairs after sleep than they did after SD. When subjects stayed awake and received an energy oversupply, the number of correctly recalled finger sequences was equal to those seen after sleep. Plasma glucose did not differ among conditions, and sleep time in the sleep conditions was not influenced by the energy intake interventions. These data indicate that the daytime energy intake level affects neither sleep's capacity to boost the consolidation of declarative and procedural memories, nor sleep's quality. However, high energy intake was followed by an improved procedural but not declarative memory consolidation under conditions of SD. This suggests that the formation of procedural memory is not only triggered by sleep but is also

  3. Effects of daytime food intake on memory consolidation during sleep or sleep deprivation.

    Science.gov (United States)

    Herzog, Nina; Friedrich, Alexia; Fujita, Naoko; Gais, Steffen; Jauch-Chara, Kamila; Oltmanns, Kerstin M; Benedict, Christian

    2012-01-01

    Sleep enhances memory consolidation. Bearing in mind that food intake produces many metabolic signals that can influence memory processing in humans (e.g., insulin), the present study addressed the question as to whether the enhancing effect of sleep on memory consolidation is affected by the amount of energy consumed during the preceding daytime. Compared to sleep, nocturnal wakefulness has been shown to impair memory consolidation in humans. Thus, a second question was to examine whether the impaired memory consolidation associated with sleep deprivation (SD) could be compensated by increased daytime energy consumption. To these aims, 14 healthy normal-weight men learned a finger tapping sequence (procedural memory) and a list of semantically associated word pairs (declarative memory). After the learning period, standardized meals were administered, equaling either ∼50% or ∼150% of the estimated daily energy expenditure. In the morning, after sleep or wakefulness, memory consolidation was tested. Plasma glucose was measured both before learning and retrieval. Polysomnographic sleep recordings were performed by electroencephalography (EEG). Independent of energy intake, subjects recalled significantly more word pairs after sleep than they did after SD. When subjects stayed awake and received an energy oversupply, the number of correctly recalled finger sequences was equal to those seen after sleep. Plasma glucose did not differ among conditions, and sleep time in the sleep conditions was not influenced by the energy intake interventions. These data indicate that the daytime energy intake level affects neither sleep's capacity to boost the consolidation of declarative and procedural memories, nor sleep's quality. However, high energy intake was followed by an improved procedural but not declarative memory consolidation under conditions of SD. This suggests that the formation of procedural memory is not only triggered by sleep but is also sensitive to the

  4. New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process

    Science.gov (United States)

    Levy, Roi; Levitan, David; Susswein, Abraham J

    2016-01-01

    Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting Aplysia feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences. Inhibiting protein synthesis eliminated the block and allowed even a brief, generally ineffective training to produce long-term memory. Memory formation depended on consolidative proteins already expressed before training. After effective training, long term memory required subsequent transcription and translation. Memory formation during the sleep phase was correlated with increased CREB1 transcription, but not CREB2 transcription. Increased C/EBP transcription was a correlate of both effective and ineffective training and of treatments not producing memory. DOI: http://dx.doi.org/10.7554/eLife.17769.001 PMID:27919318

  5. New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process.

    Science.gov (United States)

    Levy, Roi; Levitan, David; Susswein, Abraham J

    2016-12-06

    Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting Aplysia feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences. Inhibiting protein synthesis eliminated the block and allowed even a brief, generally ineffective training to produce long-term memory. Memory formation depended on consolidative proteins already expressed before training. After effective training, long term memory required subsequent transcription and translation. Memory formation during the sleep phase was correlated with increased CREB1 transcription, but not CREB2 transcription. Increased C/EBP transcription was a correlate of both effective and ineffective training and of treatments not producing memory.

  6. Possibility of "superfast" consolidation of long-term memory.

    Science.gov (United States)

    Podolski IYa

    1998-01-01

    Two new behavioural tests in rats are described which demonstrate the fast consolidation of the long-term memory (LTM) in a dangerous natural situation (water escape). It is shown that after one-trial learning of the motor skill (jumping out of the water), long-term memory traces are retained without forgetting and are resistant to the blockade of M-cholinoreceptors by scopolamine (2 mg/kg) and of D1/D2 dopamine receptors by haloperidol (10 mg/kg) as well as electroconvulsive shock applied tank wall, learning of necessary motor skills, automatization and minimization of the skilled movements in 1.5-3.0 min, after 5 to 7 trials at two-second intervals (superfast learning) is demonstrated. It is suggested that the superfast consolidation of LTM (several minutes) is possible in life-threatening situations, the necessary time being 1-2 orders of magnitude less than it is generally accepted in the modern theories of memory. The proposed behavioural models may be helpful in investigation of some fundamental physiological and molecular mechanisms of stable neuronal interactions, as a basis for LTM consolidation.

  7. Coupling of Thalamocortical Sleep Oscillations Are Important for Memory Consolidation in Humans.

    Directory of Open Access Journals (Sweden)

    Mohammad Niknazar

    Full Text Available Sleep, specifically non-rapid eye movement (NREM sleep, is thought to play a critical role in the consolidation of recent memories. Two main oscillatory activities observed during NREM, cortical slow oscillations (SO, 0.5-1.0 Hz and thalamic spindles (12-15 Hz, have been shown to independently correlate with memory improvement. Yet, it is not known how these thalamocortical events interact, or the significance of this interaction, during the consolidation process. Here, we found that systemic administration of the GABAergic drug (zolpidem increased both the phase-amplitude coupling between SO and spindles, and verbal memory improvement in humans. These results suggest that thalamic spindles that occur during transitions to the cortical SO Up state are optimal for memory consolidation. Our study predicts that the timely interactions between cortical and thalamic events during consolidation, contribute to memory improvement and is mediated by the level of inhibitory neurotransmission.

  8. Acute exercise and motor memory consolidation

    DEFF Research Database (Denmark)

    Thomas, Richard; Korsgaard Johnsen, Line; Geertsen, Svend Sparre

    2016-01-01

    where low to moderate intensities may be more suitable. The aim of this study was to investigate the role of intensity in mediating the effects of acute cardiovascular exercise on motor skill learning. We investigated the effects of different exercise intensities on the retention (performance score...... an important role in modulating the effects that a single bout of cardiovascular exercise has on the consolidation phase following motor skill learning. There appears to be a dose-response relationship in favour of higher intensity exercise in order to augment off-line effects and strengthen procedural memory.......A single bout of high intensity aerobic exercise (~90% VO2peak) was previously demonstrated to amplify off-line gains in skill level during the consolidation phase of procedural memory. High intensity exercise is not always a viable option for many patient groups or in a rehabilitation setting...

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

    Directory of Open Access Journals (Sweden)

    Shujiang eShang

    2015-07-01

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

  10. Sleep-dependent consolidation patterns reveal insights into episodic memory structure.

    Science.gov (United States)

    Oyanedel, Carlos N; Sawangjit, Anuck; Born, Jan; Inostroza, Marion

    2018-05-18

    Episodic memory formation is considered a genuinely hippocampal function. Its study in rodents has relied on two different task paradigms, i.e. the so called "what-where-when" (WW-When) task and "what-where-which" (WW-Which) task. The WW-When task aims to assess the memory for an episode as an event bound into its context defined by spatial and distinct temporal information, the WW-Which task lacks the temporal component and introduces, instead, an "occasion setter" marking the broader contextual configuration in which the event occurred. Whether both tasks measure episodic memory in an equivalent manner in terms of recollection has been controversially discussed. Here, we compared in two groups of rats the consolidating effects of sleep on episodic-like memory between both task paradigms. Sampling and test phases were separated by a 90-min morning retention interval which did or did not allow for spontaneous sleep. Results show that sleep is crucial for the consolidation of the memory on both tasks. However, consolidating effects of sleep were stronger for the WW-Which than WW-When task. Comparing performance during the post-sleep test phase revealed that WW-When memory only gradually emerged during the 3-min test period whereas WW-Which memory was readily expressed already from the first minute onward. Separate analysis of the temporal and spatial components of WW-When performance showed that the delayed episodic memory on this task originated from the temporal component which also did not emerge until the third minute of the test phase, whereas the spatial component already showed up in the first minute. In conclusion, sleep differentially affects consolidation on the two episodic-like memory tasks, with the delayed expression of WW-When memory after sleep resulting from preferential coverage of temporal aspects by this task. Copyright © 2018. Published by Elsevier Inc.

  11. Effects of Post-Training Hippocampal Injections of Midazolam on Fear Conditioning

    Science.gov (United States)

    Gafford, Georgette M.; Parsons, Ryan G.; Helmstetter, Fred J.

    2005-01-01

    Benzodiazepines have been useful tools for investigating mechanisms underlying learning and memory. The present set of experiments investigates the role of hippocampal GABA[subscript A]/benzodiazepine receptors in memory consolidation using Pavlovian fear conditioning. Rats were prepared with cannulae aimed at the dorsal hippocampus and trained…

  12. Tracking explicit and implicit long-lasting traces of fearful memories in humans.

    Science.gov (United States)

    Packard, Pau Alexander; Rodríguez-Fornells, Antoni; Stein, Lilian Milnitsky; Nicolás, Berta; Fuentemilla, Lluís

    2014-12-01

    Recent accounts of Posttraumatic Stress Disorder (PTSD) suggest that the encoding of an episode within a fearful context generates different implicit and explicit memory representations. Whilst implicit memory traces include the associated emotional states, explicit traces include a recoding into an abstract or gist-based structural context of the episode. Theoretically, the long-term preservation of implicit memory traces may facilitate the often untreatable memory intrusions in PTSD. Here, we tracked in two experiments how implicit and explicit memory traces for fearful episodes dissociate and evolve over time. Subjects (N=86) were presented with semantically-related word-lists in a contextual fear paradigm and tested for explicit memories either immediately (i.e., 30 min) or after a delay (i.e., 1 or 2 weeks) with a verbal recognition task. Skin Conductance Response (SCR) was used to assess implicit memory responses. Subjects showed high memory accuracy for words when tested immediately after encoding. At test, SCR was higher during the presentation of verbatim but not gist-based words encoded in a fearful context, and remained unchanged after 2 weeks, despite subjects being unaware of words' encoding context. We found no clear evidence of accurate explicit memory traces for the fearful or neutral contexts of words presented during encoding, either 30 min or 2 weeks afterwards. These findings indicate that the implicit, but not the explicit, memory trace of a fearful context of an episode can be detected at long-term through SCR and is dissociated from the gist-based memory. They may have implicationstowards the understanding of how the processing of fearful memoriescould lead to PTSD. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Flavones from Erythrina falcata are modulators of fear memory.

    Science.gov (United States)

    de Oliveira, Daniela Rodrigues; Zamberlam, Cláudia R; Gaiardo, Renan Barreta; Rêgo, Gizelda Maia; Cerutti, Janete M; Cavalheiro, Alberto J; Cerutti, Suzete M

    2014-08-05

    Flavonoids, which have been identified in a variety of plants, have been demonstrated to elicit beneficial effects on memory. Some studies have reported that flavonoids derived from Erythrina plants can provide such beneficial effects on memory. The aim of this study was to identify the flavonoids present in the stem bark crude extract of Erythrina falcata (CE) and to perform a bioactivity-guided study on conditioned fear memory. The secondary metabolites of CE were identified by high performance liquid chromatography combined with a diode array detector, electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI/MSn) and nuclear magnetic resonance (NMR). The buthanolic fraction (BuF) was obtained by partitioning. Subfractions from BuF (BuF1 - BuF6) and fraction flavonoidic (FfA and FfB) were obtained by flash chromatography. The BuF3 and BuF4 fractions were used for the isolation of flavonoids, which was performed using HPLC-PAD. The isolated substances were quantified by HPLC-DAD and their structures were confirmed by nuclear magnetic resonance (NMR). The activities of CE and the subfractions were monitored using a one-trial, step-down inhibitory avoidance (IA) task to identify the effects of these substances on the acquisition and extinction of conditioned fear in rats. Six subclasses of flavonoids were identified for the first time in CE. According to our behavioral data, CE, BuF, BuF3 and BuF4, the flavonoidic fractions, vitexin, isovitexin and 6-C-glycoside-diosmetin improved the acquisition of fear memory. Rats treated with BuF, BuF3 and BuF4 were particularly resistant to extinction. Nevertheless, rats treated with FfA and FfB, vitexin, isovitexin and 6-C-glycoside-diosmetin exhibited gradual reduction in conditioned fear response during the extinction retest session, which was measured at 48 to 480 h after conditioning. Our results demonstrate that vitexin, isovitexin and diosmetin-6-C-glucoside and flavonoidic fractions resulted in a significant

  14. Mind racing: The influence of exercise on long-term memory consolidation.

    Science.gov (United States)

    McNerney, M Windy; Radvansky, Gabriel A

    2015-01-01

    Over time, regular exercise can lower the risk for age-related decline in cognition. However, the immediate effects of exercise on memory consolidation in younger adults have not been fully investigated. In two experiments, the effects of exercise were assessed on three different memory tasks. These included paired-associate learning, procedural learning and text memory. Results indicate that performance on procedural learning and situation model memory was increased with exercise, regardless of if participants exercised before or after encoding. No benefit of exercise was found for paired-associate learning. These findings suggest that intense exercise may benefit certain types of memory consolidation.

  15. [Sleep-wake cycle and memory consolidation].

    Science.gov (United States)

    Baratti, Carlos M; Boccia, Mariano M; Blake, Mariano G; Acosta, Gabriela B

    2007-01-01

    Although several hypothesis and theories have been advanced as explanations for the functions of sleep, a unified theory of sleep function remains elusive. Sleep has been implicated in the plastic cerebral changes that underlie learning and memory, in particular those related to memory consolidation of recently acquired new information. Despite steady accumulations of positive findings over the last ten years, the precise role of sleep in memory and brain plasticity is unproven at all. This situation might be solved by more integrated approaches that combine behavioral and neurophysiological measurements in well described in vivo models of neuronal activity and brain plasticity.

  16. Emotional memory consolidation under lower versus higher stress conditions

    Directory of Open Access Journals (Sweden)

    Inna eKogan

    2010-12-01

    Full Text Available An exposure to stress can enhance memory for emotionally arousing experiences. The phenomenon is suggested to be amygdala-dependent and in accordance with that view the amygdala was found to modulate mnemonic processes in other brain regions. Previously, we illustrated increased amygdala activation and reduced activation of CA1 following spatial learning under high versus low emotionality conditions. When spatial learning was followed by reversal training interference, impaired retention was detected only under high emotionality conditions. Here we further evaluate the potential implications of the difference in the level of amygdala activation on the quality of the memory formed under these stress conditions. We attempted to affect spatial memory consolidation under low or high stress conditions by either introducing a foot shock interference following massed training in the water maze; by manipulating the threshold for acquisition employing either brief (3 trials or full (12 trials training sessions; or by employing a spaced training (over three days rather than massed training protocol. The current findings reveal that under heightened emotionality, the process of consolidation seems to become less effective and more vulnerable to interference; however, when memory consolidation is not interrupted, retention is improved. These differential effects might underlie the complex interactions of stress, and, particularly, of traumatic stress with memory formation processes.

  17. Memory Consolidation and Neural Substrate of Reward

    Directory of Open Access Journals (Sweden)

    Redolar-Ripoll, Diego

    2012-08-01

    Full Text Available The aim of this report is to analyze the relationships between reward and learning and memory processes. Different studies have described how information about rewards influences behavior and how the brain uses this reward information to control learning and memory processes. Reward nature seems to be processed in different ways by neurons in different brain structures, ranging from the detection and perception of rewards to the use of information about predicted rewards for the control of goal-directed behavior. The neural substrate underling this processing of reward information is a reliable way of improving learning and memory processes. Evidence from several studies indicates that this neural system can facilitate memory consolidation in a wide variety of learning tasks. From a molecular perspective, certain cardinal features of reward have been described as forms of memory. Studies of human addicts and studies in animal models of addiction show that chronic drug exposure produces stable changes in the brain at the cellular and molecular levels that underlie the long-lasting behavioral plasticity associated with addiction. These molecular and cellular adaptations involved in addiction are also implicated in learning and memory processes. Dopamine seems to be a critical common signal to activate different genetic mechanisms that ultimately remodel synapses and circuits. Despite memory is an active and complex process mediated by different brain areas, the neural substrate of reward is able to improve memory consolidation in a several paradigms. We believe that there are many equivalent traits between reward and learning and memory processes.

  18. Differential effects of non-REM and REM sleep on memory consolidation?

    OpenAIRE

    Ackermann Sandra; Rasch  Bjoern

    2013-01-01

    Sleep benefitsmemory consolidation. Previous theoretical accounts have proposed a differential role of slowwave sleep (SWS) rapid eye movement (REM) sleep and stage N2 sleep for different types of memories. For example the dual process hypothesis proposes that SWS is beneficial for declarative memories whereas REMsleep is important for consolidation of non declarative procedural and emotional memories. In fact numerous recent studies do provide further support for the crucial role of SWS (or ...

  19. TRPC3 channels critically regulate hippocampal excitability and contextual fear memory.

    Science.gov (United States)

    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.

  20. The role of negative and positive memories in fear of dental treatment

    DEFF Research Database (Denmark)

    Staugaard, Søren Risløv; Jøssing, Marit; Krohn, Christina

    2017-01-01

    is influenced by memories of positive and negative childhood experiences with dental care. More specifically, we predicted that the emotional impact, sense of reliving, rehearsal, and belief in the accuracy of a negative treatment memory would be associated with increased dental fear, while positive treatment...... memories would show the opposite relation. Methods One hundred thirty-six young adults leaving childhood dental care responded to a online measures of dental fear, the most negative and most positive memory of dental treatment, and symptoms of posttraumatic stress disorder. Results Negative memories...... of events that involved pain and dentist behaviors such as impatience or scolding were frequently described and significantly associated with dental fear and symptoms of posttraumatic stress. Positive memories were more frequent, but did not show a consistent relationship with dental fear. Conclusions...

  1. Consolidation of long-term memory: Evidence and alternatives.

    NARCIS (Netherlands)

    Meeter, M.; Murre, J.M.J.

    2004-01-01

    Memory loss in retrograde amnesia has long been held to be larger for recent periods than for remote periods, a pattern usually referred to as the Ribot gradient. One explanation for this gradient is consolidation of long-term memories. Several computational models of such a process have shown how

  2. Extinction of Conditioned Fear is Better Learned and Recalled in the Morning than in the Evening

    OpenAIRE

    Pace-Schott, Edward F.; Spencer, Rebecca M.C.; Vijayakumar, Shilpa; Ahmed, Nafis; Verga, Patrick W.; Orr, Scott P.; Pitman, Roger K.; Milad, Mohammed R.

    2013-01-01

    Sleep helps emotional memories consolidate and may promote generalization of fear extinction memory. We examined whether extinction learning and memory might differ in the morning and evening due, potentially, to circadian and/or sleep-homeostatic factors. Healthy men (N=109) in 6 groups completed a 2-session protocol. In Session 1, fear conditioning was followed by extinction learning. Partial reinforcement with mild electric shock produced conditioned skin conductance responses (SCR) to 2 d...

  3. Endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory

    OpenAIRE

    Campolongo, Patrizia; Roozendaal, Benno; Trezza, Viviana; Hauer, Daniela; Schelling, Gustav; McGaugh, James L.; Cuomo, Vincenzo

    2009-01-01

    Extensive evidence indicates that the basolateral complex of the amygdala (BLA) modulates the consolidation of memories for emotionally arousing experiences, an effect that involves the activation of the glucocorticoid system. Because the BLA expresses high densities of cannabinoid CB1 receptors, the present experiments investigated whether the endocannabinoid system in the BLA influences memory consolidation and whether glucocorticoids interact with this system. The CB1 receptor agonist WIN5...

  4. Enhancement of synchronized activity between hippocampal CA1 neurons during initial storage of associative fear memory.

    Science.gov (United States)

    Liu, Yu-Zhang; Wang, Yao; Shen, Weida; Wang, Zhiru

    2017-08-01

    Learning and memory storage requires neuronal plasticity induced in the hippocampus and other related brain areas, and this process is thought to rely on synchronized activity in neural networks. We used paired whole-cell recording in vivo to examine the synchronized activity that was induced in hippocampal CA1 neurons by associative fear learning. We found that both membrane potential synchronization and spike synchronization of CA1 neurons could be transiently enhanced after task learning, as observed on day 1 but not day 5. On day 1 after learning, CA1 neurons showed a decrease in firing threshold and rise times of suprathreshold membrane potential changes as well as an increase in spontaneous firing rates, possibly contributing to the enhancement of spike synchronization. The transient enhancement of CA1 neuronal synchronization may play important roles in the induction of neuronal plasticity for initial storage and consolidation of associative memory. The hippocampus is critical for memory acquisition and consolidation. This function requires activity- and experience-induced neuronal plasticity. It is known that neuronal plasticity is largely dependent on synchronized activity. As has been well characterized, repetitive correlated activity of presynaptic and postsynaptic neurons can lead to long-term modifications at their synapses. Studies on network activity have also suggested that memory processing in the hippocampus may involve learning-induced changes of neuronal synchronization, as observed in vivo between hippocampal CA3 and CA1 networks as well as between the rhinal cortex and the hippocampus. However, further investigation of learning-induced synchronized activity in the hippocampus is needed for a full understanding of hippocampal memory processing. In this study, by performing paired whole-cell recording in vivo on CA1 pyramidal cells (PCs) in anaesthetized adult rats, we examined CA1 neuronal synchronization before and after associative fear

  5. Fatty-acid binding proteins modulate sleep and enhance long-term memory consolidation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jason R Gerstner

    2011-01-01

    Full Text Available Sleep is thought to be important for memory consolidation, since sleep deprivation has been shown to interfere with memory processing. However, the effects of augmenting sleep on memory formation are not well known, and testing the role of sleep in memory enhancement has been limited to pharmacological and behavioral approaches. Here we test the effect of overexpressing the brain-type fatty acid binding protein (Fabp7 on sleep and long-term memory (LTM formation in Drosophila melanogaster. Transgenic flies carrying the murine Fabp7 or the Drosophila homologue dFabp had reduced baseline sleep but normal LTM, while Fabp induction produced increases in both net sleep and LTM. We also define a post-training consolidation "window" that is sufficient for the observed Fabp-mediated memory enhancement. Since Fabp overexpression increases consolidated daytime sleep bouts, these data support a role for longer naps in improving memory and provide a novel role for lipid-binding proteins in regulating memory consolidation concurrently with changes in behavioral state.

  6. Sleep Dependent Memory Consolidation in Children with Autism Spectrum Disorder.

    Science.gov (United States)

    Maski, Kiran; Holbrook, Hannah; Manoach, Dara; Hanson, Ellen; Kapur, Kush; Stickgold, Robert

    2015-12-01

    Examine the role of sleep in the consolidation of declarative memory in children with autism spectrum disorder (ASD). Case-control study. Home-based study with sleep and wake conditions. Twenty-two participants with ASD and 20 control participants between 9 and 16 y of age. Participants were trained to criterion on a spatial declarative memory task and then given a cued recall test. Retest occurred after a period of daytime wake (Wake) or a night of sleep (Sleep) with home-based polysomnography; Wake and Sleep conditions were counterbalanced. Children with ASD had poorer sleep efficiency than controls, but other sleep macroarchitectural and microarchitectural measures were comparable after controlling for age and medication use. Both groups demonstrated better memory consolidation across Sleep than Wake, although participants with ASD had poorer overall memory consolidation than controls. There was no interaction between group and condition. The change in performance across sleep, independent of medication and age, showed no significant relationships with any specific sleep parameters other than total sleep time and showed a trend toward less forgetting in the control group. This study shows that despite their more disturbed sleep quality, children with autism spectrum disorder (ASD) still demonstrate more stable memory consolidation across sleep than in wake conditions. The findings support the importance of sleep for stabilizing memory in children with and without neurodevelopmental disabilities. Our results suggest that improving sleep quality in children with ASD could have direct benefits to improving their overall cognitive functioning. © 2015 Associated Professional Sleep Societies, LLC.

  7. Angiotensin-(1-7)/Mas axis modulates fear memory and extinction in mice.

    Science.gov (United States)

    Lazaroni, Thiago Luiz do Nascimento; Bastos, Cristiane Perácio; Moraes, Márcio Flávio Dutra; Santos, Robson Souza; Pereira, Grace Schenatto

    2016-01-01

    Inappropriate defense-alerting reaction to fear is a common feature of neuropsychiatric diseases. Therefore, impairments in brain circuits, as well as in molecular pathways underlying the neurovegetative adjustments to fear may play an essential role on developing neuropsychiatric disorders. Here we tested the hypothesis that interfering with angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis homeostasis, which appears to be essential to arterial pressure control, would affect fear memory and extinction. Mas knockout (MasKO) mice, in FVB/N background, showed normal cued fear memory and extinction, but increased freezing in response to context. Next, as FVB/N has poor performance in contextual fear memory, we tested MasKO in mixed 129xC57BL/6 background. MasKO mice behaved similarly to wild-type (WT), but memory extinction was slower in contextual fear conditioning to a weak protocol (1CS/US). In addition, delayed extinction in MasKO mice was even more pronounced after a stronger protocol (3CS/US). We showed previously that Angiotensin II receptor AT1 antagonist, losantan, rescued object recognition memory deficit in MasKO mice. Here, losartan was also effective. Memory extinction was accelerated in MasKO mice after treatment with losartan. In conclusion, we showed for the first time that Ang-(1-7)/Mas axis may modulate fear memory extinction. Furthermore, we suggest MasKO mice as an animal model to study post-traumatic stress disorder (PTSD). Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Artificial theta stimulation impairs encoding of contextual fear memory.

    Directory of Open Access Journals (Sweden)

    Arto Lipponen

    Full Text Available Several experiments have demonstrated an intimate relationship between hippocampal theta rhythm (4-12 Hz and memory. Lesioning the medial septum or fimbria-fornix, a fiber track connecting the hippocampus and the medial septum, abolishes the theta rhythm and results in a severe impairment in declarative memory. To assess whether there is a causal relationship between hippocampal theta and memory formation we investigated whether restoration of hippocampal theta by electrical stimulation during the encoding phase also restores fimbria-fornix lesion induced memory deficit in rats in the fear conditioning paradigm. Male Wistar rats underwent sham or fimbria-fornix lesion operation. Stimulation electrodes were implanted in the ventral hippocampal commissure and recording electrodes in the septal hippocampus. Artificial theta stimulation of 8 Hz was delivered during 3-min free exploration of the test cage in half of the rats before aversive conditioning with three foot shocks during 2 min. Memory was assessed by total freezing time in the same environment 24 h and 28 h after fear conditioning, and in an intervening test session in a different context. As expected, fimbria-fornix lesion impaired fear memory and dramatically attenuated hippocampal theta power. Artificial theta stimulation produced continuous theta oscillations that were almost similar to endogenous theta rhythm in amplitude and frequency. However, contrary to our predictions, artificial theta stimulation impaired conditioned fear response in both sham and fimbria-fornix lesioned animals. These data suggest that restoration of theta oscillation per se is not sufficient to support memory encoding after fimbria-fornix lesion and that universal theta oscillation in the hippocampus with a fixed frequency may actually impair memory.

  9. Consolidation of an extinction memory depends on the unconditioned stimulus magnitude previously experienced during training.

    Science.gov (United States)

    Stollhoff, Nicola; Eisenhardt, Dorothea

    2009-07-29

    Here, we examine the role of the magnitude of the unconditioned stimulus (US) during classical conditioning in consolidation processes after memory retrieval. We varied the US durations during training and we test the impact of these variations on consolidation after memory retrieval with one or two conditioned stimulus-only trials. We found that the consolidation of an extinction memory depends on US duration during training and ruled out the possibility that this effect is attributable to differences in satiation after conditioning. We conclude that consolidation of an extinction memory is triggered only when the duration of the US reaches a critical threshold. This demonstrates that memory consolidation cannot be regarded as an isolated process depending solely on training conditions. Instead, it depends on the animal's previous experience as well.

  10. Stability of retrieved memory: inverse correlation with trace dominance.

    Science.gov (United States)

    Eisenberg, Mark; Kobilo, Tali; Berman, Diego E; Dudai, Yadin

    2003-08-22

    In memory consolidation, the memory trace stabilizes and becomes resistant to certain amnesic agents. The textbook account is that for any memorized item, consolidation starts and ends just once. However, evidence has accumulated that upon activation in retrieval, the trace may reconsolidate. Whereas some authors reported transient renewed susceptibility of retrieved memories to consolidation blockers, others could not detect it. Here, we report that in both conditioned taste aversion in the rat and fear conditioning in the medaka fish, the stability of retrieved memory is inversely correlated with the control of behavior by that memory. This result may explain some conflicting findings on reconsolidation of activated memories.

  11. Abnormal Fear Memory as a Model for Posttraumatic Stress Disorder.

    Science.gov (United States)

    Desmedt, Aline; Marighetto, Aline; Piazza, Pier-Vincenzo

    2015-09-01

    For over a century, clinicians have consistently described the paradoxical co-existence in posttraumatic stress disorder (PTSD) of sensory intrusive hypermnesia and declarative amnesia for the same traumatic event. Although this amnesia is considered as a critical etiological factor of the development and/or persistence of PTSD, most current animal models in basic neuroscience have focused exclusively on the hypermnesia, i.e., the persistence of a strong fear memory, neglecting the qualitative alteration of fear memory. The latest is characterized by an underrepresentation of the trauma in the context-based declarative memory system in favor of its overrepresentation in a cue-based sensory/emotional memory system. Combining psychological and neurobiological data as well as theoretical hypotheses, this review supports the idea that contextual amnesia is at the core of PTSD and its persistence and that altered hippocampal-amygdalar interaction may contribute to such pathologic memory. In a first attempt to unveil the neurobiological alterations underlying PTSD-related hypermnesia/amnesia, we describe a recent animal model mimicking in mice some critical aspects of such abnormal fear memory. Finally, this line of argument emphasizes the pressing need for a systematic comparison between normal/adaptive versus abnormal/maladaptive fear memory to identify biomarkers of PTSD while distinguishing them from general stress-related, potentially adaptive, neurobiological alterations. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Retrieval as a Fast Route to Memory Consolidation.

    Science.gov (United States)

    Antony, James W; Ferreira, Catarina S; Norman, Kenneth A; Wimber, Maria

    2017-08-01

    Retrieval-mediated learning is a powerful way to make memories last, but its neurocognitive mechanisms remain unclear. We propose that retrieval acts as a rapid consolidation event, supporting the creation of adaptive hippocampal-neocortical representations via the 'online' reactivation of associative information. We describe parallels between online retrieval and offline consolidation and offer testable predictions for future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Non-Interfering Effects of Active Post-Encoding Tasks on Episodic Memory Consolidation in Humans.

    Science.gov (United States)

    Varma, Samarth; Takashima, Atsuko; Krewinkel, Sander; van Kooten, Maaike; Fu, Lily; Medendorp, W Pieter; Kessels, Roy P C; Daselaar, Sander M

    2017-01-01

    So far, studies that investigated interference effects of post-learning processes on episodic memory consolidation in humans have used tasks involving only complex and meaningful information. Such tasks require reallocation of general or encoding-specific resources away from consolidation-relevant activities. The possibility that interference can be elicited using a task that heavily taxes our limited brain resources, but has low semantic and hippocampal related long-term memory processing demands, has never been tested. We address this question by investigating whether consolidation could persist in parallel with an active, encoding-irrelevant, minimally semantic task, regardless of its high resource demands for cognitive processing. We distinguish the impact of such a task on consolidation based on whether it engages resources that are: (1) general/executive, or (2) specific/overlapping with the encoding modality. Our experiments compared subsequent memory performance across two post-encoding consolidation periods: quiet wakeful rest and a cognitively demanding n-Back task. Across six different experiments (total N = 176), we carefully manipulated the design of the n-Back task to target general or specific resources engaged in the ongoing consolidation process. In contrast to previous studies that employed interference tasks involving conceptual stimuli and complex processing demands, we did not find any differences between n-Back and rest conditions on memory performance at delayed test, using both recall and recognition tests. Our results indicate that: (1) quiet, wakeful rest is not a necessary prerequisite for episodic memory consolidation; and (2) post-encoding cognitive engagement does not interfere with memory consolidation when task-performance has minimal semantic and hippocampally-based episodic memory processing demands. We discuss our findings with reference to resource and reactivation-led interference theories.

  14. Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training

    NARCIS (Netherlands)

    Morena, M.; Roozendaal, B.; Trezza, V.; Ratano, P.; Peloso, A.; Hauer, D.; Atsak, P.; Trabace, L.; Cuomo, V.; McGaugh, J.L.; Schelling, G.; Campolongo, P.

    2014-01-01

    Previous studies have provided extensive evidence that administration of cannabinoid drugs after training modulates the consolidation of memory for an aversive experience. The present experiments investigated whether the memory consolidation is regulated by endogenously released cannabinoids. The

  15. Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines.

    Science.gov (United States)

    Wagner, Isabella C; van Buuren, Mariët; Bovy, Leonore; Morris, Richard G; Fernández, Guillén

    2017-02-01

    Synaptic memory consolidation is thought to rely on catecholaminergic signaling. Eventually, it is followed by systems consolidation, which embeds memories in a neocortical network. Although this sequence was demonstrated in rodents, it is unclear how catecholamines affect memory consolidation in humans. Here, we tested the effects of catecholaminergic modulation on synaptic and subsequent systems consolidation. We expected enhanced memory performance and increased neocortical engagement during delayed retrieval. Additionally, we tested if this effect was modulated by individual differences in a cognitive proxy measure of baseline catecholamine synthesis capacity. Fifty-three healthy males underwent a between-subjects, double-blind, placebo-controlled procedure across 2 days. On day 1, subjects studied and retrieved object-location associations and received 20 mg of methylphenidate or placebo. Drug intake was timed so that methylphenidate was expected to affect early consolidation but not encoding or retrieval. Memory was tested again while subjects were scanned three days later. Methylphenidate did not facilitate memory performance, and there was no significant group difference in activation during delayed retrieval. However, memory representations differed between groups depending on baseline catecholamines. The placebo group showed increased activation in occipito-temporal regions but decreased connectivity with the hippocampus, associated with lower baseline catecholamine synthesis capacity. The methylphenidate group showed stronger activation in the postcentral gyrus, associated with higher baseline catecholamine synthesis capacity. Altogether, methylphenidate during early consolidation did not foster long-term memory performance, but it affected retrieval-related neural processes depending on individual levels of baseline catecholamines.

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

    Science.gov (United States)

    Kittelberger, Kara A; Piazza, Fabrizio; Tesco, Giuseppina; Reijmers, Leon G

    2012-01-01

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

  17. Natural Amyloid-Beta Oligomers Acutely Impair the Formation of a Contextual Fear Memory in Mice

    Science.gov (United States)

    Kittelberger, Kara A.; Piazza, Fabrizio; Tesco, Giuseppina; Reijmers, Leon G.

    2012-01-01

    Memory loss is one of the hallmark symptoms of Alzheimer's disease (AD). It has been proposed that soluble amyloid-beta (Abeta) oligomers acutely impair neuronal function and thereby memory. We here report that natural Abeta oligomers acutely impair contextual fear memory in mice. A natural Abeta oligomer solution containing Abeta monomers, dimers, trimers, and tetramers was derived from the conditioned medium of 7PA2 cells, a cell line that expresses human amyloid precursor protein containing the Val717Phe familial AD mutation. As a control we used 7PA2 conditioned medium from which Abeta oligomers were removed through immunodepletion. Separate groups of mice were injected with Abeta and control solutions through a cannula into the lateral brain ventricle, and subjected to fear conditioning using two tone-shock pairings. One day after fear conditioning, mice were tested for contextual fear memory and tone fear memory in separate retrieval trials. Three experiments were performed. For experiment 1, mice were injected three times: 1 hour before and 3 hours after fear conditioning, and 1 hour before context retrieval. For experiments 2 and 3, mice were injected a single time at 1 hour and 2 hours before fear conditioning respectively. In all three experiments there was no effect on tone fear memory. Injection of Abeta 1 hour before fear conditioning, but not 2 hours before fear conditioning, impaired the formation of a contextual fear memory. In future studies, the acute effect of natural Abeta oligomers on contextual fear memory can be used to identify potential mechanisms and treatments of AD associated memory loss. PMID:22238679

  18. The role of the ventromedial prefrontal cortex in memory consolidation

    NARCIS (Netherlands)

    Nieuwenhuis, I.L.C.; Takashima, A.

    2011-01-01

    System-level memory consolidation theory posits that the hippocampus initially links the neocortical representations, followed by a shift to a hippocampus-independent neocortical network. With consolidation, an increase in activity in the human subgenual ventromedial prefrontal cortex (vmPFC) has

  19. Memory reconsolidation mediates the updating of hippocampal memory content

    Directory of Open Access Journals (Sweden)

    Jonathan L C Lee

    2010-11-01

    Full Text Available The retrieval or reactivation of a memory places it into a labile state, requiring a process of reconsolidation to restabilize it. This retrieval-induced plasticity is a potential mechanism for the modification of the existing memory. Following previous data supportive of a functional role for memory reconsolidation in the modification of memory strength, here I show that hippocampal memory reconsolidation also supports the updating of contextual memory content. Using a procedure that separates the learning of pure context from footshock-motivated contextual fear learning, I demonstrate doubly dissociable hippocampal mechanisms of initial context learning and subsequent updating of the neutral contextual representation to incorporate the footshock. Contextual memory consolidation was dependent upon BDNF expression in the dorsal hippocampus, whereas the footshock modification of the contextual representation required the expression of Zif268. These mechanisms match those previously shown to be selectively involved in hippocampal memory consolidation and reconsolidation, respectively. Moreover, memory reactivation is a necessary step in modifying memory content, as inhibition of hippocampal synaptic protein degradation also prevented the footshock-mediated memory modification. Finally, dorsal hippocampal knockdown of Zif268 impaired the reconsolidation of the pure contextual memory only under conditions of weak context memory training, as well as failing to disrupt contextual freezing when a strong contextual fear memory is reactivated by further conditioning. Therefore, an adaptive function of the reactivation and reconsolidation process is to enable the updating of memory content.

  20. Acute exercise improves motor memory consolidation in preadolescent children

    DEFF Research Database (Denmark)

    Lundbye-Jensen, Jesper; Skriver, Kasper Christen; Nielsen, Jens Bo

    2017-01-01

    protocols following motor skill practice in a school setting can also improve long-term retention of motor memory in preadolescent children. Methods: Seventy-seven pre-adolescent children (age 10.5 ± 0.75 (SD)) participated in the study. Prior to the main experiment age, BMI, fitness status and general...... immediately after motor skill acquisition facilitates long-term motor memory in pre-adolescent children, presumably by promoting memory consolidation. The results also demonstrate that the effects can be accomplished in a school setting. The positive effect of both a team game (i.e., FLB) and running......Objective: The ability to acquire new motor skills is essential both during childhood and later in life. Recent studies have demonstrated that an acute bout of exercise can improve motor memory consolidation in adults. The objective of the present study was to investigate whether acute exercise...

  1. Block of glucocorticoid synthesis during re-activation inhibits extinction of an established fear memory.

    Science.gov (United States)

    Blundell, Jacqueline; Blaiss, Cory A; Lagace, Diane C; Eisch, Amelia J; Powell, Craig M

    2011-05-01

    The pharmacology of traumatic memory extinction has not been fully characterized despite its potential as a therapeutic target for established, acquired anxiety disorders, including post-traumatic stress disorder (PTSD). Here we examine the role of endogenous glucocorticoids in traumatic memory extinction. Male C57BL/6J mice were injected with corticosterone (10 mg/kg, i.p.) or metyrapone (50 mg/kg, s.c.) during re-activation of a contextual fear memory, and compared to vehicle groups (N=10-12 per group). To ensure that metyrapone was blocking corticosterone synthesis, we measured corticosterone levels following re-activation of a fear memory in metyrapone- and vehicle-treated animals. Corticosterone administration following extinction trials caused a long-lasting inhibition of the original fear memory trace. In contrast, blockade of corticosteroid synthesis with metyrapone prior to extinction trials enhanced retrieval and prevented extinction of context-dependent fear responses in mice. Further behavioral analysis suggested that the metyrapone enhancement of retrieval and prevention of extinction were not due to non-specific alterations in locomotor or anxiety-like behavior. In addition, the inhibition of extinction by metyrapone was rescued by exogenous administration of corticosterone following extinction trials. Finally, we confirmed that the rise in corticosterone during re-activation of a contextual fear memory was blocked by metyrapone. We demonstrate that extinction of a classical contextual fear memory is dependent on endogenous glucocorticoid synthesis during re-activation of a fear memory. Our data suggest that decreased glucocorticoids during fear memory re-activation may contribute to the inability to extinguish a fear memory, thus contributing to one of the core symptoms of PTSD. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Ana Montero-Pedrazuela

    Full Text Available 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.

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

    Science.gov (United States)

    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

  5. Opposite Effects of Cortisol on Consolidation of Temporal Sequence Memory during Waking and Sleep

    Science.gov (United States)

    Wilhelm, Ines; Wagner, Ullrich; Born, Jan

    2011-01-01

    Memory functions involve three stages: encoding, consolidation, and retrieval. Modulating effects of glucocorticoids (GCs) have been consistently observed for declarative memory with GCs enhancing encoding and impairing retrieval, but surprisingly, little is known on how GCs affect memory consolidation. Studies in rats suggest a beneficial effect…

  6. Molecular mechanisms underlying memory consolidation of taste information in the cortex.

    Science.gov (United States)

    Gal-Ben-Ari, Shunit; Rosenblum, Kobi

    2011-01-01

    The senses of taste and odor are both chemical senses. However, whereas an organism can detect an odor at a relatively long distance from its source, taste serves as the ultimate proximate gatekeeper of food intake: it helps in avoiding poisons and consuming beneficial substances. The automatic reaction to a given taste has been developed during evolution and is well adapted to conditions that may occur with high probability during the lifetime of an organism. However, in addition to this automatic reaction, animals can learn and remember tastes, together with their positive or negative values, with high precision and in light of minimal experience. This ability of mammalians to learn and remember tastes has been studied extensively in rodents through application of reasonably simple and well defined behavioral paradigms. The learning process follows a temporal continuum similar to those of other memories: acquisition, consolidation, retrieval, relearning, and reconsolidation. Moreover, inhibiting protein synthesis in the gustatory cortex (GC) specifically affects the consolidation phase of taste memory, i.e., the transformation of short- to long-term memory, in keeping with the general biochemical definition of memory consolidation. This review aims to present a general background of taste learning, and to focus on recent findings regarding the molecular mechanisms underlying taste-memory consolidation in the GC. Specifically, the roles of neurotransmitters, neuromodulators, immediate early genes, and translation regulation are addressed.

  7. Molecular mechanisms underlying memory consolidation of taste information in the cortex

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    Shunit eGal-Ben-Ari

    2012-01-01

    Full Text Available The senses of taste and odor are both chemical senses. However, whereas an organism can detect an odor at a relatively long distance from its source, taste serves as the ultimate proximate gatekeeper of food intake: it helps in avoiding poisons and consuming beneficial substances. The automatic reaction to a given taste has been developed during evolution and is well adapted to conditions that may occur with high probability during the lifetime of an organism. However, in addition to this automatic reaction, animals can learn and remember tastes, together with their positive or negative values, with high precision and in light of minimal experience. This ability of mammalians to learn and remember tastes has been studied extensively in rodents through application of reasonably simple and well defined behavioral paradigms. The learning process follows a temporal continuum similar to those of other memories: acquisition, consolidation, retrieval, relearning, and reconsolidation. Moreover, inhibiting protein synthesis in the gustatory cortex specifically affects the consolidation phase of taste memory, i.e., the transformation of short- to long-term memory, in keeping with the general biochemical definition of memory consolidation. This review aims to present a general background of taste learning, and to focus on recent findings regarding the molecular mechanisms underlying taste memory consolidation in the gustatory cortex. Specifically, the role of neurotransmitters, meuromodulators, immediate early genes, and translation regulation are addressed.

  8. Sleep directly following learning benefits consolidation of spatial associative memory.

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    Talamini, Lucia M; Nieuwenhuis, Ingrid L C; Takashima, Atsuko; Jensen, Ole

    2008-04-01

    The last decade has brought forth convincing evidence for a role of sleep in non-declarative memory. A similar function of sleep in episodic memory is supported by various correlational studies, but direct evidence is limited. Here we show that cued recall of face-location associations is significantly higher following a 12-h retention interval containing sleep than following an equally long period of waking. Furthermore, retention is significantly higher over a 24-h sleep-wake interval than over an equally long wake-sleep interval. This difference occurs because retention during sleep was significantly better when sleep followed learning directly, rather than after a day of waking. These data demonstrate a beneficial effect of sleep on memory that cannot be explained solely as a consequence of reduced interference. Rather, our findings suggest a competitive consolidation process, in which the fate of a memory depends, at least in part, on its relative stability at sleep onset: Strong memories tend to be preserved, while weaker memories erode still further. An important aspect of memory consolidation may thus result from the removal of irrelevant memory "debris."

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

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    Tanja eHamacher-Dang

    2013-08-01

    Full Text Available 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

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

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    Kara A Kittelberger

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

  11. Repeated Recall and PKM? Maintain Fear Memories in Juvenile Rats

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    Oliver, Chicora F.; Kabitzke, Patricia; Serrano, Peter; Egan, Laura J.; Barr, Gordon A.; Shair, Harry N.; Wiedenmayer, Christoph

    2016-01-01

    We examined the neural substrates of fear memory formation and maintenance when repeated recall was used to prevent forgetting in young animals. In contrast to adult rats, juveniles failed to show contextual fear responses at 4 d post-fear conditioning. Reconsolidation sessions 3 and 6 d after conditioning restored contextual fear responses in…

  12. Modification of Fear Memory by Pharmacological and Behavioural Interventions during Reconsolidation.

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    Thome, Janine; Koppe, Georgia; Hauschild, Sophie; Liebke, Lisa; Schmahl, Christian; Lis, Stefanie; Bohus, Martin

    2016-01-01

    Dysfunctional fear responses play a central role in many mental disorders. New insights in learning and memory suggest that pharmacological and behavioural interventions during the reconsolidation of reactivated fear memories may increase the efficacy of therapeutic interventions. It has been proposed that interventions applied during reconsolidation may modify the original fear memory, and thus prevent the spontaneous recovery and reinstatement of the fear response. We investigated whether pharmacological (propranolol) and behavioural (reappraisal, multisensory stimulation) interventions reduce fear memory, and prevent reinstatement of fear in comparison to a placebo control group. Eighty healthy female subjects underwent a differential fear conditioning procedure with three stimuli (CS). Two of these (CS+) were paired with an electric shock on day 1. On day 2, 20 subjects were pseudo-randomly assigned to either the propranolol or placebo condition, or underwent one of the two behavioural interventions after one of the two CS+ was reactivated. On day 3, all subjects underwent an extinction phase, followed by a reinstatement test. Dependent variables were US expectancy ratings, fear-potentiated startle, and skin conductance response. Differential fear responses to the reactivated and non-reactivated CS+ were observed only in the propranolol condition. Here, the non-reactivated CS+ evoked stronger fear-potentiated startle-responses compared to the placebo group. None of the interventions prevented the return of the extinguished fear response after re-exposure to the unconditioned stimulus. Our data are in line with an increasing body of research stating that the occurrence of reconsolidation may be constrained by boundary conditions such as subtle differences in experimental manipulations and instructions. In conclusion, our findings do not support a beneficial effect in using reconsolidation processes to enhance effects of psychotherapeutic interventions. This

  13. Modification of Fear Memory by Pharmacological and Behavioural Interventions during Reconsolidation

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    Thome, Janine; Koppe, Georgia; Hauschild, Sophie; Liebke, Lisa; Schmahl, Christian; Lis, Stefanie; Bohus, Martin

    2016-01-01

    Background Dysfunctional fear responses play a central role in many mental disorders. New insights in learning and memory suggest that pharmacological and behavioural interventions during the reconsolidation of reactivated fear memories may increase the efficacy of therapeutic interventions. It has been proposed that interventions applied during reconsolidation may modify the original fear memory, and thus prevent the spontaneous recovery and reinstatement of the fear response. Methods We investigated whether pharmacological (propranolol) and behavioural (reappraisal, multisensory stimulation) interventions reduce fear memory, and prevent reinstatement of fear in comparison to a placebo control group. Eighty healthy female subjects underwent a differential fear conditioning procedure with three stimuli (CS). Two of these (CS+) were paired with an electric shock on day 1. On day 2, 20 subjects were pseudo-randomly assigned to either the propranolol or placebo condition, or underwent one of the two behavioural interventions after one of the two CS+ was reactivated. On day 3, all subjects underwent an extinction phase, followed by a reinstatement test. Dependent variables were US expectancy ratings, fear-potentiated startle, and skin conductance response. Results Differential fear responses to the reactivated and non-reactivated CS+ were observed only in the propranolol condition. Here, the non-reactivated CS+ evoked stronger fear-potentiated startle-responses compared to the placebo group. None of the interventions prevented the return of the extinguished fear response after re-exposure to the unconditioned stimulus. Conclusions Our data are in line with an increasing body of research stating that the occurrence of reconsolidation may be constrained by boundary conditions such as subtle differences in experimental manipulations and instructions. In conclusion, our findings do not support a beneficial effect in using reconsolidation processes to enhance effects of

  14. Neuropeptide Y2 receptors in anteroventral BNST control remote fear memory depending on extinction training.

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    Verma, Dilip; Tasan, Ramon; Sperk, Guenther; Pape, Hans-Christian

    2018-03-01

    The anterior bed nucleus of stria terminalis (BNST) is involved in reinstatement of extinguished fear, and neuropeptide Y2 receptors influence local synaptic signaling. Therefore, we hypothesized that Y2 receptors in anteroventral BNST (BNSTav) interfere with remote fear memory and that previous fear extinction is an important variable. C57BL/6NCrl mice were fear-conditioned, and a Y2 receptor-specific agonist (NPY 3-36 ) or antagonist (JNJ-5207787) was applied in BNSTav before fear retrieval at the following day. Remote fear memory was tested on day 16 in two groups of mice, which had (experiment 1) or had not (experiment 2) undergone extinction training after conditioning. In the group with extinction training, tests of remote fear memory revealed partial retrieval of extinction, which was prevented after blockade of Y2 receptors in BNSTav. No such effect was observed in the group with no extinction training, but stimulation of Y2 receptors in BNSTav mimicked the influence of extinction during tests of remote fear memory. Pharmacological manipulation of Y2 receptors in BNSTav before fear acquisition (experiment 3) had no effect on fear memory retrieval, extinction or remote fear memory. Furthermore, partial retrieval of extinction during tests of remote fear memory was associated with changes in number of c-Fos expressing neurons in BNSTav, which was prevented or mimicked upon Y2 blockade or stimulation in BNSTav. These results indicate that Y2 receptor manipulation in BNSTav interferes with fear memory and extinction retrieval at remote stages, likely through controlling neuronal activity in BNSTav during extinction training. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Seeking a Spotless Mind: Extinction, Deconsolidation, and Erasure of Fear Memory

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    Maren, Stephen

    2011-01-01

    Learning to contend with threats in the environment is essential to survival, but dysregulation of memories for traumatic events can lead to disabling psychopathology. Recent years have witnessed an impressive growth in our understanding of the neural systems and synaptic mechanisms underlying emotional memory formation. As a consequence, interest has emerged in developing strategies for suppressing, if not eliminating, fear memories. Here I review recent work employing sophisticated behavioral, pharmacological, and molecular tools to target fear memories, placing these memories firmly behind the crosshairs of neurobiologically informed interventions. PMID:21658578

  16. Neuronal mechanisms of motor learning and motor memory consolidation in healthy old adults

    NARCIS (Netherlands)

    Berghuis, K. M. M.; Veldman, M. P.; Solnik, S.; Koch, G.; Zijdewind, I.; Hortobagyi, T.

    It is controversial whether or not old adults are capable of learning new motor skills and consolidate the performance gains into motor memory in the offline period. The underlying neuronal mechanisms are equally unclear. We determined the magnitude of motor learning and motor memory consolidation

  17. Safe taste memory consolidation is disrupted by a protein synthesis inhibitor in the nucleus accumbens shell.

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    Pedroza-Llinás, R; Ramírez-Lugo, L; Guzmán-Ramos, K; Zavala-Vega, S; Bermúdez-Rattoni, F

    2009-07-01

    Consolidation is the process by which a new memory is stabilized over time, and is dependent on de novo protein synthesis. A useful model for studying memory formation is gustatory memory, a type of memory in which a novel taste may become either safe by not being followed by negative consequences (attenuation of neophobia, AN), or aversive by being followed by post-digestive malaise (conditioned taste aversion, CTA). Here we evaluated the effects of the administration of a protein synthesis inhibitor in the nucleus accumbens (NAc) shell for either safe or aversive taste memory trace consolidation. To test the effects on CTA and AN of protein synthesis inhibition, anisomycin (100microg/microl) was bilaterally infused into the NAc shell of Wistar rats' brains. We found that post-trial protein synthesis blockade impaired the long-term safe taste memory. However, protein synthesis inhibition failed to disrupt the long-term memory of CTA. In addition, we infused anisomycin in the NAc shell after the pre-exposure to saccharin in a latent inhibition of aversive taste. We found that the protein synthesis inhibition impaired the consolidation of safe taste memory, allowing the aversive taste memory to form and consolidate. Our results suggest that protein synthesis is required in the NAc shell for consolidation of safe but not aversive taste memories, supporting the notion that consolidation of taste memory is processed in several brain regions in parallel, and implying that inhibitory interactions between both taste memory traces do occur.

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

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    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.

  19. No Associations between Interindividual Differences in Sleep Parameters and Episodic Memory Consolidation.

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    Ackermann, Sandra; Hartmann, Francina; Papassotiropoulos, Andreas; de Quervain, Dominique J-F; Rasch, Björn

    2015-06-01

    Sleep and memory are stable and heritable traits that strongly differ between individuals. Sleep benefits memory consolidation, and the amount of slow wave sleep, sleep spindles, and rapid eye movement sleep have been repeatedly identified as reliable predictors for the amount of declarative and/or emotional memories retrieved after a consolidation period filled with sleep. These studies typically encompass small sample sizes, increasing the probability of overestimating the real association strength. In a large sample we tested whether individual differences in sleep are predictive for individual differences in memory for emotional and neutral pictures. Between-subject design. Cognitive testing took place at the University of Basel, Switzerland. Sleep was recorded at participants' homes, using portable electroencephalograph-recording devices. Nine hundred-twenty-nine healthy young participants (mean age 22.48 ± 3.60 y standard deviation). None. In striking contrast to our expectations as well as numerous previous findings, we did not find any significant correlations between sleep and memory consolidation for pictorial stimuli. Our results indicate that individual differences in sleep are much less predictive for pictorial memory processes than previously assumed and suggest that previous studies using small sample sizes might have overestimated the association strength between sleep stage duration and pictorial memory performance. Future studies need to determine whether intraindividual differences rather than interindividual differences in sleep stage duration might be more predictive for the consolidation of emotional and neutral pictures during sleep. © 2015 Associated Professional Sleep Societies, LLC.

  20. Slow sleep spindle and procedural memory consolidation in patients with major depressive disorder

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    Nishida M

    2016-01-01

    Full Text Available Masaki Nishida,1 Yusaku Nakashima,2 Toru Nishikawa11Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo, 2Medical Technology Research Laboratory, Research and Development Division, Medical Business Unit, Sony Corporation, Tokyo, JapanIntroduction: Evidence has accumulated, which indicates that, in healthy individuals, sleep enhances procedural memory consolidation, and that sleep spindle activity modulates this process. However, whether sleep-dependent procedural memory consolidation occurs in patients medicated for major depressive disorder remains unclear, as are the pharmacological and physiological mechanisms that underlie this process.Methods: Healthy control participants (n=17 and patients medicated for major depressive disorder (n=11 were recruited and subjected to a finger-tapping motor sequence test (MST; nondominant hand paradigm to compare the averaged scores of different learning phases (presleep, postsleep, and overnight improvement. Participants' brain activity was recorded during sleep with 16 electroencephalography channels (between MSTs. Sleep scoring and frequency analyses were performed on the electroencephalography data. Additionally, we evaluated sleep spindle activity, which divided the spindles into fast-frequency spindle activity (12.5–16 Hz and slow-frequency spindle activity (10.5–12.5 Hz.Result: Sleep-dependent motor memory consolidation in patients with depression was impaired in comparison with that in control participants. In patients with depression, age correlated negatively with overnight improvement. The duration of slow-wave sleep correlated with the magnitude of motor memory consolidation in patients with depression, but not in healthy controls. Slow-frequency spindle activity was associated with reduction in the magnitude of motor memory consolidation in both groups.Conclusion: Because the changes in slow

  1. Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

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    Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

    2017-04-12

    Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We

  2. Selective neuronal degeneration in the retrosplenial cortex impairs the recall of contextual fear memory.

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    Sigwald, Eric L; Genoud, Manuel E; Giachero, Marcelo; de Olmos, Soledad; Molina, Víctor A; Lorenzo, Alfredo

    2016-05-01

    The retrosplenial cortex (RSC) is one of the largest cortical areas in rodents, and is subdivided in two main regions, A29 and A30, according to their cytoarchitectural organization and connectivities. However, very little is known about the functional activity of each RSC subdivision during the execution of complex cognitive tasks. Here, we used a well-established fear learning protocol that induced long-lasting contextual fear memory and showed that during evocation of the fear memory, the expression of early growth response gene 1 was up-regulated in A30, and in other brain areas implicated in fear and spatial memory, however, was down-regulated in A29, including layers IV and V. To search for the participation of A29 on fear memory, we triggered selective degeneration of neurons within cortical layers IV and V of A29 by using a non-invasive protocol that takes advantage of the vulnerability that these neurons have MK801-toxicity and the modulation of this neurodegeneration by testosterone. Application of 5 mg/kg MK801 in intact males induced negligible neuronal degeneration of A29 neurons and had no impact on fear memory retrieval. However, in orchiectomized rats, 5 mg/kg MK801 induced overt degeneration of layers IV-V neurons of A29, significantly impairing fear memory recall. Degeneration of A29 neurons did not affect exploratory or anxiety-related behavior nor altered unconditioned freezing. Importantly, protecting A29 neurons from MK801-toxicity by testosterone preserved fear memory recall in orchiectomized rats. Thus, neurons within cortical layers IV-V of A29 are critically required for efficient retrieval of contextual fear memory.

  3. Additive effect of harmane and muscimol for memory consolidation impairment in inhibitory avoidance task.

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    Nasehi, Mohammad; Morteza-Zadeh, Parastoo; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

    2016-12-17

    In the current study, we examined the effect of bilateral intra-dorsal hippocampal (intra-CA1) microinjections of GABA A receptor agents on amnesia induced by a β-carboline alkaloid, harmane in mice. We used a single-trial step-down passive avoidance task to assess memory retention and then, open-field test to assess locomotor activity. The results indicated that post-training intra-CA1 injections of bicuculline - a GABA A receptor antagonist - had no significant effect, while muscimol (0.01 and 0.1μg/mouse) - a GABA A receptor agonist - impaired memory consolidation. Post-training intra-peritoneal (i.p.) infusion of harmane (3 and 5mg/kg) decreased memory consolidation. Furthermore, post-training intra-CA1 administration of sub-threshold dose of bicuculline (0.001μg/mouse) restored, whereas muscimol (0.001μg/mouse) potentiated impairment of memory consolidation induced by harmane. The isobologram analysis revealed that there is an additive effect between harmane and muscimol on impairment of memory consolidation. Moreover, all above doses of drugs did not alter locomotor activity. These findings suggest that GABA A receptors of the CA1 area, at least partly, play a role in modulating the effect of harmane on memory consolidation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

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

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    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.

  5. Amygdala-dependent fear is regulated by Oprl1 in mice and humans with PTSD.

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    Andero, Raül; Brothers, Shaun P; Jovanovic, Tanja; Chen, Yen T; Salah-Uddin, Hasib; Cameron, Michael; Bannister, Thomas D; Almli, Lynn; Stevens, Jennifer S; Bradley, Bekh; Binder, Elisabeth B; Wahlestedt, Claes; Ressler, Kerry J

    2013-06-05

    The amygdala-dependent molecular mechanisms driving the onset and persistence of posttraumatic stress disorder (PTSD) are poorly understood. Recent observational studies have suggested that opioid analgesia in the aftermath of trauma may decrease the development of PTSD. Using a mouse model of dysregulated fear, we found altered expression within the amygdala of the Oprl1 gene (opioid receptor-like 1), which encodes the amygdala nociceptin (NOP)/orphanin FQ receptor (NOP-R). Systemic and central amygdala infusion of SR-8993, a new highly selective NOP-R agonist, impaired fear memory consolidation. In humans, a single-nucleotide polymorphism (SNP) within OPRL1 is associated with a self-reported history of childhood trauma and PTSD symptoms (n = 1847) after a traumatic event. This SNP is also associated with physiological startle measures of fear discrimination and magnetic resonance imaging analysis of amygdala-insula functional connectivity. Together, these data suggest that Oprl1 is associated with amygdala function, fear processing, and PTSD symptoms. Further, our data suggest that activation of the Oprl1/NOP receptor may interfere with fear memory consolidation, with implications for prevention of PTSD after a traumatic event.

  6. Activation of D1/5 Dopamine Receptors: A Common Mechanism for Enhancing Extinction of Fear and Reward-Seeking Behaviors.

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    Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

    2016-07-01

    Dopamine is critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in appetitive tasks. A parallel and growing literature indicates that dopamine signaling is involved in consolidation of memories into stable representations in aversive tasks such as fear conditioning. Relatively little is known about how dopamine may modulate memories that form during extinction, when organisms learn that the relation between previously associated events is severed. We investigated whether fear and reward extinction share common mechanisms that could be enhanced with dopamine D1/5 receptor activation. Pharmacological activation of dopamine D1/5 receptors (with SKF 81297) enhanced extinction of both cued and contextual fear. These effects also occurred in the extinction of cocaine-induced conditioned place preference, suggesting that the observed effects on extinction were not specific to a particular type of procedure (aversive or appetitive). A cAMP/PKA biased D1 agonist (SKF 83959) did not affect fear extinction, whereas a broadly efficacious D1 agonist (SKF 83822) promoted fear extinction. Together, these findings show that dopamine D1/5 receptor activation is a target for the enhancement of fear or reward extinction.

  7. System Consolidation of Spatial Memories in Mice: Effects of Enriched Environment

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    Joyce Bonaccorsi

    2013-01-01

    Full Text Available Environmental enrichment (EE is known to enhance learning and memory. Declarative memories are thought to undergo a first rapid and local consolidation process, followed by a prolonged process of system consolidation, which consist in a time-dependent gradual reorganization of brain regions supporting remote memory storage and crucial for the formation of enduring memories. At present, it is not known whether EE can affect the process of declarative memory system consolidation. We characterized the time course of hippocampal and cortical activation following recall of progressively more remote spatial memories. Wild-type mice either exposed to EE for 40 days or left in standard environment were subjected to spatial learning in the Morris water maze and to the probe test 1, 10, 20, 30, and 50 days after learning. Following the probe test, regional expression of the inducible immediate early gene c-Fos was mapped by immunohistochemistry, as an indicator of neuronal activity. We found that activation of the medial prefrontal cortex (mPFC, suggested to have a privileged role in processing remote spatial memories, was evident at shorter time intervals after learning in EE mice; in addition, EE induced the progressive activation of a distributed cortical network not activated in non-EE mice. This suggests that EE not only accelerates the process of mPFC recruitment but also recruits additional cortical areas into the network supporting remote spatial memories.

  8. Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation.

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    Busquets-Garcia, Arnau; Gomis-González, Maria; Srivastava, Raj Kamal; Cutando, Laura; Ortega-Alvaro, Antonio; Ruehle, Sabine; Remmers, Floortje; Bindila, Laura; Bellocchio, Luigi; Marsicano, Giovanni; Lutz, Beat; Maldonado, Rafael; Ozaita, Andrés

    2016-08-30

    Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific cell types revealed that the CB1 receptor population specifically in dopamine β-hydroxylase (DBH)-expressing cells is both necessary and sufficient for stress-induced impairment of memory consolidation, but CB1 receptors present in other neuronal populations are not involved. Strikingly, pharmacological manipulations in mice expressing CB1 receptors exclusively in DBH(+) cells revealed that both hippocampal and peripheral receptors mediate the impact of stress on memory consolidation. Thus, CB1 receptors on adrenergic and noradrenergic cells provide previously unrecognized cross-talk between central and peripheral mechanisms in the stress-dependent regulation of nonemotional memory consolidation, suggesting new potential avenues for the treatment of cognitive aspects on stress-related disorders.

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

    Science.gov (United States)

    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.

  10. Propranolol–induced Impairment of Contextual Fear Memory Reconsolidation in Rats: A similar Effect on Weak and Strong Recent and Remote Memories

    Science.gov (United States)

    Taherian, Fatemeh; Vafaei, Abbas Ali; Vaezi, Gholam Hassan; Eskandarian, Sharaf; Kashef, Adel; Rashidy-Pour, Ali

    2014-01-01

    Introduction Previous studies have demonstrated that the β-adrenergic receptor antagonist propranolol impairs fear memory reconsolidation in experimental animals. There are experimental parameters such as the age and the strength of memory that can interact with pharmacological manipulations of memory reconsolidation. In this study, we investigated the ability of the age and the strength of memory to influence the disrupting effects of propranolol on fear memory reconsolidation in rats. Methods The rats were trained in a contextual fear conditioning using two (weak training) or five (strong training) footshocks (1mA). Propranolol (10mg/kg) injection was immediately followed retrieval of either a one-day recent (weak or strong) or 36-day remote (weak or strong) contextual fear memories. Results We found that propranolol induced a long-lasting impairment of subsequent expression of recent and remote memories with either weak or strong strength. We also found no memory recovery after a weak reminder shock. Furthermore, no significant differences were found on the amount of memory deficit induced by propranolol among memories with different age and strength. Discussion Our data suggest that the efficacy of propranolol in impairing fear memory reconsolidation is not limited to the age or strength of the memory. PMID:25337385

  11. Differential consolidation and pattern reverberations within episodic cell assemblies in the mouse hippocampus.

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    Remus Oşan

    2011-02-01

    Full Text Available One hallmark feature of consolidation of episodic memory is that only a fraction of original information, which is usually in a more abstract form, is selected for long-term memory storage. How does the brain perform these differential memory consolidations? To investigate the neural network mechanism that governs this selective consolidation process, we use a set of distinct fearful events to study if and how hippocampal CA1 cells engage in selective memory encoding and consolidation. We show that these distinct episodes activate a unique assembly of CA1 episodic cells, or neural cliques, whose response-selectivity ranges from general-to-specific features. A series of parametric analyses further reveal that post-learning CA1 episodic pattern replays or reverberations are mostly mediated by cells exhibiting event intensity-invariant responses, not by the intensity-sensitive cells. More importantly, reactivation cross-correlations displayed by intensity-invariant cells encoding general episodic features during immediate post-learning period tend to be stronger than those displayed by invariant cells encoding specific features. These differential reactivations within the CA1 episodic cell populations can thus provide the hippocampus with a selection mechanism to consolidate preferentially more generalized knowledge for long-term memory storage.

  12. Reduced susceptibility to interference in the consolidation of motor memory before adolescence.

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    Shoshi Dorfberger

    2007-02-01

    Full Text Available Are children superior to adults in consolidating procedural memory? This notion has been tied to "critical," early life periods of increased brain plasticity. Here, using a motor sequence learning task, we show, in experiment 1, that a the rate of learning during a training session, b the gains accrued, without additional practice, within a 24 hours post-training interval (delayed consolidation gains, and c the long-term retention of these gains, were as effective in 9, 12 and 17-year-olds and comparable to those reported for adults. However, a follow-up experiment showed that the establishment of a memory trace for the trained sequence of movements was significantly more susceptible to interference by a subsequent motor learning experience (practicing a reversed movement sequence in the 17-year-olds compared to the 9 and 12-year-olds. Unlike the 17-year-olds, the younger age-groups showed significant delayed gains even after interference training. Altogether, our results indicate the existence of an effective consolidation phase in motor learning both before and after adolescence, with no childhood advantage in the learning or retention of a motor skill. However, the ability to co-consolidate different, successive motor experiences, demonstrated in both the 9 and 12-year-olds, diminishes after puberty, suggesting that a more selective memory consolidation process takes over from the childhood one. Only the adult consolidation process is gated by a recency effect, and in situations of multiple, clashing, experiences occurring within a short time-interval, adults may less effectively establish in memory experiences superseded by newer ones.

  13. Facilitation of Contextual Fear Extinction by Orexin-1 Receptor Antagonism Is Associated with the Activation of Specific Amygdala Cell Subpopulations.

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    Flores, África; Herry, Cyril; Maldonado, Rafael; Berrendero, Fernando

    2017-08-01

    Orexins are hypothalamic neuropeptides recently involved in the regulation of emotional memory. The basolateral amygdala, an area orchestrating fear memory processes, appears to be modulated by orexin transmission during fear extinction. However, the neuronal types within the basolateral amygdala involved in this modulation remain to be elucidated. We used retrograde tracing combined with immunofluorescence techniques in mice to identify basolateral amygdala projection neurons and cell subpopulations in this brain region influenced by orexin transmission during contextual fear extinction consolidation. Treatment with the orexin-1 receptor antagonist SB334867 increased the activity of basolateral amygdala neurons projecting to infralimbic medial prefrontal cortex during fear extinction. GABAergic interneurons expressing calbindin, but not parvalbumin, were also activated by orexin-1 receptor antagonism in the basolateral amygdala. These data identify neuronal circuits and cell populations of the amygdala associated with the facilitation of fear extinction consolidation induced by the orexin-1 receptor antagonist SB334867. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  14. Revealing context-specific conditioned fear memories with full immersion virtual reality

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    Nicole eHuff

    2011-11-01

    Full Text Available The extinction of conditioned fear is known to be context specific, and often referred to as more robustly contextually bound than the fear memory itself (Bouton, 2004. Yet, recent findings in rodents have challenged the notion that contextual fear retention is initially generalized. The context specificity of a cued-fear memory to the learning context has not been addressed in the human literature largely due to limitations in methodology. Here we adapt a novel technology to test the context specificity of cued fear conditioning using full immersion 3-dimensional virtual reality (VR. During acquisition training, healthy participants navigated through virtual environments containing dynamic snake and spider conditioned stimuli (CSs, one of which was paired with electrical wrist stimulation. During a 24-hour delayed retention test, one group returned to the same context as acquisition training whereas another group experienced the CSs in a novel context. Unconditioned stimulus (US expectancy ratings were assayed on-line during fear acquisition as an index of contingency awareness. Skin conductance responses (SCR time-locked to CS onset were the dependent measure of cued fear, and skin conductance levels during the interstimulus interval were an index of context fear. Findings indicate that early in acquisition training, participants express contingency awareness as well as differential contextual fear, whereas differential cued fear emerged later in acquisition. During the retention test, differential cued fear retention was enhanced in the group who returned to the same context as acquisition training relative to the context shift group. The results extend recent rodent work to illustrate differences in cued and context fear acquisition and the contextual specificity of recent fear memories. Findings support the use of full immersion VR as a novel tool in cognitive neuroscience to bridge rodent models of contextual phenomena underlying human

  15. β-Adrenergic signaling is required for the induction of a labile state during memory reconsolidation.

    Science.gov (United States)

    Lim, Chae-Seok; Kim, Jae-Ick; Kwak, Chuljung; Lee, Jaehyun; Jang, Eun Hae; Oh, Jihae; Kaang, Bong-Kiun

    2018-04-20

    Memory reconsolidation is the process by which previously consolidated memories reenter a labile state through reactivation of the memory trace and are actively consolidated through de novo protein synthesis. Although extensive studies have shown that β-adrenergic signaling plays a critical role in the restabilization of reactivated memory, its role in the destabilization of long-term memory is not well-studied. In this study, we found that membrane excitability increased in hippocampal CA1 neurons immediately after the retrieval of contextual fear memory. Interestingly, this increase in membrane excitability diminished after treatment with propranolol (a β-adrenergic receptor antagonist), an NMDA receptor antagonist, and a PKA inhibitor. In addition, we found that administration of propranolol prior to, but not after, the retrieval of fear memory ameliorated the memory impairment caused by anisomycin, indicating that inhibition of β-adrenergic signaling blocks the destabilization of contextual fear memory. Taken together, these results indicate that β-adrenergic signaling via NMDA receptors and PKA signaling pathway induces a labile state of long-term memory through increased neuronal membrane excitability. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Robust hippocampal responsivity during retrieval of consolidated associative memory.

    Science.gov (United States)

    Hattori, Shoai; Chen, Lillian; Weiss, Craig; Disterhoft, John F

    2015-05-01

    A contentious point in memory research is whether or not the hippocampus plays a time-limited role in the consolidation of declarative memories. A widely held view is that declarative memories are initially encoded in the hippocampus, then transferred to the neocortex for long-term storage. Alternate views argue instead that the hippocampus continues to play a role in remote memory recall. These competing theories are largely based on human amnesic and animal lesion/inactivation studies. However, in vivo electrophysiological evidence supporting these views is scarce. Given that other studies examining the role of the hippocampus in remote memory retrieval using lesion and imaging techniques in human and animal models have provided mixed results, it would be particularly useful to gain insight at the in vivo electrophysiological level. Here we report hippocampal single-neuron and theta activity recorded longitudinally during acquisition and remote retrieval of trace eyeblink conditioning. Results from conditioned rabbits were compared to those obtained from yoked pseudo-conditioned control rabbits. Results reveal continued learning-specific hippocampal activity one month after initial acquisition of the task. Our findings yield insight into the normal physiological responses of the hippocampus during memory processes and provide compelling in vivo electrophysiological evidence that the hippocampus is involved in both acquisition and retrieval of consolidated memories. © 2014 The Authors Hippocampus Published by Wiley Periodicals, Inc.

  17. Activity of the anterior cingulate cortex and ventral hippocampus underlie increases in contextual fear generalization.

    Science.gov (United States)

    Cullen, Patrick K; Gilman, T Lee; Winiecki, Patrick; Riccio, David C; Jasnow, Aaron M

    2015-10-01

    Memories for context become less specific with time resulting in animals generalizing fear from training contexts to novel contexts. Though much attention has been given to the neural structures that underlie the long-term consolidation of a context fear memory, very little is known about the mechanisms responsible for the increase in fear generalization that occurs as the memory ages. Here, we examine the neural pattern of activation underlying the expression of a generalized context fear memory in male C57BL/6J mice. Animals were context fear conditioned and tested for fear in either the training context or a novel context at recent and remote time points. Animals were sacrificed and fluorescent in situ hybridization was performed to assay neural activation. Our results demonstrate activity of the prelimbic, infralimbic, and anterior cingulate (ACC) cortices as well as the ventral hippocampus (vHPC) underlie expression of a generalized fear memory. To verify the involvement of the ACC and vHPC in the expression of a generalized fear memory, animals were context fear conditioned and infused with 4% lidocaine into the ACC, dHPC, or vHPC prior to retrieval to temporarily inactivate these structures. The results demonstrate that activity of the ACC and vHPC is required for the expression of a generalized fear memory, as inactivation of these regions returned the memory to a contextually precise form. Current theories of time-dependent generalization of contextual memories do not predict involvement of the vHPC. Our data suggest a novel role of this region in generalized memory, which should be incorporated into current theories of time-dependent memory generalization. We also show that the dorsal hippocampus plays a prolonged role in contextually precise memories. Our findings suggest a possible interaction between the ACC and vHPC controls the expression of fear generalization. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Vagus nerve stimulation enhances extinction of conditioned fear and modulates plasticity in the pathway from the infralimbic prefrontal cortex to the amygdala.

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    David Frausto Peña

    2014-09-01

    Full Text Available Fearful experiences can produce long-lasting and debilitating memories. Extinction of the fear response requires consolidation of new memories that compete with fearful associations. Subjects with posttraumatic stress disorder (PTSD show impaired extinction of conditioned fear, which is associated with decreased ventromedial prefrontal cortex (vmPFC control over amygdala activity. Vagus nerve stimulation (VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here we investigated whether pairing VNS with extinction learning facilitates plasticity between the infralimbic (IL medial prefrontal cortex and the basolateral complex of the amygdala (BLA. Rats were trained on an auditory fear conditioning task, which was followed by a retention test and one day of extinction training. Vagus nerve stimulation or sham-stimulation was administered concurrently with exposure to the fear-conditioned stimulus and retention of fear conditioning was tested again 24 hours later. VNS-treated rats demonstrated a significant reduction in freezing after a single extinction training session similar to animals that received 5x the number of extinction pairings. To study plasticity in the IL-BLA pathway, we recorded evoked field potentials in the BLA in anesthetized animals 24 h after retention testing. Brief burst stimulation in the IL produced LTD in the BLA field response in fear-conditioned and sham-treated animals. In contrast, the same stimulation resulted in potentiation of the IL-BLA pathway in the VNS-treated group. The present findings suggest that VNS promotes plasticity in the IL-BLA pathway to facilitate extinction of conditioned fear responses.

  19. Endocannabinoid signaling within the basolateral amygdala integrates multiple stress hormone effects on memory consolidation.

    Science.gov (United States)

    Atsak, Piray; Hauer, Daniela; Campolongo, Patrizia; Schelling, Gustav; Fornari, Raquel V; Roozendaal, Benno

    2015-05-01

    Glucocorticoid hormones are known to act synergistically with other stress-activated neuromodulatory systems, such as norepinephrine and corticotropin-releasing factor (CRF), within the basolateral complex of the amygdala (BLA) to induce optimal strengthening of the consolidation of long-term memory of emotionally arousing experiences. However, as the onset of these glucocorticoid actions appear often too rapid to be explained by genomic regulation, the neurobiological mechanism of how glucocorticoids could modify the memory-enhancing properties of norepinephrine and CRF remained elusive. Here, we show that the endocannabinoid system, a rapidly activated retrograde messenger system, is a primary route mediating the actions of glucocorticoids, via a glucocorticoid receptor on the cell surface, on BLA neural plasticity and memory consolidation. Furthermore, glucocorticoids recruit downstream endocannabinoid activity within the BLA to interact with both the norepinephrine and CRF systems in enhancing memory consolidation. These findings have important implications for understanding the fine-tuned crosstalk between multiple stress hormone systems in the coordination of (mal)adaptive stress and emotional arousal effects on neural plasticity and memory consolidation.

  20. Deep brain stimulation of the amygdala alleviates fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory.

    Science.gov (United States)

    Sui, Li; Huang, SiJia; Peng, BinBin; Ren, Jie; Tian, FuYing; Wang, Yan

    2014-07-01

    Deep brain stimulation (DBS) of the amygdala has been demonstrated to modulate hyperactivity of the amygdala, which is responsible for the symptoms of post-traumatic stress disorder (PTSD), and thus might be used for the treatment of PTSD. However, the underlying mechanism of DBS of the amygdala in the modulation of the amygdala is unclear. The present study investigated the effects of DBS of the amygdala on synaptic transmission and synaptic plasticity at cortical inputs to the amygdala, which is critical for the formation and storage of auditory fear memories, and fear memories. The results demonstrated that auditory fear conditioning increased single-pulse-evoked field excitatory postsynaptic potentials in the cortical-amygdala pathway. Furthermore, auditory fear conditioning decreased the induction of paired-pulse facilitation and long-term potentiation, two neurophysiological models for studying short-term and long-term synaptic plasticity, respectively, in the cortical-amygdala pathway. In addition, all these auditory fear conditioning-induced changes could be reversed by DBS of the amygdala. DBS of the amygdala also rescued auditory fear conditioning-induced enhancement of long-term retention of fear memory. These findings suggested that DBS of the amygdala alleviating fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory may underlie the neuromodulatory role of DBS of the amygdala in activities of the amygdala.

  1. White Matter Structure in Older Adults Moderates the Benefit of Sleep Spindles on Motor Memory Consolidation.

    Science.gov (United States)

    Mander, Bryce A; Zhu, Alyssa H; Lindquist, John R; Villeneuve, Sylvia; Rao, Vikram; Lu, Brandon; Saletin, Jared M; Ancoli-Israel, Sonia; Jagust, William J; Walker, Matthew P

    2017-11-29

    Sleep spindles promote the consolidation of motor skill memory in young adults. Older adults, however, exhibit impoverished sleep-dependent motor memory consolidation. The underlying pathophysiological mechanism(s) explaining why motor memory consolidation in older adults fails to benefit from sleep remains unclear. Here, we demonstrate that male and female older adults show impoverished overnight motor skill memory consolidation relative to young adults, with the extent of impairment being associated with the degree of reduced frontal fast sleep spindle density. The magnitude of the loss of frontal fast sleep spindles in older adults was predicted by the degree of reduced white matter integrity throughout multiple white matter tracts known to connect subcortical and cortical brain regions. We further demonstrate that the structural integrity of selective white matter fiber tracts, specifically within right posterior corona radiata, right tapetum, and bilateral corpus callosum, statistically moderates whether sleep spindles promoted overnight consolidation of motor skill memory. Therefore, white matter integrity within tracts known to connect cortical sensorimotor control regions dictates the functional influence of sleep spindles on motor skill memory consolidation in the elderly. The deterioration of white matter fiber tracts associated with human brain aging thus appears to be one pathophysiological mechanism influencing subcortical-cortical propagation of sleep spindles and their related memory benefits. SIGNIFICANCE STATEMENT Numerous studies have shown that sleep spindle expression is reduced and sleep-dependent motor memory is impaired in older adults. However, the mechanisms underlying these alterations have remained unknown. The present study reveals that age-related degeneration of white matter within select fiber tracts is associated with reduced sleep spindles in older adults. We further demonstrate that, within these same fiber tracts, the degree of

  2. Acute exercise and motor memory consolidation

    DEFF Research Database (Denmark)

    Thomas, Richard; Beck, Mikkel Malling; Lind, Rune Rasmussen

    2016-01-01

    High intensity aerobic exercise amplifies offline gains in procedural memory acquired during motor practice. This effect seems to be evident when exercise is placed immediately after acquisition, during the first stages of memory consolidation, but the importance of temporal proximity...... of the exercise bout used to stimulate improvements in procedural memory is unknown. The effects of three different temporal placements of high intensity exercise were investigated following visuomotor skill acquisition on the retention of motor memory in 48 young (24.0 ± 2.5 yrs), healthy male subjects randomly...... assigned to one of four groups either performing a high intensity (90% Maximal Power Output) exercise bout at 20 min (EX90), 1 h (EX90+1), 2 h (EX90+2) after acquisition or rested (CON). Retention tests were performed at 1 d (R1) and 7 d (R7). At R1 changes in performance scores after acquisition were...

  3. Rapid changes in the light/dark cycle disrupt memory of conditioned fear in mice.

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    Dawn H Loh

    Full Text Available BACKGROUND: Circadian rhythms govern many aspects of physiology and behavior including cognitive processes. Components of neural circuits involved in learning and memory, e.g., the amygdala and the hippocampus, exhibit circadian rhythms in gene expression and signaling pathways. The functional significance of these rhythms is still not understood. In the present study, we sought to determine the impact of transiently disrupting the circadian system by shifting the light/dark (LD cycle. Such "jet lag" treatments alter daily rhythms of gene expression that underlie circadian oscillations as well as disrupt the synchrony between the multiple oscillators found within the body. METHODOLOGY/PRINCIPAL FINDINGS: We subjected adult male C57Bl/6 mice to a contextual fear conditioning protocol either before or after acute phase shifts of the LD cycle. As part of this study, we examined the impact of phase advances and phase delays, and the effects of different magnitudes of phase shifts. Under all conditions tested, we found that recall of fear conditioned behavior was specifically affected by the jet lag. We found that phase shifts potentiated the stress-evoked corticosterone response without altering baseline levels of this hormone. The jet lag treatment did not result in overall sleep deprivation, but altered the temporal distribution of sleep. Finally, we found that prior experience of jet lag helps to compensate for the reduced recall due to acute phase shifts. CONCLUSIONS/SIGNIFICANCE: Acute changes to the LD cycle affect the recall of fear-conditioned behavior. This suggests that a synchronized circadian system may be broadly important for normal cognition and that the consolidation of memories may be particularly sensitive to disruptions of circadian timing.

  4. Dorsal medial prefrontal cortex contributes to conditioned taste aversion memory consolidation and retrieval.

    Science.gov (United States)

    Gonzalez, Maria Carolina; Villar, Maria Eugenia; Igaz, Lionel M; Viola, Haydée; Medina, Jorge H

    2015-12-01

    The medial prefrontal cortex (mPFC) is known for its role in decision making and memory processing, including the participation in the formation of extinction memories. However, little is known regarding its contribution to aversive memory consolidation. Here we demonstrate that neural activity and protein synthesis are required in the dorsal mPFC for memory formation of a conditioned taste aversion (CTA) task and that this region is involved in the retrieval of recent and remote long-term CTA memory. In addition, both NMDA receptor and CaMKII activity in dorsal mPFC are needed for CTA memory consolidation, highlighting the complexity of mPFC functions. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Short-term inhibition of 11β-hydroxysteroid dehydrogenase type 1 reversibly improves spatial memory but persistently impairs contextual fear memory in aged mice.

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    Wheelan, Nicola; Webster, Scott P; Kenyon, Christopher J; Caughey, Sarah; Walker, Brian R; Holmes, Megan C; Seckl, Jonathan R; Yau, Joyce L W

    2015-04-01

    High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11β-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11β-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11β-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Blocking Dopaminergic Signaling Soon after Learning Impairs Memory Consolidation in Guinea Pigs.

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    Kiera-Nicole Lee

    Full Text Available Formation of episodic memories (i.e. remembered experiences requires a process called consolidation which involves communication between the neocortex and hippocampus. However, the neuromodulatory mechanisms underlying this neocortico-hippocampal communication are poorly understood. Here, we examined the involvement of dopamine D1 receptors (D1R and D2 receptors (D2R mediated signaling on memory consolidation using the Novel Object Recognition (NOR test. We conducted the tests in male Hartley guinea pigs and cognitive behaviors were assessed in customized Phenotyper home cages utilizing Ethovision XT software from Noldus enabled for the 3-point detection system (nose, center of the body, and rear. We found that acute intraperitoneal injections of either 0.25 mg/kg SCH23390 to block D1Rs or 1.0 mg/kg sulpiride to block D2Rs soon after acquisition (which involved familiarization to two similar objects attenuated subsequent discrimination for novel objects when tested after 5-hours in the NOR test. By contrast guinea pigs treated with saline showed robust discrimination for novel objects indicating normal operational processes undergirding memory consolidation. The data suggests that involvement of dopaminergic signaling is a key post-acquisition factor in modulating memory consolidation in guinea pigs.

  7. Sexual behavior modulates contextual fear memory through dopamine D1/D5 receptors.

    Science.gov (United States)

    Bai, Hua-Yi; Cao, Jun; Liu, Na; Xu, Lin; Luo, Jian-Hong

    2009-03-01

    Traumatic events always lead to aversive emotional memory, i.e., fear memory. In contrast, positive events in daily life such as sex experiences seem to reduce aversive memory after aversive events. Thus, we hypothesized that post-traumatic pleasurable experiences, especially instinctive behaviors such as sex, might modulate traumatic memory through a memory competition mechanism. Here, we first report that male rats persistently expressed much lower fear responses when exposed to females, but not when exposed to males, for 24 h immediately after contextual fear conditioning. Remarkably, this effect of sexual behavior was blocked by either systemic or intrahippocampal injection of the dopamine D1/D5 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) and was mimicked by systemic but not intrahippocampal injection of the D1/D5 receptor agonist R(+)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol hydrochloride (SKF39393). Furthermore, as a candidate mechanism underlying contextual fear memory, the impaired induction of hippocampal long-term potentiation (LTP) elicited by conditioned fear was rescued in male rats immediately exposed to female but not male rats for 24 h. Systemic injection of the dopamine D1/D5 receptor antagonist SCH23390 or agonist SKF38393 prevented or mimicked the effect of sexual behavior on the impaired induction of hippocampal LTP. Thus, our finding suggests that dopaminergic functions may, at least partially, govern competition between contextual fear and enjoyable memories through the modulation of hippocampal LTP.

  8. Impairment in extinction of cued fear memory in syntenin-1 knockout mice.

    Science.gov (United States)

    Talukdar, Gourango; Inoue, Ran; Yoshida, Tomoyuki; Mori, Hisashi

    2018-03-01

    Syntenin-1 is a PDZ domain-containing intracellular scaffold protein involved in exosome production, synapse formation, and synaptic plasticity. We tested whether syntenin-1 can regulate learning and memory through its effects on synaptic plasticity. Specifically, we investigated the role of syntenin-1 in contextual and cued fear conditioning and extinction of conditioned fear using syntenin-1 knockout (KO) mice. Genetic disruption of syntenin-1 had little effect on contextual and cued fear memory. However, syntenin-1 KO mice exhibited selective impairment in cued fear extinction retention. This extinction retention deficit in syntenin-1 KO mice was associated with reduced c-Fos-positive neurons in the basolateral amygdala (BLA) and infralimbic cortex (IL) after extinction training and increased c-Fos-positive neurons in the BLA after an extinction retention test. Our results suggest that syntenin-1 plays an important role in extinction of cued fear memory by modulating neuronal activity in the BLA and IL. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Differential Effects of Cannabinoid Receptor Agonist on Social Discrimination and Contextual Fear in Amygdala and Hippocampus

    Science.gov (United States)

    Segev, Amir; Akirav, Irit

    2011-01-01

    We examined whether the cannabinoid receptor agonist WIN55,212-2 (WIN; 5 [mu]g/side) microinjected into the hippocampus or the amygdala would differentially affect memory processes in a neutral vs. an aversive task. In the aversive contextual fear task, WIN into the basolateral amygdala impaired fear acquisition/consolidation, but not retrieval.…

  10. Circadian modulation of consolidated memory retrieval following sleep deprivation in Drosophila.

    Science.gov (United States)

    Le Glou, Eric; Seugnet, Laurent; Shaw, Paul J; Preat, Thomas; Goguel, Valérie

    2012-10-01

    Several lines of evidence indicate that sleep plays a critical role in learning and memory. The aim of this study was to evaluate anesthesia resistant memory following sleep deprivation in Drosophila. Four to 16 h after aversive olfactory training, flies were sleep deprived for 4 h. Memory was assessed 24 h after training. Training, sleep deprivation, and memory tests were performed at different times during the day to evaluate the importance of the time of day for memory formation. The role of circadian rhythms was further evaluated using circadian clock mutants. Memory was disrupted when flies were exposed to 4 h of sleep deprivation during the consolidation phase. Interestingly, normal memory was observed following sleep deprivation when the memory test was performed during the 2 h preceding lights-off, a period characterized by maximum wake in flies. We also show that anesthesia resistant memory was less sensitive to sleep deprivation in flies with disrupted circadian rhythms. Our results indicate that anesthesia resistant memory, a consolidated memory less costly than long-term memory, is sensitive to sleep deprivation. In addition, we provide evidence that circadian factors influence memory vulnerability to sleep deprivation and memory retrieval. Taken together, the data show that memories weakened by sleep deprivation can be retrieved if the animals are tested at the optimal circadian time.

  11. Comparable Rest-related Promotion of Spatial Memory Consolidation in Younger and Older Adults

    Science.gov (United States)

    Craig, Michael; Wolbers, Thomas; Harris, Mathew A.; Hauff, Patrick; Della Sala, Sergio; Dewar, Michaela

    2017-01-01

    Flexible spatial navigation depends on cognitive mapping, a function that declines with increasing age. In young adults, a brief period of post-navigation rest promotes the consolidation/integration of spatial memories into accurate cognitive maps. We examined (1) whether rest promotes spatial memory consolidation/integration in older adults and (2) whether the magnitude of the rest benefit changes with increasing age. Young and older adults learned a route through a virtual environment, followed by a 10min delay comprising either wakeful rest or a perceptual task, and a subsequent cognitive mapping task, requiring the pointing to landmarks from different locations. Pointing accuracy was lower in the older than younger adults. However, there was a comparable rest-related enhancement in pointing accuracy in the two age groups. Together our findings suggest that (i) the age-related decline in cognitive mapping cannot be explained by increased consolidation interference in older adults, and (ii) as we grow older rest continues to support the consolidation/integration of spatial memories. PMID:27689512

  12. Medial prefrontal-hippocampal connectivity and motor memory consolidation in depression and schizophrenia

    NARCIS (Netherlands)

    Genzel, L.K.E.; Dresler, M.; Cornu, M.; Jager, E.; Konrad, B.; Adamczyk, M.; Friess, E.; Steiger, A.; Czisch, M.; Goya-Maldonado, R.

    2015-01-01

    BACKGROUND: Overnight memory consolidation is disturbed in both depression and schizophrenia, creating an ideal situation to investigate the mechanisms underlying sleep-related consolidation and to distinguish disease-specific processes from common elements in their pathophysiology. METHODS: We

  13. Xenon impairs reconsolidation of fear memories in a rat model of post-traumatic stress disorder (PTSD.

    Directory of Open Access Journals (Sweden)

    Edward G Meloni

    Full Text Available Xenon (Xe is a noble gas that has been developed for use in people as an inhalational anesthestic and a diagnostic imaging agent. Xe inhibits glutamatergic N-methyl-D-aspartate (NMDA receptors involved in learning and memory and can affect synaptic plasticity in the amygdala and hippocampus, two brain areas known to play a role in fear conditioning models of post-traumatic stress disorder (PTSD. Because glutamate receptors also have been shown to play a role in fear memory reconsolidation--a state in which recalled memories become susceptible to modification--we examined whether Xe administered after fear memory reactivation could affect subsequent expression of fear-like behavior (freezing in rats. Male Sprague-Dawley rats were trained for contextual and cued fear conditioning and the effects of inhaled Xe (25%, 1 hr on fear memory reconsolidation were tested using conditioned freezing measured days or weeks after reactivation/Xe administration. Xe administration immediately after fear memory reactivation significantly reduced conditioned freezing when tested 48 h, 96 h or 18 d after reactivation/Xe administration. Xe did not affect freezing when treatment was delayed until 2 h after reactivation or when administered in the absence of fear memory reactivation. These data suggest that Xe substantially and persistently inhibits memory reconsolidation in a reactivation and time-dependent manner, that it could be used as a new research tool to characterize reconsolidation and other memory processes, and that it could be developed to treat people with PTSD and other disorders related to emotional memory.

  14. Pre-synaptic control of remote fear extinction in the neocortex

    Directory of Open Access Journals (Sweden)

    Gisella eVetere

    2012-06-01

    Full Text Available Consolidation of remote memory enhances immediate early genes induction (IEGs, augments the expression of the presynaptic growth associated protein 43 (GAP-43, and increases the density and size of dendritic spines in anterior cingulate (aCC and infra-limbic (ILC cortices. Remote memory extinction, however, does not uniformly alter consolidation-induced structural changes. In the aCC, the density, but not the size, of spines is reset to pseudo-conditioning levels while novel thin spines are formed in the ILC. Whether IEGs and GAP-43 also undergo region-specific changes upon remote memory extinction is undetermined. Here we confirm in the same batch of mice that c-Fos induction and GAP-43 expression are increased in both the aCC and the ILC 36 days after contextual fear conditioning. We then show that, in both regions, remote memory extinction is associated with decrease of c-Fos induction but no change in GAP-43 expression thus revealing similar, although protein-specific, pre-synaptic adaptations in aCC and ILC neurons. These observations, in addition to our previous report of region-specific post-synaptic structural changes, disclose a complex pattern of extinction-driven neocortical alterations suitable to support erasure or reinstatement of fear according to the environment demand.

  15. Neural and Cellular Mechanisms of Fear and Extinction Memory Formation

    Science.gov (United States)

    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

  16. The role of sleep in declarative memory consolidation--direct evidence by intracranial EEG.

    Science.gov (United States)

    Axmacher, Nikolai; Haupt, Sven; Fernández, Guillén; Elger, Christian E; Fell, Juergen

    2008-03-01

    Two step theories of memory formation assume that an initial learning phase is followed by a consolidation stage. Memory consolidation has been suggested to occur predominantly during sleep. Very recent findings, however, suggest that important steps in memory consolidation occur also during waking state but may become saturated after some time awake. Sleep, in this model, specifically favors restoration of synaptic plasticity and accelerated memory consolidation while asleep and briefly afterwards. To distinguish between these different views, we recorded intracranial electroencephalograms from the hippocampus and rhinal cortex of human subjects while they retrieved information acquired either before or after a "nap" in the afternoon or on a control day without nap. Reaction times, hippocampal event-related potentials, and oscillatory gamma activity indicated a temporal gradient of hippocampal involvement in information retrieval on the control day, suggesting hippocampal-neocortical information transfer during waking state. On the day with nap, retrieval of recent items that were encoded briefly after the nap did not involve the hippocampus to a higher degree than retrieval of items encoded before the nap. These results suggest that sleep facilitates rapid processing through the hippocampus but is not necessary for information transfer into the neocortex per se.

  17. Neurocognitive Mechanisms of Prejudice Formation: The Role of Time-Dependent Memory Consolidation.

    Science.gov (United States)

    Enge, Luke R; Lupo, Amber K; Zárate, Michael A

    2015-07-01

    Prejudice is generally thought to derive from learned, emotion-laden experiences. The mechanisms underlying the formation of prejudice over time, however, remain unknown. In the present research, we proposed and tested hypotheses regarding prejudice formation derived from research on memory consolidation and social perception. We hypothesized that time-dependent memory consolidation would produce better implicit memory for negative out-group information and positive in-group information, compared with negative in-group information and positive out-group information. Fifty undergraduates learned positive and negative information about racial in-group (Latino) and out-group (African American) targets. Participants returned after both a short time delay (2-6 hr after the learning session) and a long time delay (48 hr after the learning session) to complete a lexical decision task. Results demonstrated that participants responded to information consistent with an in-group bias faster after a long time delay than after a short time delay. Our findings have important implications for the study of social perception and memory consolidation. © The Author(s) 2015.

  18. Brain Region-Specific Activity Patterns after Recent or Remote Memory Retrieval of Auditory Conditioned Fear

    Science.gov (United States)

    Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

    2012-01-01

    Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or…

  19. Selective REM-sleep deprivation does not diminish emotional memory consolidation in young healthy subjects.

    Science.gov (United States)

    Morgenthaler, Jarste; Wiesner, Christian D; Hinze, Karoline; Abels, Lena C; Prehn-Kristensen, Alexander; Göder, Robert

    2014-01-01

    Sleep enhances memory consolidation and it has been hypothesized that rapid eye movement (REM) sleep in particular facilitates the consolidation of emotional memory. The aim of this study was to investigate this hypothesis using selective REM-sleep deprivation. We used a recognition memory task in which participants were shown negative and neutral pictures. Participants (N=29 healthy medical students) were separated into two groups (undisturbed sleep and selective REM-sleep deprived). Both groups also worked on the memory task in a wake condition. Recognition accuracy was significantly better for negative than for neutral stimuli and better after the sleep than the wake condition. There was, however, no difference in the recognition accuracy (neutral and emotional) between the groups. In summary, our data suggest that REM-sleep deprivation was successful and that the resulting reduction of REM-sleep had no influence on memory consolidation whatsoever.

  20. Analysis of memory consolidation and evocation in rats by proton induced X-ray emission

    Energy Technology Data Exchange (ETDEWEB)

    Jobim, P.F.C., E-mail: pjobim@uol.com.br [Ion Implantation Laboratory, Physics Institute, Federal University of Rio Grande do Sul, Av. Bento Gonçalves 9500, CP 15051, CEP 91501-970, Porto Alegre (Brazil); Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Av. Paulo Gama 90050-170, Porto Alegre (Brazil); University Hospital Research Center (HCPA), Federal University of Rio Grande do Sul, 90035-003, Rua Ramiro Barcelos, Porto Alegre (Brazil); Santos, C.E.I. dos [Ion Implantation Laboratory, Physics Institute, Federal University of Rio Grande do Sul, Av. Bento Gonçalves 9500, CP 15051, CEP 91501-970, Porto Alegre (Brazil); Maurmann, N.; Reolon, G.K. [Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Av. Paulo Gama 90050-170, Porto Alegre (Brazil); University Hospital Research Center (HCPA), Federal University of Rio Grande do Sul, 90035-003, Rua Ramiro Barcelos, Porto Alegre (Brazil); Debastiani, R. [Ion Implantation Laboratory, Physics Institute, Federal University of Rio Grande do Sul, Av. Bento Gonçalves 9500, CP 15051, CEP 91501-970, Porto Alegre (Brazil); Pedroso, T.R.; Carvalho, L.M. [Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Av. Paulo Gama 90050-170, Porto Alegre (Brazil); University Hospital Research Center (HCPA), Federal University of Rio Grande do Sul, 90035-003, Rua Ramiro Barcelos, Porto Alegre (Brazil); Dias, J.F. [Ion Implantation Laboratory, Physics Institute, Federal University of Rio Grande do Sul, Av. Bento Gonçalves 9500, CP 15051, CEP 91501-970, Porto Alegre (Brazil)

    2014-08-01

    It is well known that trace elements such as Mg, Ca, Fe, Cu and Zn have a key role in synapse plasticity and learning. Learning process is conventionally divided in three distinct and complementary stages: memory acquisition, consolidation and evocation. Consolidation is the stabilization of the synaptic trace formed by acquisition, while evocation is the recall of this trace. Ion-based techniques capable of providing information concerning the elemental composition of organic tissues may be helpful to improve our understanding on memory consolidation and evocation processes. In particular, the Particle-Induced X-ray Emission (PIXE) technique can be used to analyze different biological tissues with good accuracy. In this work we explore the versatility of PIXE to measure the elemental concentrations in rat brain tissues in order to establish any possible correlation between them and the memory consolidation and evocation processes. To this end, six groups of middle-age male Wistar rats were trained and tested in a step-down Inhibitory Avoidance conditioning. After the behavior tests, the animals were decapitated in accordance with the legal procedures and their brains were removed and dissected for the PIXE analyses. The results demonstrated that there are differences in the elemental concentration among the groups and such variations may be associated with their availability to the learning processes (by memory consolidation and evocation). Moreover, the control groups circumvent the possibility that a non-specific event involved in learning tasks cause such variations. Our results suggest that PIXE may be a useful tool to investigate memory consolidation and evocation in animal models.

  1. Analysis of memory consolidation and evocation in rats by proton induced X-ray emission

    International Nuclear Information System (INIS)

    Jobim, P.F.C.; Santos, C.E.I. dos; Maurmann, N.; Reolon, G.K.; Debastiani, R.; Pedroso, T.R.; Carvalho, L.M.; Dias, J.F.

    2014-01-01

    It is well known that trace elements such as Mg, Ca, Fe, Cu and Zn have a key role in synapse plasticity and learning. Learning process is conventionally divided in three distinct and complementary stages: memory acquisition, consolidation and evocation. Consolidation is the stabilization of the synaptic trace formed by acquisition, while evocation is the recall of this trace. Ion-based techniques capable of providing information concerning the elemental composition of organic tissues may be helpful to improve our understanding on memory consolidation and evocation processes. In particular, the Particle-Induced X-ray Emission (PIXE) technique can be used to analyze different biological tissues with good accuracy. In this work we explore the versatility of PIXE to measure the elemental concentrations in rat brain tissues in order to establish any possible correlation between them and the memory consolidation and evocation processes. To this end, six groups of middle-age male Wistar rats were trained and tested in a step-down Inhibitory Avoidance conditioning. After the behavior tests, the animals were decapitated in accordance with the legal procedures and their brains were removed and dissected for the PIXE analyses. The results demonstrated that there are differences in the elemental concentration among the groups and such variations may be associated with their availability to the learning processes (by memory consolidation and evocation). Moreover, the control groups circumvent the possibility that a non-specific event involved in learning tasks cause such variations. Our results suggest that PIXE may be a useful tool to investigate memory consolidation and evocation in animal models

  2. Extinction after fear memory reactivation fails to eliminate renewal in rats.

    Science.gov (United States)

    Goode, Travis D; Holloway-Erickson, Crystal M; Maren, Stephen

    2017-07-01

    Retrieving fear memories just prior to extinction has been reported to effectively erase fear memories and prevent fear relapse. The current study examined whether the type of retrieval procedure influences the ability of extinction to impair fear renewal, a form of relapse in which responding to a conditional stimulus (CS) returns outside of the extinction context. Rats first underwent Pavlovian fear conditioning with an auditory CS and footshock unconditional stimulus (US); freezing behavior served as the index of conditioned fear. Twenty-four hours later, the rats underwent a retrieval-extinction procedure. Specifically, 1h prior to extinction (45 CS-alone trials; 44 for rats receiving a CS reminder), fear memory was retrieved by either a single exposure to the CS alone, the US alone, a CS paired with the US, or exposure to the conditioning context itself. Over the next few days, conditional freezing to the extinguished CS was tested in the extinction and conditioning context in that order (i.e., an ABBA design). In the extinction context, rats that received a CS+US trial before extinction exhibited higher levels of conditional freezing than animals in all other groups, which did not differ from one another. In the renewal context, all groups showed renewal, and none of the reactivation procedures reduced renewal relative to a control group that did not receive a reactivation procedure prior to extinction. These data suggest retrieval-extinction procedures may have limited efficacy in preventing fear renewal. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Corticosterone infused into the dorsal striatum selectively enhances memory consolidation of cued water-maze training

    NARCIS (Netherlands)

    Quirarte, Gina L.; Sofia Ledesma de la Teja, I.; Casillas, Miriam; Serafin, Norma; Prado-Alcala, Roberto A.; Roozendaal, Benno

    2009-01-01

    Glucocorticoid hormones enhance memory consolidation of hippocampus-dependent spatial/contextual learning, but little is known about their possible influence on the consolidation of procedural/implicit memory. Therefore, in this study we examined the effect of corticosterone (2, 5, or 10 ng) infused

  4. Object recognition memory: neurobiological mechanisms of encoding, consolidation and retrieval.

    Science.gov (United States)

    Winters, Boyer D; Saksida, Lisa M; Bussey, Timothy J

    2008-07-01

    Tests of object recognition memory, or the judgment of the prior occurrence of an object, have made substantial contributions to our understanding of the nature and neurobiological underpinnings of mammalian memory. Only in recent years, however, have researchers begun to elucidate the specific brain areas and neural processes involved in object recognition memory. The present review considers some of this recent research, with an emphasis on studies addressing the neural bases of perirhinal cortex-dependent object recognition memory processes. We first briefly discuss operational definitions of object recognition and the common behavioural tests used to measure it in non-human primates and rodents. We then consider research from the non-human primate and rat literature examining the anatomical basis of object recognition memory in the delayed nonmatching-to-sample (DNMS) and spontaneous object recognition (SOR) tasks, respectively. The results of these studies overwhelmingly favor the view that perirhinal cortex (PRh) is a critical region for object recognition memory. We then discuss the involvement of PRh in the different stages--encoding, consolidation, and retrieval--of object recognition memory. Specifically, recent work in rats has indicated that neural activity in PRh contributes to object memory encoding, consolidation, and retrieval processes. Finally, we consider the pharmacological, cellular, and molecular factors that might play a part in PRh-mediated object recognition memory. Recent studies in rodents have begun to indicate the remarkable complexity of the neural substrates underlying this seemingly simple aspect of declarative memory.

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

    Science.gov (United States)

    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.

  6. Short-term inhibition of 11β-hydroxysteroid dehydrogenase type 1 reversibly improves spatial memory but persistently impairs contextual fear memory in aged mice

    Science.gov (United States)

    Wheelan, Nicola; Webster, Scott P.; Kenyon, Christopher J.; Caughey, Sarah; Walker, Brian R.; Holmes, Megan C.; Seckl, Jonathan R.; Yau, Joyce L.W.

    2015-01-01

    High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11β-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11β-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11β-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals. PMID:25497454

  7. High trait anxiety: a challenge for disrupting fear memory reconsolidation

    NARCIS (Netherlands)

    Soeter, M.; Kindt, M.

    2013-01-01

    Disrupting reconsolidation may be promising in the treatment of anxiety disorders but the fear-reducing effects are thus far solely demonstrated in the average organism. A relevant question is whether disrupting fear memory reconsolidation is less effective in individuals who are vulnerable to

  8. Off-line concomitant release of dopamine and glutamate involvement in taste memory consolidation.

    Science.gov (United States)

    Guzmán-Ramos, Kioko; Osorio-Gómez, Daniel; Moreno-Castilla, Perla; Bermúdez-Rattoni, Federico

    2010-07-01

    It has been postulated that memory consolidation process requires post-learning molecular changes that will support long-term experiences. In the present study, we assessed with in vivo microdialysis and capillary electrophoresis whether such changes involve the release of neurotransmitters at post-acquisition stages. Using conditioned taste aversion paradigm we observed spontaneous off-line (i.e. in absence of stimulation) dopamine and glutamate reactivation within the insular cortex about 45 min after the stimuli association. These increments did not appear in control groups that were unable to acquire the task, and it seems to be dependent on amygdala activity since its reversible inactivation by tetrodotoxin impaired cortical off-line release of both neurotransmitters and memory consolidation. In addition, blockade of dopaminergic D1 and/or NMDA receptors before the off-line activity impaired long- but not short-term memory. These results suggest that off-line extracellular increments of glutamate and dopamine have a significant functional role in consolidation of taste memory.

  9. Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 vs. D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex.

    Science.gov (United States)

    Li, Jing Jing; Szkudlarek, Hanna; Renard, Justine; Hudson, Roger; Rushlow, Walter; Laviolette, Steven R

    2018-04-23

    Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well-established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder (PTSD) and opioid addiction. Transmission through PFC DA D4 receptors (D4R) has been shown to potentiate the emotional salience of normally non-salient emotional memories whereas transmission through PFC DA D1 receptors (D1R) has been demonstrated to selectively block recall of reward or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally sub-threshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II (CaMKII-α) or extracellular-signal-related-kinase 1-2 (ERK 1/2), following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. Significance Statement: Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex

  10. How trait anxiety, interpretation bias and memory affect acquired fear in children learning about new animals.

    Science.gov (United States)

    Field, Zoë C; Field, Andy P

    2013-06-01

    Cognitive models of vulnerability to anxiety propose that information processing biases such as interpretation bias play a part in the etiology and maintenance of anxiety disorders. However, at present little is known about the role of memory in information processing accounts of child anxiety. The current study investigates the relationships between interpretation biases, memory and fear responses when learning about new stimuli. Children (aged 8-11 years) were presented with ambiguous information regarding a novel animal, and their fear, interpretation bias, and memory for the information was measured. The main findings were: (1) trait anxiety and interpretation bias significantly predicted acquired fear; (2) interpretation bias did not significantly mediate the relationship between trait anxiety and acquired fear; (3) interpretation bias appeared to be a more important predictor of acquired fear than trait anxiety per se; and (4) the relationship between interpretation bias and acquired fear was not mediated by the number of negative memories but was mediated by the number of positive and false-positive memories. The findings suggest that information processing models of child anxiety need to explain the role of positive memory in the formation of fear responses.

  11. Dynamics of dendritic spines in the mouse auditory cortex during memory formation and memory recall.

    Science.gov (United States)

    Moczulska, Kaja Ewa; Tinter-Thiede, Juliane; Peter, Manuel; Ushakova, Lyubov; Wernle, Tanja; Bathellier, Brice; Rumpel, Simon

    2013-11-05

    Long-lasting changes in synaptic connections induced by relevant experiences are believed to represent the physical correlate of memories. Here, we combined chronic in vivo two-photon imaging of dendritic spines with auditory-cued classical conditioning to test if the formation of a fear memory is associated with structural changes of synapses in the mouse auditory cortex. We find that paired conditioning and unpaired conditioning induce a transient increase in spine formation or spine elimination, respectively. A fraction of spines formed during paired conditioning persists and leaves a long-lasting trace in the network. Memory recall triggered by the reexposure of mice to the sound cue did not lead to changes in spine dynamics. Our findings provide a synaptic mechanism for plasticity in sound responses of auditory cortex neurons induced by auditory-cued fear conditioning; they also show that retrieval of an auditory fear memory does not lead to a recapitulation of structural plasticity in the auditory cortex as observed during initial memory consolidation.

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

    Science.gov (United States)

    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.

  13. Noradrenergic Modulation of Fear Conditioning and Extinction.

    Science.gov (United States)

    Giustino, Thomas F; Maren, Stephen

    2018-01-01

    The locus coeruleus norepinephrine (LC-NE) system plays a broad role in learning and memory. Here we begin with an overview of the LC-NE system. We then consider how both direct and indirect manipulations of the LC-NE system affect cued and contextual aversive learning and memory. We propose that NE dynamically modulates Pavlovian conditioning and extinction, either promoting or impairing learning aversive processes under different levels of behavioral arousal. We suggest that under high levels of stress (e.g., during/soon after fear conditioning) the locus coeruleus (LC) promotes cued fear learning by enhancing amygdala function while simultaneously blunting prefrontal function. Under low levels of arousal, the LC promotes PFC function to promote downstream inhibition of the amygdala and foster the extinction of cued fear. Thus, LC-NE action on the medial prefrontal cortex (mPFC) might be described by an inverted-U function such that it can either enhance or hinder learning depending on arousal states. In addition, LC-NE seems to be particularly important for the acquisition, consolidation and extinction of contextual fear memories. This may be due to dense adrenoceptor expression in the hippocampus (HPC) which encodes contextual information, and the ability of NE to regulate long-term potentiation (LTP). Moreover, recent work reveals that the diversity of LC-NE functions in aversive learning and memory are mediated by functionally heterogeneous populations of LC neurons that are defined by their projection targets. Hence, LC-NE function in learning and memory is determined by projection-specific neuromodulation that accompanies various states of behavioral arousal.

  14. Noradrenergic Modulation of Fear Conditioning and Extinction

    Directory of Open Access Journals (Sweden)

    Thomas F. Giustino

    2018-03-01

    Full Text Available The locus coeruleus norepinephrine (LC-NE system plays a broad role in learning and memory. Here we begin with an overview of the LC-NE system. We then consider how both direct and indirect manipulations of the LC-NE system affect cued and contextual aversive learning and memory. We propose that NE dynamically modulates Pavlovian conditioning and extinction, either promoting or impairing learning aversive processes under different levels of behavioral arousal. We suggest that under high levels of stress (e.g., during/soon after fear conditioning the locus coeruleus (LC promotes cued fear learning by enhancing amygdala function while simultaneously blunting prefrontal function. Under low levels of arousal, the LC promotes PFC function to promote downstream inhibition of the amygdala and foster the extinction of cued fear. Thus, LC-NE action on the medial prefrontal cortex (mPFC might be described by an inverted-U function such that it can either enhance or hinder learning depending on arousal states. In addition, LC-NE seems to be particularly important for the acquisition, consolidation and extinction of contextual fear memories. This may be due to dense adrenoceptor expression in the hippocampus (HPC which encodes contextual information, and the ability of NE to regulate long-term potentiation (LTP. Moreover, recent work reveals that the diversity of LC-NE functions in aversive learning and memory are mediated by functionally heterogeneous populations of LC neurons that are defined by their projection targets. Hence, LC-NE function in learning and memory is determined by projection-specific neuromodulation that accompanies various states of behavioral arousal.

  15. On the interplay between working memory consolidation and attentional selection in controlling conscious access : Parallel processing at a cost-a comment on 'The interplay of attention and consciousness in visual search, attentional blink and working memory consolidation'

    NARCIS (Netherlands)

    Wyble, Brad; Bowman, Howard; Nieuwenstein, Mark

    On the interplay between working memory consolidation and attentional selection in controlling conscious access: parallel processing at a cost-a comment on 'The interplay of attention and consciousness in visual search, attentional blink and working memory consolidation'

  16. The relationship between masking and short-term consolidation during recall from visual working memory.

    Science.gov (United States)

    Ricker, Timothy J; Sandry, Joshua

    2018-04-10

    The presentation of a similar but irrelevant stimulus immediately following presentation of a memory item is called masking. Masking is known to reduce performance on working memory tests. This is the type of memory used to hold information in mind for brief periods of time for use in ongoing cognition. Two approaches to understanding masking effects have been proposed in different literatures. Working memory researchers often assume that the reduction in working memory performance after masking is because masking interferes with a transient sensory representation that is needed to complete consolidation into a working memory state. Researchers focused on the attentional blink, a finding that attention cannot be directed to new stimuli during working memory consolidation, have an alternative theory. Attentional blink researchers assume that masking slows the short-term consolidation process, thereby extending the length of the attentional blink. In two experiments, we contrast these two approaches to explaining masking effects and investigate the validity of both hypotheses. Some aspects of both approaches are validated, but neither theoretical perspective alone sufficiently explains the entire pattern of results. © 2018 New York Academy of Sciences.

  17. Engagement of the PFC in Consolidation and Recall of Recent Spatial Memory

    Science.gov (United States)

    Leon, Wanda C.; Bruno, Martin A.; Allard, Simon; Nader, Karim; Cuello, A. Claudio

    2010-01-01

    The standard model of system consolidation proposes that memories are initially hippocampus dependent and become hippocampus independent over time. Previous studies have demonstrated the involvement of the medial prefrontal cortex (mPFC) in the retrieval of remote memories. The transformations required to make a memory undergo system's…

  18. REGULAR REHEARSAL HELPS IN CONSOLIDATION OF LONG TERM MEMORY

    Directory of Open Access Journals (Sweden)

    Milind Parle

    2006-03-01

    Full Text Available Memory, one of the most complex functions of the brain comprises of multiple components such as perception, registration, consolidation, storage, retrieval and decay. The present study was undertaken to evaluate the impact of different training sessions on the retention capacity of rats. The capacity of retention of learnt task was measured using exteroceptive behavioral models such as Hexagonal swimming pool apparatus, Hebb-Williams maze and Elevated plus-maze. A total of 150 rats divided into fifteen groups were employed in the present study. The animals were subjected to different training sessions during first three days. The ability to retain the learned task was tested after single, sub-acute, acute, sub-chronic and chronic exposure to above exteroceptive memory models in separate groups of animals. The memory score of all animals was recorded after 72 h, 192 h and 432 h of their last training trial. Rats of single exposure group did not show any effect on memory. Sub-acute training group animals showed improved memory up to 72 h only, where as in acute and sub-chronic training groups this memory improvement was extended up to 192 h. The rats, which were subjected to chronic exposures showed a significant improvement in retention capacity that lasted up to a period of eighteen days. These observations suggest that repeated rehearsals at regular intervals are probably necessary for consolidation of long-term memory. It was observed that sub-acute, acute and sub-chronic exposures, improved the retrieval ability of rats but this memory improving effect was short lived. Thus, rehearsal or training plays a crucial role in enhancing one's capacity of retaining the learnt information

  19. Structural Components of Synaptic Plasticity and Memory Consolidation

    Science.gov (United States)

    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

  20. Corticosterone regulates fear memory via Rac1 activity in the hippocampus.

    Science.gov (United States)

    Gan, Ping; Ding, Ze-Yang; Gan, Cheng; Mao, Rong-Rong; Zhou, Heng; Xu, Lin; Zhou, Qi-Xin

    2016-09-01

    Stressful events can generate enduring memories, which may induce certain psychiatric disorders such as post-traumatic stress disorder (PTSD). However, the underlying molecular mechanisms in these processes remain unclear. In this study, we examined whether the active form of the small G protein Rac1, Rac1-GTP, is involved in fear memory. Firstly, we detected the time course changes of Rac1-GTP after foot shocks (a strong stressor) and exogenous corticosterone (CORT) treatment. The data showed that stress and CORT induced the downregulation of Rac1-GTP in the hippocampus. Changes in the serum CORT level were negatively correlated with the level of Rac1-GTP. Additionally, a glucocorticoid receptor antagonist, RU38486, not only recovered the expression of Rac1-GTP but also impaired fear memory. Furthermore, systemic administration of NSC23766, an inhibitor of Rac1-GTP, improved fear memory at 1.5 and 24h. Therefore, Rac1 activity plays a critical role in stress-related cognition and may be a potential target in stress-related disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. The effect of exogenous cortisol during sleep on the behavioral and neural correlates of emotional memory consolidation in humans.

    Science.gov (United States)

    van Marle, Hein J F; Hermans, Erno J; Qin, Shaozheng; Overeem, Sebastiaan; Fernández, Guillén

    2013-09-01

    A host of animal work demonstrates that the retention benefit for emotionally aversive over neutral memories is regulated by glucocorticoid action during memory consolidation. Particularly, glucocorticoids may affect systems-level processes that promote the gradual reorganization of emotional memory traces. These effects remain largely uninvestigated in humans. Therefore, in this functional magnetic resonance imaging study we administered hydrocortisone during a polysomnographically monitored night of sleep directly after healthy volunteers studied negative and neutral pictures in a double-blind, placebo-controlled, between-subjects design. The following evening memory consolidation was probed during a recognition memory test in the MR scanner by assessing the difference in brain activity associated with memory for the consolidated items studied before sleep and new, unconsolidated items studied shortly before test (remote vs. recent memory paradigm). Hydrocortisone administration resulted in elevated cortisol levels throughout the experimental night with no group difference at recent encoding or test. Behaviorally, we showed that cortisol enhanced the difference between emotional and neutral consolidated memory, effectively prioritizing emotional memory consolidation. On a neural level, we found that cortisol reduced amygdala reactivity related to the retrieval of these same consolidated, negative items. These findings show that cortisol administration during first post-encoding sleep had a twofold effect on the first 24h of emotional memory consolidation. While cortisol prioritized recognition memory for emotional items, it reduced reactivation of the neural circuitry underlying emotional responsiveness during retrieval. These findings fit recent theories on emotional depotentiation following consolidation during sleep, although future research should establish the sleep-dependence of this effect. Moreover, our data may shed light on mechanisms underlying

  2. Grin1 receptor deletion within CRF neurons enhances fear memory.

    Directory of Open Access Journals (Sweden)

    Georgette Gafford

    Full Text Available Corticotropin releasing factor (CRF dysregulation is implicated in mood and anxiety disorders such as posttraumatic stress disorder (PTSD. CRF is expressed in areas engaged in fear and anxiety processing including the central amygdala (CeA. Complicating our ability to study the contribution of CRF-containing neurons to fear and anxiety behavior is the wide variety of cell types in which CRF is expressed. To manipulate specific subpopulations of CRF containing neurons, our lab has developed a mouse with a Cre recombinase gene driven by a CRF promoter (CRFp3.0Cre (Martin et al., 2010. In these studies, mice that have the gene that encodes NR1 (Grin1 flanked by loxP sites (floxed were crossed with our previously developed CRFp3.0Cre mouse to selectively disrupt Grin1 within CRF containing neurons (Cre+/fGrin1+. We find that disruption of Grin1 in CRF neurons did not affect baseline levels of anxiety, locomotion, pain sensitivity or exploration of a novel object. However, baseline expression of Grin1 was decreased in Cre+/fGrin1+ mice as measured by RTPCR. Cre+/fGrin1+ mice showed enhanced auditory fear acquisition and retention without showing any significant effect on fear extinction. We measured Gria1, the gene that encodes AMPAR1 and the CREB activator Creb1 in the amygdala of Cre+/fGrin1+ mice after fear conditioning. Both Gria1 and Creb1 were enhanced in the amygdala after training. To determine if the Grin1-expressing CRF neurons within the CeA are responsible for the enhancement of fear memory in adults, we infused a lentivirus with Cre driven by a CRF promoter (LV pCRF-Cre/fGrin1+ into the CeA of floxed Grin1 mice. Cre driven deletion of Grin1 specifically within CRF expressing cells in the CeA also resulted in enhanced fear memory acquisition and retention. Altogether, these findings suggest that selective disruption of Grin1 within CeA CRF neurons strongly enhances fear memory.

  3. What drives sleep-dependent memory consolidation: greater gain or less loss?

    Science.gov (United States)

    Fenn, Kimberly M; Hambrick, David Z

    2013-06-01

    When memory is tested after a delay, performance is typically better if the retention interval includes sleep. However, it is unclear what accounts for this well-established effect. It is possible that sleep enhances the retrieval of information, but it is also possible that sleep protects against memory loss that normally occurs during waking activity. We developed a new research approach to investigate these possibilities. Participants learned a list of paired-associate items and were tested on the items after a 12-h interval that included waking or sleep. We analyzed the number of items gained versus the number of items lost across time. The sleep condition showed more items gained and fewer items lost than did the wake condition. Furthermore, the difference between the conditions (favoring sleep) in lost items was greater than the difference in gain, suggesting that loss prevention may primarily account for the effect of sleep on declarative memory consolidation. This finding may serve as an empirical constraint on theories of memory consolidation.

  4. Protein Synthesis Underlies Post-Retrieval Memory Consolidation to a Restricted Degree Only when Updated Information Is Obtained

    Science.gov (United States)

    Rodriguez-Ortiz, Carlos J.; De la Cruz, Vanesa; Gutierrez, Ranier; Bermudez-Rattoni, Federico

    2005-01-01

    Consolidation theory proposes that through the synthesis of new proteins recently acquired memories are strengthened over time into a stable long-term memory trace. However, evidence has accumulated suggesting that retrieved memory is susceptible to disruption, seeming to consolidate again (reconsolidate) to be retained in long-term storage. Here…

  5. Sleep modulates the neural substrates of both spatial and contextual memory consolidation.

    Directory of Open Access Journals (Sweden)

    Géraldine Rauchs

    Full Text Available It is known that sleep reshapes the neural representations that subtend the memories acquired while navigating in a virtual environment. However, navigation is not process-pure, as manifold learning components contribute to performance, notably the spatial and contextual memory constituents. In this context, it remains unclear whether post-training sleep globally promotes consolidation of all of the memory components embedded in virtual navigation, or rather favors the development of specific representations. Here, we investigated the effect of post-training sleep on the neural substrates of the consolidation of spatial and contextual memories acquired while navigating in a complex 3D, naturalistic virtual town. Using fMRI, we mapped regional cerebral activity during various tasks designed to tap either the spatial or the contextual memory component, or both, 72 h after encoding with or without sleep deprivation during the first post-training night. Behavioral performance was not dependent upon post-training sleep deprivation, neither in a natural setting that engages both spatial and contextual memory processes nor when looking more specifically at each of these memory representations. At the neuronal level however, analyses that focused on contextual memory revealed distinct correlations between performance and neuronal activity in frontal areas associated with recollection processes after post-training sleep, and in the parahippocampal gyrus associated with familiarity processes in sleep-deprived participants. Likewise, efficient spatial memory was associated with posterior cortical activity after sleep whereas it correlated with parahippocampal/medial temporal activity after sleep deprivation. Finally, variations in place-finding efficiency in a natural setting encompassing spatial and contextual elements were associated with caudate activity after post-training sleep, suggesting the automation of navigation. These data indicate that post

  6. Serial consolidation of orientation information into visual short-term memory.

    Science.gov (United States)

    Liu, Taosheng; Becker, Mark W

    2013-06-01

    Previous research suggests that there is a limit to the rate at which items can be consolidated in visual short-term memory (VSTM). This limit could be due to either a serial or a limited-capacity parallel process. Historically, it has proven difficult to distinguish between these two types of processes. In the present experiment, we took a novel approach that allowed us to do so. Participants viewed two oriented gratings either sequentially or simultaneously and reported one of the gratings' orientation via method of adjustment. Performance was worse for the simultaneous than for the sequential condition. We fit the data with a mixture model that assumes performance is limited by a noisy memory representation plus random guessing. Critically, the serial and limited-capacity parallel processes made distinct predictions regarding the model's guessing and memory-precision parameters. We found strong support for a serial process, which implies that one can consolidate only a single orientation into VSTM at a time.

  7. The anticancer estrogen receptor antagonist tamoxifen impairs consolidation of inhibitory avoidance memory through estrogen receptor alpha.

    Science.gov (United States)

    Lichtenfels, Martina; Dornelles, Arethuza da Silva; Petry, Fernanda Dos Santos; Blank, Martina; de Farias, Caroline Brunetto; Roesler, Rafael; Schwartsmann, Gilberto

    2017-11-01

    Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats. In the first experiment, Wistar female rats received a single oral dose of tamoxifen (1, 3, or 10 mg/kg) or saline by gavage immediately after training and were tested for memory consolidation 24 h after training. In the second experiment, rats received a single dose of 1 mg/kg tamoxifen or saline by gavage 3 h after training and were tested 24 h after training for memory consolidation. In the third experiment, rats received a subcutaneous injection with estrogen receptor α agonist or estrogen receptor beta agonist 30 min before the training. After training, rats received a single oral dose of tamoxifen 1 mg/kg or saline and were tested 24 h after training. In the fourth experiment, rats were trained and tested 24 h later. Immediately after test, rats received a single dose of tamoxifen (1 mg/kg) or saline by gavage and were given four additional daily test trials followed by a re-instatement. Tamoxifen at 1 mg/kg impaired memory consolidation when given immediately after training and the estrogen receptor alpha agonist improved the tamoxifen-related memory impairment. Moreover, tamoxifen impairs memory consolidation of the test. These findings indicate that estrogen receptors regulate the early phase of memory consolidation and the effects of tamoxifen on memory consolidation.

  8. Noradrenergic activation of the basolateral amygdala modulates the consolidation of object-in-context recognition memory

    OpenAIRE

    Barsegyan, Areg; McGaugh, James L.; Roozendaal, Benno

    2014-01-01

    Noradrenergic activation of the basolateral complex of the amygdala (BLA) is well known to enhance the consolidation of long-term memory of highly emotionally arousing training experiences. The present study investigated whether such noradrenergic activation of the BLA also influences the consolidation of object-in-context recognition memory, a low-arousing training task assessing episodic-like memory. Male Sprague-Dawley rats were exposed to two identical objects in one context for either 3 ...

  9. Effects of stress and corticosterone in two post-training periods, on spatial memory consolidation in adult male Wistar rats.

    Directory of Open Access Journals (Sweden)

    Jeimmy Marcela Cerón

    2015-04-01

    Full Text Available Memory consolidation is the process of gradual stabilization of long-term memory after learning (Alberini & Taubenfeld, 2008. This process involves the activation of intracellular signaling cascades that lead to the reorganization of synaptic proteins. Activation of these signaling pathways can regulate gene expression and protein synthesis (Brivanlou & Darnell, 2002. It is considered that the new proteins synthesized after learning are responsible for the changes in the neural architecture associated with memory consolidation (Mileusnic, 2004. In this sense, it has been shown that consolidation may be interrupted by inhibiting protein synthesis, leading to forgetfulness of the experience (Meeter & Murre, 2004. Although the dominant hypothesis is that memory consolidation requires a single molecular cascade, it has been suggested that multiple sets of synaptic modifications are required to reinforce changes after memory acquisition (Wittenber & Tsien, 2002. Consistently, recent studies have shown that protein synthesis associated with memory consolidation occurs in at least two post-training periods: immediately and 3-6 hours after training (Igaz et al., 2002; Bekinschtein et al., 2007. These memory consolidation periods share some molecular phenomena; however, each period is also associated with events that are different from the other (Igaz et al., 2002. To date, there is a substantial amount of evidence showing that stressful events may facilitate neuronal function and cognition. The term "stress" usually refers to a nonspecific response of the body to stimuli that threaten the physiological/psychological homeostasis (Selye, 1976; Chrousos et al., 1988. The stress response is associated with the activation of two physiological systems: the hypothalamic-pituitary-adrenal (HPA axis and the sympathetic adrenomedullary (SAM. Glucocorticoids (cortisol in humans and corticosterone in rodents are steroid hormones secreted by the adrenal glands as a

  10. Time course of scopolamine effect on memory consolidation and forgetting in rats.

    Science.gov (United States)

    Popović, Miroljub; Giménez de Béjar, Verónica; Popović, Natalija; Caballero-Bleda, María

    2015-02-01

    The effect of scopolamine on the consolidation and forgetting of emotional memory has not been completely elucidated yet. The aim of the present study was to investigate the time course of scopolamine effect on consolidation and forgetting of passive avoidance response. In a first experiment of the present study, we tested the effect of scopolamine (1mg/kg, i.p., immediately after acquisition), on 24h and 48h retention performance of the step-through passive avoidance task, in adult male Wistar rats. On the 24h retested trial, the latency of the passive avoidance response was significantly lower, while on the 48h retested trial it was significantly higher in scopolamine than in the saline-treated group. In a second experiment, we assessed the 24h time course of scopolamine (1mg/kg) effect on memory consolidation in passive avoidance task. We found that scopolamine administration only within the first six and half hours after acquisition improved memory consolidation in 48h retention performance. Finally, a third experiment was performed on the saline- and scopolamine-treated rats (given immediately after acquisition) that on the 48h retention test did not step through into the dark compartment during the cut-off time. These animals were retested weekly for up to first three months, and after that, every three months until the end of experiment (i.e., 15 months after acquisition). The passive avoidance response in the saline treated group lasted up to 6 weeks after acquisition, while in the scopolamine treated group 50% of animals conserved the initial level of passive avoidance response until the experiment end point. In conclusion, the present data suggest that (1) improving or impairment effect of scopolamine given in post-training periods depends on delay of retention trial, (2) memory consolidation process could be modify by scopolamine within first six and half hours after training and (3) scopolamine could delay forgetting of emotional memory. Copyright

  11. Alpha1-adrenergic receptor blockade in the VTA modulates fear memories and stress responses.

    Science.gov (United States)

    Solecki, Wojciech B; Szklarczyk, Klaudia; Klasa, Adam; Pradel, Kamil; Dobrzański, Grzegorz; Przewłocki, Ryszard

    2017-08-01

    Activity of the ventral tegmental area (VTA) and its terminals has been implicated in the Pavlovian associative learning of both stressful and rewarding stimuli. However, the role of the VTA noradrenergic signaling in fear responses remains unclear. We aimed to examine how alpha 1 -adrenergic receptor (α 1 -AR) signaling in the VTA affects conditioned fear. The role of α 1 -AR was assessed using the micro-infusions into the VTA of the selective antagonists (0.1-1µg/0.5µl prazosin and 1µg/0.5µl terazosin) in acquisition and expression of fear memory. In addition, we performed control experiments with α 1 -AR blockade in the mammillary bodies (MB) - a brain region with α 1 -AR expression adjacent to the VTA. Intra-VTA but not intra-MB α 1 -AR blockade prevented formation and retrieval of fear memories. Importantly, local administration of α 1 -AR antagonists did not influence footshock sensitivity, locomotion or anxiety-like behaviors. Similarly, α 1 -AR blockade in the VTA had no effects on negative affect measured as number of 22kHz ultrasonic vocalizations during fear conditioning training. We propose that noradrenergic signaling in the VTA via α 1 -AR regulates formation and retrieval of fear memories but not other behavioral responses to stressful environmental stimuli. It enhances the encoding of environmental stimuli by the VTA to form and retrieve conditioned fear memories and to predict future behavioral outcomes. Our results provide novel insight into the role of the VTA α 1 -AR signaling in the regulation of stress responsiveness and fear memory. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  12. Changes in corticospinal excitability during consolidation predict acute exercise-induced off-line gains in procedural memory

    DEFF Research Database (Denmark)

    Ostadan, Fatemeh; Centeno, Carla; Daloze, Jean-Felix

    2016-01-01

    A single bout of cardiovascular exercise performed immediately after practicing a motor task improves the long-term retention of the skill through an optimization of memory consolidation. However, the specific brain mechanisms underlying the effects of acute cardiovascular exercise on procedural...... exercise correlated with the magnitude of off-line gains in skill level assessed in a retention test performed 8h after motor practice. A single bout of exercise modulates short-term neuroplasticity mechanisms subserving consolidation processes that predict off-line gains in procedural memory....... memory are poorly understood. We sought to determine if a single bout of exercise modifies corticospinal excitability (CSE) during the early stages of memory consolidation. In addition, we investigated if changes in CSE are associated with exercise-induced off-line gains in procedural memory...

  13. Tracking the fear memory engram: discrete populations of neurons within amygdala, hypothalamus, and lateral septum are specifically activated by auditory fear conditioning

    Science.gov (United States)

    Wilson, Yvette M.; Gunnersen, Jenny M.; Murphy, Mark

    2015-01-01

    Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used fos-tau-lacZ (FTL) transgenic mice to identify discrete populations of neurons in amygdala and hypothalamus, which were specifically activated by fear conditioning to a context. Here we have examined neuronal activation due to fear conditioning to a more specific auditory cue. Discrete populations of learning-specific neurons were identified in only a small number of locations in the brain, including those previously found to be activated in amygdala and hypothalamus by context fear conditioning. These populations, each containing only a relatively small number of neurons, may be directly involved in fear learning and memory. PMID:26179231

  14. A Time for Learning and a Time for Sleep : The Effect of Sleep Deprivation on Contextual Fear Conditioning at Different Times of the Day

    NARCIS (Netherlands)

    Hagewoud, Roelina; Whitcomb, Shamiso N.; Heeringa, Amarins N.; Havekes, Robbert; Koolhaas, Jaap M.; Meerlo, Peter

    2010-01-01

    Study Objectives: Sleep deprivation negatively affects memory consolidation, especially in the case of hippocampus-dependent memories. Studies in rodents have shown that 5 hours of sleep deprivation immediately following footshock exposure selectively impairs the formation of a contextual fear

  15. A role for central nervous growth hormone-releasing hormone signaling in the consolidation of declarative memories.

    Directory of Open Access Journals (Sweden)

    Manfred Hallschmid

    Full Text Available Contributions of somatotropic hormonal activity to memory functions in humans, which are suggested by clinical observations, have not been systematically examined. With previous experiments precluding a direct effect of systemic growth hormone (GH on acute memory formation, we assessed the role of central nervous somatotropic signaling in declarative memory consolidation. We examined the effect of intranasally administered growth hormone releasing-hormone (GHRH; 600 µg that has direct access to the brain and suppresses endogenous GHRH via an ultra-short negative feedback loop. Twelve healthy young men learned word-pair associates at 2030 h and were administered GHRH and placebo, respectively, at 2100 h. Retrieval was tested after 11 hours of wakefulness. Compared to placebo, intranasal GHRH blunted GH release within 3 hours after substance administration and reduced the number of correctly recalled word-pairs by ∼12% (both P<0.05. The impairment of declarative memory consolidation was directly correlated to diminished GH concentrations (P<0.05. Procedural memory consolidation as examined by the parallel assessment of finger sequence tapping performance was not affected by GHRH administration. Our findings indicate that intranasal GHRH, by counteracting endogenous GHRH release, impairs hippocampal memory processing. They provide first evidence for a critical contribution of central nervous somatotropic activity to hippocampus-dependent memory consolidation.

  16. Fear memory in a neurodevelopmental model of schizophrenia based on the postnatal blockade of NMDA receptors.

    Science.gov (United States)

    Latusz, Joachim; Radaszkiewicz, Aleksandra; Bator, Ewelina; Wędzony, Krzysztof; Maćkowiak, Marzena

    2017-02-01

    Epidemiological data have indicated that memory impairment is observed during adolescence in groups at high risk for schizophrenia and might precede the appearance of schizophrenia symptoms in adulthood. In the present study, we used a neurodevelopmental model of schizophrenia based on the postnatal blockade of N-methyl-d-aspartate (NMDA) receptors in rats to investigate fear memory in adolescence and adulthood. The rats were treated with increasing doses of CGP 37849 (CGP), a competitive antagonist of the NMDA receptor (1.25mg/kg on days 1, 3, 6, 9; 2.5mg/kg on days 12, 15, 18 and 5mg/kg on day 21). Fear memory was analysed in delay and trace fear conditioning. Sensorimotor gating deficit, which is another cognitive symptom of schizophrenia, was also determined in adolescent and adult CGP-treated rats. Postnatal CGP administration disrupted cue- and context-dependent fear memory in adolescent rats in both delay and trace conditioning. In contrast, CGP administration evoked impairment only in cue-dependent fear memory in rats exposed to trace but not delay fear conditioning. The postnatal blockade of NMDA receptors induced sensorimotor gating deficits in adult rats but not in adolescent rats. The postnatal blockade of NMDA receptors induced fear memory impairment in adolescent rats before the onset of neurobehavioral deficits associated with schizophrenia. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  17. Amygdala-Dependent Molecular Mechanisms of the Tac2 Pathway in Fear Learning.

    Science.gov (United States)

    Andero, Raül; Daniel, Sarah; Guo, Ji-Dong; Bruner, Robert C; Seth, Shivani; Marvar, Paul J; Rainnie, Donald; Ressler, Kerry J

    2016-10-01

    Recently we determined that activation of the tachykinin 2 (Tac2) pathway in the central amygdala (CeA) is necessary and sufficient for the modulation of fear memories. The Tac2 pathway includes the Tac2 gene, which encodes the neuropeptide neurokinin B and its corresponding receptor neurokinin 3 receptor (NK3R). In this study, using Tac2-cre and Tac2-GFP mice, we applied a combination of in vivo (optogenetics) and multiple in vitro techniques to further explore the mechanisms of action within the Tac2 pathway. In transgenic mice that express ChR2 solely in Tac2 neurons, in vivo optogenetic stimulation of CeA Tac2-expressing neurons during fear acquisition enhanced fear memory consolidation and drove action potential firing in vitro. In addition, Tac2-CeA neurons were shown to co-express striatal-enriched protein tyrosine phosphatase, which may have an important role in regulating Nk3R signaling during fear conditioning. These data extend our current understanding for the underlying mechanism(s) for the role of the Tac2 pathway in the regulation of fear memory, which may serve as a new therapeutic target in the treatment of fear-related disorders.

  18. Amygdala-Dependent Molecular Mechanisms of the Tac2 Pathway in Fear Learning

    Science.gov (United States)

    Andero, Raül; Daniel, Sarah; Guo, Ji-Dong; Bruner, Robert C; Seth, Shivani; Marvar, Paul J; Rainnie, Donald; Ressler, Kerry J

    2016-01-01

    Recently we determined that activation of the tachykinin 2 (Tac2) pathway in the central amygdala (CeA) is necessary and sufficient for the modulation of fear memories. The Tac2 pathway includes the Tac2 gene, which encodes the neuropeptide neurokinin B and its corresponding receptor neurokinin 3 receptor (NK3R). In this study, using Tac2–cre and Tac2–GFP mice, we applied a combination of in vivo (optogenetics) and multiple in vitro techniques to further explore the mechanisms of action within the Tac2 pathway. In transgenic mice that express ChR2 solely in Tac2 neurons, in vivo optogenetic stimulation of CeA Tac2-expressing neurons during fear acquisition enhanced fear memory consolidation and drove action potential firing in vitro. In addition, Tac2–CeA neurons were shown to co-express striatal-enriched protein tyrosine phosphatase, which may have an important role in regulating Nk3R signaling during fear conditioning. These data extend our current understanding for the underlying mechanism(s) for the role of the Tac2 pathway in the regulation of fear memory, which may serve as a new therapeutic target in the treatment of fear-related disorders. PMID:27238620

  19. No Effect of Cathodal Transcranial Direct Current Stimulation on Fear Memory in Healthy Human Subjects

    Directory of Open Access Journals (Sweden)

    Aditya Mungee

    2016-11-01

    Full Text Available Background: Studies have demonstrated that fear memories can be modified using non-invasive methods. Recently, we demonstrated that anodal transcranial direct current stimulation (tDCS of the right dorsolateral prefrontal cortex is capable of enhancing fear memories. Here, we examined the effects of cathodal tDCS of the right dorsolateral prefrontal cortex during fear reconsolidation in humans. Methods: Seventeen young, healthy subjects were randomly assigned to two groups, which underwent fear conditioning with mild electric stimuli paired with a visual stimulus. Twenty-four hours later, both groups were shown a reminder of the conditioned fearful stimulus. Shortly thereafter, they received either tDCS (right prefrontal—cathodal, left supraorbital—anodal for 20 min at 1 mA, or sham stimulation. A day later, fear responses of both groups were compared. Results: On Day 3, during fear response assessment, there were no significant differences between the tDCS and sham group (p > 0.05. Conclusion: We conclude that cathodal tDCS of the right dorsolateral prefrontal cortex (right prefrontal—cathodal, left supraorbital—anodal did not influence fear memories.

  20. Rapid eye movement sleep deprivation disrupts consolidation but not reconsolidation of novel object recognition memory in rats.

    Science.gov (United States)

    Chen, Lin; Tian, Shaowen; Ke, Jie

    2014-03-20

    There is increasing evidence that sleep plays a critical role in memory consolidation. However, there are comparatively few studies that have assessed the relationship between sleep and memory reconsolidation. In the present study, we explored the effects of rapid eye movement sleep deprivation (RSD) on the consolidation (experiment 1) and reconsolidation (experiment 2) of novel object recognition memory in rats. In experiment 1 behavioral procedure involved two training phases: sample and test. Rats were subjected to 6h RSD starting either immediately after sample (exposed to 2 objects) or 6h later. In experiment 2 behavioral procedure involved three training phases: sample, reactivation and test. Rats were subjected to 6h RSD starting either immediately after reactivation (exposed to the same 2 sample objects to reactivate the memory trace) or 6h later. Results from experiment 1 showed that post-sample RSD from 0 to 6h but not 6 to 12h disrupted novel object recognition memory consolidation. However, we found that post-reactivation RSD whether from 0 to 6h or 6 to 12h had no effect on novel object recognition memory reconsolidation in experiment 2. The results indicated that RSD selectively disrupted consolidation of novel object recognition memory, suggesting a dissociation effect of RSD on consolidation and reconsolidation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Glucocorticoid Effects on Memory Consolidation Depend on Functional Interactions between the Medial Prefrontal Cortex and Basolateral Amygdala

    NARCIS (Netherlands)

    Roozendaal, Benno; McReynolds, Jayme R.; Van der Zee, Eddy A.; Lee, Sangkwan; McGaugh, James L.; McIntyre, Christa K.

    2009-01-01

    Considerable evidence indicates that the basolateral complex of the amygdala (BLA) interacts with efferent brain regions in mediating glucocorticoid effects on memory consolidation. Here, we investigated whether glucocorticoid influences on the consolidation of memory for emotionally arousing

  2. Effect of positive emotion on consolidation of memory for faces: the modulation of facial valence and facial gender.

    Science.gov (United States)

    Wang, Bo

    2013-01-01

    Studies have shown that emotion elicited after learning enhances memory consolidation. However, no prior studies have used facial photos as stimuli. This study examined the effect of post-learning positive emotion on consolidation of memory for faces. During the learning participants viewed neutral, positive, or negative faces. Then they were assigned to a condition in which they either watched a 9-minute positive video clip, or a 9-minute neutral video. Then 30 minutes after the learning participants took a surprise memory test, in which they made "remember", "know", and "new" judgements. The findings are: (1) Positive emotion enhanced consolidation of recognition for negative male faces, but impaired consolidation of recognition for negative female faces; (2) For males, recognition for negative faces was equivalent to that for positive faces; for females, recognition for negative faces was better than that for positive faces. Our study provides the important evidence that effect of post-learning emotion on memory consolidation can extend to facial stimuli and such an effect can be modulated by facial valence and facial gender. The findings may shed light on establishing models concerning the influence of emotion on memory consolidation.

  3. False Context Fear Memory in Rats

    Science.gov (United States)

    Bae, Sarah; Holmes, Nathan M.; Westbrook, R. Frederick

    2015-01-01

    Four experiments used rats to study false context fear memories. In Experiment 1, rats were pre-exposed to a distinctive chamber (context A) or to a control environment (context C), shocked after a delay in a second chamber (context B) and tested either in B or A. Rats pre-exposed to A froze just as much as control rats in B but more than control…

  4. Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory

    Science.gov (United States)

    Atsak, Piray; Hauer, Daniela; Campolongo, Patrizia; Schelling, Gustav; McGaugh, James L.; Roozendaal, Benno

    2012-01-01

    There is extensive evidence that glucocorticoid hormones impair the retrieval of memory of emotionally arousing experiences. Although it is known that glucocorticoid effects on memory retrieval impairment depend on rapid interactions with arousal-induced noradrenergic activity, the exact mechanism underlying this presumably nongenomically mediated glucocorticoid action remains to be elucidated. Here, we show that the hippocampal endocannabinoid system, a rapidly activated retrograde messenger system, is involved in mediating glucocorticoid effects on retrieval of contextual fear memory. Systemic administration of corticosterone (0.3–3 mg/kg) to male Sprague–Dawley rats 1 h before retention testing impaired the retrieval of contextual fear memory without impairing the retrieval of auditory fear memory or directly affecting the expression of freezing behavior. Importantly, a blockade of hippocampal CB1 receptors with AM251 prevented the impairing effect of corticosterone on retrieval of contextual fear memory, whereas the same impairing dose of corticosterone increased hippocampal levels of the endocannabinoid 2-arachidonoylglycerol. We also found that antagonism of hippocampal β-adrenoceptor activity with local infusions of propranolol blocked the memory retrieval impairment induced by the CB receptor agonist WIN55,212–2. Thus, these findings strongly suggest that the endocannabinoid system plays an intermediary role in regulating rapid glucocorticoid effects on noradrenergic activity in impairing memory retrieval of emotionally arousing experiences. PMID:22331883

  5. The neuronal PAS domain protein 4 (Npas4 is required for new and reactivated fear memories.

    Directory of Open Access Journals (Sweden)

    Jonathan E Ploski

    Full Text Available The Neuronal PAS domain protein 4 (Npas4 is a neuronal activity-dependent immediate early gene that has recently been identified as a transcription factor which regulates the transcription of genes that control inhibitory synapse development and synaptic plasticity. The role Npas4 in learning and memory, however, is currently unknown. Here, we systematically examine the role of Npas4 in auditory Pavlovian fear conditioning, an amygdala-dependent form of emotional learning. In our first series of experiments, we show that Npas4 mRNA and protein are regulated in the rat lateral nucleus of the amygdala (LA in a learning-dependent manner. Further, knockdown of Npas4 protein in the LA via adeno-associated viral (AAV mediated gene delivery of RNAi was observed to impair fear memory formation, while innate fear and the expression of fear memory were not affected. In our second series of experiments, we show that Npas4 protein is regulated in the LA by retrieval of an auditory fear memory and that knockdown of Npas4 in the LA impairs retention of a reactivated, but not a non-reactivated, fear memory. Collectively, our findings provide the first comprehensive look at the functional role of Npas4 in learning and memory.

  6. Young and Old Pavlovian Fear Memories Can Be Modified with Extinction Training during Reconsolidation in Humans

    Science.gov (United States)

    Steinfurth, Elisa C. K.; Kanen, Jonathan W.; Raio, Candace M.; Clem, Roger L.; Huganir, Richard L.; Phelps, Elizabeth A.

    2014-01-01

    Extinction training during reconsolidation has been shown to persistently diminish conditioned fear responses across species. We investigated in humans if older fear memories can benefit similarly. Using a Pavlovian fear conditioning paradigm we compared standard extinction and extinction after memory reactivation 1 d or 7 d following acquisition.…

  7. The effect of psilocin on memory acquisition, retrieval and consolidation in rat.

    Directory of Open Access Journals (Sweden)

    Lukas eRambousek

    2014-05-01

    Full Text Available The involvement of the serotonin system in the pathophysiology of schizophrenia has been elucidated by experiments with hallucinogens. Application of a hallucinogen to humans leads to changes in perception, cognition, emotions and induction of psychotic-like symptoms that resemble symptoms of schizophrenia. In rodent studies, their acute administration affects sensorimotor gating, locomotor activity, social behavior and cognition including working memory, the phenotypes are considered as an animal model of schizophrenia. The complexity and singularity of human cognition raises questions about the validity of animal models utilizing agonists of 5-HT2A receptors. The present study thus investigated the effect of psilocin on memory acquisition, reinforced retrieval and memory consolidation in rats. Psilocin is a main metabolite of psilocybin acting as an agonist at 5-HT2A receptors with a contribution of 5-HT2C and 5-HT1A receptors. First, we tested the effect of psilocin on the acquisition of a Carousel maze, a spatial task requiring navigation using distal cues, attention and cognitive coordination. Psilocin significantly impaired the acquisition of the Carousel Maze at both doses (1 and 4 mg/kg. The higher dose of psilocin blocked the learning processes even in an additional session when the rats received only saline. Next, we examined the effect of psilocin on reinforced retrieval and consolidation in the Morris water maze (MWM. The dose of 4 mg/kg disrupted reinforced retrieval in the Morris water maze. However, the application of a lower dose was without any significant effect. Finally, neither the low nor high dose of psilocin injected post-training caused a deficit in memory consolidation in the MWM. Taken together, the psilocin dose dependently impaired the acquisition of the Carousel maze and reinforced retrieval in MWM; however, it had no effect on memory consolidation.

  8. Memory consolidation from seconds to weeks: A three-stage neural network model with autonomous reinstatement dynamics

    Directory of Open Access Journals (Sweden)

    Florian eFiebig

    2014-07-01

    Full Text Available Declarative long-term memories are not created at an instant. Gradual stabilization and temporally shifting dependence of acquired declarative memories on different brain regions - called systems consolidation - can be tracked in time by lesion experiments. The observation of temporally graded retrograde amnesia following hippocampal lesions, points to a gradual transfer of memory from hippocampus to neocortical long-term memory. Spontaneous reactivations of hippocampal memories, as observed in place cell reactivations during slow-wave-sleep, are supposed to drive neocortical reinstatements and facilitate this process.We propose a functional neural network implementation of these ideas and furthermore suggest an extended three-stage framework that also includes the prefrontal cortex and bridges the temporal chasm between working memory percepts on the scale of seconds and consolidated long-term memory on the scale of weeks or months.We show that our three-stage model can autonomously produce the necessary stochastic reactivation dynamics for successful episodic memory consolidation. The resulting learning system is shown to exhibit classical memory effects seen in experimental studies, such as retrograde and anterograde amnesia after simulated hippocampal lesioning; furthermore the model reproduces peculiar biological findings on memory modulation, such as retrograde facilitation of memory after suppressed acquisition of new long-term memories - similar to the effects of benzodiazepines on memory.

  9. Neuronal mechanisms of motor learning and motor memory consolidation in healthy old adults.

    Science.gov (United States)

    Berghuis, K M M; Veldman, M P; Solnik, S; Koch, G; Zijdewind, I; Hortobágyi, T

    2015-06-01

    It is controversial whether or not old adults are capable of learning new motor skills and consolidate the performance gains into motor memory in the offline period. The underlying neuronal mechanisms are equally unclear. We determined the magnitude of motor learning and motor memory consolidation in healthy old adults and examined if specific metrics of neuronal excitability measured by magnetic brain stimulation mediate the practice and retention effects. Eleven healthy old adults practiced a wrist extension-flexion visuomotor skill for 20 min (MP, 71.3 years), while a second group only watched the templates without movements (attentional control, AC, n = 11, 70.5 years). There was 40 % motor learning in MP but none in AC (interaction, p learn a new motor skill and consolidate the learned skill into motor memory, processes that are most likely mediated by disinhibitory mechanisms. These results are relevant for the increasing number of old adults who need to learn and relearn movements during motor rehabilitation.

  10. Learning and memory in conditioned fear extinction: effects of d-cycloserine

    NARCIS (Netherlands)

    Vervliet, B.

    2008-01-01

    This review addresses the effects of the cognitive enhancer D-cycloserine (DCS) on the memory processes that occur in conditioned fear extinction, which is the experimental model for exposure techniques to reduce clinical anxiety. All reported rat studies show an enhanced fear extinction effect when

  11. Protein synthesis underlies post-retrieval memory consolidation to a restricted degree only when updated information is obtained

    OpenAIRE

    Rodriguez-Ortiz, Carlos J.; De la Cruz, Vanesa; Gutiérrez, Ranier; Bermudez-Rattoni, Federico

    2005-01-01

    Consolidation theory proposes that through the synthesis of new proteins recently acquired memories are strengthened over time into a stable long-term memory trace. However, evidence has accumulated suggesting that retrieved memory is susceptible to disruption, seeming to consolidate again (reconsolidate) to be retained in long-term storage. Here we show that intracortical blockade of protein synthesis in the gustatory cortex after retrieval of taste-recognition memory disrupts previously con...

  12. Declarative and Non-declarative Memory Consolidation in Children with Sleep Disorder.

    Science.gov (United States)

    Csábi, Eszter; Benedek, Pálma; Janacsek, Karolina; Zavecz, Zsófia; Katona, Gábor; Nemeth, Dezso

    2015-01-01

    Healthy sleep is essential in children's cognitive, behavioral, and emotional development. However, remarkably little is known about the influence of sleep disorders on different memory processes in childhood. Such data could give us a deeper insight into the effect of sleep on the developing brain and memory functions and how the relationship between sleep and memory changes from childhood to adulthood. In the present study we examined the effect of sleep disorder on declarative and non-declarative memory consolidation by testing children with sleep-disordered breathing (SDB) which is characterized by disrupted sleep structure. We used a story recall task to measure declarative memory and Alternating Serial Reaction time (ASRT) task to assess non-declarative memory. This task enables us to measure two aspects of non-declarative memory, namely general motor skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 12 h offline period with sleep. Our data showed that children with SDB exhibited a generally lower declarative memory performance both in the learning and testing phase; however, both the SDB and control groups exhibited retention of the previously recalled items after the offline period. Here we showed intact non-declarative consolidation in SDB group in both sequence-specific and general motor skill. These findings suggest that sleep disorders in childhood have a differential effect on different memory processes (online vs. offline) and give us insight into how sleep disturbances affects developing brain.

  13. Tet1 oxidase regulates neuronal gene transcription, active DNA hydroxymethylation, object location memory, and threat recognition memory

    Directory of Open Access Journals (Sweden)

    Dinesh Kumar

    2015-10-01

    Full Text Available A dynamic equilibrium between DNA methylation and demethylation of neuronal activity-regulated genes is crucial for memory processes. However, the mechanisms underlying this equilibrium remain elusive. Tet1 oxidase has been shown to play a key role in the active DNA demethylation in the central nervous system. In this study, we used Tet1 gene knockout (Tet1KO mice to examine the involvement of Tet1 in memory consolidation and storage in the adult brain. We found that Tet1 ablation leads to altered expression of numerous neuronal activity-regulated genes, compensatory upregulation of active demethylation pathway genes, and upregulation of various epigenetic modifiers. Moreover, Tet1KO mice showed an enhancement in the consolidation and storage of threat recognition (cued and contextual fear conditioning and object location memories. We conclude that Tet1 plays a critical role in regulating neuronal transcription and in maintaining the epigenetic state of the brain associated with memory consolidation and storage.

  14. Dorsoventral and Proximodistal Hippocampal Processing Account for the Influences of Sleep and Context on Memory (Re)consolidation: A Connectionist Model.

    Science.gov (United States)

    Lines, Justin; Nation, Kelsey; Fellous, Jean-Marc

    2017-01-01

    The context in which learning occurs is sufficient to reconsolidate stored memories and neuronal reactivation may be crucial to memory consolidation during sleep. The mechanisms of context-dependent and sleep-dependent memory (re)consolidation are unknown but involve the hippocampus. We simulated memory (re)consolidation using a connectionist model of the hippocampus that explicitly accounted for its dorsoventral organization and for CA1 proximodistal processing. Replicating human and rodent (re)consolidation studies yielded the following results. (1) Semantic overlap between memory items and extraneous learning was necessary to explain experimental data and depended crucially on the recurrent networks of dorsal but not ventral CA3. (2) Stimulus-free, sleep-induced internal reactivations of memory patterns produced heterogeneous recruitment of memory items and protected memories from subsequent interference. These simulations further suggested that the decrease in memory resilience when subjects were not allowed to sleep following learning was primarily due to extraneous learning. (3) Partial exposure to the learning context during simulated sleep (i.e., targeted memory reactivation) uniformly increased memory item reactivation and enhanced subsequent recall. Altogether, these results show that the dorsoventral and proximodistal organization of the hippocampus may be important components of the neural mechanisms for context-based and sleep-based memory (re)consolidations.

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

    Science.gov (United States)

    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.

  16. Hippocampal dendritic spines remodeling and fear memory are modulated by GABAergic signaling within the basolateral amygdala complex.

    Science.gov (United States)

    Giachero, Marcelo; Calfa, Gaston D; Molina, Victor A

    2015-05-01

    GABAergic signaling in the basolateral amygdala complex (BLA) plays a crucial role on the modulation of the stress influence on fear memory. Moreover, accumulating evidence suggests that the dorsal hippocampus (DH) is a downstream target of BLA neurons in contextual fear. Given that hippocampal structural plasticity is proposed to provide a substrate for the storage of long-term memories, the main aim of this study is to evaluate the modulation of GABA neurotransmission in the BLA on spine density in the DH following stress on contextual fear learning. The present findings show that prior stressful experience promoted contextual fear memory and enhanced spine density in the DH. Intra-BLA infusion of midazolam, a positive modulator of GABAa sites, prevented the facilitating influence of stress on both fear retention and hippocampal dendritic spine remodeling. Similarly to the stress-induced effects, the blockade of GABAa sites within the BLA ameliorated fear memory emergence and induced structural remodeling in the DH. These findings suggest that GABAergic transmission in BLA modulates the structural changes in DH associated to the influence of stress on fear memory. © 2015 Wiley Periodicals, Inc.

  17. The effect of selective REM-sleep deprivation on the consolidation and affective evaluation of emotional memories.

    Science.gov (United States)

    Wiesner, Christian D; Pulst, Julika; Krause, Fanny; Elsner, Marike; Baving, Lioba; Pedersen, Anya; Prehn-Kristensen, Alexander; Göder, Robert

    2015-07-01

    Emotion boosts the consolidation of events in the declarative memory system. Rapid eye movement (REM) sleep is believed to foster the memory consolidation of emotional events. On the other hand, REM sleep is assumed to reduce the emotional tone of the memory. Here, we investigated the effect of selective REM-sleep deprivation, SWS deprivation, or wake on the affective evaluation and consolidation of emotional and neutral pictures. Prior to an 9-h retention interval, sixty-two healthy participants (23.5 ± 2.5 years, 32 female, 30 male) learned and rated their affect to 80 neutral and 80 emotionally negative pictures. Despite rigorous deprivation of REM sleep or SWS, the residual sleep fostered the consolidation of neutral and negative pictures. Furthermore, emotional arousal helped to memorize the pictures. The better consolidation of negative pictures compared to neutral ones was most pronounced in the SWS-deprived group where a normal amount of REM sleep was present. This emotional memory bias correlated with REM sleep only in the SWS-deprived group. Furthermore, emotional arousal to the pictures decreased over time, but neither sleep nor wake had any differential effect. Neither the comparison of the affective ratings (arousal, valence) during encoding and recognition, nor the affective ratings of the recognized targets and rejected distractors supported the hypothesis that REM sleep dampens the emotional reaction to remembered stimuli. The data suggest that REM sleep fosters the consolidation of emotional memories but has no effect on the affective evaluation of the remembered contents. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Nielson, Kristy A; Bryant, Ted

    2005-07-01

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

  19. Tet1 Oxidase Regulates Neuronal Gene Transcription, Active DNA Hydroxy-methylation, Object Location Memory, and Threat Recognition Memory.

    Science.gov (United States)

    Kumar, Dinesh; Aggarwal, Milan; Kaas, Garrett A; Lewis, John; Wang, Jing; Ross, Daniel L; Zhong, Chun; Kennedy, Andrew; Song, Hongjun; Sweatt, J David

    2015-10-01

    A dynamic equilibrium between DNA methylation and demethylation of neuronal activity-regulated genes is crucial for memory processes. However, the mechanisms underlying this equilibrium remain elusive. Tet1 oxidase has been shown to play a key role in the active DNA demethylation in the CNS. In this study, we used Tet1 gene knockout (Tet1KO) mice to examine the involvement of Tet1 in memory consolidation and storage in the adult brain. We found that Tet1 ablation leads to: altered expression of numerous neuronal activity-regulated genes, compensatory upregulation of active demethylation pathway genes, and upregulation of various epigenetic modifiers. Moreover, Tet1KO mice showed an enhancement in the consolidation and storage of threat recognition (cued and contextual fear conditioning) and object location memories. We conclude that Tet1 plays a critical role in regulating neuronal transcription and in maintaining the epigenetic state of the brain associated with memory consolidation and storage.

  20. Loss of Ensemble Segregation in Dentate Gyrus, but Not in Somatosensory Cortex, during Contextual Fear Memory Generalization

    Directory of Open Access Journals (Sweden)

    Marie Yokoyama

    2016-11-01

    Full Text Available The details of contextual or episodic memories are lost and generalized with the passage of time. Proper generalization may underlie the formation and assimilation of semantic memories and enable animals to adapt to ever-changing environments, whereas overgeneralization of fear memory evokes maladaptive fear responses to harmless stimuli, which is a symptom of anxiety disorders such as post-traumatic stress disorder (PTSD. To understand the neural basis of fear memory generalization, we investigated the patterns of neuronal ensemble reactivation during memory retrieval when contextual fear memory expression is generalized using transgenic mice that allowed us to visualize specific neuronal ensembles activated during memory encoding and retrieval. We found preferential reactivations of neuronal ensembles in the primary somatosensory cortex, when mice were returned to the conditioned context to retrieve their memory 1 day after conditioning. In the hippocampal dentate gyrus (DG, exclusively separated ensemble reactivation was observed when mice were exposed to a novel context. These results suggest that the DG as well as the somatosensory cortex were likely to distinguish the two different contexts at the ensemble activity level when memory is not generalized at the behavioral level. However, 9 days after conditioning when animals exhibited generalized fear, the unique reactivation pattern in the DG, but not in the somatosensory cortex, was lost. Our results suggest that the alternations in the ensemble representation within the DG, or in upstream structures that link the sensory cortex to the hippocampus, may underlie generalized contextual fear memory expression.

  1. Evaluation Effects of Verapamil as a Calcium Channel Blocker on Acquisition, Consolidation and Retrieval of Memory in Mice

    Directory of Open Access Journals (Sweden)

    Nooshin Masoudian

    2015-04-01

    Full Text Available Many factors are involved in learning and memory processes including brain nuclei, neurotransmitter systems, and the activity of ion channels. Studies showed inconsistent effects of calcium channel blockers on learning process, especially memory consolidation; however, little is known about their effect on memory acquisition and retrieval. Accordingly, the present study aimed to determine the effects of verapamil calcium channel antagonist as a representative of the phenylalkylamine group on different stages of memory and learning processes including acquisition, consolidation and retrieval in mice. In this experimental study, 150 male albino mice with a mean weight of 30 g were used. The mice were trained in a passive avoidance-learning task (1 mA shock for 2 seconds for evaluation of memory acquisition and consolidation and 3 seconds for evaluation of memory retrieval. The effect of verapamil (1, 2.5, 5, 10, and 20 mg/kg on memory consolidation and the most effective dose of consolidation phase on memory acquisition and retrieval was assessed. For the evaluation of memory consolidation, the animals received the drug intraperitoneally immediately after training, while for evaluation of memory acquisition and retrieval, the drug was injected one hour before training. Memory retrieval test was performed 48 hours after training (the length of time it took the animal to enter the dark part of the device. The results showed that verapamil injection exerted no effect on memory acquisition and consolidation; nevertheless, it was capable to disrupt memory retrieval in 10 and 20 mg doses. These results indicate that as a phenylalkylamine calcium channel antagonist, high doses of verapamil can impair memory. Normal 0 false false false EN-US X-NONE AR-SA /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso

  2. Autobiographical memory and hyperassociativity in the dreaming brain: Implications for memory consolidation in sleep

    Directory of Open Access Journals (Sweden)

    Caroline L Horton

    2015-07-01

    Full Text Available In this paper we argue that autobiographical memory activity across sleep and wake can provide insight into the nature of dreaming, and vice versa. Activated memories within the sleeping brain reflect one’s personal life history (autobiography. They can appear in largely fragmentary forms and differ from conventional manifestations of episodic memory. Autobiographical memories in dreams can be sampled from non-REM as well as REM periods, which contain fewer episodic references and become more bizarre across the night. Salient fragmented memory features are activated in sleep and re-bound with fragments not necessarily emerging from the same memory, thus de-contextualising those memories and manifesting as experiences that differ from waking conceptions. The constructive nature of autobiographical recall further encourages synthesis of these hyper-associated images into an episode via recalling and reporting dreams. We use a model of autobiographical memory to account for the activation of memories in dreams as a reflection of sleep-dependent memory consolidation processes. We focus in particular on the hyperassociative nature of autobiographical memory during sleep.

  3. Declarative and non-declarative memory consolidation in children with sleep disorder

    Directory of Open Access Journals (Sweden)

    Eszter eCsabi

    2016-01-01

    Full Text Available Healthy sleep is essential in children’s cognitive, behavioral, and emotional development. However, remarkably little is known about the influence of sleep disorders on different memory processes in childhood. Such data could give us a deeper insight into the effect of sleep on the developing brain and memory functions and how the relationship between sleep and memory changes from childhood to adulthood. In the present study we examined the effect of sleep disorder on declarative and non-declarative memory consolidation by testing children with sleep-disordered breathing (SDB which is characterized by disrupted sleep structure. We used a story recall task to measure declarative memory and Alternating Serial Reaction Time (ASRT task to assess non-declarative memory. This task enables us to measure two aspects of non-declarative memory, namely general motor skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 12-hour offline period with sleep. Our data showed that children with SDB exhibited a generally lower declarative memory performance both in the learning and testing phase; however, both the SDB and control groups exhibited retention of the previously recalled items after the offline period. Here we showed intact non-declarative consolidation in SDB group in both sequence-specific and general motor skill. These findings suggest that sleep disorders in childhood have a differential effect on different memory processes (online vs. offline and give us insight into how sleep disturbances affects developing brain.

  4. Non-interfering effects of active post-encoding tasks on episodic memory consolidation in humans

    NARCIS (Netherlands)

    Varma, S.; Takashima, A.; Krewinkel, S.C.; Kooten, M.E. van; Fu, L.; Medendorp, W.P.; Kessels, R.P.C.; Daselaar, S.M.

    2017-01-01

    So far, studies that investigated interference effects of post-learning processes on episodic memory consolidation in humans have only used tasks involving complex and meaningful information. Such tasks require reallocation of general or encoding-specific resources away from consolidation-relevant

  5. Forced Migration of Colombians : Fear, Historical Memory and ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    This project follows two years of successful research under project 102661 on forced migration of Colombians within Colombia and to Ecuador and Canada. Researchers in Colombia and Canada investigated the ways in which fear, historical memory and social representation by and about forced migrants influence their ...

  6. "The seven sins" of the Hebbian synapse: can the hypothesis of synaptic plasticity explain long-term memory consolidation?

    Science.gov (United States)

    Arshavsky, Yuri I

    2006-10-01

    Memorizing new facts and events means that entering information produces specific physical changes within the brain. According to the commonly accepted view, traces of memory are stored through the structural modifications of synaptic connections, which result in changes of synaptic efficiency and, therefore, in formations of new patterns of neural activity (the hypothesis of synaptic plasticity). Most of the current knowledge on learning and initial stages of memory consolidation ("synaptic consolidation") is based on this hypothesis. However, the hypothesis of synaptic plasticity faces a number of conceptual and experimental difficulties when it deals with potentially permanent consolidation of declarative memory ("system consolidation"). These difficulties are rooted in the major intrinsic self-contradiction of the hypothesis: stable declarative memory is unlikely to be based on such a non-stable foundation as synaptic plasticity. Memory that can last throughout an entire lifespan should be "etched in stone." The only "stone-like" molecules within living cells are DNA molecules. Therefore, I advocate an alternative, genomic hypothesis of memory, which suggests that acquired information is persistently stored within individual neurons through modifications of DNA, and that these modifications serve as the carriers of elementary memory traces.

  7. A fear-inducing odor alters PER2 and c-Fos expression in brain regions involved in fear memory.

    Directory of Open Access Journals (Sweden)

    Harry Pantazopoulos

    Full Text Available Evidence demonstrates that rodents learn to associate a foot shock with time of day, indicating the formation of a fear related time-stamp memory, even in the absence of a functioning SCN. In addition, mice acquire and retain fear memory better during the early day compared to the early night. This type of memory may be regulated by circadian pacemakers outside of the SCN. As a first step in testing the hypothesis that clock genes are involved in the formation of a time-stamp fear memory, we exposed one group of mice to fox feces derived odor (TMT at ZT 0 and one group at ZT 12 for 4 successive days. A separate group with no exposure to TMT was also included as a control. Animals were sacrificed one day after the last exposure to TMT, and PER2 and c-Fos protein were quantified in the SCN, amygdala, hippocampus, and piriform cortex. Exposure to TMT had a strong effect at ZT 0, decreasing PER2 expression at this time point in most regions except the SCN, and reversing the normal rhythm of PER2 expression in the amygdala and piriform cortex. These changes were accompanied by increased c-Fos expression at ZT0. In contrast, exposure to TMT at ZT 12 abolished the rhythm of PER2 expression in the amygdala. In addition, increased c-Fos expression at ZT 12 was only detected in the central nucleus of the amygdala in the TMT12 group. TMT exposure at either time point did not affect PER2 or c-Fos in the SCN, indicating that under a light-dark cycle, the SCN rhythm is stable in the presence of repeated exposure to a fear-inducing stimulus. Taken together, these results indicate that entrainment to a fear-inducing stimulus leads to changes in PER2 and c-Fos expression that are detected 24 hours following the last exposure to TMT, indicating entrainment of endogenous oscillators in these regions. The observed effects on PER2 expression and c-Fos were stronger during the early day than during the early night, possibly to prepare appropriate systems at ZT 0 to

  8. Prior stress promotes the generalization of contextual fear memories: Involvement of the gabaergic signaling within the basolateral amygdala complex.

    Science.gov (United States)

    Bender, C L; Otamendi, A; Calfa, G D; Molina, V A

    2018-04-20

    Fear generalization occurs when a response, previously acquired with a threatening stimulus, is transferred to a similar one. However, it could be maladaptive when stimuli that do not represent a real threat are appraised as dangerous, which is a hallmark of several anxiety disorders. Stress exposure is a major risk factor for the occurrence of anxiety disorders and it is well established that it influences different phases of fear memory; nevertheless, its impact on the generalization of contextual fear memories has been less studied. In the present work, we have characterized the impact of acute restraint stress prior to contextual fear conditioning on the generalization of this fear memory, and the role of the GABAergic signaling within the basolateral amygdala complex (BLA) on the stress modulatory effects. We have found that a single stress exposure promoted the generalization of this memory trace to a different context that was well discriminated in unstressed conditioned animals. Moreover, this effect was dependent on the formation of a contextual associative memory and on the testing order (i.e., conditioning context first vs generalization context first). Furthermore, we observed that increasing GABA-A signaling by intra-BLA midazolam administration prior to the stressful session exposure prevented the generalization of fear memory, whereas intra-BLA administration of the GABA-A antagonist (Bicuculline), prior to fear conditioning, induced the generalization of fear memory in unstressed rats. We concluded that stress exposure, prior to contextual fear conditioning, promotes the generalization of fear memory and that the GABAergic transmission within the BLA has a critical role in this phenomenon. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Sleep, Dreams, and Memory Consolidation: The Role of the Stress Hormone Cortisol

    Science.gov (United States)

    Payne, Jessica D.; Nadel, Lynn

    2004-01-01

    We discuss the relationship between sleep, dreams, and memory, proposing that the content of dreams reflects aspects of memory consolidation taking place during the different stages of sleep. Although we acknowledge the likely involvement of various neuromodulators in these phenomena, we focus on the hormone cortisol, which is known to exert…

  10. Endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory

    NARCIS (Netherlands)

    Campolongo, Patrizia; Roozendaal, Benno; Trezza, Viviana; Hauer, Daniela; Schelling, Gustav; McGaugh, James L.; Cuomo, Vincenzo

    2009-01-01

    Extensive evidence indicates that the basolateral complex of the amygdala (BLA) modulates the consolidation of memories for emotionally arousing experiences, an effect that involves the activation of the glucocorticoid system. Because the BLA expresses high densities of cannabinoid CB1 receptors,

  11. Alternative conceptions of memory consolidation and the role of the hippocampus at the systems level in rodents.

    Science.gov (United States)

    Sutherland, R J; Lehmann, H

    2011-06-01

    We discuss very recent experiments with rodents addressing the idea that long-term memories initially depending on the hippocampus, over a prolonged period, become independent of it. No unambiguous recent evidence exists to substantiate that this occurs. Most experiments find that recent and remote memories are equally affected by hippocampus damage. Nearly all experiments that report spared remote memories suffer from two problems: retrieval could be based upon substantial regions of spared hippocampus and recent memory is tested at intervals that are of the same order of magnitude as cellular consolidation. Accordingly, we point the way beyond systems consolidation theories, both the Standard Model of Consolidation and the Multiple Trace Theory, and propose a simpler multiple storage site hypothesis. On this view, with event reiterations, different memory representations are independently established in multiple networks. Many detailed memories always depend on the hippocampus; the others may be established and maintained independently. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice.

    Science.gov (United States)

    Tuscher, Jennifer J; Szinte, Julia S; Starrett, Joseph R; Krentzel, Amanda A; Fortress, Ashley M; Remage-Healey, Luke; Frick, Karyn M

    2016-07-01

    The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal E2 synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E2 in the dorsal hippocampus observed 30min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E2 synthesis. Finally, aromatase inhibition did not prevent exogenous E2 from enhancing hippocampal memory consolidation, indicating that hippocampal E2 synthesis is not necessary for exogenous E2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally-synthesized E2 is necessary for hippocampus-dependent memory consolidation in rodents. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Regular rehearsal helps in consolidation of long term memory.

    Science.gov (United States)

    Parle, Milind; Singh, Nirmal; Vasudevan, Mani

    2006-01-01

    Memory, one of the most complex functions of the brain comprises of multiple components such as perception, registration, consolidation, storage, retrieval and decay. The present study was undertaken to evaluate the impact of different training sessions on the retention capacity of rats. The capacity of retention of learnt task was measured using exteroceptive behavioral models such as Hexagonal swimming pool apparatus, Hebb-Williams maze and Elevated plus-maze. A total of 150 rats divided into fifteen groups were employed in the present study. The animals were subjected to different training sessions during first three days. The ability to retain the learned task was tested after single, sub-acute, acute, sub-chronic and chronic exposure to above exteroceptive memory models in separate groups of animals. The memory score of all animals was recorded after 72 h, 192 h and 432 h of their last training trial. Rats of single exposure group did not show any effect on memory. Sub-acute training group animals showed improved memory up to 72 h only, where as in acute and sub-chronic training groups this memory improvement was extended up to 192 h. The rats, which were subjected to chronic exposures showed a significant improvement in retention capacity that lasted up to a period of eighteen days. These observations suggest that repeated rehearsals at regular intervals are probably necessary for consolidation of long-term memory. It was observed that sub-acute, acute and sub-chronic exposures, improved the retrieval ability of rats but this memory improving effect was short lived. Thus, rehearsal or training plays a crucial role in enhancing one's capacity of retaining the learnt information. Key PointsThe present study underlines the importance of regular rehearsals in enhancing one's capacity of retaining the learnt information. " Sub-acute, acute & sub-chronic rehearsals result in storing of information for a limited period of time.Quick decay of information or

  14. Myosin light chain kinase regulates synaptic plasticity and fear learning in the lateral amygdala.

    Science.gov (United States)

    Lamprecht, R; Margulies, D S; Farb, C R; Hou, M; Johnson, L R; LeDoux, J E

    2006-01-01

    Learning and memory depend on signaling molecules that affect synaptic efficacy. The cytoskeleton has been implicated in regulating synaptic transmission but its role in learning and memory is poorly understood. Fear learning depends on plasticity in the lateral nucleus of the amygdala. We therefore examined whether the cytoskeletal-regulatory protein, myosin light chain kinase, might contribute to fear learning in the rat lateral amygdala. Microinjection of ML-7, a specific inhibitor of myosin light chain kinase, into the lateral nucleus of the amygdala before fear conditioning, but not immediately afterward, enhanced both short-term memory and long-term memory, suggesting that myosin light chain kinase is involved specifically in memory acquisition rather than in posttraining consolidation of memory. Myosin light chain kinase inhibitor had no effect on memory retrieval. Furthermore, ML-7 had no effect on behavior when the training stimuli were presented in a non-associative manner. Anatomical studies showed that myosin light chain kinase is present in cells throughout lateral nucleus of the amygdala and is localized to dendritic shafts and spines that are postsynaptic to the projections from the auditory thalamus to lateral nucleus of the amygdala, a pathway specifically implicated in fear learning. Inhibition of myosin light chain kinase enhanced long-term potentiation, a physiological model of learning, in the auditory thalamic pathway to the lateral nucleus of the amygdala. When ML-7 was applied without associative tetanic stimulation it had no effect on synaptic responses in lateral nucleus of the amygdala. Thus, myosin light chain kinase activity in lateral nucleus of the amygdala appears to normally suppress synaptic plasticity in the circuits underlying fear learning, suggesting that myosin light chain kinase may help prevent the acquisition of irrelevant fears. Impairment of this mechanism could contribute to pathological fear learning.

  15. Context Memory Formation Requires Activity-Dependent Protein Degradation in the Hippocampus

    Science.gov (United States)

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

    2017-01-01

    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…

  16. Harnessing reconsolidation to weaken fear and appetitive memories: A meta-analysis of post-retrieval extinction effects.

    Science.gov (United States)

    Kredlow, M Alexandra; Unger, Leslie D; Otto, Michael W

    2016-03-01

    A new understanding of the mechanisms of memory retrieval and reconsolidation holds the potential for improving exposure-based treatments. Basic research indicates that following fear extinction, safety and fear memories may compete, raising the possibility of return of fear. One possible solution is to modify original fear memories through reconsolidation interference, reducing the likelihood of return of fear. Postretrieval extinction is a behavioral method of reconsolidation interference that has been explored in the context of conditioned fear and appetitive memory paradigms. This meta-analysis examines the magnitude of postretrieval extinction effects and potential moderators of these effects. A PubMed and PsycINFO search was conducted through June 2014. Sixty-three comparisons examining postretrieval extinction for preventing the return of fear or appetitive responses in animals or humans met inclusion criteria. Postretrieval extinction demonstrated a significant, small-to-moderate effect (g = .40) for further reducing the return of fear in humans and a significant, large effect (g = 0.89) for preventing the return of appetitive responses in animals relative to standard extinction. For fear outcomes in animals, effects were small (g = 0.21) and nonsignificant, but moderated by the number of animals housed together and the duration of time between postretrieval extinction/extinction and test. Across paradigms, these findings support the efficacy of this preclinical strategy for preventing the return of conditioned fear and appetitive responses. Overall, findings to date support the continued translation of postretrieval extinction research to human and clinical applications, with particular application to the treatment of anxiety, traumatic stress, and substance use disorders. (c) 2016 APA, all rights reserved).

  17. Enhanced Memory Consolidation Via Automatic Sound Stimulation During Non-REM Sleep.

    Science.gov (United States)

    Leminen, Miika M; Virkkala, Jussi; Saure, Emma; Paajanen, Teemu; Zee, Phyllis C; Santostasi, Giovanni; Hublin, Christer; Müller, Kiti; Porkka-Heiskanen, Tarja; Huotilainen, Minna; Paunio, Tiina

    2017-03-01

    Slow-wave sleep (SWS) slow waves and sleep spindle activity have been shown to be crucial for memory consolidation. Recently, memory consolidation has been causally facilitated in human participants via auditory stimuli phase-locked to SWS slow waves. Here, we aimed to develop a new acoustic stimulus protocol to facilitate learning and to validate it using different memory tasks. Most importantly, the stimulation setup was automated to be applicable for ambulatory home use. Fifteen healthy participants slept 3 nights in the laboratory. Learning was tested with 4 memory tasks (word pairs, serial finger tapping, picture recognition, and face-name association). Additional questionnaires addressed subjective sleep quality and overnight changes in mood. During the stimulus night, auditory stimuli were adjusted and targeted by an unsupervised algorithm to be phase-locked to the negative peak of slow waves in SWS. During the control night no sounds were presented. Results showed that the sound stimulation increased both slow wave (p = .002) and sleep spindle activity (p memory performance was compared between stimulus and control nights, we found a significant effect in word pair task but not in other memory tasks. The stimulation did not affect sleep structure or subjective sleep quality. We showed that the memory effect of the SWS-targeted individually triggered single-sound stimulation is specific to verbal associative memory. Moreover, the ambulatory and automated sound stimulus setup was promising and allows for a broad range of potential follow-up studies in the future. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society].

  18. Requirement of NMDA receptor reactivation for consolidation and storage of nondeclarative taste memory revealed by inducible NR1 knockout.

    Science.gov (United States)

    Cui, Zhenzhong; Lindl, Kathryn A; Mei, Bing; Zhang, Shuqing; Tsien, Joe Z

    2005-08-01

    We employed an inducible, reversible and region-specific gene knockout technique to investigate the requirements for cortical NMDA receptors (NMDAR) during the various stages (acquisition, consolidation and storage, and retrieval) of nondeclarative, hippocampal-independent memory in mice using a conditioned taste aversion memory paradigm. Here we show that temporary knockout of the cortical NMDAR during either the learning or postlearning consolidation stage, but not during the retrieval stage, causes severe performance deficits in the 1-month taste memory retention tests. More importantly, we found that the consolidation and storage of the long-term nondeclarative taste memories requires cortical NMDAR reactivation. Thus, the dynamic engagement of the NMDAR during the postlearning stage leads us to postulate that NMDAR reactivation-mediated synaptic re-entry reinforcement is crucial for overcoming the destabilizing effects intrinsic to synaptic protein turnover and for achieving consolidation and storage of nondeclarative memories in the brain.

  19. Retrieval cues that trigger reconsolidation of associative fear memory are not necessarily an exact replica of the original learning experience.

    Science.gov (United States)

    Soeter, Marieke; Kindt, Merel

    2015-01-01

    Disrupting the process of memory reconsolidation may point to a novel therapeutic strategy for the permanent reduction of fear in patients suffering from anxiety disorders. However both in animal and human studies the retrieval cue typically involves a re-exposure to the original fear-conditioned stimulus (CS). A relevant question is whether abstract cues not directly associated with the threat event also trigger reconsolidation, given that anxiety disorders often result from vicarious or unobtrusive learning for which no explicit memory exists. Insofar as the fear memory involves a flexible representation of the original learning experience, we hypothesized that the process of memory reconsolidation may also be triggered by abstract cues. We addressed this hypothesis by using a differential human fear-conditioning procedure in two distinct fear-learning groups. We predicted that if fear learning involves discrimination on basis of perceptual cues within one semantic category (i.e., the perceptual-learning group, n = 15), the subsequent ambiguity of the abstract retrieval cue would not trigger memory reconsolidation. In contrast, if fear learning involves discriminating between two semantic categories (i.e., categorical-learning group, n = 15), an abstract retrieval cue would unequivocally reactivate the fear memory and might subsequently trigger memory reconsolidation. Here we show that memory reconsolidation may indeed be triggered by another cue than the one that was present during the original learning occasion, but this effect depends on the learning history. Evidence for fear memory reconsolidation was inferred from the fear-erasing effect of one pill of propranolol (40 mg) systemically administered upon exposure to the abstract retrieval cue. Our finding that reconsolidation of a specific fear association does not require exposure to the original retrieval cue supports the feasibility of reconsolidation-based interventions for emotional disorders.

  20. Retrieval cues that trigger reconsolidation of associative fear memory are not necessarily an exact replica of the original learning experience

    Directory of Open Access Journals (Sweden)

    Marieke eSoeter

    2015-05-01

    Full Text Available Disrupting the process of memory reconsolidation may point to a novel therapeutic strategy for the permanent reduction of fear in patients suffering from anxiety disorders. However both in animal and human studies the retrieval cue typically involves a re-exposure to the original fear-conditioned stimulus. A relevant question is whether abstract cues not directly associated with the threat event also trigger reconsolidation, given that anxiety disorders often result from vicarious or unobtrusive learning for which no explicit memory exists. Insofar as the fear memory involves a flexible representation of the original learning experience, we hypothesized that the process of memory reconsolidation may also be triggered by abstract cues. We addressed this hypothesis by using a differential human fear-conditioning procedure in two distinct fear-learning groups. We predicted that if fear learning involves discrimination on basis of perceptual cues within one semantic category (i.e., the perceptual-learning group, n = 15, the subsequent ambiguity of the abstract retrieval cue would not trigger memory reconsolidation. In contrast, if fear learning involves discriminating between two semantic categories (i.e., categorical-learning group, n = 15, an abstract retrieval cue would unequivocally reactivate the fear memory and might subsequently trigger memory reconsolidation. Here we show that memory reconsolidation may indeed be triggered by another cue than the one that was present during the original learning occasion, but this effect depends on the learning history. Evidence for fear memory reconsolidation was inferred from the fear-erasing effect of one pill of propranolol (40 mg systemically administered upon exposure to the abstract retrieval cue. Our finding that reconsolidation of a specific fear association does not require exposure to the original retrieval cue supports the feasibility of reconsolidation-based interventions for emotional disorders.

  1. Moderate Partially Reduplicated Conditioned Stimuli as Retrieval Cue Can Increase Effect on Preventing Relapse of Fear to Compound Stimuli

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    Junjiao Li

    2017-11-01

    Full Text Available The theory of memory reconsolidation argues that consolidated memory is not unchangeable. Once a memory is reactivated it may go back into an unstable state and need new protein synthesis to be consolidated again, which is called “memory reconsolidation”. Boundary studies have shown that interfering with reconsolidation through pharmacologic or behavioral intervention can lead to the updating of the initial memory, for example, erasing undesired memories. Behavioral procedures based on memory reconsolidation interference have been shown to be an effective way to inhibit fear memory relapse after extinction. However, the effectiveness of retrieval–extinction differs by subtle differences in the protocol of the reactivation session. This represents a challenge with regard to finding an optimal operational model to facilitate its clinical use for patients suffering from pathogenic memories such as those associated with post-traumatic stress disorder. Most of the laboratory models for fear learning have used a single conditioned stimulus (CS paired with an unconditioned stimulus (US. This has simplified the real situation of traumatic events to an excessive degree, and thus, limits the clinical application of the findings based on these models. Here, we used a basic visual compound CS model as the CS to ascertain whether partial repetition of the compound CSs in conditioning can reactivate memory into reconsolidation. The results showed that the no retrieval group or the 1/3 ratio retrieval group failed to open the memory reconsolidation time window. The 2/3 repetition retrieval group and the whole repetition retrieval group were able to prevent fear reinstatement, whereas only a 2/3 ratio repetition of the initial compound CS as a reminder could inhibit spontaneous recovery. We inferred that a retrieval–extinction paradigm was also effective in a more complex model of fear if a sufficient prediction error (PE could be generated in the

  2. Moderate Partially Reduplicated Conditioned Stimuli as Retrieval Cue Can Increase Effect on Preventing Relapse of Fear to Compound Stimuli

    Science.gov (United States)

    Li, Junjiao; Chen, Wei; Caoyang, Jingwen; Wu, Wenli; Jie, Jing; Xu, Liang; Zheng, Xifu

    2017-01-01

    The theory of memory reconsolidation argues that consolidated memory is not unchangeable. Once a memory is reactivated it may go back into an unstable state and need new protein synthesis to be consolidated again, which is called “memory reconsolidation”. Boundary studies have shown that interfering with reconsolidation through pharmacologic or behavioral intervention can lead to the updating of the initial memory, for example, erasing undesired memories. Behavioral procedures based on memory reconsolidation interference have been shown to be an effective way to inhibit fear memory relapse after extinction. However, the effectiveness of retrieval–extinction differs by subtle differences in the protocol of the reactivation session. This represents a challenge with regard to finding an optimal operational model to facilitate its clinical use for patients suffering from pathogenic memories such as those associated with post-traumatic stress disorder. Most of the laboratory models for fear learning have used a single conditioned stimulus (CS) paired with an unconditioned stimulus (US). This has simplified the real situation of traumatic events to an excessive degree, and thus, limits the clinical application of the findings based on these models. Here, we used a basic visual compound CS model as the CS to ascertain whether partial repetition of the compound CSs in conditioning can reactivate memory into reconsolidation. The results showed that the no retrieval group or the 1/3 ratio retrieval group failed to open the memory reconsolidation time window. The 2/3 repetition retrieval group and the whole repetition retrieval group were able to prevent fear reinstatement, whereas only a 2/3 ratio repetition of the initial compound CS as a reminder could inhibit spontaneous recovery. We inferred that a retrieval–extinction paradigm was also effective in a more complex model of fear if a sufficient prediction error (PE) could be generated in the reactivation period

  3. Consolidation of an olfactory memory trace in the olfactory bulb is required for learning-induced survival of adult-born neurons and long-term memory.

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    Florence Kermen

    Full Text Available BACKGROUND: It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days, but not a massed (within day, learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb. CONCLUSION/SIGNIFICANCE: We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival during olfactory learning is governed by consolidation in the olfactory bulb strongly argues in favor of a role for bulbar adult-born neurons in supporting olfactory memory.

  4. Consolidation of an olfactory memory trace in the olfactory bulb is required for learning-induced survival of adult-born neurons and long-term memory.

    Science.gov (United States)

    Kermen, Florence; Sultan, Sébastien; Sacquet, Joëlle; Mandairon, Nathalie; Didier, Anne

    2010-08-13

    It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis. Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days), but not a massed (within day), learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb. We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival during olfactory learning is governed by consolidation in the olfactory bulb strongly argues in favor of a role for bulbar adult-born neurons in supporting olfactory memory.

  5. A dream model: Reactivation and re-encoding mechanisms for sleep-dependent memory consolidation

    NARCIS (Netherlands)

    Kachergis, G.E.; Kleijn, R. de; Hommel, B.; Papafragou, A.; Grodner, D.; Mirman, D.; Trueswell, J.

    2016-01-01

    We humans spend almost a third of our lives asleep, and there is mounting evidence that sleep not only maintains, but actually improves many of our cognitive functions. Memory consolidation - the process of crystallizing and integrating memories into knowledge and skills - is particularly benefitted

  6. Extinction after retrieval: effects on the associative and nonassociative components of remote contextual fear memory.

    Science.gov (United States)

    Costanzi, Marco; Cannas, Sara; Saraulli, Daniele; Rossi-Arnaud, Clelia; Cestari, Vincenzo

    2011-01-01

    Long-lasting memories of adverse experiences are essential for individuals' survival but are also involved, in the form of recurrent recollections of the traumatic experience, in the aetiology of anxiety diseases (e.g., post-traumatic stress disorder [PTSD]). Extinction-based erasure of fear memories has long been pursued as a behavioral way to treat anxiety disorders; yet, such a procedure turns out to be transient, context-dependent, and ineffective unless it is applied immediately after trauma. Recent evidence indicates that, in both rats and humans, extinction training can prevent the return of fear if administered within the reconsolidation window, when memories become temporarily labile and susceptible of being updated. Here, we show that the reconsolidation-extinction procedure fails to prevent the spontaneous recovery of a remote contextual fear memory in a mouse model of PTSD, as well as the long-lasting behavioral abnormalities induced by traumatic experience on anxiety and in both social and cognitive domains (i.e., social withdrawal and spatial learning deficits). Such a failure appears to be related to the ineffectiveness of the reconsolidation-extinction procedure in targeting the pathogenic process of fear sensitization, a nonassociative component of traumatic memory that causes animals to react aberrantly to harmless stimuli. This indicates fear sensitization as a major target for treatments aimed at mitigating anxiety and the behavioral outcomes of traumatic experiences.

  7. Inhibition of Rac1 Activity in the Hippocampus Impairs the Forgetting of Contextual Fear Memory.

    Science.gov (United States)

    Jiang, Lizhu; Mao, Rongrong; Zhou, Qixin; Yang, Yuexiong; Cao, Jun; Ding, Yuqiang; Yang, Yuan; Zhang, Xia; Li, Lingjiang; Xu, Lin

    2016-03-01

    Fear is crucial for survival, whereas hypermnesia of fear can be detrimental. Inhibition of the Rac GTPase is recently reported to impair the forgetting of initially acquired memory in Drosophila. Here, we investigated whether inhibition of Rac1 activity in rat hippocampus could contribute to the hypermnesia of contextual fear. We found that spaced but not massed training of contextual fear conditioning caused inhibition of Rac1 activity in the hippocampus and heightened contextual fear. Furthermore, intrahippocampal injection of the Rac1 inhibitor NSC23766 heightened contextual fear in massed training, while Rac1 activator CN04-A weakened contextual fear in spaced training rats. Our study firstly demonstrates that contextual fear memory in rats is actively regulated by Rac1 activity in the hippocampus, which suggests that the forgetting impairment of traumatic events in posttraumatic stress disorder may be contributed to the pathological inhibition of Rac1 activity in the hippocampus.

  8. Updating Procedures Can Reorganize the Neural Circuit Supporting a Fear Memory.

    Science.gov (United States)

    Kwapis, Janine L; Jarome, Timothy J; Ferrara, Nicole C; Helmstetter, Fred J

    2017-07-01

    Established memories undergo a period of vulnerability following retrieval, a process termed 'reconsolidation.' Recent work has shown that the hypothetical process of reconsolidation is only triggered when new information is presented during retrieval, suggesting that this process may allow existing memories to be modified. Reconsolidation has received increasing attention as a possible therapeutic target for treating disorders that stem from traumatic memories, yet little is known about how this process changes the original memory. In particular, it is unknown whether reconsolidation can reorganize the neural circuit supporting an existing memory after that memory is modified with new information. Here, we show that trace fear memory undergoes a protein synthesis-dependent reconsolidation process following exposure to a single updating trial of delay conditioning. Further, this reconsolidation-dependent updating process appears to reorganize the neural circuit supporting the trace-trained memory, so that it better reflects the circuit supporting delay fear. Specifically, after a trace-to-delay update session, the amygdala is now required for extinction of the updated memory but the retrosplenial cortex is no longer required for retrieval. These results suggest that updating procedures could be used to force a complex, poorly defined memory circuit to rely on a better-defined neural circuit that may be more amenable to behavioral or pharmacological manipulation. This is the first evidence that exposure to new information can fundamentally reorganize the neural circuit supporting an existing memory.

  9. Memory for fearful faces across development: specialization of amygdala nuclei and medial temporal lobe structures.

    Science.gov (United States)

    Pinabiaux, Charlotte; Hertz-Pannier, Lucie; Chiron, Catherine; Rodrigo, Sébastian; Jambaqué, Isabelle; Noulhiane, Marion

    2013-01-01

    Enhanced memory for emotional faces is a significant component of adaptive social interactions, but little is known on its neural developmental correlates. We explored the role of amygdaloid complex (AC) and medial temporal lobe (MTL) in emotional memory recognition across development, by comparing fMRI activations of successful memory encoding of fearful and neutral faces in children (n = 12; 8-12 years) and adolescents (n = 12; 13-17 years). Memory for fearful faces was enhanced compared with neutral ones in adolescents, as opposed to children. In adolescents, activations associated with successful encoding of fearful faces were centered on baso-lateral AC nuclei, hippocampus, enthorhinal and parahippocampal cortices. In children, successful encoding of fearful faces relied on activations of centro-mesial AC nuclei, which was not accompanied by functional activation of MTL memory structures. Successful encoding of neutral faces depended on activations in anterior MTL region (hippocampal head and body) in adolescents, but more posterior ones (hippocampal tail and parahippocampal cortex) in children. In conclusion, two distinct functional specializations emerge from childhood to adolescence and result in the enhancement of memory for these particular stimuli: the specialization of baso-lateral AC nuclei, which is associated with the expertise in processing emotional facial expression, and which is intimately related to the specialization of MTL memory network. How the interplay between specialization of AC nuclei and of MTL memory structures is fundamental for the edification of social interactions remains to be elucidated.

  10. Memory for fearful faces across development: specialization of amygdala nuclei and medial temporal lobe structures

    Directory of Open Access Journals (Sweden)

    Charlotte ePinabiaux

    2013-12-01

    Full Text Available Enhanced memory for emotional faces is a significant component of adaptive social interactions, but little is known on its neural developmental correlates. We explored the role of amygdaloid complex (AC and medial temporal lobe (MTL in emotional memory recognition across development, by comparing fMRI activations of successful memory encoding of fearful and neutral faces in children (n=12; 8-12 years and adolescents (n=12; 13-17 years. Memory for fearful faces was enhanced compared with neutral ones in adolescents, as opposed to children. In adolescents, activations associated with successful encoding of fearful faces were centered on baso-lateral AC nuclei, hippocampus, enthorhinal and parahippocampal cortices. In children, successful encoding of fearful faces relied on activations of centro-mesial AC nuclei, which was not accompanied by functional activation of MTL memory structures. Successful encoding of neutral faces depended on activations in anterior MTL region (hippocampal head and body in adolescents, but more posterior ones (hippocampal tail and parahippocampal cortex in children. In conclusion, two distinct functional specializations emerge from childhood to adolescence and result in the enhancement of memory for these particular stimuli: the specialization of baso-lateral AC nuclei, which is associated with the expertise in processing emotional facial expression, and which is intimately related to the specialization of MTL memory network. How the interplay between specialization of AC nuclei and of MTL memory structures is fundamental for the edification of social interactions remains to be elucidated.

  11. Post-Retrieval Late Process Contributes to Persistence of Reactivated Fear Memory

    Science.gov (United States)

    Nakayama, Daisuke; Yamasaki, Yoshiko; Matsuki, Norio; Nomura, Hiroshi

    2013-01-01

    Several studies have demonstrated the mechanisms involved in memory persistence after learning. However, little is known about memory persistence after retrieval. In this study, a protein synthesis inhibitor, anisomycin, was infused into the basolateral amygdala of mice 9.5 h after retrieval of contextual conditioned fear. Anisomycin attenuated…

  12. The role of sleep in human declarative memory consolidation.

    Science.gov (United States)

    Alger, Sara E; Chambers, Alexis M; Cunningham, Tony; Payne, Jessica D

    2015-01-01

    Through a variety of methods, researchers have begun unraveling the mystery of why humans spend one-third of their lives asleep. Though sleep likely serves multiple functions, it has become clear that the sleeping brain offers an ideal environment for solidifying newly learned information in the brain. Sleep , which comprises a complex collection of brain states, supports the consolidation of many different types of information. It not only promotes learning and memory stabilization, but also memory reorganization that can lead to various forms of insightful behavior. As this chapter will describe, research provides ample support for these crucial cognitive functions of sleep . Focusing on the declarative memory system in humans, we review the literature regarding the benefits of sleep for both neutral and emotionally salient declarative memory. Finally, we discuss the literature regarding the impact of sleep on emotion regulation.

  13. Consolidation and reconsolidation are impaired by oral propranolol administered before but not after memory (re)activation in humans.

    Science.gov (United States)

    Thomas, Émilie; Saumier, Daniel; Pitman, Roger K; Tremblay, Jacques; Brunet, Alain

    2017-07-01

    Propranolol administered immediately after learning or after recall has been found to impair memory consolidation or reconsolidation (respectively) in animals, but less reliably so in humans. Since reconsolidation impairment has been proposed as a treatment for mental disorders that have at their core an emotional memory, it is desirable to understand how to reliably reduce the strength of pathogenic memories in humans. We postulated that since humans (unlike experimental animals) typically receive propranolol orally, this introduces a delay before this drug can exert its memory impairment effects, which may render it less effective. As a means to test this, in two double-blind placebo-controlled experiments, we examined the capacity of propranolol to impair consolidation and reconsolidation as a function of timing of ingestion in healthy subjects. In Experiment 1, (n=36), propranolol administered immediately after learning or recall failed to impair the consolidation or reconsolidation of the memory of a standardized slideshow with an accompanying emotional story. In Experiment 2 (n=50), propranolol given 60-75min before learning or recall successfully impaired memory consolidation and reconsolidation. These results suggest that it is possible to achieve reliable memory impairment in humans if propranolol is given before learning or before recall, but not after. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Divided attention improves delayed, but not immediate retrieval of a consolidated memory.

    Science.gov (United States)

    Kessler, Yoav; Vandermorris, Susan; Gopie, Nigel; Daros, Alexander; Winocur, Gordon; Moscovitch, Morris

    2014-01-01

    A well-documented dissociation between memory encoding and retrieval concerns the role of attention in the two processes. The typical finding is that divided attention (DA) during encoding impairs future memory, but retrieval is relatively robust to attentional manipulations. However, memory research in the past 20 years had demonstrated that retrieval is a memory-changing process, in which the strength and availability of information are modified by various characteristics of the retrieval process. Based on this logic, several studies examined the effects of DA during retrieval (Test 1) on a future memory test (Test 2). These studies yielded inconsistent results. The present study examined the role of memory consolidation in accounting for the after-effect of DA during retrieval. Initial learning required a classification of visual stimuli, and hence involved incidental learning. Test 1 was administered 24 hours after initial learning, and therefore required retrieval of consolidated information. Test 2 was administered either immediately following Test 1 or after a 24-hour delay. Our results show that the effect of DA on Test 2 depended on this delay. DA during Test 1 did not affect performance on Test 2 when it was administered immediately, but improved performance when Test 2 was given 24-hours later. The results are consistent with other findings showing long-term benefits of retrieval difficulty. Implications for theories of reconsolidation in human episodic memory are discussed.

  15. Post-Training Reversible Disconnection of the Ventral Hippocampal-Basolateral Amygdaloid Circuits Impairs Consolidation of Inhibitory Avoidance Memory in Rats

    Science.gov (United States)

    Wang, Gong-Wu; Liu, Jian; Wang, Xiao-Qin

    2017-01-01

    The ventral hippocampus (VH) and the basolateral amygdala (BLA) are both crucial in inhibitory avoidance (IA) memory. However, the exact role of the VH-BLA circuit in IA memory consolidation is unclear. This study investigated the effect of post-training reversible disconnection of the VH-BLA circuit in IA memory consolidation. Male Wistar rats…

  16. Intranasal Cotinine Plus Krill Oil Facilitates Fear Extinction, Decreases Depressive-Like Behavior, and Increases Hippocampal Calcineurin A Levels in Mice.

    Science.gov (United States)

    Alvarez-Ricartes, Nathalie; Oliveros-Matus, Patricia; Mendoza, Cristhian; Perez-Urrutia, Nelson; Echeverria, Florencia; Iarkov, Alexandre; Barreto, George E; Echeverria, Valentina

    2018-02-27

    Failure in fear extinction is one of the more troublesome characteristics of posttraumatic stress disorder (PTSD). Cotinine facilitates fear memory extinction and reduces depressive-like behavior when administered 24 h after fear conditioning in mice. In this study, it was investigated the behavioral and molecular effects of cotinine, and other antidepressant preparations infused intranasally. Intranasal (IN) cotinine, IN krill oil, IN cotinine plus krill oil, and oral sertraline were evaluated on depressive-like behavior and fear retention and extinction after fear conditioning in C57BL/6 mice. Since calcineurin A has been involved in facilitating fear extinction in rodents, we also investigated changes of calcineurin in the hippocampus, a region key on contextual fear extinction. Short-term treatment with cotinine formulations was superior to krill oil and oral sertraline in reducing depressive-like behavior and fear consolidation and enhancing contextual fear memory extinction in mice. IN krill oil slowed the extinction of fear. IN cotinine preparations increased the levels of calcineurin A in the hippocampus of conditioned mice. In the light of the results, the future investigation of the use of IN cotinine preparations for the extinction of contextual fear memory and treatment of treatment-resistant depression (TRD) in PTSD is discussed.

  17. Extinction partially reverts structural changes associated with remote fear memory

    DEFF Research Database (Denmark)

    Vetere, Gisella; Restivo, Leonardo; Novembre, Giovanni

    2011-01-01

    Structural synaptic changes occur in medial prefrontal cortex circuits during remote memory formation. Whether extinction reverts or further reshapes these circuits is, however, unknown. Here we show that the number and the size of spines were enhanced in anterior cingulate (aCC) and infralimbic...... the remote memory network, suggesting that the preserved network properties might sustain reactivation of extinguished conditioned fear....

  18. Harnessing Reconsolidation to Weaken Fear and Appetitive Memories: A Meta-Analysis of Post-Retrieval Extinction Effects

    Science.gov (United States)

    Kredlow, M. Alexandra; Unger, Leslie D.; Otto, Michael W.

    2015-01-01

    A new understanding of the mechanisms of memory retrieval and reconsolidation holds the potential for improving exposure-based treatments. Basic research indicates that following fear extinction, safety and fear memories may compete, raising the possibility of return of fear. One possible solution is to modify original fear memories through reconsolidation interference, reducing the likelihood of return of fear. Post-retrieval extinction is a behavioral method of reconsolidation interference that has been explored in the context of conditioned fear and appetitive memory paradigms. This meta-analysis examines the magnitude of post-retrieval extinction effects and potential moderators of these effects. A PubMed and PsycINFO search was conducted through June 2014. Sixty-three comparisons examining post-retrieval extinction for preventing the return of fear or appetitive responses in animals or humans met inclusion criteria. Post-retrieval extinction demonstrated a significant, small-to-moderate effect (g = .40) for further reducing the return of fear in humans and a significant, large effect (g = 0.89) for preventing the return of appetitive responses in animals relative to standard extinction. For fear outcomes in animals, effects were small (g = 0.21) and non-significant, but moderated by the number of animals housed together and the duration of time between post-retrieval extinction/extinction and test. Across paradigms, these findings support the efficacy of this pre-clinical strategy for preventing the return of conditioned fear and appetitive responses. Overall, findings to date support the continued translation of post-retrieval extinction research to human and clinical applications, with particular application to the treatment of anxiety, traumatic stress, and substance use disorders. PMID:26689086

  19. Infralimbic dopamine D2 receptors mediate glucocorticoid-induced facilitation of auditory fear memory extinction in rats.

    Science.gov (United States)

    Dadkhah, Masoumeh; Abdullahi, Payman Raise; Rashidy-Pour, Ali; Sameni, Hamid Reza; Vafaei, Abbas Ali

    2018-03-01

    The infralimbic (IL) cortex of the medial prefrontal cortex plays an important role in the extinction of fear memory. Also, it has been showed that both brain glucocorticoid and dopamine receptors are involved in many processes such as fear extinction that drive learning and memory; however, the interaction of these receptors in the IL cortex remains unclear. We examined a putative interaction between the effects of glucocorticoid and dopamine receptors stimulation in the IL cortex on fear memory extinction in an auditory fear conditioning paradigm in male rats. Corticosterone (the endogenous glucocorticoid receptor ligand), or RU38486 (the synthetic glucocorticoid receptor antagonist) microinfusion into the IL cortex 10 min before test 1 attenuated auditory fear expression at tests 1-3, suggesting as an enhancement of fear extinction. The effect of corticosterone, but not RU38486 was counteracted by the dopamine D2 receptor antagonist sulpiride pre-treatment administered into the IL (at a dose that failed to alter freezing behavior on its own). In contrast, intra-IL infusion of the dopamine D1 receptor antagonist SCH23390 pre-treatment failed to alter freezing behavior. These findings provide evidence for the involvement of the IL cortex D2 receptors in CORT-induced facilitation of fear memory extinction. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Ensemble coding of context-dependent fear memory in the amygdala

    OpenAIRE

    Orsini, Caitlin A.; Yan, Chen; Maren, Stephen

    2013-01-01

    After fear conditioning, presenting the conditioned stimulus (CS) alone yields a context-specific extinction memory; fear is suppressed in the extinction context, but renews in any other context. The context-dependence of extinction is mediated by a brain circuit consisting of the hippocampus, prefrontal cortex and amygdala. In the present work, we sought to determine at what level of this circuit context-dependent representations of the CS emerge. To explore this question, we used cellula...

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

    Science.gov (United States)

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

    2014-01-01

    The noradrenergic activity in the basolateral amygdala (BLA) was reported to be involved in the regulation of object recognition memory. As the BLA expresses high density of receptors for Neuropeptide S (NPS), we investigated whether the BLA is involved in mediating NPS's effects on object recognition memory consolidation and whether such effects require noradrenergic activity. Intracerebroventricular infusion of NPS (1nmol) post training facilitated 24-h memory in a mouse novel object recognition task. The memory-enhancing effect of NPS could be blocked by the β-adrenoceptor antagonist propranolol. Furthermore, post-training intra-BLA infusions of NPS (0.5nmol/side) improved 24-h memory for objects, which was impaired by co-administration of propranolol (0.5μg/side). Taken together, these results indicate that NPS interacts with the BLA noradrenergic system in improving object recognition memory during consolidation. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Chau, Lily S; Galvez, Roberto

    2012-01-01

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

  3. Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation.

    Science.gov (United States)

    Hoffman, Ann N; Parga, Alejandro; Paode, Pooja R; Watterson, Lucas R; Nikulina, Ella M; Hammer, Ronald P; Conrad, Cheryl D

    2015-04-01

    The chronically stressed brain may present a vulnerability to develop maladaptive fear-related behaviors in response to a traumatic event. In rodents, chronic stress leads to amygdala hyperresponsivity and dendritic hypertrophy and produces a post traumatic stress disorder (PTSD)-like phenotype that includes exaggerated fear learning following Pavlovian fear conditioning and resistance to extinction. It is unknown whether chronic stress-induced enhanced fear memories are vulnerable to disruption via reconsolidation blockade, as a novel therapeutic approach for attenuating exaggerated fear memories. We used a chronic stress procedure in a rat model (wire mesh restraint for 6h/d/21d) to create a vulnerable brain that leads to a PTSD-like phenotype. We then examined freezing behavior during acquisition, reactivation and after post-reactivation rapamycin administration (i.p., 40mg/kg) in a Pavlovian fear conditioning paradigm to determine its effects on reconsolidation as well as the subsequent functional activation of limbic structures using zif268 mRNA. Chronic stress increased amygdala zif268 mRNA during fear memory retrieval at reactivation. Moreover, these enhanced fear memories were unaffected by post reactivation rapamycin to disrupt long-term fear memory. Also, post-reactivation long term memory processing was also associated with increased amygdala (LA and BA), and decreased hippocampal CA1 zif268 mRNA expression. These results suggest potential challenges for reconsolidation blockade as an effective approach in treating exaggerated fear memories, as in PTSD. Our findings also support chronic stress manipulations combined with fear conditioning as a useful preclinical approach to study a PTSD-like phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Histone Acetylation is Recruited in Consolidation as a Molecular Feature of Stronger Memories

    Science.gov (United States)

    Federman, Noel; Fustinana, Maria Sol; Romano, Arturo

    2009-01-01

    Gene expression is a key process for memory consolidation. Recently, the participation of epigenetic mechanisms like histone acetylation was evidenced in long-term memories. However, until now the training strength required and the persistence of the chromatin acetylation recruited are not well characterized. Here we studied whether histone…

  5. True or false? Memory is differentially affected by stress-induced cortisol elevations and sympathetic activity at consolidation and retrieval.

    Science.gov (United States)

    Smeets, Tom; Otgaar, Henry; Candel, Ingrid; Wolf, Oliver T

    2008-11-01

    Adrenal stress hormones released in response to acute stress may yield memory-enhancing effects when released post-learning and impairing effects at memory retrieval, especially for emotional memory material. However, so far these differential effects of stress hormones on the various memory phases for neutral and emotional memory material have not been demonstrated within one experiment. This study investigated whether, in line with their effects on true memory, stress and stress-induced adrenal stress hormones affect the encoding, consolidation, and retrieval of emotional and neutral false memories. Participants (N=90) were exposed to a stressor before encoding, during consolidation, before retrieval, or were not stressed and then were subjected to neutral and emotional versions of the Deese-Roediger-McDermott word list learning paradigm. Twenty-four hours later, recall of presented words (true recall) and non-presented critical lure words (false recall) was assessed. Results show that stress exposure resulted in superior true memory performance in the consolidation stress group and reduced true memory performance in the retrieval stress group compared to the other groups, predominantly for emotional words. These memory-enhancing and memory-impairing effects were strongly related to stress-induced cortisol and sympathetic activity measured via salivary alpha-amylase levels. Neutral and emotional false recall, on the other hand, was neither affected by stress exposure, nor related to cortisol and sympathetic activity following stress. These results demonstrate the importance of stress-induced hormone-related activity in enhancing memory consolidation and in impairing memory retrieval, in particular for emotional memory material.

  6. Post-training amphetamine administration enhances memory consolidation in appetitive Pavlovian conditioning: Implications for drug addiction.

    Science.gov (United States)

    Simon, Nicholas W; Setlow, Barry

    2006-11-01

    It has been suggested that some of the addictive potential of psychostimulant drugs of abuse such as amphetamine may result from their ability to enhance memory for drug-related experiences through actions on memory consolidation. This experiment examined whether amphetamine can specifically enhance consolidation of memory for a Pavlovian association between a neutral conditioned stimulus (CS-a light) and a rewarding unconditioned stimulus (US-food), as Pavlovian conditioning of this sort plays a major role in drug addiction. Male Long-Evans rats were given six training sessions consisting of 8 CS presentations followed by delivery of the food into a recessed food cup. After the 1st, 3rd, and 5th session, rats received subcutaneous injections of amphetamine (1.0 or 2.0 mg/kg) or saline vehicle immediately following training. Conditioned responding was assessed using the percentage of time rats spent in the food cup during the CS relative to a pre-CS baseline period. Both amphetamine-treated groups showed significantly more selective conditioned responding than saline controls. In a control experiment, there were no differences among groups given saline, 1.0 or 2.0 mg/kg amphetamine 2 h post-training, suggesting that immediate post-training amphetamine enhanced performance specifically through actions on memory consolidation rather than through non-mnemonic processes. This procedure modeled Pavlovian learning involved in drug addiction, in which the emotional valence of a drug reward is transferred to neutral drug-predictive stimuli such as drug paraphernalia. These data suggest that amphetamine may contribute to its addictive potential through actions specifically on memory consolidation.

  7. Optogenetic Activation of Presynaptic Inputs in Lateral Amygdala Forms Associative Fear Memory

    Science.gov (United States)

    Kwon, Jeong-Tae; Nakajima, Ryuichi; Hyung-Su, Kim; Jeong, Yire; Augustine, George J.; Han, Jin-Hee

    2014-01-01

    In Pavlovian fear conditioning, the lateral amygdala (LA) has been highlighted as a key brain site for association between sensory cues and aversive stimuli. However, learning-related changes are also found in upstream sensory regions such as thalamus and cortex. To isolate the essential neural circuit components for fear memory association, we…

  8. Distinctive Roles for Amygdalar CREB in Reconsolidation and Extinction of Fear Memory

    Science.gov (United States)

    Tronson, Natalie C.; Wiseman, Shari L.; Neve, Rachael L.; Nestler, Eric J.; Olausson, Peter; Taylor, Jane R.

    2012-01-01

    Cyclic AMP response element binding protein (CREB) plays a critical role in fear memory formation. Here we determined the role of CREB selectively within the amygdala in reconsolidation and extinction of auditory fear. Viral overexpression of the inducible cAMP early repressor (ICER) or the dominant-negative mCREB, specifically within the lateral…

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

    Directory of Open Access Journals (Sweden)

    Lily S Chau

    2012-10-01

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

  10. Divided attention improves delayed, but not immediate retrieval of a consolidated memory.

    Directory of Open Access Journals (Sweden)

    Yoav Kessler

    Full Text Available A well-documented dissociation between memory encoding and retrieval concerns the role of attention in the two processes. The typical finding is that divided attention (DA during encoding impairs future memory, but retrieval is relatively robust to attentional manipulations. However, memory research in the past 20 years had demonstrated that retrieval is a memory-changing process, in which the strength and availability of information are modified by various characteristics of the retrieval process. Based on this logic, several studies examined the effects of DA during retrieval (Test 1 on a future memory test (Test 2. These studies yielded inconsistent results. The present study examined the role of memory consolidation in accounting for the after-effect of DA during retrieval. Initial learning required a classification of visual stimuli, and hence involved incidental learning. Test 1 was administered 24 hours after initial learning, and therefore required retrieval of consolidated information. Test 2 was administered either immediately following Test 1 or after a 24-hour delay. Our results show that the effect of DA on Test 2 depended on this delay. DA during Test 1 did not affect performance on Test 2 when it was administered immediately, but improved performance when Test 2 was given 24-hours later. The results are consistent with other findings showing long-term benefits of retrieval difficulty. Implications for theories of reconsolidation in human episodic memory are discussed.

  11. Memory consolidation and expression of object recognition are susceptible to retroactive interference.

    Science.gov (United States)

    Villar, María Eugenia; Martinez, María Cecilia; Lopes da Cunha, Pamela; Ballarini, Fabricio; Viola, Haydee

    2017-02-01

    With the aim of analyzing if object recognition long-term memory (OR-LTM) formation is susceptible to retroactive interference (RI), we submitted rats to sequential sample sessions using the same arena but changing the identity of a pair of objects placed in it. Separate groups of animals were tested in the arena in order to evaluate the LTM for these objects. Our results suggest that OR-LTM formation was retroactively interfered within a critical time window by the exploration of a new, but not familiar, object. This RI acted on the consolidation of the object explored in the first sample session because its OR-STM measured 3h after training was not affected, whereas the OR-LTM measured at 24h was impaired. This sample session also impaired the expression of OR memory when it took place before the test. Moreover, local inactivation of the dorsal Hippocampus (Hp) or the medial Prefrontal Cortex (mPFC) previous to the exploration of the second pair of objects impaired their consolidation restoring the LTM for the objects explored in the first session. This data suggests that both brain regions are involved in the processing of OR-memory and also that if those regions are engaged in another process before finishing the first consolidation process its LTM will be impaired by RI. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Sleep promotes consolidation of emotional memory in healthy children but not in children with attention-deficit hyperactivity disorder.

    Directory of Open Access Journals (Sweden)

    Alexander Prehn-Kristensen

    Full Text Available Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline and delayed (target retrieval session. The emotional memory bias was baseline-corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake. We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.

  13. Sleep Promotes Consolidation of Emotional Memory in Healthy Children but Not in Children with Attention-Deficit Hyperactivity Disorder

    Science.gov (United States)

    Prehn-Kristensen, Alexander; Munz, Manuel; Molzow, Ina; Wilhelm, Ines; Wiesner, Christian D.; Baving, Lioba

    2013-01-01

    Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline–corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD. PMID:23734235

  14. Sleep promotes consolidation of emotional memory in healthy children but not in children with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Prehn-Kristensen, Alexander; Munz, Manuel; Molzow, Ina; Wilhelm, Ines; Wiesner, Christian D; Baving, Lioba

    2013-01-01

    Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline-corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.

  15. Long-term potentiation in the amygdala: a cellular mechanism of fear learning and memory.

    Science.gov (United States)

    Sigurdsson, Torfi; Doyère, Valérie; Cain, Christopher K; LeDoux, Joseph E

    2007-01-01

    Much of the research on long-term potentiation (LTP) is motivated by the question of whether changes in synaptic strength similar to LTP underlie learning and memory. Here we discuss findings from studies on fear conditioning, a form of associative learning whose neural circuitry is relatively well understood, that may be particularly suited for addressing this question. We first review the evidence suggesting that fear conditioning is mediated by changes in synaptic strength at sensory inputs to the lateral nucleus of the amygdala. We then discuss several outstanding questions that will be important for future research on the role of synaptic plasticity in fear learning. The results gained from these studies may shed light not only on fear conditioning, but may also help unravel more general cellular mechanisms of learning and memory.

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

    Science.gov (United States)

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

    2015-02-01

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

  17. Acute Exercise and Motor Memory Consolidation: The Role of Exercise Timing

    Directory of Open Access Journals (Sweden)

    Richard Thomas

    2016-01-01

    Full Text Available High intensity aerobic exercise amplifies offline gains in procedural memory acquired during motor practice. This effect seems to be evident when exercise is placed immediately after acquisition, during the first stages of memory consolidation, but the importance of temporal proximity of the exercise bout used to stimulate improvements in procedural memory is unknown. The effects of three different temporal placements of high intensity exercise were investigated following visuomotor skill acquisition on the retention of motor memory in 48 young (24.0 ± 2.5 yrs, healthy male subjects randomly assigned to one of four groups either performing a high intensity (90% Maximal Power Output exercise bout at 20 min (EX90, 1 h (EX90+1, 2 h (EX90+2 after acquisition or rested (CON. Retention tests were performed at 1 d (R1 and 7 d (R7. At R1 changes in performance scores after acquisition were greater for EX90 than CON (p<0.001 and EX90+2 (p=0.001. At R7 changes in performance scores for EX90, EX90+1, and EX90+2 were higher than CON (p<0.001, p=0.008, and p=0.008, resp.. Changes for EX90 at R7 were greater than EX90+2 (p=0.049. Exercise-induced improvements in procedural memory diminish as the temporal proximity of exercise from acquisition is increased. Timing of exercise following motor practice is important for motor memory consolidation.

  18. Anisomycin administered in the olfactory bulb and dorsal hippocampus impaired social recognition memory consolidation in different time-points.

    Science.gov (United States)

    Pena, R R; Pereira-Caixeta, A R; Moraes, M F D; Pereira, G S

    2014-10-01

    To identify an individual as familiar, rodents form a specific type of memory named social recognition memory. The olfactory bulb (OB) is an important structure for social recognition memory, while the hippocampus recruitment is still controversial. The present study was designed to elucidate the OB and the dorsal hippocampus contribution to the consolidation of social memory. For that purpose, we tested the effect of anisomycin (ANI), which one of the effects is the inhibition of protein synthesis, on the consolidation of social recognition memory. Swiss adult mice with cannulae implanted into the CA1 region of the dorsal hippocampus or into the OB were exposed to a juvenile during 5 min (training session; TR), and once again 1.5 h or 24 h later to test social short-term memory (S-STM) or social long-term memory (S-LTM), respectively. To study S-LTM consolidation, mice received intra-OB or intra-CA1 infusion of saline or ANI immediately, 3, 6 or 18 h after TR. ANI impaired S-LTM consolidation in the OB, when administered immediately or 6h after TR. In the dorsal hippocampus, ANI was amnesic only if administered 3 h after TR. Furthermore, the infusion of ANI in either OB or CA1, immediately after training, did not affect S-STM. Moreover, ANI administered into the OB did not alter the animal's performance in the buried food-finding task. Altogether, our results suggest the consolidation of S-LTM requires both OB and hippocampus participation, although in different time points. This study may help shedding light on the specific roles of the OB and dorsal hippocampus in social recognition memory. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Consolidation differentially modulates schema effects on memory for items and associations

    NARCIS (Netherlands)

    van Kesteren, Marlieke T R; Rijpkema, Mark; Ruiter, Dirk J; Fernández, Guillén

    2013-01-01

    Newly learned information that is congruent with a preexisting schema is often better remembered than information that is incongrSaveuent. This schema effect on memory has previously been associated to more efficient encoding and consolidation mechanisms. However, this effect is not always

  20. Consolidation differentially modulates schema effects on memory for items and associations

    NARCIS (Netherlands)

    Kesteren, M.T. van; Rijpkema, M.J.P.; Ruiter, D.J.; Fernandez, G.S.E.

    2013-01-01

    Newly learned information that is congruent with a preexisting schema is often better remembered than information that is incongruent. This schema effect on memory has previously been associated to more efficient encoding and consolidation mechanisms. However, this effect is not always consistently

  1. Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation

    OpenAIRE

    Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-01-01

    Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured s...

  2. Sleep and memory consolidation: motor performance and proactive interference effects in sequence learning.

    Science.gov (United States)

    Borragán, Guillermo; Urbain, Charline; Schmitz, Rémy; Mary, Alison; Peigneux, Philippe

    2015-04-01

    That post-training sleep supports the consolidation of sequential motor skills remains debated. Performance improvement and sensitivity to proactive interference are both putative measures of long-term memory consolidation. We tested sleep-dependent memory consolidation for visuo-motor sequence learning using a proactive interference paradigm. Thirty-three young adults were trained on sequence A on Day 1, then had Regular Sleep (RS) or were Sleep Deprived (SD) on the night after learning. After two recovery nights, they were tested on the same sequence A, then had to learn a novel, potentially competing sequence B. We hypothesized that proactive interference effects on sequence B due to the prior learning of sequence A would be higher in the RS condition, considering that proactive interference is an indirect marker of the robustness of sequence A, which should be better consolidated over post-training sleep. Results highlighted sleep-dependent improvement for sequence A, with faster RTs overnight for RS participants only. Moreover, the beneficial impact of sleep was specific to the consolidation of motor but not sequential skills. Proactive interference effects on learning a new material at Day 4 were similar between RS and SD participants. These results suggest that post-training sleep contributes to optimizing motor but not sequential components of performance in visuo-motor sequence learning. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Encoding of Discriminative Fear Memory by Input-Specific LTP in the Amygdala.

    Science.gov (United States)

    Kim, Woong Bin; Cho, Jun-Hyeong

    2017-08-30

    In auditory fear conditioning, experimental subjects learn to associate an auditory conditioned stimulus (CS) with an aversive unconditioned stimulus. With sufficient training, animals fear conditioned to an auditory CS show fear response to the CS, but not to irrelevant auditory stimuli. Although long-term potentiation (LTP) in the lateral amygdala (LA) plays an essential role in auditory fear conditioning, it is unknown whether LTP is induced selectively in the neural pathways conveying specific CS information to the LA in discriminative fear learning. Here, we show that postsynaptically expressed LTP is induced selectively in the CS-specific auditory pathways to the LA in a mouse model of auditory discriminative fear conditioning. Moreover, optogenetically induced depotentiation of the CS-specific auditory pathways to the LA suppressed conditioned fear responses to the CS. Our results suggest that input-specific LTP in the LA contributes to fear memory specificity, enabling adaptive fear responses only to the relevant sensory cue. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Boosting long-term memory via wakeful rest: intentional rehearsal is not necessary, consolidation is sufficient.

    Science.gov (United States)

    Dewar, Michaela; Alber, Jessica; Cowan, Nelson; Della Sala, Sergio

    2014-01-01

    People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as 'foreign names in a bridge club abroad' and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is not dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is sufficient for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.

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

    Directory of Open Access Journals (Sweden)

    Timothy J Jarome

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

  6. Reconsolidation or extinction: transcription factor switch in the determination of memory course after retrieval.

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    de la Fuente, Verónica; Freudenthal, Ramiro; Romano, Arturo

    2011-04-13

    In fear conditioning, aversive stimuli are readily associated with contextual features. A brief reexposure to the training context causes fear memory reconsolidation, whereas a prolonged reexposure induces memory extinction. The regulation of hippocampal gene expression plays a key role in contextual memory consolidation and reconsolidation. However, the mechanisms that determine whether memory will reconsolidate or extinguish are not known. Here, we demonstrate opposing roles for two evolutionarily related transcription factors in the mouse hippocampus. We found that nuclear factor-κB (NF-κB) is required for fear memory reconsolidation. Conversely, calcineurin phosphatase inhibited NF-κB and induced nuclear factor of activated T-cells (NFAT) nuclear translocation in the transition between reconsolidation and extinction. Accordingly, the hippocampal inhibition of both calcineurin and NFAT independently impaired memory extinction, whereas inhibition of NF-κB enhanced memory extinction. These findings represent the first insight into the molecular mechanisms that determine memory reprocessing after retrieval, supporting a transcriptional switch that directs memory toward reconsolidation or extinction. The precise molecular characterization of postretrieval processes has potential importance to the development of therapeutic strategies for fear memory disorders.

  7. Common influences of non-competitive NMDA receptor antagonists on the consolidation and reconsolidation of cocaine-cue memory.

    Science.gov (United States)

    Alaghband, Yasaman; Marshall, John F

    2013-04-01

    Environmental stimuli or contexts previously associated with rewarding drugs contribute importantly to relapse among addicts, and research has focused on neurobiological processes maintaining those memories. Much research shows contributions of cell surface receptors and intracellular signaling pathways in maintaining associations between rewarding drugs (e.g., cocaine) and concurrent cues/contexts; these memories can be degraded at the time of their retrieval through reconsolidation interference. Much less studied is the consolidation of drug-cue memories during their acquisition. The present experiments use the cocaine-conditioned place preference (CPP) paradigm in rats to directly compare, in a consistent setting, the effects of N-methyl-D-aspartate (NMDA) glutamate receptor antagonists MK-801 and memantine on the consolidation and reconsolidation of cocaine-cue memories. For the consolidation studies, animals were systemically administered MK-801 or memantine immediately following training sessions. To investigate the effects of these NMDA receptor antagonists on the retention of previously established cocaine-cue memories, animals were systemically administered MK-801 or memantine immediately after memory retrieval. Animals given either NMDA receptor antagonist immediately following training sessions did not establish a preference for the cocaine-paired compartment. Post-retrieval administration of either NMDA receptor antagonist attenuated the animals' preference for the cocaine-paired compartment. Furthermore, animals given NMDA receptor antagonists post-retrieval showed a blunted response to cocaine-primed reinstatement. Using two distinct NMDA receptor antagonists in a common setting, these findings demonstrate that NMDA receptor-dependent processes contribute both to the consolidation and reconsolidation of cocaine-cue memories, and they point to the potential utility of treatments that interfere with drug-cue memory reconsolidation.

  8. The role of β-arrestin-2 on Fear/anxious-related memory in a rat model of Post-traumatic stress disorder.

    Science.gov (United States)

    Ding, Jinlan; Han, Fang; Wen, Lili; Xiao, Bing; Shi, Yuxiu

    2017-04-15

    Post-traumatic stress disorder (PTSD) can be categorised as a disorder of dysregulated fear processing. In the formation and development of PTSD, whether fear/anxious-related memory is regulated by β-arrestin-2, and happened along the signal transduction pathways remains unknown. We used single prolonged stress (SPS) as the animal model of PTSD. Next, elevated plus maze tests (EPM) was performed to examine fear/anxious memory- related behaviors. Then, we detected β-arrestin-2, PDE-4, and signal transduction pathways with immunofluorescence, co-immunoprecipitation, immunohistochemistry, Elisa, western blot, RT-PCR, and real-time PCR. Our data indicated that SPS caused fear/anxious memory-related behaviors enhancement. The low expression of β-arrestin-2, PDE-4 and their complex on SPS 7d, and high expression of signal transduction pathways on SPS7d in basolateral amygdala (BLA). That indicating that β-arrestin-2 is critical for the formation of abnormal fear/anxious memory in PTSD; and fear/anxious memory occured through signal transduction pathways. Finally, these results suggest that β-arrestin-2, PDE-4 and signal transduction pathways may be by influencing the fear/anxious memory thereby involved in the formation and development of PTSD. Copyright © 2017. Published by Elsevier B.V.

  9. Acute Exercise Improves Motor Memory Consolidation in Preadolescent Children

    Directory of Open Access Journals (Sweden)

    Jesper Lundbye-Jensen

    2017-04-01

    Full Text Available Objective: The ability to acquire new motor skills is essential both during childhood and later in life. Recent studies have demonstrated that an acute bout of exercise can improve motor memory consolidation in adults. The objective of the present study was to investigate whether acute exercise protocols following motor skill practice in a school setting can also improve long-term retention of motor memory in preadolescent children.Methods: Seventy-seven pre-adolescent children (age 10.5 ± 0.75 (SD participated in the study. Prior to the main experiment age, BMI, fitness status and general physical activity level was assessed in all children and they were then randomly allocated to three groups. All children practiced a visuomotor tracking task followed by 20 min of rest (CON, high intensity intermittent floorball (FLB or running (RUN with comparable exercise intensity and duration for exercise groups. Delayed retention of motor memory was assessed 1 h, 24 h and 7 days after motor skill acquisition.Results: During skill acquisition, motor performance improved significantly to the immediate retention test with no differences between groups. One hour following skill acquisition, motor performance decreased significantly for RUN. Twenty-four hours following skill acquisition there was a tendency towards improved performance for FLB but no significant effects. Seven days after motor practice however, both FLB and RUN performed better when compared to their immediate retention test indicating significant offline gains. This effect was not observed for CON. In contrast, 7 days after motor practice, retention of motor memory was significantly better for FLB and RUN compared to CON. No differences were observed when comparing FLB and RUN.Conclusions: Acute intense intermittent exercise performed immediately after motor skill acquisition facilitates long-term motor memory in pre-adolescent children, presumably by promoting memory consolidation. The

  10. Two waves of proteasome-dependent protein degradation in the hippocampus are required for recognition memory consolidation.

    Science.gov (United States)

    Figueiredo, Luciana S; Dornelles, Arethuza S; Petry, Fernanda S; Falavigna, Lucio; Dargél, Vinicius A; Köbe, Luiza M; Aguzzoli, Cristiano; Roesler, Rafael; Schröder, Nadja

    2015-04-01

    Healthy neuronal function and synaptic modification require a concert of synthesis and degradation of proteins. Increasing evidence indicates that protein turnover mediated by proteasome activity is involved in long-term synaptic plasticity and memory. However, its role in different phases of memory remains debated, and previous studies have not examined the possible requirement of protein degradation in recognition memory. Here, we show that the proteasome inhibitor, lactacystin (LAC), infused into the CA1 area of the hippocampus at two specific time points during consolidation, impairs 24-retention of memory for object recognition in rats. Administration of LAC after retrieval did not affect retention. These findings provide the first evidence for a requirement of proteasome activity in recognition memory, indicate that protein degradation in the hippocampus is necessary during selective time windows of memory consolidation, and further our understanding of the role of protein turnover in memory formation. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Role of beta-adrenoceptors in memory consolidation: beta3-adrenoceptors act on glucose uptake and beta2-adrenoceptors on glycogenolysis.

    Science.gov (United States)

    Gibbs, Marie E; Hutchinson, Dana S; Summers, Roger J

    2008-09-01

    Noradrenaline, acting via beta(2)- and beta(3)-adrenoceptors (AR), enhances memory formation in single trial-discriminated avoidance learning in day-old chicks by mechanisms involving changes in metabolism of glucose and/or glycogen. Earlier studies of memory consolidation in chicks implicated beta(3)- rather than beta(2)-ARs in enhancement of memory consolidation by glucose, but did not elucidate whether stimulation of glucose uptake or of glycolysis was responsible. This study examines the role of glucose transport in memory formation using central injection of the nonselective facilitative glucose transporter (GLUT) inhibitor cytochalasin B, the endothelial/astrocytic GLUT-1 inhibitor phloretin and the Na(+)/energy-dependent endothelial glucose transporter (SGLT) inhibitor phlorizin. Cytochalasin B inhibited memory when injected into the mesopallium (avian cortex) either close to or between 25 and 45 min after training, whereas phloretin and phlorizin only inhibited memory at 30 min. This suggested that astrocytic/endothelial (GLUT-1) transport is critical at the time of consolidation, whereas a different transporter, probably the neuronal glucose transporter (GLUT-3), is important at the time of training. Inhibition of glucose transport by cytochalasin B, phloretin, or phlorizin also interfered with beta(3)-AR-mediated memory enhancement 20 min posttraining, whereas inhibition of glycogenolysis interfered with beta(2)-AR agonist enhancement of memory. We conclude that in astrocytes (1) activities of both GLUT-1 and SGLT are essential for memory consolidation 30 min posttraining; (2) neuronal GLUT-3 is essential at the time of training; and (3) beta(2)- and beta(3)-ARs consolidate memory by different mechanisms; beta(3)-ARs stimulate central glucose transport, whereas beta(2)-ARs stimulate central glycogenolysis.

  12. Evidence for parallel consolidation of motion direction and orientation into visual short-term memory.

    Science.gov (United States)

    Rideaux, Reuben; Apthorp, Deborah; Edwards, Mark

    2015-02-12

    Recent findings have indicated the capacity to consolidate multiple items into visual short-term memory in parallel varies as a function of the type of information. That is, while color can be consolidated in parallel, evidence suggests that orientation cannot. Here we investigated the capacity to consolidate multiple motion directions in parallel and reexamined this capacity using orientation. This was achieved by determining the shortest exposure duration necessary to consolidate a single item, then examining whether two items, presented simultaneously, could be consolidated in that time. The results show that parallel consolidation of direction and orientation information is possible, and that parallel consolidation of direction appears to be limited to two. Additionally, we demonstrate the importance of adequate separation between feature intervals used to define items when attempting to consolidate in parallel, suggesting that when multiple items are consolidated in parallel, as opposed to serially, the resolution of representations suffer. Finally, we used facilitation of spatial attention to show that the deterioration of item resolution occurs during parallel consolidation, as opposed to storage. © 2015 ARVO.

  13. Neuropharmacology of memory consolidation and reconsolidation: Insights on central cholinergic mechanisms.

    Science.gov (United States)

    Blake, M G; Krawczyk, M C; Baratti, C M; Boccia, M M

    2014-01-01

    Central cholinergic system is critically involved in all known memory processes. Endogenous acetylcholine release by cholinergic neurons is necessary for modulation of acquisition, encoding, consolidation, reconsolidation, extinction, retrieval and expression. Experiments from our laboratory are mainly focused on elucidating the mechanisms by which acetylcholine modulates memory processes. Blockade of hippocampal alpha-7-nicotinic receptors (α7-nAChRs) with the antagonist methyllycaconitine impairs memory reconsolidation. However, the administration of a α7-nAChR agonist (choline) produce a paradoxical modulation, causing memory enhancement in mice trained with a weak footshock, but memory impairment in animals trained with a strong footshock. All these effects are long-lasting, and depend on the age of the memory trace. This review summarizes and discusses some of our recent findings, particularly regarding the involvement of α7-nAChRs on memory reconsolidation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. EphrinA4 mimetic peptide targeted to EphA binding site impairs the formation of long-term fear memory in lateral amygdala.

    Science.gov (United States)

    Dines, M; Lamprecht, R

    2014-09-30

    Fear conditioning leads to long-term fear memory formation and is a model for studying fear-related psychopathologies conditions such as phobias and posttraumatic stress disorder. Long-term fear memory formation is believed to involve alterations of synaptic efficacy mediated by changes in synaptic transmission and morphology in lateral amygdala (LA). EphrinA4 and its cognate Eph receptors are intimately involved in regulating neuronal morphogenesis, synaptic transmission and plasticity. To assess possible roles of ephrinA4 in fear memory formation we designed and used a specific inhibitory ephrinA4 mimetic peptide (pep-ephrinA4) targeted to EphA binding site. We show that this peptide, composed of the ephrinA4 binding domain, interacts with EphA4 and inhibits ephrinA4-induced phosphorylation of EphA4. Microinjection of the pep-ephrinA4 into rat LA 30 min before training impaired long- but not short-term fear conditioning memory. Microinjection of a control peptide derived from a nonbinding E helix site of ephrinA4, that does not interact with EphA, had no effect on fear memory formation. Microinjection of pep-ephrinA4 into areas adjacent to the amygdala had no effect on fear memory. Acute systemic administration of pep-ephrinA4 1 h after training also impaired long-term fear conditioning memory formation. These results demonstrate that ephrinA4 binding sites in LA are essential for long-term fear memory formation. Moreover, our research shows that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear and anxiety disorders.

  15. Region-specific role of Rac in nucleus accumbens core and basolateral amygdala in consolidation and reconsolidation of cocaine-associated cue memory in rats.

    Science.gov (United States)

    Ding, Zeng-Bo; Wu, Ping; Luo, Yi-Xiao; Shi, Hai-Shui; Shen, Hao-Wei; Wang, Shen-Jun; Lu, Lin

    2013-08-01

    Drug reinforcement and the reinstatement of drug seeking are associated with the pathological processing of drug-associated cue memories that can be disrupted by manipulating memory consolidation and reconsolidation. Ras-related C3 botulinum toxin substrate (Rac) is involved in memory processing by regulating actin dynamics and neural structure plasticity. The nucleus accumbens (NAc) and amygdala have been implicated in the consolidation and reconsolidation of emotional memories. Therefore, we hypothesized that Rac in the NAc and amygdala plays a role in the consolidation and reconsolidation of cocaine-associated cue memory. Conditioned place preference (CPP) and microinjection of Rac inhibitor NSC23766 were used to determine the role of Rac in the NAc and amygdala in the consolidation and reconsolidation of cocaine-associated cue memory in rats. Microinjections of NSC23766 into the NAc core but not shell, basolateral (BLA), or central amygdala (CeA) after each cocaine-conditioning session inhibited the consolidation of cocaine-induced CPP. A microinjection of NSC23766 into the BLA but not CeA, NAc core, or NAc shell immediately after memory reactivation induced by exposure to a previously cocaine-paired context disrupted the reconsolidation of cocaine-induced CPP. The effect of memory disruption on cocaine reconsolidation was specific to reactivated memory, persisted at least 2 weeks, and was not reinstated by a cocaine-priming injection. Our findings indicate that Rac in the NAc core and BLA are required for the consolidation and reconsolidation of cocaine-associated cue memory, respectively.

  16. Higher-Order Sensory Cortex Drives Basolateral Amygdala Activity during the Recall of Remote, but Not Recently Learned Fearful Memories.

    Science.gov (United States)

    Cambiaghi, Marco; Grosso, Anna; Likhtik, Ekaterina; Mazziotti, Raffaele; Concina, Giulia; Renna, Annamaria; Sacco, Tiziana; Gordon, Joshua A; Sacchetti, Benedetto

    2016-02-03

    Negative experiences are quickly learned and long remembered. Key unresolved issues in the field of emotional memory include identifying the loci and dynamics of memory storage and retrieval. The present study examined neural activity in the higher-order auditory cortex Te2 and basolateral amygdala (BLA) and their crosstalk during the recall of recent and remote fear memories. To this end, we obtained local field potentials and multiunit activity recordings in Te2 and BLA of rats that underwent recall at 24 h and 30 d after the association of an acoustic conditioned (CS, tone) and an aversive unconditioned stimulus (US, electric shock). Here we show that, during the recall of remote auditory threat memories in rats, the activity of the Te2 and BLA is highly synchronized in the theta frequency range. This functional connectivity stems from memory consolidation processes because it is present during remote, but not recent, memory retrieval. Moreover, the observed increase in synchrony is cue and region specific. A preponderant Te2-to-BLA directionality characterizes this dialogue, and the percentage of time Te2 theta leads the BLA during remote memory recall correlates with a faster latency to freeze to the auditory conditioned stimulus. The blockade of this information transfer via Te2 inhibition with muscimol prevents any retrieval-evoked neuronal activity in the BLA and animals are unable to retrieve remote memories. We conclude that memories stored in higher-order sensory cortices drive BLA activity when distinguishing between learned threatening and neutral stimuli. How and where in the brain do we store the affective/motivational significance of sensory stimuli acquired through life experiences? Scientists have long investigated how "limbic" structures, such as the amygdala, process affective stimuli. Here we show that retrieval of well-established threat memories requires the functional interplay between higher-order components of the auditory cortex and the

  17. Cronobacter sakazakii infection alters serotonin transporter and improved fear memory retention in the rats

    Directory of Open Access Journals (Sweden)

    Bhagavathi Sundaram eSivamaruthi

    2015-09-01

    Full Text Available It is well established that Cronobacter sakazakii infection cause septicemia, necrotizingenterocolitis (NEC and meningitis. In the present study, we tested whether the C. sakazakii infection alter the learning and memory through serotonin transporter (SERT. To investigate the possible effect on SERT, on postnatal day (PND-15, wistar rat pups were administered with single dose of C. sakazakii culture (Infected group: IF; 107 CFU or 100μL of Luria-Bertani broth (LB; Medium Control: MC or without any treatment (Naïve control: NC. All the individuals were subjected to passive avoidance test on PND-30 to test their fear memory. We show that single dose of C. sakazakii infection improved fear memory retention. Subsequently, we show that C. sakazakii infection induced the activation of Toll-like receptor-3 (TLR-3 and heat-shock proteins-90 (Hsp-90. On the other hand, level of serotonin (5-HT and SERT protein was down-regulated. Furthermore, we show that C. sakazakii infection up-regulate microRNA (miR-16 expression. The observed results highlight that C. sakazakii infections was responsible for improved fear memory retention and may have reduced the level of SERT protein, which is possibly associated with the interaction of up-regulated Hsp-90 with SERT protein or miR-16 with SERT mRNA. Taken together, observed results suggest that C. sakazakkii infection alter the fear memory possibly through SERT. Hence, this model may be effective to test the C. sakazakii infection induced changes in synaptic plasticity through SERT and effect of other pharmacological agents against pathogen induced memory disorder.

  18. Sleep-related declarative memory consolidation and verbal replay during sleep talking in patients with REM sleep behavior disorder.

    Directory of Open Access Journals (Sweden)

    Ginevra Uguccioni

    Full Text Available OBJECTIVE: To determine if sleep talkers with REM sleep behavior disorder (RBD would utter during REM sleep sentences learned before sleep, and to evaluate their verbal memory consolidation during sleep. METHODS: Eighteen patients with RBD and 10 controls performed two verbal memory tasks (16 words from the Free and Cued Selective Reminding Test and a 220-263 word long modified Story Recall Test in the evening, followed by nocturnal video-polysomnography and morning recall (night-time consolidation. In 9 patients with RBD, daytime consolidation (morning learning/recall, evening recall was also evaluated with the modified Story Recall Test in a cross-over order. Two RBD patients with dementia were studied separately. Sleep talking was recorded using video-polysomnography, and the utterances were compared to the studied texts by two external judges. RESULTS: Sleep-related verbal memory consolidation was maintained in patients with RBD (+24±36% words as in controls (+9±18%, p=0.3. The two demented patients with RBD also exhibited excellent nighttime consolidation. The post-sleep performance was unrelated to the sleep measures (including continuity, stages, fragmentation and apnea-hypopnea index. Daytime consolidation (-9±19% was worse than night-time consolidation (+29±45%, p=0.03 in the subgroup of 9 patients with RBD. Eleven patients with RBD spoke during REM sleep and pronounced a median of 20 words, which represented 0.0003% of sleep with spoken language. A single patient uttered a sentence that was judged to be semantically (but not literally related to the text learned before sleep. CONCLUSION: Verbal declarative memory normally consolidates during sleep in patients with RBD. The incorporation of learned material within REM sleep-associated sleep talking in one patient (unbeknownst to himself at the semantic level suggests a replay at a highly cognitive creative level.

  19. A cortical–hippocampal–cortical loop of information processing during memory consolidation

    Science.gov (United States)

    Rothschild, Gideon; Eban, Elad; Frank, Loren M

    2018-01-01

    Hippocampal replay during sharp-wave ripple events (SWRs) is thought to drive memory consolidation in hippocampal and cortical circuits. Changes in neocortical activity can precede SWR events, but whether and how these changes influence the content of replay remains unknown. Here we show that during sleep there is a rapid cortical–hippocampal–cortical loop of information flow around the times of SWRs. We recorded neural activity in auditory cortex (AC) and hippocampus of rats as they learned a sound-guided task and during sleep. We found that patterned activation in AC precedes and predicts the subsequent content of hippocampal activity during SWRs, while hippocampal patterns during SWRs predict subsequent AC activity. Delivering sounds during sleep biased AC activity patterns, and sound-biased AC patterns predicted subsequent hippocampal activity. These findings suggest that activation of specific cortical representations during sleep influences the identity of the memories that are consolidated into long-term stores. PMID:27941790

  20. Boosting long-term memory via wakeful rest: intentional rehearsal is not necessary, consolidation is sufficient.

    Directory of Open Access Journals (Sweden)

    Michaela Dewar

    Full Text Available People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as 'foreign names in a bridge club abroad' and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is not dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is sufficient for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.

  1. Pattern Analyses Reveal Separate Experience-Based Fear Memories in the Human Right Amygdala.

    Science.gov (United States)

    Braem, Senne; De Houwer, Jan; Demanet, Jelle; Yuen, Kenneth S L; Kalisch, Raffael; Brass, Marcel

    2017-08-23

    Learning fear via the experience of contingencies between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US) is often assumed to be fundamentally different from learning fear via instructions. An open question is whether fear-related brain areas respond differently to experienced CS-US contingencies than to merely instructed CS-US contingencies. Here, we contrasted two experimental conditions where subjects were instructed to expect the same CS-US contingencies while only one condition was characterized by prior experience with the CS-US contingency. Using multivoxel pattern analysis of fMRI data, we found CS-related neural activation patterns in the right amygdala (but not in other fear-related regions) that dissociated between whether a CS-US contingency had been instructed and experienced versus merely instructed. A second experiment further corroborated this finding by showing a category-independent neural response to instructed and experienced, but not merely instructed, CS presentations in the human right amygdala. Together, these findings are in line with previous studies showing that verbal fear instructions have a strong impact on both brain and behavior. However, even in the face of fear instructions, the human right amygdala still shows a separable neural pattern response to experience-based fear contingencies. SIGNIFICANCE STATEMENT In our study, we addressed a fundamental problem of the science of human fear learning and memory, namely whether fear learning via experience in humans relies on a neural pathway that can be separated from fear learning via verbal information. Using two new procedures and recent advances in the analysis of brain imaging data, we localized purely experience-based fear processing and memory in the right amygdala, thereby making a direct link between human and animal research. Copyright © 2017 the authors 0270-6474/17/378116-15$15.00/0.

  2. The cortical structure of consolidated memory: a hypothesis on the role of the cingulate-entorhinal cortical connection.

    Science.gov (United States)

    Insel, Nathan; Takehara-Nishiuchi, Kaori

    2013-11-01

    Daily experiences are represented by networks of neurons distributed across the neocortex, bound together for rapid storage and later retrieval by the hippocampus. While the hippocampus is necessary for retrieving recent episode-based memory associations, over time, consolidation processes take place that enable many of these associations to be expressed independent of the hippocampus. It is generally thought that mechanisms of consolidation involve synaptic weight changes between cortical regions; or, in other words, the formation of "horizontal" cortico-cortical connections. Here, we review anatomical, behavioral, and physiological data which suggest that the connections in and between the entorhinal and cingulate cortices may be uniquely important for the long-term storage of memories that initially depend on the hippocampus. We propose that current theories of consolidation that divide memory into dual systems of hippocampus and neocortex might be improved by introducing a third, middle layer of entorhinal and cingulate allocortex, the synaptic weights within which are necessary and potentially sufficient for maintaining initially hippocampus-dependent associations over long time periods. This hypothesis makes a number of still untested predictions, and future experiments designed to address these will help to fill gaps in the current understanding of the cortical structure of consolidated memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. The consolidation of implicit sequence memory in obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Eszter Csabi

    Full Text Available Obstructive Sleep Apnea (OSA Syndrome is a relatively frequent sleep disorder characterized by disrupted sleep patterns. It is a well-established fact that sleep has beneficial effect on memory consolidation by enhancing neural plasticity. Implicit sequence learning is a prominent component of skill learning. However, the formation and consolidation of this fundamental learning mechanism remains poorly understood in OSA. In the present study we examined the consolidation of different aspects of implicit sequence learning in patients with OSA. We used the Alternating Serial Reaction Time task to measure general skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 10-hour offline period with sleep. Our data showed differences in offline changes of general skill learning between the OSA and control group. The control group demonstrated offline improvement from evening to morning, while the OSA group did not. In contrast, we did not observe differences between the groups in offline changes in sequence-specific learning. Our findings suggest that disrupted sleep in OSA differently affects neural circuits involved in the consolidation of sequence learning.

  4. Selective inhibition of miR-92 in hippocampal neurons alters contextual fear memory.

    Science.gov (United States)

    Vetere, Gisella; Barbato, Christian; Pezzola, Silvia; Frisone, Paola; Aceti, Massimiliano; Ciotti, MariaTeresa; Cogoni, Carlo; Ammassari-Teule, Martine; Ruberti, Francesca

    2014-12-01

    Post-transcriptional gene regulation mediated by microRNAs (miRNAs) is implicated in memory formation; however, the function of miR-92 in this regulation is uncharacterized. The present study shows that training mice in contextual fear conditioning produces a transient increase in miR-92 levels in the hippocampus and decreases several miR-92 gene targets, including: (i) the neuronal Cl(-) extruding K(+) Cl(-) co-transporter 2 (KCC2) protein; (ii) the cytoplasmic polyadenylation protein (CPEB3), an RNA-binding protein regulator of protein synthesis in neurons; and (iii) the transcription factor myocyte enhancer factor 2D (MEF2D), one of the MEF2 genes which negatively regulates memory-induced structural plasticity. Selective inhibition of endogenous miR-92 in CA1 hippocampal neurons, by a sponge lentiviral vector expressing multiple sequences imperfectly complementary to mature miR-92 under the control of the neuronal specific synapsin promoter, leads to up-regulation of KCC2, CPEB3 and MEF2D, impairs contextual fear conditioning, and prevents a memory-induced increase in the spine density. Taken together, the results indicate that neuronal-expressed miR-92 is an endogenous fine regulator of contextual fear memory in mice. © 2014 Wiley Periodicals, Inc.

  5. MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms?

    Science.gov (United States)

    Feduccia, Allison A; Mithoefer, Michael C

    2018-06-08

    MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase 3 clinical trials and received Breakthrough Therapy designation by the FDA. MDMA used as an adjunct during psychotherapy sessions has demonstrated effectiveness and acceptable safety in reducing PTSD symptoms in Phase 2 trials, with durable remission of PTSD diagnosis in 68% of participants. The underlying psychological and neurological mechanisms for the robust effects in mitigating PTSD are being investigated in animal models and in studies of healthy volunteers. This review explores the potential role of memory reconsolidation and fear extinction during MDMA-assisted psychotherapy. MDMA enhances release of monoamines (serotonin, norepinephrine, dopamine), hormones (oxytocin, cortisol), and other downstream signaling molecules (BDNF) to dynamically modulate emotional memory circuits. By reducing activation in brain regions implicated in the expression of fear- and anxiety-related behaviors, namely the amygdala and insula, and increasing connectivity between the amygdala and hippocampus, MDMA may allow for reprocessing of traumatic memories and emotional engagement with therapeutic processes. Based on the pharmacology of MDMA and the available translational literature of memory reconsolidation, fear learning, and PTSD, this review suggests a neurobiological rationale to explain, at least in part, the large effect sizes demonstrated for MDMA in treating PTSD. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Effects of stress related acute exercise on consolidation of implicit motor memory

    Directory of Open Access Journals (Sweden)

    Farhad Ghadiri

    2012-12-01

    Full Text Available Introduction: Extensive evidence documents arousal modulation of declarative memory in humans. However, little is known about the arousal modulation of implicit motor memory. The purpose of this study was to examine the effects of a post-acquisition acute exercise stress on implicit motor memory consolidation.Materials and Methods: Forty healthy subjects were randomly divided into stress (10 men and 10 woman and non- stress (10 men and 10 woman groups. Experiment consisted of two phases of acquisition and retention. Serial Color matching (SCM task was used for this study. In acquisition period, all groups practiced the task for six blocks of 150 trials. Following, the stress group performed exercise on a treadmill until the moment of exhaustion while the non stress group did rest. In retention, all groups practiced the SCM task in one block. During the experiment the trends of saliva cortisol changes were measured.Results: Acute exercise stress leads to a significant increase in salivary cortisol level. While the non-stress group did not show enhancement of SCRT learning across the 24 hours delay interval, the stress group showed substantial enhancement across the same time (P<0.05.Conclusion: Our findings indicate that acute stress after acquisition can facilitate the implicit motor memory consolidation.

  7. Transcranial electrical currents to probe EEG brain rhythms and memory consolidation during sleep in humans.

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    Lisa Marshall

    Full Text Available Previously the application of a weak electric anodal current oscillating with a frequency of the sleep slow oscillation (∼0.75 Hz during non-rapid eye movement sleep (NonREM sleep boosted endogenous slow oscillation activity and enhanced sleep-associated memory consolidation. The slow oscillations occurring during NonREM sleep and theta oscillations present during REM sleep have been considered of critical relevance for memory formation. Here transcranial direct current stimulation (tDCS oscillating at 5 Hz, i.e., within the theta frequency range (theta-tDCS is applied during NonREM and REM sleep. Theta-tDCS during NonREM sleep produced a global decrease in slow oscillatory activity conjoint with a local reduction of frontal slow EEG spindle power (8-12 Hz and a decrement in consolidation of declarative memory, underlining the relevance of these cortical oscillations for sleep-dependent memory consolidation. In contrast, during REM sleep theta-tDCS appears to increase global gamma (25-45 Hz activity, indicating a clear brain state-dependency of theta-tDCS. More generally, results demonstrate the suitability of oscillating-tDCS as a tool to analyze functions of endogenous EEG rhythms and underlying endogenous electric fields as well as the interactions between EEG rhythms of different frequencies.

  8. Beyond a Mask and Against the Bottleneck: Retroactive Dual-Task Interference During Working Memory Consolidation of a Masked Visual Target

    NARCIS (Netherlands)

    Nieuwenstein, Mark; Wyble, Brad

    While studies on visual memory commonly assume that the consolidation of a visual stimulus into working memory is interrupted by a trailing mask, studies on dual-task interference suggest that the consolidation of a stimulus can continue for several hundred milliseconds after a mask. As a result,

  9. Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA).

    Science.gov (United States)

    Young, Matthew B; Norrholm, Seth D; Khoury, Lara M; Jovanovic, Tanja; Rauch, Sheila A M; Reiff, Collin M; Dunlop, Boadie W; Rothbaum, Barbara O; Howell, Leonard L

    2017-10-01

    3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA's broad pharmacological profile, further investigation is warranted before moving to a complex clinical population. We aimed to inform clinical research by providing a translational model of MDMA's effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction. We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training. MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA's effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA's effect by 5-HTT inhibition also downregulated 5-HT 2A -mediated behavior, and 5-HT 2A antagonism disrupted MDMA's effect on extinction. We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT 2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.

  10. Remembering the object you fear: brain potentials during recognition of spiders in spider-fearful individuals.

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    Michalowski, Jaroslaw M; Weymar, Mathias; Hamm, Alfons O

    2014-01-01

    In the present study we investigated long-term memory for unpleasant, neutral and spider pictures in 15 spider-fearful and 15 non-fearful control individuals using behavioral and electrophysiological measures. During the initial (incidental) encoding, pictures were passively viewed in three separate blocks and were subsequently rated for valence and arousal. A recognition memory task was performed one week later in which old and new unpleasant, neutral and spider pictures were presented. Replicating previous results, we found enhanced memory performance and higher confidence ratings for unpleasant when compared to neutral materials in both animal fearful individuals and controls. When compared to controls high animal fearful individuals also showed a tendency towards better memory accuracy and significantly higher confidence during recognition of spider pictures, suggesting that memory of objects prompting specific fear is also facilitated in fearful individuals. In line, spider-fearful but not control participants responded with larger ERP positivity for correctly recognized old when compared to correctly rejected new spider pictures, thus showing the same effects in the neural signature of emotional memory for feared objects that were already discovered for other emotional materials. The increased fear memory for phobic materials observed in the present study in spider-fearful individuals might result in an enhanced fear response and reinforce negative beliefs aggravating anxiety symptomatology and hindering recovery.

  11. Noradrenergic activation of the basolateral amygdala modulates the consolidation of object-in-context recognition memory

    Directory of Open Access Journals (Sweden)

    Areg eBarsegyan

    2014-05-01

    Full Text Available Noradrenergic activation of the basolateral complex of the amygdala (BLA is well known to enhance the consolidation of long-term memory of highly emotionally arousing training experiences. The present study investigated whether such noradrenergic activation of the BLA also influences the consolidation of object-in-context recognition memory, a low-arousing training task assessing episodic-like memory. Male Sprague–Dawley rats were exposed to two identical objects in one context for either 3 or 10 min, immediately followed by exposure to two other identical objects in a distinctly different context. Immediately after the training they received bilateral intra-BLA infusions of norepinephrine (0.3, 1.0 or 3.0 μg or the β-adrenoceptor antagonist propranolol (0.1, 0.3 or 1.0 μg. On the 24-h retention test, rats were placed back into one of the training contexts with one copy of each of the two training objects. Thus, although both objects were familiar, one of the objects had not previously been encountered in this particular test context. Hence, if the animal generated a long-term memory for the association between an object and its context, it would spend significantly more time exploring the object that was not previously experienced in this context. Saline-infused control rats exhibited poor 24-h retention when given 3 min of training and good retention when given 10 min of training. Norepinephrine administered after 3 min of object-in-context training induced a dose-dependent memory enhancement, whereas propranolol administered after 10 min of training produced memory impairment. These findings provide evidence that posttraining noradrenergic activation of the BLA also enhances the consolidation of memory of object-in-context recognition training, enabling accuracy of episodic-like memories.

  12. Interaction between episodic and semantic memory networks in the acquisition and consolidation of novel spoken words

    NARCIS (Netherlands)

    Takashima, A.; Bakker, I.; Hell, J.G. van; Janzen, G.; McQueen, J.M.

    2017-01-01

    When a novel word is learned, its memory representation is thought to undergo a process of consolidation and integration. In this study, we tested whether the neural representations of novel words change as a function of consolidation by observing brain activation patterns just after learning and

  13. Deep brain stimulation, histone deacetylase inhibitors and glutamatergic drugs rescue resistance to fear extinction in a genetic mouse model

    Science.gov (United States)

    Whittle, Nigel; Schmuckermair, Claudia; Gunduz Cinar, Ozge; Hauschild, Markus; Ferraguti, Francesco; Holmes, Andrew; Singewald, Nicolas

    2013-01-01

    Anxiety disorders are characterized by persistent, excessive fear. Therapeutic interventions that reverse deficits in fear extinction represent a tractable approach to treating these disorders. We previously reported that 129S1/SvImJ (S1) mice show no extinction learning following normal fear conditioning. We now demonstrate that weak fear conditioning does permit fear reduction during massed extinction training in S1 mice, but reveals specific deficiency in extinction memory consolidation/retrieval. Rescue of this impaired extinction consolidation/retrieval was achieved with d-cycloserine (N-methly-d-aspartate partial agonist) or MS-275 (histone deacetylase (HDAC) inhibitor), applied after extinction training. We next examined the ability of different drugs and non-pharmacological manipulations to rescue the extreme fear extinction deficit in S1 following normal fear conditioning with the ultimate aim to produce low fear levels in extinction retrieval tests. Results showed that deep brain stimulation (DBS) by applying high frequency stimulation to the nucleus accumbens (ventral striatum) during extinction training, indeed significantly reduced fear during extinction retrieval compared to sham stimulation controls. Rescue of both impaired extinction acquisition and deficient extinction consolidation/retrieval was achieved with prior extinction training administration of valproic acid (a GABAergic enhancer and HDAC inhibitor) or AMN082 [metabotropic glutamate receptor 7 (mGlu7) agonist], while MS-275 or PEPA (AMPA receptor potentiator) failed to affect extinction acquisition in S1 mice. Collectively, these data identify potential beneficial effects of DBS and various drug treatments, including those with HDAC inhibiting or mGlu7 agonism properties, as adjuncts to overcome treatment resistance in exposure-based therapies. This article is part of a Special Issue entitled ‘Cognitive Enhancers’. PMID:22722028

  14. Topographic contribution of early visual cortex to short-term memory consolidation: a transcranial magnetic stimulation study.

    Science.gov (United States)

    van de Ven, Vincent; Jacobs, Christianne; Sack, Alexander T

    2012-01-04

    The neural correlates for retention of visual information in visual short-term memory are considered separate from those of sensory encoding. However, recent findings suggest that sensory areas may play a role also in short-term memory. We investigated the functional relevance, spatial specificity, and temporal characteristics of human early visual cortex in the consolidation of capacity-limited topographic visual memory using transcranial magnetic stimulation (TMS). Topographically specific TMS pulses were delivered over lateralized occipital cortex at 100, 200, or 400 ms into the retention phase of a modified change detection task with low or high memory loads. For the high but not the low memory load, we found decreased memory performance for memory trials in the visual field contralateral, but not ipsilateral to the side of TMS, when pulses were delivered at 200 ms into the retention interval. A behavioral version of the TMS experiment, in which a distractor stimulus (memory mask) replaced the TMS pulses, further corroborated these findings. Our findings suggest that retinotopic visual cortex contributes to the short-term consolidation of topographic visual memory during early stages of the retention of visual information. Further, TMS-induced interference decreased the strength (amplitude) of the memory representation, which most strongly affected the high memory load trials.

  15. Effects of Postnatal Serotonin Agonism on Fear Response and Memory

    Science.gov (United States)

    The neurotransmitter serotonin (5-HT) also acts as a neurogenic compound in the developing brain. Early administration of a 5-HT agonist could alter the development of the serotonergic circuitry, altering behaviors mediated by 5-HT signaling, such as memory, fear and aggression. White leghorn chicks...

  16. Ensemble coding of context-dependent fear memory in the amygdala.

    Science.gov (United States)

    Orsini, Caitlin A; Yan, Chen; Maren, Stephen

    2013-01-01

    After fear conditioning, presenting the conditioned stimulus (CS) alone yields a context-specific extinction memory; fear is suppressed in the extinction context, but renews in any other context. The context-dependence of extinction is mediated by a brain circuit consisting of the hippocampus, prefrontal cortex (PFC) and amygdala. In the present work, we sought to determine at what level of this circuit context-dependent representations of the CS emerge. To explore this question, we used cellular compartment analysis of temporal activity by fluorescent in situ hybridization (catFISH). This method exploits the intracellular expression profile of the immediate early gene (IEG), Arc, to visualize neuronal activation patterns to two different behavioral experiences. Rats were fear conditioned in one context and extinguished in another; 24 h later, they were sequentially exposed to the CS in the extinction context and another context. Control rats were also tested in each context, but were never extinguished. We assessed Arc mRNA expression within the basal amygdala (BA), lateral amygdala (LA), ventral hippocampus (VH), prelimbic cortex (PL) and infralimbic cortex (IL). We observed that the sequential retention tests induced context-dependent patterns of Arc expression in the BA, LA, and IL of extinguished rats; this was not observed in non-extinguished controls. In general, non-extinguished animals had proportionately greater numbers of non-selective (double-labeled) neurons than extinguished animals. Collectively, these findings suggest that extinction learning results in pattern separation, particularly within the BA, in which unique neuronal ensembles represent fear memories after extinction.

  17. Ensemble coding of context-dependent fear memory in the amygdala

    Directory of Open Access Journals (Sweden)

    Caitlin A Orsini

    2013-12-01

    Full Text Available After fear conditioning, presenting the conditioned stimulus (CS alone yields a context-specific extinction memory; fear is suppressed in the extinction context, but renews in any other context. The context-dependence of extinction is mediated by a brain circuit consisting of the hippocampus, prefrontal cortex and amygdala. In the present work, we sought to determine at what level of this circuit context-dependent representations of the CS emerge. To explore this question, we used cellular compartment analysis of temporal activity by fluorescent in situ hybridization (catFISH. This method exploits the intracellular expression profile of the immediate early gene, Arc, to visualize neuronal activation patterns to two different behavioral experiences. Rats were fear conditioned in one context and extinguished in another; twenty-four hours later, they were sequentially exposed to the CS in the extinction context and another context. Control rats were also tested in each context, but were never extinguished. We assessed Arc mRNA expression within the basal amygdala (BA, lateral amygdala (LA, ventral hippocampus (VH, prelimbic cortex (PL and infralimbic cortex (IL. We observed that the sequential retention tests induced context-dependent patterns of Arc expression in the BA, LA, and IL of extinguished rats; this was not observed in non-extinguished controls. In general, non-extinguished animals had proportionately greater numbers of non-selective (double-labeled neurons than extinguished animals. Collectively, these findings suggest that extinction learning results in pattern separation, particularly within the BA, in which unique neuronal ensembles represent fear memories after extinction.

  18. Enhancing memory performance after organic brain disease relies on retrieval processes rather than encoding or consolidation

    NARCIS (Netherlands)

    Hildebrandt, H.; Gehrmann, A.; Mödden, C.; Eling, P.A.T.M.

    2011-01-01

    Neuropsychological rehabilitation of memory performance is still a controversial topic, and rehabilitation studies have not analyzed to which stage of memory processing (encoding, consolidation, or retrieval) enhancement may be attributed. We first examined the efficacy of a computer training

  19. ONTOLOGIES REPRESENTATION AND MANAGEMENT, AS A SEMANTIC TOOL FOR ORGANIZATIONAL MEMORY CONSOLIDATION

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    Mangiuc Dragos Marian

    2009-05-01

    Full Text Available The present paper is a component of an exploratory research project focused on discovering new ways to build, organize and consolidate organizational memory for an economic entity by means of the new a€śSemantic Weba€ť technologies and also encloses some

  20. Impaired fear memory specificity associated with deficient endocannabinoid-dependent long-term plasticity.

    Science.gov (United States)

    Lovelace, Jonathan W; Vieira, Philip A; Corches, Alex; Mackie, Ken; Korzus, Edward

    2014-06-01

    In addition to its central role in learning and memory, N-methyl D-aspartate receptor (NMDAR)-dependent signaling regulates central glutamatergic synapse maturation and has been implicated in schizophrenia. We have transiently induced NMDAR hypofunction in infant mice during postnatal days 7-11, followed by testing fear memory specificity and presynaptic plasticity in the prefrontal cortex (PFC) in adult mice. We show that transient NMDAR hypofunction during early brain development, coinciding with the maturation of cortical plasticity results in a loss of an endocannabinoid (eCB)-mediated form of long-term depression (eCB-LTD) at adult central glutamatergic synapses, while another form of presynaptic long-term depression mediated by the metabotropic glutamate receptor 2/3 (mGluR2/3-LTD) remains intact. Mice with this selective impairment of presynaptic plasticity also showed deficits in fear memory specificity. The observed deficit in cortical presynaptic plasticity may represent a neural maladaptation contributing to network instability and abnormal cognitive functioning.

  1. Biased interpretation and memory in children with varying levels of spider fear.

    Science.gov (United States)

    Klein, Anke M; Titulaer, Geraldine; Simons, Carlijn; Allart, Esther; de Gier, Erwin; Bögels, Susan M; Becker, Eni S; Rinck, Mike

    2014-01-01

    This study investigated multiple cognitive biases in children simultaneously, to investigate whether spider-fearful children display an interpretation bias, a recall bias, and source monitoring errors, and whether these biases are specific for spider-related materials. Furthermore, the independent ability of these biases to predict spider fear was investigated. A total of 121 children filled out the Spider Anxiety and Disgust Screening for Children (SADS-C), and they performed an interpretation task, a memory task, and a Behavioural Assessment Test (BAT). As expected, a specific interpretation bias was found: Spider-fearful children showed more negative interpretations of ambiguous spider-related scenarios, but not of other scenarios. We also found specific source monitoring errors: Spider-fearful children made more fear-related source monitoring errors for the spider-related scenarios, but not for the other scenarios. Only limited support was found for a recall bias. Finally, interpretation bias, recall bias, and source monitoring errors predicted unique variance components of spider fear.

  2. An unconditioned stimulus retrieval extinction procedure to prevent the return of fear memory.

    Science.gov (United States)

    Liu, Jianfeng; Zhao, Liyan; Xue, Yanxue; Shi, Jie; Suo, Lin; Luo, Yixiao; Chai, Baisheng; Yang, Chang; Fang, Qin; Zhang, Yan; Bao, Yanping; Pickens, Charles L; Lu, Lin

    2014-12-01

    Conditioned fear memories can be updated by extinction during reconsolidation, and this effect is specific to the reactivated conditioned stimulus (CS). However, a traumatic event can be associated with several cues, and each cue can potentially trigger recollection of the event. We introduced a technique to target all diverse cues associated with an aversive event that causes fear. In human experiments, 161 subjects underwent modified fear conditioning, in which they were exposed to an unconditioned stimulus (US) or unreinforced CS to reactivate the memory and then underwent extinction, spontaneous recovery, and reinstatement. In animal experiments, 343 rats underwent contextual fear conditioning under a similar protocol as that used in the human experiments. We also explored the molecular alterations after US reactivation in rats. Presentation of a lower intensity US before extinction disrupted the associations between the different CS and reactivated US in both humans and rats. This effect persisted for at least 6 months in humans and was selective to the reactivated US. This procedure was also effective for remote memories in both humans and rats. Compared with the CS, the US induced stronger endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid glutamate receptors 1 and 2 and stronger activation of protein kinase A, p70S6 kinase, and cyclic adenosine monophosphate response element binding protein in the dorsal hippocampus in rats. These findings demonstrate that a modified US retrieval extinction strategy may have a potential impact on therapeutic approaches to prevent the return of fear. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Memantine facilitates memory consolidation and reconsolidation in the day-old chick.

    Science.gov (United States)

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

    2012-05-01

    Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist that has been approved for the treatment of the cognitive deficits noted in Alzheimer's disease. While there is a body of research that supports memantine's facilitative action upon memory compromise, this series of studies aimed to investigate the effects of this drug in healthy animals with intact memory functioning. A 0.1 mM dose of memantine injected immediately after a weakly aversive training event (i.e. 20% v/v methyl anthranilate) was found to enhance passive avoidance learning for this event in day-old chicks up to 24 h following training. The same dose of memantine was also observed to enhance memory for the training event when it was administered in conjunction with a reminder trial. These results suggest that memantine is capable of facilitating both memory consolidation as well as memory reconsolidation. It was concluded that memantine's mechanism may involve the short-term or intermediate memory phases of the Gibbs and Ng model of memory, and that the current findings represent enhancement of intact memory, rather than amelioration of memory compromise. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  4. Noradrenergic action in prefrontal cortex in the late stage of memory consolidation

    NARCIS (Netherlands)

    Tronel, Sophie; Feenstra, Matthijs G. P.; Sara, Susan J.

    2004-01-01

    These experiments investigated the role of the noradrenergic system in the late stage of memory consolidation and in particular its action at beta receptors in the prelimbic region (PL) of the prefrontal cortex in the hours after training. Rats were trained in a rapidly acquired, appetitively

  5. An overview of the neuro-cognitive processes involved in the encoding, consolidation, and retrieval of true and false memories.

    Science.gov (United States)

    Straube, Benjamin

    2012-07-24

    Perception and memory are imperfect reconstructions of reality. These reconstructions are prone to be influenced by several factors, which may result in false memories. A false memory is the recollection of an event, or details of an episode, that did not actually occur. Memory formation comprises at least three different sub-processes: encoding, consolidation and the retrieval of the learned material. All of these sub-processes are vulnerable for specific errors and consequently may result in false memories. Whereas, processes like imagery, self-referential encoding or spreading activation can lead to the formation of false memories at encoding, semantic generalization during sleep and updating processes due to misleading post event information, in particular, are relevant at the consolidation stage. Finally at the retrieval stage, monitoring processes, which are assumed to be essential to reject false memories, are of specific importance. Different neuro-cognitive processes have been linked to the formation of true and false memories. Most consistently the medial temporal lobe and the medial and lateral prefrontal cortex have been reported with regard to the formation of true and false memories. Despite the fact that all phases entailing memory formation, consolidation of stored information and retrieval processes, are relevant for the forming of false memories, most studies focused on either memory encoding or retrieval. Thus, future studies should try to integrate data from all phases to give a more comprehensive view on systematic memory distortions. An initial outline is developed within this review to connect the different memory stages and research strategies.

  6. An overview of the neuro-cognitive processes involved in the encoding, consolidation, and retrieval of true and false memories

    Science.gov (United States)

    2012-01-01

    Perception and memory are imperfect reconstructions of reality. These reconstructions are prone to be influenced by several factors, which may result in false memories. A false memory is the recollection of an event, or details of an episode, that did not actually occur. Memory formation comprises at least three different sub-processes: encoding, consolidation and the retrieval of the learned material. All of these sub-processes are vulnerable for specific errors and consequently may result in false memories. Whereas, processes like imagery, self-referential encoding or spreading activation can lead to the formation of false memories at encoding, semantic generalization during sleep and updating processes due to misleading post event information, in particular, are relevant at the consolidation stage. Finally at the retrieval stage, monitoring processes, which are assumed to be essential to reject false memories, are of specific importance. Different neuro-cognitive processes have been linked to the formation of true and false memories. Most consistently the medial temporal lobe and the medial and lateral prefrontal cortex have been reported with regard to the formation of true and false memories. Despite the fact that all phases entailing memory formation, consolidation of stored information and retrieval processes, are relevant for the forming of false memories, most studies focused on either memory encoding or retrieval. Thus, future studies should try to integrate data from all phases to give a more comprehensive view on systematic memory distortions. An initial outline is developed within this review to connect the different memory stages and research strategies. PMID:22827854

  7. Hippocampal damage causes retrograde but not anterograde memory loss for context fear discrimination in rats.

    Science.gov (United States)

    Lee, Justin Q; Sutherland, Robert J; McDonald, Robert J

    2017-09-01

    There is a substantial body of evidence that the hippocampus (HPC) plays and essential role in context discrimination in rodents. Studies reporting anterograde amnesia (AA) used repeated, alternating, distributed conditioning and extinction sessions to measure context fear discrimination. In addition, there is uncertainty about the extent of damage to the HPC. Here, we induced conditioned fear prior to discrimination tests and rats sustained extensive, quantified pre- or post-training HPC damage. Unlike previous work, we found that extensive HPC damage spares context discrimination, we observed no AA. There must be a non-HPC system that can acquire long-term memories that support context fear discrimination. Post-training HPC damage caused retrograde amnesia (RA) for context discrimination, even when rats are fear conditioned for multiple sessions. We discuss the implications of these findings for understanding the role of HPC in long-term memory. © 2017 Wiley Periodicals, Inc.

  8. Does recall after sleep-dependent memory consolidation reinstate sensitivity to retroactive interference?

    Science.gov (United States)

    Deliens, Gaétane; Schmitz, Rémy; Caudron, Isaline; Mary, Alison; Leproult, Rachel; Peigneux, Philippe

    2013-01-01

    Previous studies have shown that newly encoded memories are more resistant to retroactive interference when participants are allowed to sleep after learning the original material, suggesting a sleep-related strengthening of memories. In the present study, we investigated delayed, long-term effects of sleep vs. sleep deprivation (SD) on the first post-training night on memory consolidation and resistance to interference. On day 1, participants learned a list of unrelated word pairs (AB), either in the morning or in the evening, then spent the post-training night in a sleep or sleep deprivation condition, in a within-subject paradigm. On day 4, at the same time of day, they learned a novel list of word pairs (AC) in which 50% of the word pairs stemmed with the same word than in the AB list, resulting in retroactive interference. Participants had then to recall items from the AB list upon presentation of the "A" stem. Recall was marginally improved in the evening, as compared to the morning learning group. Most importantly, retroactive interference effects were found in the sleep evening group only, contrary to the hypothesis that sleep exerts a protective role against intrusion by novel but similar learning. We tentatively suggest that these results can be explained in the framework of the memory reconsolidation theory, stating that exposure to similar information sets back consolidated items in a labile form again sensitive to retroactive interference. In this context, sleep might not protect against interference but would promote an update of existing episodic memories while preventing saturation of the memory network due to the accumulation of dual traces.

  9. Does recall after sleep-dependent memory consolidation reinstate sensitivity to retroactive interference?

    Directory of Open Access Journals (Sweden)

    Gaétane Deliens

    Full Text Available Previous studies have shown that newly encoded memories are more resistant to retroactive interference when participants are allowed to sleep after learning the original material, suggesting a sleep-related strengthening of memories. In the present study, we investigated delayed, long-term effects of sleep vs. sleep deprivation (SD on the first post-training night on memory consolidation and resistance to interference. On day 1, participants learned a list of unrelated word pairs (AB, either in the morning or in the evening, then spent the post-training night in a sleep or sleep deprivation condition, in a within-subject paradigm. On day 4, at the same time of day, they learned a novel list of word pairs (AC in which 50% of the word pairs stemmed with the same word than in the AB list, resulting in retroactive interference. Participants had then to recall items from the AB list upon presentation of the "A" stem. Recall was marginally improved in the evening, as compared to the morning learning group. Most importantly, retroactive interference effects were found in the sleep evening group only, contrary to the hypothesis that sleep exerts a protective role against intrusion by novel but similar learning. We tentatively suggest that these results can be explained in the framework of the memory reconsolidation theory, stating that exposure to similar information sets back consolidated items in a labile form again sensitive to retroactive interference. In this context, sleep might not protect against interference but would promote an update of existing episodic memories while preventing saturation of the memory network due to the accumulation of dual traces.

  10. Dopamine and extinction: a convergence of theory with fear and reward circuitry.

    Science.gov (United States)

    Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

    2014-02-01

    Research on dopamine lies at the intersection of sophisticated theoretical and neurobiological approaches to learning and memory. Dopamine has been shown to be critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in reward-related tasks. A parallel and growing literature indicates that dopamine is involved in fear conditioning and extinction. These studies are consistent with long-standing ideas about appetitive-aversive interactions in learning theory and they speak to the general nature of cellular and molecular processes that underlie behavior. We review the behavioral and neurobiological literature showing a role for dopamine in fear conditioning and extinction. At a cellular level, we review dopamine signaling and receptor pharmacology, cellular and molecular events that follow dopamine receptor activation, and brain systems in which dopamine functions. At a behavioral level, we describe theories of learning and dopamine function that could describe the fundamental rules underlying how dopamine modulates different aspects of learning and memory processes. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Dopamine and extinction: A convergence of theory with fear and reward circuitry

    Science.gov (United States)

    Abraham, Antony D.; Neve, Kim A.; Lattal, K. Matthew

    2014-01-01

    Research on dopamine lies at the intersection of sophisticated theoretical and neurobiological approaches to learning and memory. Dopamine has been shown to be critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine’s function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in reward-related tasks. A parallel and growing literature indicates that dopamine is involved in fear conditioning and extinction. These studies are consistent with long-standing ideas about appetitive-aversive interactions in learning theory and they speak to the general nature of cellular and molecular processes that underlie behavior. We review the behavioral and neurobiological literature showing a role for dopamine in fear conditioning and extinction. At a cellular level, we review dopamine signaling and receptor pharmacology, cellular and molecular events that follow dopamine receptor activation, and brain systems in which dopamine functions. At a behavioral level, we describe theories of learning and dopamine function that could describe the fundamental rules underlying how dopamine modulates different aspects of learning and memory processes. PMID:24269353

  12. A BDNF Sensitive Mechanism Is Involved in the Fear Memory Resulting from the Interaction between Stress and the Retrieval of an Established Trace

    Science.gov (United States)

    Giachero, Marcelo; Bustos, Silvia G.; Calfa, Gaston; Molina, Victor A.

    2013-01-01

    The present study investigates the fear memory resulting from the interaction of a stressful experience and the retrieval of an established fear memory trace. Such a combination enhanced both fear expression and fear retention in adult Wistar rats. Likewise, midazolam intra-basolateral amygdala (BLA) infusion prior to stress attenuated the…

  13. Effects of ketamine, dexmedetomidine and propofol anesthesia on emotional memory consolidation in rats: Consequences for the development of post-traumatic stress disorder.

    Science.gov (United States)

    Morena, Maria; Berardi, Andrea; Peloso, Andrea; Valeri, Daniela; Palmery, Maura; Trezza, Viviana; Schelling, Gustav; Campolongo, Patrizia

    2017-06-30

    Intensive Care Unit (ICU) or emergency care patients, exposed to traumatic events, are at increased risk for Post-Traumatic Stress Disorder (PTSD) development. Commonly used sedative/anesthetic agents can interfere with the mechanisms of memory formation, exacerbating or attenuating the memory for the traumatic event, and subsequently promote or reduce the risk of PTSD development. Here, we evaluated the effects of ketamine, dexmedetomidine and propofol on fear memory consolidation and subsequent cognitive and emotional alterations related to traumatic stress exposure. Immediately following an inhibitory avoidance training, rats were intraperitoneally injected with ketamine (100-125mg/kg), dexmedetomidine (0.3-0.4mg/kg) or their vehicle and tested for 48h memory retention. Furthermore, the effects of ketamine (125mg/kg), dexmedetomidine (0.4mg/kg), propofol (300mg/kg) or their vehicle on long-term memory and social interaction were evaluated two weeks after drug injection in a rat PTSD model. Ketamine anesthesia increased memory retention without altering the traumatic memory strength in the PTSD model. However, ketamine induced a long-term reduction of social behavior. Conversely, dexmedetomidine markedly impaired memory retention, without affecting long-lasting cognitive or emotional behaviors in the PTSD model. We have previously shown that propofol anesthesia enhanced 48h memory retention. Here, we found that propofol induced an enduring traumatic memory enhancement and anxiogenic effects in the PTSD model. These findings provide new evidence for clinical studies showing that the use of ketamine or propofol anesthesia in emergency care and ICU might be more likely to promote the development of PTSD, while dexmedetomidine might have prophylactic effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Beyond extinction: erasing human fear responses and preventing the return of fear

    NARCIS (Netherlands)

    Kindt, M.; Soeter, M.; Vervliet, B.

    2009-01-01

    Animal studies have shown that fear memories can change when recalled, a process referred to as reconsolidation. We found that oral administration of the beta-adrenergic receptor antagonist propranolol before memory reactivation in humans erased the behavioral expression of the fear memory 24 h

  15. Deficient fear extinction memory in posttraumatic stress disorder.

    Science.gov (United States)

    Wicking, Manon; Steiger, Frauke; Nees, Frauke; Diener, Slawomira J; Grimm, Oliver; Ruttorf, Michaela; Schad, Lothar R; Winkelmann, Tobias; Wirtz, Gustav; Flor, Herta

    2016-12-01

    Posttraumatic stress disorder (PTSD) might be maintained by deficient extinction memory. We used a cued fear conditioning design with extinction and a post-extinction phase to provoke the return of fear and examined the role of the interplay of amygdala, hippocampus and prefrontal regions. We compared 18 PTSD patients with two healthy control groups: 18 trauma-exposed subjects without PTSD (nonPTSD) and 18 healthy controls (HC) without trauma experience. They underwent a three-day ABC-conditioning procedure in a functional magnetic resonance imaging scanner. Two geometric shapes that served as conditioned stimuli (CS) were presented in the context of virtual reality scenes. Electric painful stimuli were delivered after one of the two shapes (CS+) during acquisition (in context A), while the other (CS-) was never paired with pain. Extinction was performed in context B and extinction memory was tested in a novel context C. The PTSD patients showed significantly higher differential skin conductance responses than the non-PTSD and HC and higher differential amygdala and hippocampus activity than the HC in context C. In addition, elevated arousal to the CS+ during extinction and to the CS- throughout the experiment was present in the PTSD patients but self-reported differential valence or contingency were not different. During extinction recall, differential amygdala activity correlated positively with the intensity of numbing and ventromedial prefrontal cortex activity correlated positively with behavioral avoidance. PTSD patients show heightened return of fear in neural and peripheral measures. In addition, self-reported arousal was high to both danger (CS+) and safety (CS-) cues. These results suggest that a deficient maintenance of extinction and a failure to identify safety signals might contribute to PTSD symptoms, whereas non-PTSD subjects seem to show normal responses. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Modulating influences of memory strength and sensitivity of the retrieval test on the detectability of the sleep consolidation effect.

    Science.gov (United States)

    Schoch, Sarah F; Cordi, Maren J; Rasch, Björn

    2017-11-01

    Emotionality can increase recall probability of memories as emotional information is highly relevant for future adaptive behavior. It has been proposed that memory processes acting during sleep selectively promote the consolidation of emotional memories, so that neutral memories no longer profit from sleep consolidation after learning. This appears as a selective effect of sleep for emotional memories. However, other factors contribute to the appearance of a consolidation benefit and influence this interpretation. Here we show that the strength of the memory trace before sleep and the sensitivity of the retrieval test after sleep are critical factors contributing to the detection of the benefit of sleep on memory for emotional and neutral stimuli. 228 subjects learned emotional and neutral pictures and completed a free recall after a 12-h retention interval of either sleep or wakefulness. We manipulated memory strength by including an immediate retrieval test before the retention interval in half of the participants. In addition, we varied the sensitivity of the retrieval test by including an interference learning task before retrieval testing in half of the participants. We show that a "selective" benefit of sleep for emotional memories only occurs in the condition with high memory strength. Furthermore, this "selective" benefit disappeared when we controlled for the memory strength before the retention interval and used a highly sensitive retrieval test. Our results indicate that although sleep benefits are more robust for emotional memories, neutral memories similarly profit from sleep after learning when more sensitive indicators are used. We conclude that whether sleep benefits on memory appear depends on several factors, including emotion, memory strength and sensitivity of the retrieval test. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation within the Amygdala

    OpenAIRE

    Aubry, Antonio V.; Serrano, Peter A.; Burghardt, Nesha S.

    2016-01-01

    Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by w...

  18. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation Within the Amygdala

    OpenAIRE

    Antonio Aubry; Antonio Aubry; Peter Serrano; Peter Serrano; Nesha Burghardt; Nesha Burghardt

    2016-01-01

    Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by...

  19. Extinction of conditioned fear is better learned and recalled in the morning than in the evening.

    Science.gov (United States)

    Pace-Schott, Edward F; Spencer, Rebecca M C; Vijayakumar, Shilpa; Ahmed, Nafis A K; Verga, Patrick W; Orr, Scott P; Pitman, Roger K; Milad, Mohammed R

    2013-11-01

    Sleep helps emotional memories consolidate and may promote generalization of fear extinction memory. We examined whether extinction learning and memory might differ in the morning and evening due, potentially, to circadian and/or sleep-homeostatic factors. Healthy men (N = 109) in 6 groups completed a 2-session protocol. In Session 1, fear conditioning was followed by extinction learning. Partial reinforcement with mild electric shock produced conditioned skin conductance responses (SCRs) to 2 differently colored lamps (CS+), but not a third color (CS-), within the computer image of a room (conditioning context). One CS+ (CS + E) but not the other (CS + U) was immediately extinguished by un-reinforced presentations in a different room (extinction context). Delay durations of 3 h (within AM or PM), 12 h (morning-to-evening or evening-to-morning) or 24 h (morning-to-morning or evening-to-evening) followed. In Session 2, extinction recall and contextual fear renewal were tested. We observed no significant effects of the delay interval on extinction memory but did observe an effect of time-of-day. Fear extinction was significantly better if learned in the morning (p = .002). Collapsing across CS + type, there was smaller morning differential SCR at both extinction recall (p = .003) and fear renewal (p = .005). Morning extinction recall showed better generalization from the CS + E to CS + U with the response to the CS + U significantly larger than to the CS + E only in the evening (p = .028). Thus, extinction is learned faster and its memory is better generalized in the morning. Cortisol and testosterone showed the expected greater salivary levels in the morning when higher testosterone/cortisol ratio also predicted better extinction learning. Circadian factors may promote morning extinction. Alternatively, evening homeostatic sleep pressure may impede extinction and favor recall of conditioned fear. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Sleep spindles: a physiological marker of age-related changes in gray matter in brain regions supporting motor skill memory consolidation.

    Science.gov (United States)

    Fogel, Stuart; Vien, Catherine; Karni, Avi; Benali, Habib; Carrier, Julie; Doyon, Julien

    2017-01-01

    Sleep is necessary for the optimal consolidation of procedural learning, and in particular, for motor sequential skills. Motor sequence learning remains intact with age, but sleep-dependent consolidation is impaired, suggesting that memory deficits for procedural skills are specifically impacted by age-related changes in sleep. Age-related changes in spindles may be responsible for impaired motor sequence learning consolidation, but the morphological basis for this deficit is unknown. Here, we found that gray matter in the hippocampus and cerebellum was positively correlated with both sleep spindles and offline improvements in performance in young participants but not in older participants. These results suggest that age-related changes in gray matter in the hippocampus relate to spindles and may underlie age-related deficits in sleep-related motor sequence memory consolidation. In this way, spindles can serve as a biological marker for structural brain changes and the related memory deficits in older adults. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Effects of Model Performances on Music Skill Acquisition and Overnight Memory Consolidation

    Science.gov (United States)

    Cash, Carla D.; Allen, Sarah E.; Simmons, Amy L.; Duke, Robert A.

    2014-01-01

    This study was designed to investigate the extent to which the presentation of an auditory model prior to learning a novel melody affects performance during active practice and the overnight consolidation of procedural memory. During evening training sessions, 32 nonpianist musicians practiced a 13-note keyboard melody with their left…

  2. Nuclear protein phosphatase-1: an epigenetic regulator of fear memory and amygdala long-term potentiation.

    Science.gov (United States)

    Koshibu, K; Gräff, J; Mansuy, I M

    2011-01-26

    Complex brain diseases and neurological disorders in human generally result from the disturbance of multiple genes and signaling pathways. These disturbances may derive from mutations, deletions, translocations or rearrangements of specific gene(s). However, over the past years, it has become clear that such disturbances may also derive from alterations in the epigenome affecting several genes simultaneously. Our work recently demonstrated that epigenetic mechanisms in the adult brain are in part regulated by protein phosphatase 1 (PP1), a protein Ser/Thr phosphatase that negatively regulates hippocampus-dependent long-term memory (LTM) and synaptic plasticity. PP1 is abundant in brain structures involved in emotional processing like the amygdala, it may therefore be involved in the regulation of fear memory, a form of memory related to post-traumatic stress disorder (PTSD) in human. Here, we demonstrate that PP1 is a molecular suppressor of fear memory and synaptic plasticity in the amygdala that can control chromatin remodeling in neurons. We show that the selective inhibition of the nuclear pool of PP1 in amygdala neurons significantly alters posttranslational modifications (PTMs) of histones and the expression of several memory-associated genes. These alterations correlate with enhanced fear memory, and with an increase in long-term potentiation (LTP) that is transcription-dependent. Our results underscore the importance of nuclear PP1 in the amygdala as an epigenetic regulator of emotional memory, and the relevance of protein phosphatases as potential targets for therapeutic treatment of brain disorders like PTSD. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Effects of Early Serotonin Programming on Fear Response, Memory and Aggression

    Science.gov (United States)

    The neurotransmitter serotonin (5-HT) also acts as a neurogenic compound in the developing brain. Early administration of a 5-HT agonist could alter development of serotonergic circuitry, altering behaviors mediated by 5-HT signaling, including memory, fear and aggression. The present study was desi...

  4. The Sensitivity of Memory Consolidation and Reconsolidation to Inhibitors of Protein Synthesis and Kinases: Computational Analysis

    Science.gov (United States)

    Zhang, Yili; Smolen, Paul; Baxter, Douglas A.; Byrne, John H.

    2010-01-01

    Memory consolidation and reconsolidation require kinase activation and protein synthesis. Blocking either process during or shortly after training or recall disrupts memory stabilization, which suggests the existence of a critical time window during which these processes are necessary. Using a computational model of kinase synthesis and…

  5. Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs.

    Science.gov (United States)

    Varela, Carmen; Weiss, Sarah; Meyer, Retsina; Halassa, Michael; Biedenkapp, Joseph; Wilson, Matthew A; Goosens, Ki Ann; Bendor, Daniel

    2016-01-01

    The hippocampus is critical for the storage of new autobiographical experiences as memories. Following an initial encoding stage in the hippocampus, memories undergo a process of systems-level consolidation, which leads to greater stability through time and an increased reliance on neocortical areas for retrieval. The extent to which the retrieval of these consolidated memories still requires the hippocampus is unclear, as both spared and severely degraded remote memory recall have been reported following post-training hippocampal lesions. One difficulty in definitively addressing the role of the hippocampus in remote memory retrieval is the precision with which the entire volume of the hippocampal region can be inactivated. To address this issue, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), a chemical-genetic tool capable of highly specific neuronal manipulation over large volumes of brain tissue. We find that remote (>7 weeks after acquisition), but not recent (1-2 days after acquisition) contextual fear memories can be recalled after injection of the DREADD agonist (CNO) in animals expressing the inhibitory DREADD in the entire hippocampus. Our data demonstrate a time-dependent role of the hippocampus in memory retrieval, supporting the standard model of systems consolidation.

  6. The Regulation of Cytokine Networks in Hippocampal CA1 Differentiates Extinction from Those Required for the Maintenance of Contextual Fear Memory after Recall

    Science.gov (United States)

    Scholz, Birger; Doidge, Amie N.; Barnes, Philip; Hall, Jeremy; Wilkinson, Lawrence S.; Thomas, Kerrie L.

    2016-01-01

    We investigated the distinctiveness of gene regulatory networks in CA1 associated with the extinction of contextual fear memory (CFM) after recall using Affymetrix GeneChip Rat Genome 230 2.0 Arrays. These data were compared to previously published retrieval and reconsolidation-attributed, and consolidation datasets. A stringent dual normalization and pareto-scaled orthogonal partial least-square discriminant multivariate analysis together with a jack-knifing-based cross-validation approach was used on all datasets to reduce false positives. Consolidation, retrieval and extinction were correlated with distinct patterns of gene expression 2 hours later. Extinction-related gene expression was most distinct from the profile accompanying consolidation. A highly specific feature was the discrete regulation of neuroimmunological gene expression associated with retrieval and extinction. Immunity–associated genes of the tyrosine kinase receptor TGFβ and PDGF, and TNF families’ characterized extinction. Cytokines and proinflammatory interleukins of the IL-1 and IL-6 families were enriched with the no-extinction retrieval condition. We used comparative genomics to predict transcription factor binding sites in proximal promoter regions of the retrieval-regulated genes. Retrieval that does not lead to extinction was associated with NF-κB-mediated gene expression. We confirmed differential NF-κBp65 expression, and activity in all of a representative sample of our candidate genes in the no-extinction condition. The differential regulation of cytokine networks after the acquisition and retrieval of CFM identifies the important contribution that neuroimmune signalling plays in normal hippocampal function. Further, targeting cytokine signalling upon retrieval offers a therapeutic strategy to promote extinction mechanisms in human disorders characterised by dysregulation of associative memory. PMID:27224427

  7. Stress following extinction learning leads to a context-dependent return of fear.

    Science.gov (United States)

    Hamacher-Dang, Tanja C; Merz, Christian J; Wolf, Oliver T

    2015-04-01

    It has been suggested that extinction-based therapy benefits from administration of the stress hormone cortisol. However, it is unclear whether similar effects can be obtained by inducing stress instead of administering cortisol, and whether the effects also persist if memory is tested in a different context (renewal test) or after exposure to an aversive stimulus (reinstatement). The present study therefore applied a fear conditioning (context A, day 1) and extinction (context B, day 2) paradigm in healthy men. After fear extinction, participants were exposed to a stress or control procedure (n = 20 each). Fear retrieval was tested in contexts A and B on day 3. Postextinction stress increased skin conductance responses to the extinguished stimulus in the retrieval and reinstatement test especially in the acquisition context. The context-dependent return of fear may reflect enhancing effects of stress on the consolidation of contextual cues. Copyright © 2014 Society for Psychophysiological Research.

  8. Hippocampal Arc (Arg3.1) expression is induced by memory recall and required for memory reconsolidation in trace fear conditioning.

    Science.gov (United States)

    Chia, Chester; Otto, Tim

    2013-11-01

    Mounting evidence suggests that long-lasting, protein synthesis-dependent changes in synaptic strength accompany both the initial acquisition and subsequent recall of specific memories. Within brain areas thought to be important for learning and memory, including the hippocampus, learning-related plasticity is likely mediated in part by NMDA receptor activation and experience-dependent changes in gene expression. In the present study, we examined the role of activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) expression in the acquisition, recall, and reconsolidation of memory in a trace fear conditioning paradigm. First, we show that the expression of Arc protein in ventral hippocampus (VH) is dramatically enhanced by memory recall 24h after the acquisition of trace fear conditioning, and that both memory recall and the associated recall-induced enhancement of Arc expression are blocked by pre-training administration of 2-amino-5-phosphonovaleric acid (APV). Next, we show that while infusion of Arc antisense oligodeoxynucleotides (ODNs) into VH prior to testing had little effect on memory recall, it significantly reduced both Arc protein expression and freezing behavior during subsequent testing sessions. Collectively, these results suggest that Arc/Arg3.1 protein plays an important functional role in both the initial acquisition of hippocampal-dependent memory and the reconsolidation of these memories after recall. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Fact retrieval and memory consolidation for a movement sequence: bidirectional effects of 'unrelated' cognitive tasks on procedural memory.

    Directory of Open Access Journals (Sweden)

    Rachel Tibi

    Full Text Available The generation of long-term memory for motor skills can be modulated by subsequent motor experiences that interfere with the consolidation process. Recent studies suggest that even a non-motor task may adversely affect some aspects of motor sequence memory. Here we show that motor sequence memory can be either enhanced or reduced, by different cognitive tasks. Participants were trained in performing finger movement sequences. Fully explicit instructions about the target sequence were given before practice. The buildup of procedural knowledge was tested at three time-points: immediately before training (T1, after practice (T2, and 24 hours later (T3. Each participant performed the task on two separate occasions; training on a different movement sequence on each occasion. In one condition, interference, participants performed a non-motor task immediately after T2. Half the participants solved simple math problems and half performed a simple semantic judgment task. In the baseline condition there was no additional task. All participants improved significantly between T1 and T2 (within-session gains. In addition, in the baseline condition, performance significantly improved between T2 and T3 (delayed 'off-line' gains. Solving math problems significantly enhanced these delayed gains in motor performance, whereas performing semantic decisions significantly reduced delayed gains compared to baseline. Thus, procedural motor memory consolidation can be either enhanced or inhibited by subsequent cognitive experiences. These effects do not require explicit or implicit new learning. The retrieval of unrelated, non-motor, well established knowledge can modulate procedural memory.

  10. Memantine prevents memory consolidation failure induced by soluble beta amyloid in rats

    Directory of Open Access Journals (Sweden)

    Paolo eTucci

    2014-09-01

    Full Text Available It has been well documented that β-amyloid peptide accumulation and aggregation in the brain plays a crucial role in the pathophysiology of Alzheimer’s disease (AD. However, a new orientation of the amyloid cascade hypothesis has evidenced that soluble forms of the peptide (sAβ are involved in Aβ-induced cognitive impairment and cause rapid disruption of the synaptic mechanisms underlying memory. The primary aim of this study was to elucidate the effects of sAβ, acutely injected intracerebrally (i.c.v., 4 µM, on the short term and long term memory of young adult male rats, by using the novel object recognition task. Glutamatergic receptors have been proposed as mediating the effect of Aβ on synaptic plasticity and memory. Thus, we also investigated the effects of sAβ on prefrontal cortex (PFC glutamate release and the specific contribution of N-methyl-D-aspartate (NMDA receptor modulation to the effects of sAβ administration on the cognitive parameters evaluated. We found that a single i.c.v. injection of sAβ 2h before testing did not alter the ability of rats to differentiate between a familiar and a novel object, in a short term memory test, while it was able to negatively affect consolidation/retrieval of long term memory. Moreover, a significant increase of glutamate levels was found in PFC of rats treated with the peptide 2 h earlier. Interestingly, memory deficit induced by sAβ was reversed by a NMDA-receptor antagonist, memantine (5 mg/kg i.p, administered immediately after the familiarization trial (T1. On the contrary, memantine administered 30 min before T1 trial, was not able to rescue long term memory impairment. Taken together, our results suggest that an acute i.c.v. injection of sAβ peptide interferes with the consolidation/retrieval of long term memory. Moreover, such sAβ-induced effect indicates the involvement of glutamatergic system, proposing that NMDA receptor inhibition might prevent or lead to the recovery of

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

    Science.gov (United States)

    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

  12. The interhemispheric CA1 circuit governs rapid generalisation but not fear memory.

    Science.gov (United States)

    Zhou, Heng; Xiong, Gui-Jing; Jing, Liang; Song, Ning-Ning; Pu, De-Lin; Tang, Xun; He, Xiao-Bing; Xu, Fu-Qiang; Huang, Jing-Fei; Li, Ling-Jiang; Richter-Levin, Gal; Mao, Rong-Rong; Zhou, Qi-Xin; Ding, Yu-Qiang; Xu, Lin

    2017-12-19

    Encoding specificity theory predicts most effective recall by the original conditions at encoding, while generalization endows recall flexibly under circumstances which deviate from the originals. The CA1 regions have been implicated in memory and generalization but whether and which locally separated mechanisms are involved is not clear. We report here that fear memory is quickly formed, but generalization develops gradually over 24 h. Generalization but not fear memory is impaired by inhibiting ipsilateral (ips) or contralateral (con) CA1, and by optogenetic silencing of the ipsCA1 projections onto conCA1. By contrast, in vivo fEPSP recordings reveal that ipsCA1-conCA1 synaptic efficacy is increased with delay over 24 h when generalization is formed but it is unchanged if generalization is disrupted. Direct excitation of ipsCA1-conCA1 synapses using chemogenetic hM3Dq facilitates generalization formation. Thus, rapid generalization is an active process dependent on bilateral CA1 regions, and encoded by gradual synaptic learning in ipsCA1-conCA1 circuit.

  13. Promoting Sleep Oscillations and Their Functional Coupling by Transcranial Stimulation Enhances Memory Consolidation in Mild Cognitive Impairment.

    Science.gov (United States)

    Ladenbauer, Julia; Ladenbauer, Josef; Külzow, Nadine; de Boor, Rebecca; Avramova, Elena; Grittner, Ulrike; Flöel, Agnes

    2017-07-26

    Alzheimer's disease (AD) not only involves loss of memory functions, but also prominent deterioration of sleep physiology, which is already evident at the stage of mild cognitive impairment (MCI). Cortical slow oscillations (SO; 0.5-1 Hz) and thalamocortical spindle activity (12-15 Hz) during sleep, and their temporal coordination, are considered critical for memory formation. We investigated the potential of slow oscillatory transcranial direct current stimulation (so-tDCS), applied during a daytime nap in a sleep-state-dependent manner, to modulate these activity patterns and sleep-related memory consolidation in nine male and seven female human patients with MCI. Stimulation significantly increased overall SO and spindle power, amplified spindle power during SO up-phases, and led to stronger synchronization between SO and spindle power fluctuations in EEG recordings. Moreover, visual declarative memory was improved by so-tDCS compared with sham stimulation and was associated with stronger synchronization. These findings indicate a well-tolerated therapeutic approach for disordered sleep physiology and memory deficits in MCI patients and advance our understanding of offline memory consolidation. SIGNIFICANCE STATEMENT In the light of increasing evidence that sleep disruption is crucially involved in the progression of Alzheimer's disease (AD), sleep appears as a promising treatment target in this pathology, particularly to counteract memory decline. This study demonstrates the potential of a noninvasive brain stimulation method during sleep in patients with mild cognitive impairment (MCI), a precursor of AD, and advances our understanding of its mechanism. We provide first time evidence that slow oscillatory transcranial stimulation amplifies the functional cross-frequency coupling between memory-relevant brain oscillations and improves visual memory consolidation in patients with MCI. Copyright © 2017 the authors 0270-6474/17/377111-14$15.00/0.

  14. Noradrenergic Action in Prefrontal Cortex in the Late Stage of Memory Consolidation

    Science.gov (United States)

    Tronel, Sophie; Feenstra, Matthijs G. P.; Sara, Susan J.

    2004-01-01

    These experiments investigated the role of the noradrenergic system in the late stage of memory consolidation and in particular its action at beta receptors in the prelimbic region (PL) of the prefrontal cortex in the hours after training. Rats were trained in a rapidly acquired, appetitively motivated foraging task based on olfactory…

  15. The role of calsenilin/DREAM/KChIP3 in contextual fear conditioning.

    Science.gov (United States)

    Alexander, Jon C; McDermott, Carmel M; Tunur, Tumay; Rands, Vicky; Stelly, Claire; Karhson, Debra; Bowlby, Mark R; An, W Frank; Sweatt, J David; Schrader, Laura A

    2009-03-01

    Potassium channel interacting proteins (KChIPs) are members of a family of calcium binding proteins that interact with Kv4 potassium (K(+)) channel primary subunits and also act as transcription factors. The Kv4 subunit is a primary K(+) channel pore-forming subunit, which contributes to the somatic and dendritic A-type currents throughout the nervous system. These A-type currents play a key role in the regulation of neuronal excitability and dendritic processing of incoming synaptic information. KChIP3 is also known as calsenilin and as the transcription factor, downstream regulatory element antagonist modulator (DREAM), which regulates a number of genes including prodynorphin. KChIP3 and Kv4 primary channel subunits are highly expressed in hippocampus, an area of the brain important for learning and memory. Through its various functions, KChIP3 may play a role in the regulation of synaptic plasticity and learning and memory. We evaluated the role of KChIP3 in a hippocampus-dependent memory task, contextual fear conditioning. Male KChIP3 knockout (KO) mice showed significantly enhanced memory 24 hours after training as measured by percent freezing. In addition, we found that membrane association and interaction with Kv4.2 of KChIP3 protein was significantly decreased and nuclear KChIP3 expression was increased six hours after the fear conditioning training paradigm with no significant change in KChIP3 mRNA. In addition, prodynorphin mRNA expression was significantly decreased six hours after fear conditioning training in wild-type (WT) but not in KO animals. These data suggest a role for regulation of gene expression by KChIP3/DREAM/calsenilin in consolidation of contextual fear conditioning memories.

  16. The effect of exogenous cortisol during sleep on the behavioral and neural correlates of emotional memory consolidation in humans

    NARCIS (Netherlands)

    Marle, H.J.F. van; Hermans, E.J.; Qin, S.; Overeem, S.; Fernandez, G.S.E.

    2013-01-01

    A host of animal work demonstrates that the retention benefit for emotionally aversive over neutral memories is regulated by glucocorticoid action during memory consolidation. Particularly, glucocorticoids may affect systems-level processes that promote the gradual reorganization of emotional memory

  17. Beyond a mask and against the bottleneck: retroactive dual-task interference during working memory consolidation of a masked visual target.

    Science.gov (United States)

    Nieuwenstein, Mark; Wyble, Brad

    2014-06-01

    While studies on visual memory commonly assume that the consolidation of a visual stimulus into working memory is interrupted by a trailing mask, studies on dual-task interference suggest that the consolidation of a stimulus can continue for several hundred milliseconds after a mask. As a result, estimates of the time course of working memory consolidation differ more than an order of magnitude. Here, we contrasted these opposing views by examining if and for how long the processing of a masked display of visual stimuli can be disturbed by a trailing 2-alternative forced choice task (2-AFC; a color discrimination task or a visual or auditory parity judgment task). The results showed that the presence of the 2-AFC task produced a pronounced retroactive interference effect that dissipated across stimulus onset asynchronies of 250-1,000 ms, indicating that the processing elicited by the 2-AFC task interfered with the gradual consolidation of the earlier shown stimuli. Furthermore, this interference effect occurred regardless of whether the to-be-remembered stimuli comprised a string of letters or an unfamiliar complex visual shape, and it occurred regardless of whether these stimuli were masked. Conversely, the interference effect was reduced when the memory load for the 1st task was reduced, or when the 2nd task was a color detection task that did not require decision making. Taken together, these findings show that the formation of a durable and consciously accessible working memory trace for a briefly shown visual stimulus can be disturbed by a trailing 2-AFC task for up to several hundred milliseconds after the stimulus has been masked. By implication, the current findings challenge the common view that working memory consolidation involves an immutable central processing bottleneck, and they also make clear that consolidation does not stop when a stimulus is masked. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  18. Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction

    Science.gov (United States)

    Whittle, N; Maurer, V; Murphy, C; Rainer, J; Bindreither, D; Hauschild, M; Scharinger, A; Oberhauser, M; Keil, T; Brehm, C; Valovka, T; Striessnig, J; Singewald, N

    2016-01-01

    Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory. PMID:27922638

  19. Common chromosomal fragile sites (CFS) may be involved in normal and traumatic cognitive stress memory consolidation and altered nervous system immunity.

    Science.gov (United States)

    Gericke, G S

    2010-05-01

    Previous reports of specific patterns of increased fragility at common chromosomal fragile sites (CFS) found in association with certain neurobehavioural disorders did not attract attention at the time due to a shift towards molecular approaches to delineate neuropsychiatric disorder candidate genes. Links with miRNA, altered methylation and the origin of copy number variation indicate that CFS region characteristics may be part of chromatinomic mechanisms that are increasingly linked with neuroplasticity and memory. Current reports of large-scale double-stranded DNA breaks in differentiating neurons and evidence of ongoing DNA demethylation of specific gene promoters in adult hippocampus may shed new light on the dynamic epigenetic changes that are increasingly appreciated as contributing to long-term memory consolidation. The expression of immune recombination activating genes in key stress-induced memory regions suggests the adoption by the brain of this ancient pattern recognition and memory system to establish a structural basis for long-term memory through controlled chromosomal breakage at highly specific genomic regions. It is furthermore considered that these mechanisms for management of epigenetic information related to stress memory could be linked, in some instances, with the transfer of the somatically acquired information to the germline. Here, rearranged sequences can be subjected to further selection and possible eventual retrotranscription to become part of the more stable coding machinery if proven to be crucial for survival and reproduction. While linkage of cognitive memory with stress and fear circuitry and memory establishment through structural DNA modification is proposed as a normal process, inappropriate activation of immune-like genomic rearrangement processes through traumatic stress memory may have the potential to lead to undesirable activation of neuro-inflammatory processes. These theories could have a significant impact on the

  20. Involvement of nitric oxide in granisetron improving effect on scopolamine-induced memory impairment in mice.

    Science.gov (United States)

    Javadi-Paydar, Mehrak; Zakeri, Marjan; Norouzi, Abbas; Rastegar, Hossein; Mirazi, Naser; Dehpour, Ahmad Reza

    2012-01-06

    Granisetron, a serotonin 5-HT(3) receptor antagonist, widely used as an antiemetic drug following chemotherapy, has been found to improve learning and memory. In this study, effects of granisetron on spatial recognition memory and fear memory and the involvement of nitric oxide (NO) have been determined in a Y-maze and passive avoidance test. Granisetron (3, 10mg/kg, intraperitoneally) was administered to scopolamine-induced memory-impaired mice prior to acquisition, consolidation and retrieval phases, either in the presence or in the absence of a non-specific NO synthase inhibitor, l-NAME (3, 10mg/kg, intraperitoneally); a specific inducible NO synthase (iNOS) inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750 mg/kg). It is demonstrated that granisetron improved memory acquisition in a dose-dependent manner, but it was ineffective on consolidation and retrieval phases of memory. The beneficial effect of granisetron (10mg/kg) on memory acquisition was significantly reversed by l-NAME (10mg/kg) and aminoguanidine (100mg/kg); however, l-arginine (750 mg/kg) did not potentiate the effect of sub-effective dose of granisetron (3mg/kg) in memory acquisition phase. It is concluded that nitric oxide is probably involved in improvement of memory acquisition by granisetron in both spatial recognition memory and fear memory. This article is part of a Special Issue entitled The Cognitive Neuroscience. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Real-world-time simulation of memory consolidation in a large-scale cerebellar model

    Directory of Open Access Journals (Sweden)

    Masato eGosui

    2016-03-01

    Full Text Available We report development of a large-scale spiking network model of thecerebellum composed of more than 1 million neurons. The model isimplemented on graphics processing units (GPUs, which are dedicatedhardware for parallel computing. Using 4 GPUs simultaneously, we achieve realtime simulation, in which computer simulation ofcerebellar activity for 1 sec completes within 1 sec in thereal-world time, with temporal resolution of 1 msec.This allows us to carry out a very long-term computer simulationof cerebellar activity in a practical time with millisecond temporalresolution. Using the model, we carry out computer simulationof long-term gain adaptation of optokinetic response (OKR eye movementsfor 5 days aimed to study the neural mechanisms of posttraining memoryconsolidation. The simulation results are consistent with animal experimentsand our theory of posttraining memory consolidation. These resultssuggest that realtime computing provides a useful means to studya very slow neural process such as memory consolidation in the brain.

  2. Consolidation ou résistance à l'interférence ?Etude de la contribution des états de sommeil aux processus post-apprentissage de consolidation et de résistance à l'interférence lexicale et émotionnelle rétroactive./Consolidation or protection against interference? an investigation of sleep stages contribution in post-learning memory consolidation and protection against lexical and emotional retroactive interference processes.

    OpenAIRE

    Deliens, Gaétane

    2013-01-01

    Although a relative consensus exists about the contribution of post-learning sleep in the consolidation of novel information in long term memory, the definition of the respective contributions of sleep stages in memory consolidation processes remains a matter of debates. Scrima (1982) proposed the hypothesis that Slow Waves Sleep (SWS) contributes preventing retroactive interference on recently acquired information, whereas Rapid Eyes Movement sleep (REM) contributes consolidating this inform...

  3. Procedural and declarative memory performance, and the memory consolidation function of sleep, in recent and abstinent Ecstasy/MDMA users

    Science.gov (United States)

    Blagrove, Mark; Seddon, Jennifer; George, Sophie; Parrott, Andrew C.; Stickgold, Robert; Walker, Matthew; Jones, Katy; Morgan, Michael J.

    2013-01-01

    This study assessed the effects of ecstasy/MDMA on declarative memory (Rivermead Behavioral Memory task - RBMT), on procedural learning (Finger Tapping Task - FTT), and on the memory consolidation function of sleep for these two tasks. Testing occurred in 2 afternoon testing sessions, 24 hours apart so that a full period of sleep was allowed between them. Groups were: Non-drug taking Controls (n=24); Recent Ecstasy/MDMA users, who had taken ecstasy and/or MDMA 2–3 days before the first testing session (n=25), and Abstinent Ecstasy/MDMA users, who had not taken ecstasy/MDMA for at least 8 days before the first session (n=17). The recent ecstasy/MDMA users performed significantly worse than controls on the RBMT (mean recall 76.1% of control group recall), but did not differ from controls on FTT performance. Correspondingly there was a significant regression between the continuous variable of recency of ecstasy/MDMA use and RBMT performance. However, there was an interaction between ecstasy/MDMA use and subsequent other drug use. Controls had similar RBMT scores to recent ecstasy/MDMA users who did not take other drugs 48 – 24 hours before testing, but scored significantly better than recent ecstasy/MDMA users who took various other drugs (mainly cannabis) 48 – 24 hours before testing. For both tasks the control, recent ecstasy/MDMA and abstinent ecstasy/MDMA users did not differ in their change of performance across 24 hours; there was thus no evidence that ecstasy/MDMA impairs the memory consolidation function of sleep for either declarative or procedural memory. For participants in the two ecstasy/MDMA groups greater lifetime consumption of ecstasy tablets was associated with significantly more deficits in procedural memory. Furthermore, greater lifetime consumption of ecstasy tablets and of cocaine, were also associated with significantly more deficits in declarative memory. PMID:20615932

  4. The effect of chronic corticosterone on fear learning and memory depends on dose and the testing protocol.

    Science.gov (United States)

    Marks, W N; Fenton, E Y; Guskjolen, A J; Kalynchuk, L E

    2015-03-19

    Chronic exposure to the stress hormone corticosterone (CORT) is known to alter plasticity within hippocampal and amygdalar circuits that mediate fear learning and memory. The purpose of this experiment was to clarify the effects of chronic CORT on Pavlovian fear conditioning, which is dependent on intact hippocampal and amygdalar activity. In particular, we assessed whether the effect of chronic CORT on fear learning and memory is influenced by two factors-the dose of CORT and the order in which rats are tested for freezing to context versus tone cues. Male Long-Evans rats received low-dose CORT (5mg/kg), high-dose CORT (40mg/kg), or vehicle injections once daily for 21days. On day 22, the rats were trained in a fear-conditioning paradigm. On days 23 and 24, the rats were tested for the retrieval of fear memories to context and tone cues in a counterbalanced way-half the rats received context testing on day 23 and then tone testing on day 24 and half the rats received tone testing on day 23 followed by context testing on day 24. Our results revealed dose-dependent effects of CORT on memory retrieval: Rats injected with high-dose CORT froze significantly more than control rats to both context and tone cues regardless of what testing day these cues were presented. However, rats injected with low-dose CORT froze significantly more than control rats to tone cues only. We also found an order effect in that the effects of CORT on freezing were greater on the second day of testing, regardless of whether that testing was to context or tones cues. This order effect may be due to a lack of extinction in the CORT rats. Overall, these results suggest a relationship between stress intensity and testing conditions that should be taken into account when assessing the effect of stress on fear memories. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Cystathionine-β-synthase-derived hydrogen sulfide is required for amygdalar long-term potentiation and cued fear memory in rats.

    Science.gov (United States)

    Chen, Hai-Bo; Wu, Wen-Ning; Wang, Wei; Gu, Xun-Hu; Yu, Bin; Wei, Bo; Yang, Yuan-Jian

    2017-04-01

    Hydrogen sulfide (H 2 S) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that H 2 S regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous H 2 S is required for amygdalar long-term potentiation (LTP) induction and cued fear memory formation remains unclear. Here, we show that cystathionine-β-synthase (CBS), the predominant H 2 S-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of H 2 S in the lateral amygdala (LA) region. Incubating brain slices with CBS inhibitor significantly prevented the induction of NMDA receptors (NMDARs)-dependent LTP in the thalamo-LA pathway, and intra-LA infusion of CBS inhibitor impaired cued fear memory in rats. Notably, treatment with H 2 S donor, but not CBS activator, significantly reversed the impairments of LTP and fear memory caused by CBS inhibition. Mechanismly, inhibition of CBS activity led to a reduction in NMDAR-mediated synaptic response in the thalamo-LA pathway, and treatment with H 2 S donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived H 2 S is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous H 2 S might involve the regulation of NMDAR function. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Factors affecting graded and ungraded memory loss following hippocampal lesions.

    Science.gov (United States)

    Winocur, Gordon; Moscovitch, Morris; Sekeres, Melanie J

    2013-11-01

    This review evaluates three current theories--Standard Consolidation (Squire & Wixted, 2011), Overshadowing (Sutherland, Sparks, & Lehmann, 2010), and Multiple Trace-Transformation (Winocur, Moscovitch, & Bontempi, 2010)--in terms of their ability to account for the role of the hippocampus in recent and remote memory in animals. Evidence, based on consistent findings from tests of spatial memory and memory for acquired food preferences, favours the transformation account, but this conclusion is undermined by inconsistent results from studies that measured contextual fear memory, probably the most commonly used test of hippocampal involvement in anterograde and retrograde memory. Resolution of this issue may depend on exercising greater control over critical factors (e.g., contextual environment, amount of pre-exposure to the conditioning chamber, the number and distribution of foot-shocks) that can affect the representation of the memory shortly after learning and over the long-term. Research strategies aimed at characterizing the neural basis of long-term consolidation/transformation, as well as other outstanding issues are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Endocannabinoid signaling within the basolateral amygdala integrates multiple stress hormone effects on memory consolidation

    NARCIS (Netherlands)

    Atsak, P.; Hauer, D.; Campolongo, P.; Schelling, G.; Fornari, R.V.; Roozendaal, B.

    2015-01-01

    Glucocorticoid hormones are known to act synergistically with other stress-activated neuromodulatory systems, such as norepinephrine and corticotropin-releasing factor (CRF), within the basolateral complex of the amygdala (BLA) to induce optimal strengthening of the consolidation of long-term memory

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

    Science.gov (United States)

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

    2012-12-01

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

  9. Effects of cannabinoid CB1 receptor antagonist rimonabant in consolidation and reconsolidation of methamphetamine reward memory in mice.

    Science.gov (United States)

    Yu, Lu-lu; Wang, Xue-yi; Zhao, Mei; Liu, Yu; Li, Yan-qin; Li, Fang-qiong; Wang, Xiaoyi; Xue, Yan-xue; Lu, Lin

    2009-06-01

    Previous studies have shown that cannabinoid CB1 receptors play an important role in specific aspects of learning and memory, yet there has been no systematic study focusing on the involvement of cannabinoid CB1 receptors in methamphetamine-related reward memory. The purpose of this study was to examine whether rimonabant, a cannabinoid CB1 receptor antagonist, would disrupt the consolidation and reconsolidation of methamphetamine-related reward memory, using conditioned place preference paradigm (CPP). Separate groups of male Kunming mice were trained to acquire methamphetamine CPP. Vehicle or rimonabant (1 mg/kg or 3 mg/kg, i.p.) was given at different time points: immediately after each CPP training session (consolidation), 30 min before the reactivation of CPP (retrieval), or immediately after the reactivation of CPP (reconsolidation). Methamphetamine CPP was retested 24 h and 1 and 2 weeks after rimonabant administration. Rimonabant at doses of 1 and 3 mg/kg significantly inhibited the consolidation of methamphetamine CPP. Only high-dose rimonabant (3 mg/kg) disrupted the retrieval and reconsolidation of methamphetamine CPP. Rimonabant had no effect on methamphetamine CPP in the absence of methamphetamine CPP reactivation. Our findings suggest that cannabinoid CB1 receptors play a major role in methamphetamine reward memory, and cannabinoid CB1 receptor antagonists may be a potential pharmacotherapy to manage relapse associated with drug-reward-related memory.

  10. Timing matters: negative emotion elicited 5 min but not 30 min or 45 min after learning enhances consolidation of internal-monitoring source memory.

    Science.gov (United States)

    Wang, Bo; Bukuan, Sun

    2015-05-01

    Two experiments examined the time-dependent effects of negative emotion on consolidation of item and internal-monitoring source memory. In Experiment 1, participants (n=121) learned a list of words. They were asked to read aloud half of the words and to think about the remaining half. They were instructed to memorize each word and its associative cognitive operation ("reading" versus "thinking"). Immediately following learning they conducted free recall and then watched a 3-min either neutral or negative video clip when 5 min, 30 min or 45 min had elapsed after learning. Twenty-four hours later they returned to take surprise tests for item and source memory. Experiment 2 was similar to Experiment 1 except that participants, without conducting an immediate test of free recall, took tests of source memory for all encoded words both immediately and 24 h after learning. Experiment 1 showed that negative emotion enhanced consolidation of item memory (as measured by retention ratio of free recall) regardless of delay of emotion elicitation and that negative emotion enhanced consolidation of source memory when it was elicited at a 5 min delay but reduced consolidation of source memory when it was elicited at a 30 min delay; when elicited at a 45 min delay, negative emotion had little effect. Furthermore, Experiment 2 replicated the enhancement effect on source memory in the 5 min delay even when participants were tested on all the encoded words. The current study partially replicated prior studies on item memory and extends the literature by providing evidence for a time-dependent effect of negative emotion on consolidation of source memory based on internal monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Hearing something emotional influences memory for what was just seen: How arousal amplifies effects of competition in memory consolidation.

    Science.gov (United States)

    Ponzio, Allison; Mather, Mara

    2014-12-01

    Enhanced memory for emotional items often comes at the cost of memory for the background scenes. Because emotional foreground items both induce arousal and attract attention, it is not clear whether the emotion effects are simply the result of shifts in visual attention during encoding or whether arousal has effects beyond simple attention capture. In the current study, participants viewed a series of scenes that each either had a foreground object or did not have one, and then, after each image, heard either an emotionally arousing negative sound or a neutral sound. After a 24-hr delay, they returned for a memory test for the objects and scenes. Postencoding arousal decreased recognition memory of scenes shown behind superimposed objects but not memory of scenes shown alone. These findings support the hypothesis that arousal amplifies the effects of competition between mental representations, influencing memory consolidation of currently active representations.

  12. Changes in Context-Specificity during Memory Reconsolidation: Selective Effects of Hippocampal Lesions

    Science.gov (United States)

    Winocur, Gordon; Frankland, Paul W.; Sekeres, Melanie; Fogel, Stuart; Moscovitch, Morris

    2009-01-01

    After acquisition, memories associated with contextual fear conditioning pass through a labile phase, in which they are vulnerable to hippocampal lesions, to a more stable state, via consolidation, in which they engage extrahippocampal structures and are resistant to such disruption. The process is accompanied by changes in the form of the memory…

  13. Intrahippocampal injection of Cortistatin-14 impairs recognition memory consolidation in mice through activation of sst2, ghrelin and GABAA/B receptors.

    Science.gov (United States)

    Jiang, Jinhong; Peng, Yali; He, Zhen; Wei, Lijuan; Jin, Weidong; Wang, Xiaoli; Chang, Min

    2017-07-01

    Cortistatin-14 (CST-14), a neuropeptide related to somatostatin, is primarily localized within the cortex and hippocampus. In the hippocampus, CST-14 inhibits CA1 neuronal pyramidal cell firing and co-exists with GABA. However, its role in cognitive is still not clarified. The first aim of our study was to elucidate the role of CST-14 signaling in consolidation and reconsolidation of recognition memory in mice, using novel object recognition task. The results showed that central CST-14 induced in impairment of long-term and short-term recognition memory, indicating memory consolidation impairment effect. Similarly, we found that CST-14 did not impaired long-term and short-term reconsolidation recognition memory. To further investigate the underlying mechanisms of CST-14 in memory process, we used cyclosomatostatin (c-SOM, a selective sst 1-5 receptor antagonist), cyanamid154806 (a selective sst 2 receptor antagonist), ODN-8 (a high affinity and selectivity compound for sst 3 receptor), [d-Lys 3 ]GHRP-6 (a selective ghrelin receptor antagonist), picrotoxin (PTX, a GABA A receptor antagonist), and sacolfen (a GABA B receptor antagonist) to research its effects in recognition. Our results firstly indicated that the memory-impairing effects of CST-14 were significantly reversed by c-SOM, cyanamid154806, [d-Lys 3 ]GHRP-6, PTX and sacolfen, but not ODN-8, suggesting that the blockage of recognition memory consolidation induced by CST-14 involves sst 2 , ghrelin and GABA system. The present study provides a potential strategy to regulate memory processes, providing new evidence that reconsolidation is not a simple reiteration of consolidation. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Myosin II Motor Activity in the Lateral Amygdala Is Required for Fear Memory Consolidation

    Science.gov (United States)

    Gavin, Cristin F.; Rubio, Maria D.; Young, Erica; Miller, Courtney; Rumbaugh, Gavin

    2012-01-01

    Learning induces dynamic changes to the actin cytoskeleton that are required to support memory formation. However, the molecular mechanisms that mediate filamentous actin (F-actin) dynamics during learning and memory are poorly understood. Myosin II motors are highly expressed in actin-rich growth structures including dendritic spines, and we have…

  15. MEMORY MODULATION

    Science.gov (United States)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

  16. The neurobiology of consolidations, or, how stable is the engram?

    Science.gov (United States)

    Dudai, Yadin

    2004-01-01

    Consolidation is the progressive postacquisition stabilization of long-term memory. The term is commonly used to refer to two types of processes: synaptic consolidation, which is accomplished within the first minutes to hours after learning and occurs in all memory systems studied so far; and system consolidation, which takes much longer, and in which memories that are initially dependent upon the hippocampus undergo reorganization and may become hippocampal-independent. The textbook account of consolidation is that for any item in memory, consolidation starts and ends just once. Recently, a heated debate has been revitalized on whether this is indeed the case, or, alternatively, whether memories become labile and must undergo some form of renewed consolidation every time they are activated. This debate focuses attention on fundamental issues concerning the nature of the memory trace, its maturation, persistence, retrievability, and modifiability.

  17. TrkB blockade in the hippocampus after training or retrieval impairs memory: protection from consolidation impairment by histone deacetylase inhibition.

    Science.gov (United States)

    Blank, Martina; Petry, Fernanda S; Lichtenfels, Martina; Valiati, Fernanda E; Dornelles, Arethuza S; Roesler, Rafael

    2016-03-01

    Relatively little is known about the requirement of signaling initiated by brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), in the early phases of memory consolidation, as well as about its possible functional interactions with epigenetic mechanisms. Here we show that blocking TrkB in the dorsal hippocampus after learning or retrieval impairs retention of memory for inhibitory avoidance (IA). More importantly, the impairing effect of TrkB antagonism on consolidation was completely prevented by the histone deacetylase (HDAC) inhibitor sodium butyrate (NaB). Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or NaB before training, followed by an infusion of either vehicle (VEH) or the selective TrkB antagonist ANA-12 immediately after training. In a second experiment, the infusions were administered before and after retrieval. ANA-12 after either training or retrieval produced a significant impairment in a subsequent memory retention test. Pretraining administration of NaB prevented the effect of ANA-12, although NaB given before retrieval did not alter the impairment resulting from TrkB blockade. The results indicate that inhibition of BDNF/TrkB in the hippocampus can hinder consolidation and reconsolidation of IA memory. However, TrkB activity is not required for consolidation in the presence of NaB, suggesting that a dysfunction in BDNF/TrkB signaling can be fully compensated by HDAC inhibition to allow hippocampal memory formation.

  18. To Replay, Perchance to Consolidate.

    Directory of Open Access Journals (Sweden)

    Lisa Genzel

    2015-10-01

    Full Text Available After a memory is formed, it continues to be processed by the brain. These "off-line" processes consolidate the memory, leading to its enhancement and to changes in memory circuits. Potentially, these memory changes are driven by off-line replay of the pattern of neuronal activity present when the memory was being formed. A new study by Dhaksin Ramanathan and colleagues, published in PLOS Biology, demonstrates that replay occurs predominately after the acquisition of a new motor skill and that it is related to changes in memory performance and to the subsequent changes in memory circuits. Together, these observations reveal the importance of neuronal replay in the consolidation of novel motor skills.

  19. Synaptic consolidation across multiple timescales

    Directory of Open Access Journals (Sweden)

    Lorric Ziegler

    2014-03-01

    Full Text Available The brain is bombarded with a continuous stream of sensory events, but retains only a small subset in memory. The selectivity of memory formation prevents our memory from being overloaded with irrelevant items that would rapidly bring the brain to its storage limit; moreover, selectivity also prevents overwriting previously formed memories with new ones. Memory formation in the hippocampus, as well as in other brain regions, is thought to be linked to changes in the synaptic connections between neurons. In this view, sensory events imprint traces at the level of synapses that reflect potential memory items. The question of memory selectivity can therefore be reformulated as follows: what are the reasons and conditions that some synaptic traces fade away whereas others are consolidated and persist? Experimentally, changes in synaptic strength induced by 'Hebbian' protocols fade away over a few hours (early long-term potentiation or e-LTP, unless these changes are consolidated. The experiments and conceptual theory of synaptic tagging and capture (STC provide a mechanistic explanation for the processes involved in consolidation. This theory suggests that the initial trace of synaptic plasticity sets a tag at the synapse, which then serves as a marker for potential consolidation of the changes in synaptic efficacy. The actual consolidation processes, transforming e-LTP into late LTP (l-LTP, require the capture of plasticity-related proteins (PRP. We translate the above conceptual model into a compact computational model that accounts for a wealth of in vitro data including experiments on cross-tagging, tag-resetting and depotentiation. A central ingredient is that synaptic traces are described with several variables that evolve on different time scales. Consolidation requires the transmission of information from a 'fast' synaptic trace to a 'slow' one through a 'write' process, including the formation of tags and the production of PRP for the

  20. p300/CBP Histone Acetyltransferase Activity Is Required for Newly Acquired and Reactivated Fear Memories in the Lateral Amygdala

    Science.gov (United States)

    Maddox, Stephanie A.; Watts, Casey S.; Schafe, Glenn E.

    2013-01-01

    Modifications in chromatin structure have been widely implicated in memory and cognition, most notably using hippocampal-dependent memory paradigms including object recognition, spatial memory, and contextual fear memory. Relatively little is known, however, about the role of chromatin-modifying enzymes in amygdala-dependent memory formation.…