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Sample records for fear memory consolidation

  1. Reversible plasticity of fear memory-encoding amygdala synaptic circuits even after fear memory consolidation.

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    Ingie Hong

    Full Text Available It is generally believed that after memory consolidation, memory-encoding synaptic circuits are persistently modified and become less plastic. This, however, may hinder the remaining capacity of information storage in a given neural circuit. Here we consider the hypothesis that memory-encoding synaptic circuits still retain reversible plasticity even after memory consolidation. To test this, we employed a protocol of auditory fear conditioning which recruited the vast majority of the thalamic input synaptic circuit to the lateral amygdala (T-LA synaptic circuit; a storage site for fear memory with fear conditioning-induced synaptic plasticity. Subsequently the fear memory-encoding synaptic circuits were challenged with fear extinction and re-conditioning to determine whether these circuits exhibit reversible plasticity. We found that fear memory-encoding T-LA synaptic circuit exhibited dynamic efficacy changes in tight correlation with fear memory strength even after fear memory consolidation. Initial conditioning or re-conditioning brought T-LA synaptic circuit near the ceiling of their modification range (occluding LTP and enhancing depotentiation in brain slices prepared from conditioned or re-conditioned rats, while extinction reversed this change (reinstating LTP and occluding depotentiation in brain slices prepared from extinguished rats. Consistently, fear conditioning-induced synaptic potentiation at T-LA synapses was functionally reversed by extinction and reinstated by subsequent re-conditioning. These results suggest reversible plasticity of fear memory-encoding circuits even after fear memory consolidation. This reversible plasticity of memory-encoding synapses may be involved in updating the contents of original memory even after memory consolidation.

  2. Reversible Plasticity of Fear Memory-Encoding Amygdala Synaptic Circuits Even after Fear Memory Consolidation

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    Hong, Ingie; Kim, Jihye; Lee, Junuk; Park, Sungmo; Song, Beomjong; Kim, Jeongyeon; An, Bobae; Park, Kyungjoon; Lee, Hyun Woo; Lee, Seungbok; Kim, Hyun; Park, Sang-Hyun; Eom, Khee Dong; Lee, Sukwon; Choi, Sukwoo

    2011-01-01

    It is generally believed that after memory consolidation, memory-encoding synaptic circuits are persistently modified and become less plastic. This, however, may hinder the remaining capacity of information storage in a given neural circuit. Here we consider the hypothesis that memory-encoding synaptic circuits still retain reversible plasticity even after memory consolidation. To test this, we employed a protocol of auditory fear conditioning which recruited the vast majority of the thalamic...

  3. Sleep deprivation impairs consolidation of cued fear memory in rats.

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    Kumar, Tankesh; Jha, Sushil K

    2012-01-01

    Post-learning sleep facilitates negative memory consolidation and also helps preserve it over several years. It is believed, therefore, that sleep deprivation may help prevent consolidation of fearful memory. Its effect, however, on consolidation of negative/frightening memories is not known. Cued fear-conditioning (CuFC) is a widely used model to understand the neural basis of negative memory associated with anxiety disorders. In this study, we first determined the suitable circadian timing for consolidation of CuFC memory and changes in sleep architecture after CuFC. Thereafter, we studied the effect of sleep deprivation on CuFC memory consolidation. Three sets of experiments were performed in male Wistar rat (n=51). In experiment-I, animals were conditioned to cued-fear by presenting ten tone-shock paired stimuli during lights-on (7 AM) (n=9) and lights-off (7 PM) (n=9) periods. In experiment-II, animals were prepared for polysomnographic recording (n=8) and changes in sleep architecture after CuFC was determined. Further in experiment-III, animals were cued fear-conditioned during the lights-off period and were randomly divided into four groups: Sleep-Deprived (SD) (n=9), Non-Sleep Deprived (NSD) (n=9), Stress Control (SC) (n=9) and Tone Control (n=7). Percent freezing amount, a hallmark of fear, was compared statistically in these groups. Rats trained during the lights-off period exhibited significantly more freezing compared to lights-on period. In CuFC trained animals, total sleep amount did not change, however, REM sleep decreased significantly. Further, out of total sleep time, animals spent proportionately more time in NREM sleep. Nevertheless, SD animals exhibited significantly less freezing compared to NSD and SC groups. These data suggest that sleep plays an important role in the consolidation of cued fear-conditioned memory.

  4. Sleep deprivation impairs consolidation of cued fear memory in rats.

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    Tankesh Kumar

    Full Text Available Post-learning sleep facilitates negative memory consolidation and also helps preserve it over several years. It is believed, therefore, that sleep deprivation may help prevent consolidation of fearful memory. Its effect, however, on consolidation of negative/frightening memories is not known. Cued fear-conditioning (CuFC is a widely used model to understand the neural basis of negative memory associated with anxiety disorders. In this study, we first determined the suitable circadian timing for consolidation of CuFC memory and changes in sleep architecture after CuFC. Thereafter, we studied the effect of sleep deprivation on CuFC memory consolidation. Three sets of experiments were performed in male Wistar rat (n=51. In experiment-I, animals were conditioned to cued-fear by presenting ten tone-shock paired stimuli during lights-on (7 AM (n=9 and lights-off (7 PM (n=9 periods. In experiment-II, animals were prepared for polysomnographic recording (n=8 and changes in sleep architecture after CuFC was determined. Further in experiment-III, animals were cued fear-conditioned during the lights-off period and were randomly divided into four groups: Sleep-Deprived (SD (n=9, Non-Sleep Deprived (NSD (n=9, Stress Control (SC (n=9 and Tone Control (n=7. Percent freezing amount, a hallmark of fear, was compared statistically in these groups. Rats trained during the lights-off period exhibited significantly more freezing compared to lights-on period. In CuFC trained animals, total sleep amount did not change, however, REM sleep decreased significantly. Further, out of total sleep time, animals spent proportionately more time in NREM sleep. Nevertheless, SD animals exhibited significantly less freezing compared to NSD and SC groups. These data suggest that sleep plays an important role in the consolidation of cued fear-conditioned memory.

  5. 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.

  6. Impairment of fear memory consolidation and expression by antihistamines.

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    Nonaka, Ayako; Masuda, Fumitaka; Nomura, Hiroshi; Matsuki, Norio

    2013-02-01

    Antihistamines are widely used to treat allergy symptoms. First-generation antihistamines have adverse effects on the central nervous system (CNS), such as hypnotic and amnesic effects, whereas second-generation antihistamines have poor brain penetration, and therefore, have fewer CNS-related adverse effects. Memory consists of several phases, including acquisition, consolidation, expression, and extinction. It remains unclear whether these phases are affected by antihistamines. We investigated the effects of diphenhydramine, a first-generation antihistamine, and levocetirizine and olopatadine, second-generation antihistamines, on memory phases. Mice were subjected to fear conditioning on day 1 and tested on day 2. Antihistamines were administered before conditioning, immediately after conditioning, or before the test session. Diphenhydramine (30mg/kg) decreased freezing time when administered immediately after conditioning or before the test session. These effects were not attributable to a change in locomotor activity. Levocetirizine (0.1, 1, 10mg/kg) and olopatadine (1, 10, 20mg/kg) had no effects on conditioned fear. We also examined the effect of diphenhydramine and levocetirizine on the expression of an activity-dependent gene associated with the test session. Diphenhydramine, but not levocetirizine, increased Arc transcription in the central nucleus of the amygdala. These data indicate that diphenhydramine, but not levocetirizine or olopatadine, impairs the consolidation and expression of conditioned fear. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. 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…

  8. Sleep Deprivation Selectively Impairs Memory Consolidation for Contextual Fear Conditioning

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    Graves, Laurel A.; Heller, Elizabeth A.; Pack, Allan I.; Abel, Ted

    2003-01-01

    Many behavioral and electrophysiological studies in animals and humans have suggested that sleep and circadian rhythms influence memory consolidation. In rodents, hippocampus-dependent memory may be particularly sensitive to sleep deprivation after training, as spatial memory in the Morris water maze is impaired by rapid eye movement sleep deprivation following training. Spatial learning in the Morris water maze, however, requires multiple training trials and performan...

  9. 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

  10. 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

  11. 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.

  12. Altered resting-state brain activity at functional MRI during automatic memory consolidation of fear conditioning.

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    Feng, Tingyong; Feng, Pan; Chen, Zhencai

    2013-07-26

    Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms of fear acquisition and extinction. However, the neural mechanism of automatic memory consolidation of fear conditioning is still unclear. To address this question, we measured brain activity following fear acquisition using resting-state functional magnetic resonance imaging (rs-fMRI). In the current study, we used a marker of fMRI, amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to quantify the spontaneous brain activity. Brain activity correlated to fear memory consolidation was observed in parahippocampus, insula, and thalamus in resting-state. Furthermore, after acquired fear conditioning, compared with control group some brain areas showed ALFF increased in ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC) in the experimental group, whereas some brain areas showed decreased ALFF in striatal regions (caudate, putamen). Moreover, the change of ALFF in vmPFC was positively correlated with the subjective fear ratings. These findings suggest that the parahippocampus, insula, and thalamus are the neural substrates of fear memory consolidation. The difference in activity could be attributed to a homeostatic process in which the vmPFC and ACC were involved in the fear recovery process, and change of ALFF in vmPFC predicts subjective fear ratings. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Effects of transcranial direct current stimulation (tDCS on consolidation of fear memory

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    Manish eAsthana

    2013-09-01

    Full Text Available It has been shown that applying transcranial direct current stimulation (tDCS over the dorsolateral prefrontal cortex (DLPFC influences declarative memory processes. This study investigates the efficacy of tDCS on emotional memory consolidation, especially experimental fear conditioning. We applied an auditory fear-conditioning paradigm; in which two differently colored squares (blue and yellow were presented as conditioned stimuli (CS and an auditory stimulus as unconditioned stimulus (UCS. Sixty-nine participants were randomly assigned into three groups: anodal, cathodal and sham stimulation. The participants of the two active groups (i.e., anodal and cathodal received tDCS over the left DLPFC for 12 minutes after fear conditioning. The effect of fear conditioning and consolidation (24 hours later was measured by assessing the skin conductance response (SCR to the CS. The results provide evidence that cathodal stimulation of the left DLPFC leads to an inhibitory effect on fear memory consolidation compared to anodal and sham stimulation, as indicated by decreased SCRs to CS+ presentation during extinction training at day 2. In conclusion, current work suggests that cathodal stimulation interferes with processes of fear memory consolidation.

  14. 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

  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. 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.

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

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    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.

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

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    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.

  19. Sequential learning during contextual fear conditioning guides the rate of systems consolidation: Implications for consolidation of multiple memory traces.

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    Pedraza, Lizeth K; Sierra, Rodrigo O; Crestani, Ana P; Quillfeldt, Jorge A; de Oliveira Alvares, Lucas

    2017-05-01

    Systems consolidation has been described as a time-dependent reorganization process involving the neocortical and hippocampal networks underlying memory storage and retrieval. Previous studies of our lab were able to demonstrate that systems consolidation is a dynamic process, rather than a merely passive, time-dependent phenomenon. Here, we studied the influence of sequential learning in contextual fear conditioning (CFC) with different training intensities in the time-course of hippocampal dependency and contextual specificity. We found that sequential learning with high-intensity shocks during CFC induces generalization of the first learning (context A) and maintains contextual specificity of the second learning (context B) 15 days after acquisition. Moreover, subsequent experiences reorganize brain structures involved in retrieval, accelerating the involvement of cortical structures and diminishing the hippocampal participation. Exposure to original context before novelty seems to only induce context specificity in hippocampal-dependent memories. We propose that systems consolidation could be considered a potential biological mechanism for reducing possible interferences between similar memory traces. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. 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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    Marco Cambiaghi

    2017-07-01

    Full Text Available 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

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

    Science.gov (United States)

    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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  10. Memory consolidation

    NARCIS (Netherlands)

    Takashima, A.; Bakker, I.; Schmid, H.-J.

    2016-01-01

    In order to make use of novel experiences and knowledge to guide our future behavior, we must keep large amounts of information accessible for retrieval. The memory system that stores this information needs to be flexible in order to rapidly incorporate incoming information, but also requires that

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

    Science.gov (United States)

    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.

  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. 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...

  14. 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...

  15. 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.

  16. Roles of hippocampal GABA(A) and muscarinic receptors in consolidation of context memory and context-shock association in contextual fear conditioning: a double dissociation study.

    Science.gov (United States)

    Chang, Shih-Dar; Liang, K C

    2012-07-01

    Contextual fear conditioning involves forming a context representation and associating it to a shock, both of which involved the dorsal hippocampus (DH) according to our recent findings. This study tested further whether the two processes may rely on different neurotransmitter systems in the DH. Male Wistar rats with cannula implanted into the DH were subjected to a two-phase training paradigm of contextual fear conditioning to separate context learning from context-shock association in two consecutive days. Immediately after each training phase, different groups of rats received bilateral intra-DH infusion of the GABA(A) agonist muscimol, 5HT(1A) agonist 8-OH-DPAT, NMDA antagonist APV or muscarinic antagonist scopolamine at various doses. On the third day, freezing behavior was tested in the conditioning context. Results showed that intra-DH infusion of muscimol impaired conditioned freezing only if it was given after context learning. In contrast, scopolamine impaired conditioned freezing only if it was given after context-shock training. Posttraining infusion of 8-OH-DPAT or APV had no effect on conditioned freezing when the drug was given at either phase. These results showed double dissociation for the hippocampal GABAergic and cholinergic systems in memory consolidation of contextual fear conditioning: forming context memory required deactivation of the GABA(A) receptors, while forming context-shock memory involved activation of the muscarinic receptors. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. [Mechanisms for regulation of fear conditioning and memory].

    Science.gov (United States)

    Kida, Satoshi

    2014-11-01

    Pavlovian fear conditioning is a model of fear learning and memory. The mechanisms regulating fear conditioning and memory have been investigated in humans and rodents. In this paradigm, animals learn and memorize an association between a conditioned stimulus (CS), such as context, and an unconditioned stimulus (US), such as an electrical footshock that induces fear. Fear memory generated though fear conditioning is stabilized via a memory consolidation process. Moreover, recent studies have shown the existence of memory processes that control fear memory following the retrieval of consolidated memory. Indeed, when fear memory is retrieved by re-exposure to the CS, the retrieved memory is re-stabilized via the reconsolidation process. On the other hand, the retrieval of fear memory by prolonged re-exposure to the CS also leads to fear memory extinction, new inhibitory learning against the fear memory, in which animals learn that they do not need to respond to the CS. Importantly, the reinforcement of fear memory after retrieval (i.e., re-experience such as flashbacks or nightmares) has been thought to be associated with the development of emotional disorders such as post-traumatic stress disorder (PTSD). In this review, I summarize recent progress in studies on the mechanism of fear conditioning and memory consolidation, reconsolidation and extinction, and furthermore, introduce our recent establishment of a mouse PTSD model that shows enhancement of fear memory after retrieval.

  18. Exercising control over memory consolidation

    OpenAIRE

    Robertson, Edwin M.; Takacs, Adam

    2017-01-01

    Exercise can improve human cognition. A mechanistic connection between exercise and cognition has been revealed in several recent studies. Exercise increases cortical excitability and this in turn leads to enhanced memory consolidation. Together these studies dovetail with our growing understanding of memory consolidation and how it is regulated through changes in motor cortical excitability.

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

    Science.gov (United States)

    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.

  20. Inhibition of PKA anchoring to A-kinase anchoring proteins impairs consolidation and facilitates extinction of contextual fear memories

    NARCIS (Netherlands)

    Nijholt, Ingrid M.; Ostroveanu, Anghelus; Scheper, Wouter A.; Penke, Botond; Luiten, Paul G. M.; Van der Zee, Eddy A.; Eisel, Ulrich L. M.

    Both genetic and pharmacological studies demonstrated that contextual fear conditioning is critically regulated by cyclic AMP-dependent protein kinase (PKA). Since PKA is a broad range protein kinase, a mechanism for confining its activity is required. It has been shown that intracellular spatial

  1. 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.

  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. Memory consolidation in sleep disorders.

    Science.gov (United States)

    Cellini, Nicola

    2017-10-01

    In recent years sleep-related memory consolidation has become a central topic in the sleep research field. Several studies have shown that in healthy individuals sleep promotes memory consolidation. Notwithstanding this, the consequences of sleep disorders on offline memory consolidation remain poorly investigated. Research studies indicate that patients with insomnia, obstructive sleep apnea, and narcolepsy often exhibit sleep-related impairment in the consolidation of declarative and procedural information. On the other hand, patients with parasomnias, such as sleep-walking, night terrors and rapid eye movement (REM) behavior disorder, do not present any memory impairment. These studies suggest that only sleep disorders characterized by increased post-learning arousal and disrupted sleep architecture seem to be associated with offline memory consolidation issues. Such impairments, arising already in childhood, may potentially affect the development and maintenance of an individual's cognitive abilities, reducing their quality of life and increasing the risk of accidents. However, promising findings suggest that successfully treating sleep symptoms can result in the restoration of memory functions and marked reduction of direct and indirect societal costs of sleep disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Activation of Metabotropic Glutamate Receptor Type 2/3 Supports the Involvement of the Hippocampal Mossy Fiber Pathway on Contextual Fear Memory Consolidation

    Science.gov (United States)

    Daumas, Stephanie; Ceccom, Johnatan; Halley, Helene; Frances, Bernard; Lassalle, Jean-Michel

    2009-01-01

    Elucidating the functional properties of the dentate gyrus (DG), CA3, and CA1 areas is critical for understanding the role of the dorsal hippocampus in contextual fear memory processing. In order to specifically disrupt various hippocampal inputs, we used region-specific infusions of DCG-IV, the metabotropic glutamate receptor agonist, which…

  6. 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…

  7. 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

  8. 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).

  9. 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.

  10. 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…

  11. 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.

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

    Science.gov (United States)

    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.

  13. Histaminergic ligands injected into the nucleus basalis magnocellularis differentially affect fear conditioning consolidation.

    Science.gov (United States)

    Benetti, Fernando; Baldi, Elisabetta; Bucherelli, Corrado; Blandina, Patrizio; Passani, Maria Beatrice

    2013-04-01

    The role of the nucleus basalis magnocellularis (NBM) in fear conditioning encoding is well established. In the present report, we investigate the involvement of the NBM histaminergic system in consolidating fear memories. The NBM was injected bilaterally with ligands of histaminergic receptors immediately after contextual fear conditioning. Histaminergic compounds, either alone or in combination, were stereotaxically administered to different groups of adult male Wistar rats and memory was assessed as conditioned freezing duration 72 h after administration. This protocol prevents interference with NBM function during either acquisition or retrieval phases, hence restricting the effect of pharmacological manipulations to fear memory consolidation. The results presented here demonstrate that post-training H3 receptors (H3R) blockade with the antagonist/inverse agonist thioperamide or activation with immepip in the NBM potentiates or decreases, respectively, freezing response at retrieval. Thioperamide induced memory enhancement seems to depend on H2R, but not H1R activation, as the H2R antagonist zolantidine blocked the effect of thioperamide, whereas the H1R antagonist pyrilamine was ineffective. Furthermore, the H2R agonist ampthamine improved fear memory expression independently of the H3R agonist effect. Our results indicate that activation of post-synaptic H2R within the NBM by endogenous histamine is responsible for the potentiated expression of fear responses. The results are discussed in terms of activation of H3 auto- and heteroreceptors within the NBM and the differential effect of H3R ligands on fear memory consolidation in distinct brain regions.

  14. Erasing fear memories with extinction training.

    Science.gov (United States)

    Quirk, Gregory J; Paré, Denis; Richardson, Rick; Herry, Cyril; Monfils, Marie H; Schiller, Daniela; Vicentic, Aleksandra

    2010-11-10

    Decades of behavioral studies have confirmed that extinction does not erase classically conditioned fear memories. For this reason, research efforts have focused on the mechanisms underlying the development of extinction-induced inhibition within fear circuits. However, recent studies in rodents have uncovered mechanisms that stabilize and destabilize fear memories, opening the possibility that extinction might be used to erase fear memories. This symposium focuses on several of these new developments, which involve the timing of extinction training. Extinction-induced erasure of fear occurs in very young rats, but is lost with the development of perineuronal nets in the amygdala that render fear memories impervious to extinction. Moreover, extinction administered during the reconsolidation phase, when fear memory is destabilized, updates the fear association as safe, thereby preventing the return of fear, in both rats and humans. The use of modified extinction protocols to eliminate fear memories complements existing pharmacological strategies for strengthening extinction.

  15. Erasing fear memories with extinction training

    OpenAIRE

    Quirk, Gregory J.; Paré, Denis; Richardson, Rick; Herry, Cyril; Monfils, Marie H.; Schiller, Daniela; Vicentic, Aleksandra

    2010-01-01

    Decades of behavioral studies have confirmed that extinction does not erase classically-conditioned fear memories. For this reason, research efforts have focused on the mechanisms underlying the development of extinction-induced inhibition within fear circuits. However, recent studies in rodents have uncovered mechanisms that stabilize and destabilize fear memories, opening the possibility that extinction might be used to erase fear memories. This symposium focuses on several of these new dev...

  16. Negative Reinforcement Impairs Overnight Memory Consolidation

    Science.gov (United States)

    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…

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. Fimbria-fornix and entorhinal cortex differential contribution to contextual and cued fear conditioning consolidation in rats.

    Science.gov (United States)

    Baldi, Elisabetta; Liuzzo, Antonino; Bucherelli, Corrado

    2013-04-10

    The Fimbria-Fornix (FF) and Entorhinal Cortex (EC) are the primary interfaces between the hippocampus and, respectively, subcortical structures and cortical areas. Their mnemonic role has been repeatedly proposed. In order to investigate their role in fear conditioning, FF and EC were subjected to bilateral fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that had undergone training for fear conditioning to an acoustic stimulus (CS) and context. TTX was stereotaxically injected into animals of different groups at increasing post-acquisition delays. Memory was assessed as conditioned freezing duration measured during retention testing, performed 72 and 96 h after TTX administration in a counterbalanced manner. The results showed that FF inactivation, performed immediately after conditioning, did not disrupt consolidation of either contextual or auditory fear memory. On the contrary, EC inactivation performed at the same time was followed by both contextual and CS fear response retention impairment. EC inactivation performed 1.5h post-acquisition impaired only contextual fear response retention. EC inactivation performed 24h after acquisition training had no effect on the consolidation process. The present findings show a clearly different role of FF and EC in fear conditioning consolidation in the rat. The results are discussed in relation to their known connections with the hippocampus. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Memory consolidation in the cerebellar cortex.

    Directory of Open Access Journals (Sweden)

    Daniel O Kellett

    2010-07-01

    Full Text Available Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABAA agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage.

  4. Memory, Sleep and Dreaming: Experiencing Consolidation

    OpenAIRE

    Wamsley, Erin J.; Stickgold, Robert

    2011-01-01

    It is now well established that post-learning sleep is beneficial for human memory performance. At the same time, it has long been known that learning experiences influence the content of subsequent sleep mentation (i.e., “dreaming”). Here, we review evidence that newly encoded memories are reactivated and consolidated in the sleeping brain, and that this process is directly reflected in the content of concomitant sleep mentation, providing a valuable window into the mnemonic functions of sle...

  5. 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.

  6. Autobiographical thinking interferes with episodic memory consolidation.

    Directory of Open Access Journals (Sweden)

    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.

  7. Inhibition of prefrontal protein synthesis following recall does not disrupt memory for trace fear conditioning

    Directory of Open Access Journals (Sweden)

    Dash Pramod K

    2006-10-01

    Full Text Available Abstract Background The extent of similarity between consolidation and reconsolidation is not yet fully understood. One of the differences noted is that not every brain region involved in consolidation exhibits reconsolidation. In trace fear conditioning, the hippocampus and the medial prefrontal cortex (mPFC are required for consolidation of long-term memory. We have previously demonstrated that trace fear memory is susceptible to infusion of the protein synthesis inhibitor anisomycin into the hippocampus following recall. In the present study, we examine whether protein synthesis inhibition in the mPFC following recall similarly results in the observation of reconsolidation of trace fear memory. Results Targeted intra-mPFC infusions of anisomycin or vehicle were performed immediately following recall of trace fear memory at 24 hours, or at 30 days, following training in a one-day or a two-day protocol. The present study demonstrates three key findings: 1 trace fear memory does not undergo protein synthesis dependent reconsolidation in the PFC, regardless of the intensity of the training, and 2 regardless of whether the memory is recent or remote, and 3 intra-mPFC inhibition of protein synthesis immediately following training impaired remote (30 days memory. Conclusion These results suggest that not all structures that participate in memory storage are involved in reconsolidation. Alternatively, certain types of memory-related information may reconsolidate, while other components of memory may not.

  8. 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.

  9. Dissociating response systems: erasing fear from memory

    NARCIS (Netherlands)

    Soeter, A.C.; Kindt, M.

    2010-01-01

    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

  10. 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

  11. Acute exercise and motor memory consolidation

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...... 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...

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

    OpenAIRE

    Joels, Gil; Lamprecht, Raphael

    2014-01-01

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

  13. 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

  14. Sleep-Dependent Memory Consolidation in Children.

    Science.gov (United States)

    Maski, Kiran P

    2015-06-01

    In the past 30 years, much research has been conducted elucidating the role of sleep in memory and learning; however, the interaction between sleep and cognitive functioning may be unknown in clinical realms. This article serves to provide a primer on sleep-dependent memory consolidation, a process in which memory is stabilized or even enhanced over a period of sleep. Given the increased amounts of sleep needed in infancy and childhood, the link between sleep and neuronal plasticity is highlighted in this article. Furthermore, sleep disruptions are common to children with neurodevelopmental disorders such as attention-deficit hyperactivity disorder; thus, recent studies showing direct relationships between sleep and memory functioning in such vulnerable groups are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Erasing Fear : Effect of Disrupting Fear Memory Reconsolidation on Central and Peripheral Nervous System Activity

    OpenAIRE

    Ågren, Thomas

    2012-01-01

    Fear memories, here defined as learned associations between a stimulus and a physiological fear reaction, are formed through fear conditioning. In animals, fear memories, present in the lateral amygdala, undergo reconsolidation after recall. Moreover, this reconsolidation process can be disrupted both pharmacologically and behaviourally, resulting in a reduced fear response to the stimulus. This thesis examines the attenuation of fear memories by disrupting reconsolidation in humans, using me...

  16. 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.

  17. 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.

  18. Post-training Meditation Promotes Motor Memory Consolidation

    OpenAIRE

    Immink, Maarten A.

    2016-01-01

    Following training, motor memory consolidation is thought to involve either memory stabilization or off-line learning processes. The extent to which memory stabilization or off-line learning relies on post-training wakeful periods or sleep is not clear and thus, novel research approaches are needed to further explore the conditions that promote motor memory consolidation. The present experiment represents the first empirical test of meditation as potential facilitator of motor memory consol...

  19. The retrosplenial cortex is involved in the formation of memory for context and trace fear conditioning.

    Science.gov (United States)

    Kwapis, Janine L; Jarome, Timothy J; Lee, Jonathan L; Helmstetter, Fred J

    2015-09-01

    The retrosplenial cortex (RSC) is known to play a role in the retrieval of context memory, but its involvement in memory formation and consolidation is unclear. To better characterize the role of the RSC, we tested its involvement in the formation and retrieval of memory for trace fear conditioning, a task that requires the association of two cues separated by an empty period of time. We have previously shown that trace fear extinction requires the RSC (Kwapis, Jarome, Lee, Gilmartin, & Helmstetter, 2014) and have hypothesized that trace memory may be stored in a distributed cortical network that includes prelimbic and retrosplenial cortices (Kwapis, Jarome, & Helmstetter, 2015). Whether the RSC participates in acquiring and storing cued trace fear, however, is currently unknown. Here, we demonstrate that blocking protein synthesis in the RSC before, but not after acquisition impairs rats' memory for trace CS and context fear without affecting memory for the CS in standard delay fear conditioning. We also show that NMDA receptor blockade in the RSC transiently impairs memory retrieval for trace, but not delay memory. The RSC therefore appears to critically contribute to formation of trace and context fear memory in addition to its previously recognized role in context memory retrieval. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. 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.

  1. 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...

  2. An Additional Prior Retrieval Alters the Effects of a Retrieval-Extinction Procedure on Recent and Remote Fear Memory

    Directory of Open Access Journals (Sweden)

    Xianli An

    2018-01-01

    Full Text Available Several studies have shown that the isolated retrieval of a consolidated fear memory can induce a labile phase, during which extinction training can prevent the reinstatement, a form of relapse in which fear response to a fear-provoking context returns when a mild shock is presented. However, fear memory retrieval may also have another opposing result: the enhancement of fear memory. This implies that the fear memory trace can be modified by a brief retrieval. Unclear is whether the fear-impairing effect of retrieval-extinction (RE is altered by a prior brief retrieval. The present study investigated the responses of recent and remote fear memories to the RE procedure after the presentation of an additional prior retrieval (priRet. We found that a single RE procedure effectively blocked the reinstatement of 2-day recent contextual fear memory. The memory-impairing effect of the RE procedure on recent fear was not observed when priRet was presented 6 or 24 h before the RE procedure. In contrast to the 2-day recent memory, the RE procedure failed to block the reinstatement of 36-day remote fear memory but successfully disrupted the return of remote fear memory after priRet. This memory-disruptive effect on remote memory did not occur when priRet was performed in a novel context. Nimodipine administration revealed that the blockade of priRet-induced processes recovered the effects of the RE procedure on both recent and remote fear memories. Our findings suggest that the susceptibility of recent and remote fear memories to RE procedures can be altered by an additional retrieval.

  3. 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.

  4. 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...

  5. Memory consolidation reconfigures neural pathways involved in the suppression of emotional memories.

    Science.gov (United States)

    Liu, Yunzhe; Lin, Wanjun; Liu, Chao; Luo, Yuejia; Wu, Jianhui; Bayley, Peter J; Qin, Shaozheng

    2016-11-29

    The ability to suppress unwanted emotional memories is crucial for human mental health. Through consolidation over time, emotional memories often become resistant to change. However, how consolidation impacts the effectiveness of emotional memory suppression is still unknown. Using event-related fMRI while concurrently recording skin conductance, we investigated the neurobiological processes underlying the suppression of aversive memories before and after overnight consolidation. Here we report that consolidated aversive memories retain their emotional reactivity and become more resistant to suppression. Suppression of consolidated memories involves higher prefrontal engagement, and less concomitant hippocampal and amygdala disengagement. In parallel, we show a shift away from hippocampal-dependent representational patterns to distributed neocortical representational patterns in the suppression of aversive memories after consolidation. These findings demonstrate rapid changes in emotional memory organization with overnight consolidation, and suggest possible neurobiological bases underlying the resistance to suppression of emotional memories in affective disorders.

  6. 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.

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

    Science.gov (United States)

    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. Effects of memory age and interval of fear extinction sessions on contextual fear extinction.

    Science.gov (United States)

    Matsuda, Shingo; Matsuzawa, Daisuke; Ishii, Daisuke; Tomizawa, Haruna; Shimizu, Eiji

    2014-08-22

    Fear extinction is a major task in our understanding of the biological mechanisms of exposure therapy, one of the most used treatments for stress-related disorders. It was recently reported that an extinction of 5 consecutive days prevents spontaneous recovery of fear memory. Memory age and the timing of fear extinction influence the effect of fear extinction. In this study, we used contextual fear extinction in adult male mice to examine whether memory age influences an extinction of 5 consecutive days and whether consecutiveness is necessary to prevent spontaneous recovery. Our results showed that, although fear memory was not affected by the passage of time, the old fear memory (28 days after fear conditioning) was more sensitive to fear extinction than the young fear memory (7 days after fear conditioning). Additionally, we demonstrated that consecutiveness of extinction sessions is not necessary to prevent spontaneous recovery. Instead, fear extinction sessions at spaced intervals were found to be more effective than consecutive extinction sessions for young fear memory. Our results suggest that taking memory age and the interval of fear extinction sessions into consideration would help to optimize exposure therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. 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.

  10. 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.

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

    OpenAIRE

    Maski, Kiran; Steinhart, Erin; Holbrook, Hannah; Katz, Eliot S.; Kapur, Kush; Stickgold, Robert

    2017-01-01

    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 consoli...

  12. Optogenetic disruption of sleep continuity impairs memory consolidation

    OpenAIRE

    Rolls, Asya; Colas, Damien; Adamantidis, Antoine; Carter, Matt; Lanre-Amos, Tope; Heller, H. Craig; de Lecea, Luis

    2011-01-01

    Memory consolidation has been proposed as a function of sleep. However, sleep is a complex phenomenon characterized by several features including duration, intensity, and continuity. Sleep continuity is disrupted in different neurological and psychiatric conditions, many of which are accompanied by memory deficits. This finding has raised the question of whether the continuity of sleep is important for memory consolidation. However, current techniques used in sleep research cannot manipulate ...

  13. 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.

  14. 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.

  15. 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…

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

    Science.gov (United States)

    Qureshi, Munazah F; Jha, Sushil K

    2017-01-01

    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 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.

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

    Science.gov (United States)

    Qureshi, Munazah F.; Jha, Sushil K.

    2017-01-01

    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 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. PMID:29238297

  18. 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.

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

    Science.gov (United States)

    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…

  20. Sleep-dependent memory consolidation and its implications for psychiatry.

    Science.gov (United States)

    Goerke, Monique; Müller, Notger G; Cohrs, Stefan

    2017-02-01

    Both sleep disturbance and memory impairment are very common in psychiatric disorders. Since sleep has been shown to play a role in the process of transferring newly acquired information into long-term memory, i.e., consolidation, it is important to highlight this link in the context of psychiatric disorders. Along these lines, after providing a brief overview of healthy human sleep, current neurobiological models on sleep-dependent memory consolidation and resultant opportunities to manipulate the memory consolidation process, recent findings on sleep disturbances and sleep-dependent memory consolidation in patients with insomnia, major depression, schizophrenia, and post-traumatic stress disorder are systematically reviewed. Furthermore, possible underlying neuropathologies and their implications on therapeutic strategies are discussed. This review aims at sensitizing the reader for recognizing sleep disturbances as a potential contributor to cognitive deficits in several disorders, a fact which is often overlooked up to date.

  1. 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.

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

    Science.gov (United States)

    Wang, Bo

    2015-05-01

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

  3. The Membrane Proximal Region of AMPA Receptors in Lateral Amygdala is Essential for Fear Memory Formation.

    Science.gov (United States)

    Ganea, Dan A; Dines, Monica; Basu, Sreetama; Lamprecht, Raphael

    2015-11-01

    The membrane proximal region (MPR) of AMPA receptor (AMPAR) is needed for receptor trafficking and synaptic plasticity. However, its roles in long-term memory formation are not known. To assess the possible roles of AMPAR-MPR in rat lateral amygdala (LA) in short- and long-term fear memory formation, we used glutamate receptors (GluAs)-MPR competitive peptides MPR(DD) and MPR(AA). The MPR(DD) peptide is derived from GluA1 MPR and was previously shown to impair synaptic plasticity and to inhibit GluA1 containing AMPAR insertion into the synapse in an activity-dependent manner. The MPR(AA) peptide is derived from GluA2/4 MPR, and this receptor fragment was shown to be essential for GluA4 protein interaction needed for its insertion into the neuronal membrane and synapse. The peptides were linked to a TAT peptide (TAT-MPR(DD) and TAT-MPR(AA)) to facilitate internalization into LA cells. Infusion of the TAT-MPR(DD) peptide into LA 30 min before fear conditioning led to a significant impairment of long-term fear memory formation. Injection of TAT-MPR(DD) peptide into LA 30 min before fear conditioning impaired short-term fear memory formation. The TAT-MPR(DD) peptide had no effect on memory retrieval when injected into LA 30 min before fear memory test. Infusion of the TAT-MPR(AA) peptide into LA 30 min before fear conditioning led to a significant impairment of long-term fear memory formation. In contrast, the TAT-MPR(AA) had no effect on short-term fear memory formation. A TAT-control peptide had no effect on short- or long-term fear memory. These results show that the AMPAR-MPR in LA is needed for fear memory formation and that the MPR region of GluA1 is essential for acquisition of memory, whereas the MPR region of GluA4 is essential for long-term fear memory consolidation.

  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. 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

  6. The Time Course of Consolidation in Visual Working Memory

    Science.gov (United States)

    Vogel, Edward K.; Woodman, Geoffrey F.; Luck, Steven J.

    2006-01-01

    How long does it take to form a durable representation in visual working memory? Several theorists have proposed that this consolidation process is very slow. Here, we measured the time course of consolidation. Observers performed a change-detection task for colored squares, and shortly after the presentation of the first array, pattern masks were…

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

    Science.gov (United States)

    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.

  8. A Bird's Eye View of Sleep-Dependent Memory Consolidation.

    Science.gov (United States)

    Brawn, Timothy P; Margoliash, Daniel

    2015-01-01

    How new experiences are solidified into long-lasting memories is a central question in the study of brain and behavior. One of the most intriguing discoveries in memory research is that brain activity during sleep helps to transform newly learned information and skills into robust memories. Though the first experimental work linking sleep and memory was conducted 90 years ago by Jenkins and Dallenbach, the case for sleep-dependent memory consolidation has only garnered strong support in the last decade. Recent studies in humans provide extensive behavioral, imaging, and polysomnographic data supporting sleep consolidation of a broad range of memory tasks. Likewise, studies in a few animal model systems have elucidated potential mechanisms contributing to sleep consolidation such as neural reactivation and synaptic homeostasis. Here, we present an overview of sleep-dependent memory consolidation, focusing on how investigations of sleep and learning in birds have complemented the progress made in mammalian systems by emphasizing a strong connection between behavior and physiology. We begin by describing the behavioral approach that has been utilized to demonstrate sleep consolidation in humans. We then address neural reactivation in the rodent hippocampal system as a putative mechanism of sleep consolidation. Next, we discuss the role of sleep in the learning and maintenance of song in zebra finches. We note that while both the rodent and zebra finch systems provide evidence for sleep-dependent memory changes in physiology and behavior, neither duplicates the pattern of changes most commonly observed in humans. Finally, we present a recently developed model of sleep consolidation involving auditory classification learning in European starlings , which has the potential to connect behavioral evidence of sleep consolidation as developed in humans with underlying neural mechanisms observable in animals.

  9. Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation

    Science.gov (United States)

    Ognjanovski, Nicolette; Schaeffer, Samantha; Wu, Jiaxing; Mofakham, Sima; Maruyama, Daniel; Zochowski, Michal; Aton, Sara J.

    2017-04-01

    Activity in hippocampal area CA1 is essential for consolidating episodic memories, but it is unclear how CA1 activity patterns drive memory formation. We find that in the hours following single-trial contextual fear conditioning (CFC), fast-spiking interneurons (which typically express parvalbumin (PV)) show greater firing coherence with CA1 network oscillations. Post-CFC inhibition of PV+ interneurons blocks fear memory consolidation. This effect is associated with loss of two network changes associated with normal consolidation: (1) augmented sleep-associated delta (0.5-4 Hz), theta (4-12 Hz) and ripple (150-250 Hz) oscillations; and (2) stabilization of CA1 neurons' functional connectivity patterns. Rhythmic activation of PV+ interneurons increases CA1 network coherence and leads to a sustained increase in the strength and stability of functional connections between neurons. Our results suggest that immediately following learning, PV+ interneurons drive CA1 oscillations and reactivation of CA1 ensembles, which directly promotes network plasticity and long-term memory formation.

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

    Science.gov (United States)

    Basu, Sreetama; Kustanovich, Irina; Lamprecht, Raphael

    2016-01-01

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

  11. Hippocampo-cortical coupling mediates memory consolidation during sleep.

    Science.gov (United States)

    Maingret, Nicolas; Girardeau, Gabrielle; Todorova, Ralitsa; Goutierre, Marie; Zugaro, Michaël

    2016-07-01

    Memory consolidation is thought to involve a hippocampo-cortical dialog during sleep to stabilize labile memory traces for long-term storage. However, direct evidence supporting this hypothesis is lacking. We dynamically manipulated the temporal coordination between the two structures during sleep following training on a spatial memory task specifically designed to trigger encoding, but not memory consolidation. Reinforcing the endogenous coordination between hippocampal sharp wave-ripples, cortical delta waves and spindles by timed electrical stimulation resulted in a reorganization of prefrontal cortical networks, along with subsequent increased prefrontal responsivity to the task and high recall performance on the next day, contrary to control rats, which performed at chance levels. Our results provide, to the best of our knowledge, the first direct evidence for a causal role of a hippocampo-cortical dialog during sleep in memory consolidation, and indicate that the underlying mechanism involves a fine-tuned coordination between sharp wave-ripples, delta waves and spindles.

  12. 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.

  13. Propranolol disrupts consolidation of emotional memory in Lymnaea.

    Science.gov (United States)

    Shymansky, Tamila; Hughes, Emily; Rothwell, Cailin M; Lukowiak, Ken

    2018-03-01

    The therapeutic efficacy of the synthetic β-adrenergic receptor blocker, propranolol, for the treatment of post-traumatic stress disorder (PTSD) is currently being debated. Mixed results have been published regarding propranolol's ability to disrupt the consolidation and reconsolidation of memories. Here, we use the invertebrate model Lymnaea to study propranolol's ability to disrupt consolidation of memories formed under varying various types of stress which cause differing degrees of emotional memory. We show that when propranolol is administered immediately following operant conditioning, only the consolidation process of memories enhanced by individual stressors (i.e. a non-emotional memory) is susceptible to disruption. However, when propranolol is administered prior to training, only memories enhanced by a combination of stressors leading to an emotional memory are susceptible to disruption. These data suggest that the time of propranolol administration, as well as the type of memory formed play a key role in propranolol's ability to obstruct memory consolidation. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Maski, Kiran; Steinhart, Erin; Holbrook, Hannah; Katz, Eliot S; Kapur, Kush; Stickgold, Robert

    2017-01-01

    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, Pmemory 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 = 2.03, P = 0.04]. NREM slow oscillation power did not correlate with memory

  15. 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…

  16. 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.

  17. Different genetic factors underlie fear conditioning and episodic memory.

    Science.gov (United States)

    Fredrikson, Mats; Annas, Peter; Hettema, John M

    2015-08-01

    Fear conditioning seems to account for the acquisition of post-traumatic stress disorder, whereas conscious recall of events in aftermath of trauma reflects episodic memory. Studies show that both fear conditioning and episodic memory are heritable, but no study has evaluated whether they reflect common or separate genetic factors. To this end, we studied episodic memory and fear conditioning in 173 healthy twin pairs using visual stimuli predicting unconditioned electric shocks. Fear conditioning acquisition and extinction was determined using conditioned visual stimuli predicting unconditioned mild electric shocks, whereas electrodermal activity served as the fear learning index. Episodic memory was evaluated using cued recall of pictorial stimuli unrelated to conditioning. We used multivariate structural equation modeling to jointly analyze memory performance and acquisition as well as extinction of fear conditioning. Best-fit twin models estimated moderate genetic loadings for conditioning and memory measures, with no genetic covariation between them. Individual differences in fear conditioning and episodic memory reflect distinct genetically influenced processes, suggesting that the genetic risk for learning-induced anxiety disorders includes at least two memory-related genetic factors. These findings are consistent with the facts that the two separate learning forms are distant in their evolutionary development, involve different brain mechanisms, and support that genetically independent memory systems are pivotal in the development and maintenance of syndromes related to fear learning.

  18. 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

  19. 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.

  20. Memory Reactivation and Consolidation during Sleep

    Science.gov (United States)

    Paller, Ken A.; Voss, Joel L.

    2004-01-01

    Do our memories remain static during sleep, or do they change? We argue here that memory change is not only a natural result of sleep cognition, but further, that such change constitutes a fundamental characteristic of declarative memories. In general, declarative memories change due to retrieval events at various times after initial learning and…

  1. 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.

  2. High Trait Anxiety: A Challenge for Disrupting Fear Memory Reconsolidation

    Science.gov (United States)

    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. PMID:24260096

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Acute Exercise and Motor Memory Consolidation

    DEFF Research Database (Denmark)

    Thomas, Richard

    implications for different settings, including rehabilitation, schools and sports, it is currently unclear to what extent the parameters within exercise itself differentially affect the consolidation process of motor skill learning. The aim of this thesis was, therefore, to investigate the variables...... of exercise intensity, timing and type on the consolidation of visuomotor skill learning, to obtain further understanding of the behavioral effects and underlying mechanisms. Study I focused on the role of exercise intensity and included a low (EX45: 45% Wmax) and high (EX90: 90% Wmax) intensity aerobic......-acquisition level and CON. There were no between-group differences 1 day for the exercise groups. Exercise type did not differentially affect the consolidation and retention of the visuomotor skill learning. Conclusions: Acute exercise modulates the consolidation of newly acquired motor skills in humans...

  5. CA1 hippocampal network activity changes during sleep-dependent memory consolidation

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    Nicolette N Ognjanovski

    2014-04-01

    Full Text Available A period of sleep over the first few hours following single-trial contextual fear conditioning (CFC is essential for hippocampally-mediated memory consolidation. Recent studies have uncovered intracellular mechanisms required for memory formation that are affected by post-conditioning sleep and sleep deprivation. However, almost nothing is known about the circuit-level activity changes during sleep that underlie activation of these intracellular pathways. Here we continuously record neuronal activity from the CA1 region of freely-behaving mice to characterize neuronal and network activity changes occurring during active memory consolidation. C57BL/6J mice were implanted with custom stereotrode recording arrays to monitor activity of individual CA1 neurons, local field potentials (LFPs, and electromyographic activity. Sleep architecture and state-specific CA1 activity patterns were assessed during a 24 h baseline recording period, and for 24 h following either single-trial CFC or Sham conditioning. We find that consolidation of CFC is not associated with significant sleep architecture changes, but is accompanied by long-lasting increases in CA1 neuronal firing, as well as increases in delta, theta, and gamma-frequency CA1 LFP activity. These changes occurred in both sleep and wakefulness, and may drive synaptic plasticity within the hippocampus during memory formation. We also find that functional connectivity within the CA1 network, assessed through functional clustering analysis (FCA of spike timing relationships among recorded neurons, becomes more stable during consolidation of CFC. This increase in network stability was not present following Sham conditioning, was most evident during post-CFC slow wave sleep, and was negligible during post-CFC wakefulness. Thus in the interval between encoding and recall, slow wave sleep may stabilize the hippocampal contextual fear memory trace by promoting CA1 network stability.

  6. Sleep-dependent memory consolidation and accelerated forgetting.

    Science.gov (United States)

    Atherton, Kathryn E; Nobre, Anna C; Zeman, Adam Z; Butler, Christopher R

    2014-05-01

    Accelerated long-term forgetting (ALF) is a form of memory impairment in which learning and initial retention of information appear normal but subsequent forgetting is excessively rapid. ALF is most commonly associated with epilepsy and, in particular, a form of late-onset epilepsy called transient epileptic amnesia (TEA). ALF provides a novel opportunity to investigate post-encoding memory processes, such as consolidation. Sleep is implicated in the consolidation of memory in healthy people and a deficit in sleep-dependent memory consolidation has been proposed as an explanation for ALF. If this proposal were correct, then sleep would not benefit memory retention in people with ALF as much as in healthy people, and ALF might only be apparent when the retention interval contains sleep. To test this theory, we compared performance on a sleep-sensitive memory task over a night of sleep and a day of wakefulness. We found, contrary to the hypothesis, that sleep benefits memory retention in TEA patients with ALF and that this benefit is no smaller in magnitude than that seen in healthy controls. Indeed, the patients performed significantly more poorly than the controls only in the wake condition and not the sleep condition. Patients were matched to controls on learning rate, initial retention, and the effect of time of day on cognitive performance. These results indicate that ALF is not caused by a disruption of sleep-dependent memory consolidation. Instead, ALF may be due to an encoding abnormality that goes undetected on behavioural assessments of learning, or by a deficit in memory consolidation processes that are not sleep-dependent. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Post-training meditation promotes motor memory consolidation

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    Maarten A Immink

    2016-11-01

    Full Text Available Following training, motor memory consolidation is thought to involve either memory stabilization or off-line learning processes. The extent to which memory stabilization or off-line learning relies on post-training wakeful periods or sleep is not clear and thus, novel research approaches are needed to further explore the conditions that promote motor memory consolidation. The present experiment represents the first empirical test of meditation as potential facilitator of motor memory consolidation. Twelve adult residents of a yoga center with a mean of nine years meditation experience were trained on a sequence key pressing task. Three hours after training, the meditation group completed a 30 minute session of yoga nidra meditation while a control group completed 30 minutes of light work duties. A wakeful period of 4.5 hours followed meditation after which participants completed a test involving both trained and untrained sequences. Training performance did not significantly differ between groups. Comparison of group performance at test, revealed a performance benefit of post-training meditation but this was limited to trained sequences only. That the post-training meditation performance benefit was specific to trained sequences is consistent with the notion of meditation promoting motor memory consolidation as opposed to general motor task performance benefits from meditation. Further, post-training meditation appears to have promoted motor memory stabilization as opposed to off-line learning. These findings represent the first demonstration of meditation related motor memory consolidation and are consistent with a growing body of literature demonstrating the benefits of meditation for cognitive function, including memory.

  8. Post-training Meditation Promotes Motor Memory Consolidation.

    Science.gov (United States)

    Immink, Maarten A

    2016-01-01

    Following training, motor memory consolidation is thought to involve either memory stabilization or off-line learning processes. The extent to which memory stabilization or off-line learning relies on post-training wakeful periods or sleep is not clear and thus, novel research approaches are needed to further explore the conditions that promote motor memory consolidation. The present experiment represents the first empirical test of meditation as potential facilitator of motor memory consolidation. Twelve adult residents of a yoga center with a mean of 9 years meditation experience were trained on a sequence key pressing task. Three hours after training, the meditation group completed a 30 min session of yoga nidra meditation while a control group completed 30 min of light work duties. A wakeful period of 4.5 h followed meditation after which participants completed a test involving both trained and untrained sequences. Training performance did not significantly differ between groups. Comparison of group performance at test, revealed a performance benefit of post-training meditation but this was limited to trained sequences only. That the post-training meditation performance benefit was specific to trained sequences is consistent with the notion of meditation promoting motor memory consolidation as opposed to general motor task performance benefits from meditation. Further, post-training meditation appears to have promoted motor memory stabilization as opposed to off-line learning. These findings represent the first demonstration of meditation related motor memory consolidation and are consistent with a growing body of literature demonstrating the benefits of meditation for cognitive function, including memory.

  9. A key role for nectin-1 in the ventral hippocampus in contextual fear memory.

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    Martina Fantin

    Full Text Available Nectins are cell adhesion molecules that are widely expressed in the brain. Nectin expression shows a dynamic spatiotemporal regulation, playing a role in neural migratory processes during development. Nectin-1 and nectin-3 and their heterophilic trans-interactions are important for the proper formation of synapses. In the hippocampus, nectin-1 and nectin-3 localize at puncta adherentia junctions and may play a role in synaptic plasticity, a mechanism essential for memory and learning. We evaluated the potential involvement of nectin-1 and nectin-3 in memory consolidation using an emotional learning paradigm. Rats trained for contextual fear conditioning showed transient nectin-1-but not nectin-3-protein upregulation in synapse-enriched hippocampal fractions at about 2 h posttraining. The upregulation of nectin-1 was found exclusively in the ventral hippocampus and was apparent in the synaptoneurosomal fraction. This upregulation was induced by contextual fear conditioning but not by exposure to context or shock alone. When an antibody against nectin-1, R165, was infused in the ventral-hippocampus immediately after training, contextual fear memory was impaired. However, treatment with the antibody in the dorsal hippocampus had no effect in contextual fear memory formation. Similarly, treatment with the antibody in the ventral hippocampus did not interfere with acoustic memory formation. Further control experiments indicated that the effects of ventral hippocampal infusion of the nectin-1 antibody in contextual fear memory cannot be ascribed to memory non-specific effects such as changes in anxiety-like behavior or locomotor behavior. Therefore, we conclude that nectin-1 recruitment to the perisynaptic environment in the ventral hippocampus plays an important role in the formation of contextual fear memories. Our results suggest that these mechanisms could be involved in the connection of emotional and contextual information processed in the

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

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    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.

  11. 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).

  12. 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

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

    Directory of Open Access Journals (Sweden)

    Yuzhe Li

    2016-09-01

    Full Text Available 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.

  14. 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.

  15. Optogenetic disruption of sleep continuity impairs memory consolidation.

    Science.gov (United States)

    Rolls, Asya; Colas, Damien; Adamantidis, Antoine; Carter, Matt; Lanre-Amos, Tope; Heller, H Craig; de Lecea, Luis

    2011-08-09

    Memory consolidation has been proposed as a function of sleep. However, sleep is a complex phenomenon characterized by several features including duration, intensity, and continuity. Sleep continuity is disrupted in different neurological and psychiatric conditions, many of which are accompanied by memory deficits. This finding has raised the question of whether the continuity of sleep is important for memory consolidation. However, current techniques used in sleep research cannot manipulate a single sleep feature while maintaining the others constant. Here, we introduce the use of optogenetics to investigate the role of sleep continuity in memory consolidation. We optogenetically targeted hypocretin/orexin neurons, which play a key role in arousal processes. We used optogenetics to activate these neurons at different intervals in behaving mice and were able to fragment sleep without affecting its overall amount or intensity. Fragmenting sleep after the learning phase of the novel object recognition (NOR) task significantly decreased the performance of mice on the subsequent day, but memory was unaffected if the average duration of sleep episodes was maintained at 62-73% of normal. These findings demonstrate the use of optogenetic activation of arousal-related nuclei as a way to systematically manipulate a specific feature of sleep. We conclude that regardless of the total amount of sleep or sleep intensity, a minimal unit of uninterrupted sleep is crucial for memory consolidation.

  16. Sculpting memory during sleep: concurrent consolidation and forgetting.

    Science.gov (United States)

    Feld, Gordon B; Born, Jan

    2017-06-01

    There is compelling evidence that sleep actively supports the formation of long-lasting memory representations. Experimental cuing of memories proved that neural replay of representations during sleep plays a causal role for this consolidation, which has also been shown to promote neocortical synaptic plasticity and spine formation. Concurrently, sleep has been proposed to facilitate forgetting through processes of synaptic renormalisation. This view received indirect support by findings in humans of sleep enhancing TMS-evoked plasticity and capabilities for encoding new information. First direct behavioural evidence of sleep inducing forgetting has only recently emerged after encoding large amounts of stimuli in adults. We propose forgetting complements sleep-dependent consolidation and facilitates gist abstraction especially at high memory loads, when reactivation-based consolidation reaches capacity limits. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Rapid eye movement sleep deprivation does not affect fear memory reconsolidation in rats.

    Science.gov (United States)

    Tian, Shaowen; Huang, Fulian; Li, Peng; Ouyang, Xinping; Li, Zengbang; Deng, Haifeng; Yang, Yufeng

    2009-09-29

    There is increasing evidence that sleep may be involved in memory consolidation. However, there remain comparatively few studies that have explored the relationship between sleep and memory reconsolidation. At present study, we tested the effects of rapid eye movement sleep deprivation (RSD) on the reconsolidation of cued (experiment 1) and contextual (experiment 2) fear memory in rats. Behaviour procedure involved four training phases: habituation, fear conditioning, reactivation and test. Rats were subjected to 6h RSD starting either immediately after reactivation or 6h later. The control rats were returned to their home cages immediately after reactivation and left undisturbed. Contrary to those hypotheses speculating a potential role of sleep in reconsolidation, we found that post-reactivation RSD whether from 0 to 6h or 6 to 12h had no effect on the reconsolidation of both cued and contextual fear memory. However, our present results did not exclude the potential roles of non-rapid eye movement sleep in the reconsolidation of fear memory or sleep in the reconsolidation of other memory paradigms.

  18. Synaptic Mechanisms of Memory Consolidation during Sleep Slow Oscillations.

    Science.gov (United States)

    Wei, Yina; Krishnan, Giri P; Bazhenov, Maxim

    2016-04-13

    Sleep is critical for regulation of synaptic efficacy, memories, and learning. However, the underlying mechanisms of how sleep rhythms contribute to consolidating memories acquired during wakefulness remain unclear. Here we studied the role of slow oscillations, 0.2-1 Hz rhythmic transitions between Up and Down states during stage 3/4 sleep, on dynamics of synaptic connectivity in the thalamocortical network model implementing spike-timing-dependent synaptic plasticity. We found that the spatiotemporal pattern of Up-state propagation determines the changes of synaptic strengths between neurons. Furthermore, an external input, mimicking hippocampal ripples, delivered to the cortical network results in input-specific changes of synaptic weights, which persisted after stimulation was removed. These synaptic changes promoted replay of specific firing sequences of the cortical neurons. Our study proposes a neuronal mechanism on how an interaction between hippocampal input, such as mediated by sharp wave-ripple events, cortical slow oscillations, and synaptic plasticity, may lead to consolidation of memories through preferential replay of cortical cell spike sequences during slow-wave sleep. Sleep is critical for memory and learning. Replay during sleep of temporally ordered spike sequences related to a recent experience was proposed to be a neuronal substrate of memory consolidation. However, specific mechanisms of replay or how spike sequence replay leads to synaptic changes that underlie memory consolidation are still poorly understood. Here we used a detailed computational model of the thalamocortical system to report that interaction between slow cortical oscillations and synaptic plasticity during deep sleep can underlie mapping hippocampal memory traces to persistent cortical representation. This study provided, for the first time, a mechanistic explanation of how slow-wave sleep may promote consolidation of recent memory events. Copyright © 2016 the authors 0270-6474/16/364231-17$15.00/0.

  19. Sleep and cortisol interact to support memory consolidation.

    Science.gov (United States)

    Bennion, Kelly A; Mickley Steinmetz, Katherine R; Kensinger, Elizabeth A; Payne, Jessica D

    2015-03-01

    Separate lines of research have demonstrated that rises in cortisol can benefit memory consolidation, as can the occurrence of sleep soon after encoding. For the first time, we demonstrate that pre-learning cortisol interacts with sleep to benefit memory consolidation, particularly for negative arousing items. Resting cortisol levels during encoding were positively correlated with subsequent memory, but only following a period of sleep. There was no such relation following a period of wakefulness. Using eye tracking, we further reveal that for negative stimuli, this facilitative effect may arise because cortisol strengthens the relationship between looking time at encoding and subsequent memory. We suggest that elevated cortisol may "tag" attended information as important to remember at the time of encoding, thus enabling sleep-based processes to optimally consolidate salient information in a selective manner. Neuroimaging data suggest that this optimized consolidation leads to a refinement of the neural processes recruited for successful retrieval of negative stimuli, with the retrieval of items attended in the presence of elevated cortisol and consolidated over a night of sleep associated with activity in the amygdala and vmPFC. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Does age worsen sleep-dependent memory consolidation?

    Science.gov (United States)

    Cherdieu, Melaine; Reynaud, Emanuelle; Uhlrich, Josselin; Versace, Remy; Mazza, Stephanie

    2014-02-01

    Slow wave sleep (SWS) is known to favour episodic memory consolidation. Given that ageing is associated with a reduction in SWS and episodic memory impairment, our aim was to investigate whether memory continues to benefit from sleep in older adults. Episodic memory consolidation was tested in 20 young (22.1 ± 1.7 years) and 20 older volunteers (68.9 ± 5.3 years) who performed a visuospatial two-dimensional object-location task. Retention capacities were evaluated after 12 h of wakefulness or 12 h of sleep. Performances before and after the interval allowed us to calculate a forgetting rate. Sleep architecture was measured by polysomnography (older adults = 410 min; young adults: 467 min). Our results showed that the beneficial effect of sleep on memory consolidation was reduced in older adults compared to young adults. In older adults, sleep did not enhance memory consolidation significantly compared to wakefulness. Sleep prevented young adults from forgetting (-0.10% ± 2.1), while the forgetting rate in older adults was still important after a period of sleep (16.60% ± 4.2; P = 0.05). The sleep architecture of older adults was characterized by a decrease in sleep efficiency (-12%; P sleep was observed (-1%; not significant) and no correlation was found with performance. Age-related changes in sleep parameters may have a negative impact on memory consolidation in older adults. © 2013 European Sleep Research Society.

  1. 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.

  2. The Limited Capacity of Sleep-Dependent Memory Consolidation

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. Resting state networks and memory consolidation

    OpenAIRE

    Albert, Neil B.; Robertson, Edwin M.; Mehta, Puja; Miall, R. Chris

    2009-01-01

    Despite their name, resting state networks (RSNs) provide a clear indication that the human brain may be hard-working. Unlike the cardiac and respiratory systems, which greatly reduce their rate of function during periods of inactivity, the human brain may have additional responsibilities during rest. One particularly intriguing function performed by the resting brain is the consolidation of recent learned information, which is known to take place over a period of several hours after learning...

  5. 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.

  6. Does sleep benefit memory consolidation in children with focal epilepsy?

    OpenAIRE

    Chan, S.; Pressler, R.; Boyd, S. G.; Baldeweg, T.; Cross, J. H.

    2017-01-01

    OBJECTIVE: Children with epilepsy have high rates of both cognitive impairment and sleep disruption. It is thus assumed that sleep-dependent memory consolidation is vulnerable to ongoing epileptic activity, but direct evidence of this is limited. METHODS: We performed a within-subject comparison of memory retention across intervals of wake or overnight sleep. Healthy children (n = 21, 6-16 years, 12 female) and children with focal epilepsy (n = 22, 6-16 years, 9 female) performed verbal and v...

  7. Bidirectional effects of cannabidiol on contextual fear memory extinction

    Directory of Open Access Journals (Sweden)

    Chenchen Song

    2016-12-01

    Full Text Available Cannabidiol (CBD has been established to have both acute and long-lasting effects to reduce fear memory expression. The long-lasting impact might be mediated by an enhancement of memory extinction or an impairment of memory reconsolidation. Here, we directly compared the effects of i.p. injections of cannabidiol (10 mg/kg with those of the NMDA receptor antagonist MK-801 (0.1 mg/kg and partial agonist D-cycloserine (DCS; 15 mg/kg in order to determine the mnemonic basis of long-term fear reduction. We showed that under conditions of strong fear conditioning, CBD reduced contextual fear memory expression both acutely during the extinction session as well as later at a fear retention test. The latter test reduction was replicated by DCS, but MK-801 instead elevated test freezing. In contrast, when initial conditioning was weaker, CBD and MK-801 had similar effects to increase freezing at the fear retention test relative to vehicle controls, whereas DCS had no observable impact. This pattern of results is consistent with CBD enhancing contextual fear memory extinction when the initial conditioning is strong, but impairing extinction when conditioning is weak. This bidirectional effect of CBD may be related to stress levels induced by conditioning and evoked at retrieval during extinction, rather than the strength of the memory per se.

  8. Sleep's Function in the Spontaneous Recovery and Consolidation of Memories

    Science.gov (United States)

    Drosopoulos, Spyridon; Schulze, Claudia; Fischer, Stefan; Born, Jan

    2007-01-01

    Building on 2 previous studies (B. R. Ekstrand, 1967; B. R. Ekstrand, M. J. Sullivan, D. F. Parker, & J. N. West, 1971), the authors present 2 experiments that were aimed at characterizing the role of retroactive interference in sleep-associated declarative memory consolidation. Using an A-B, A-C paradigm with lists of word pairs in Experiment 1,…

  9. 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.

  10. 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

  11. Persistence of Amygdala-Hippocampal Connectivity and Multi-Voxel Correlation Structures During Awake Rest After Fear Learning Predicts Long-Term Expression of Fear

    NARCIS (Netherlands)

    Hermans, E.J.; Kanen, J.W.; Tambini, A.; Fernandez, G.; Davachi, L.; Phelps, E.A.

    2017-01-01

    After encoding, memories undergo a process of consolidation that determines long-term retention. For conditioned fear, animal models postulate that consolidation involves reactivations of neuronal assemblies supporting fear learning during postlearning "offline" periods. However, no human studies to

  12. 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.

  13. 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.

  14. Laugh yourself to sleep: memory consolidation for humorous information.

    Science.gov (United States)

    Chambers, Alexis M; Payne, Jessica D

    2014-05-01

    There is extensive evidence that emotional information is better remembered than neutral information across long delays, especially if the delay interval contains an opportunity for sleep. However, as prior studies have focused on memory for negative stimuli, it is unclear whether positive memories benefit from time and sleep as well. To investigate the consolidation of positive memories, the current study examined differences in memory for humorous and non-humorous cartoons. While prior evidence demonstrates that humorous information is preferentially remembered relative to non-humorous information over brief delays, it is unknown whether this benefit lasts across longer delay intervals or whether sleep is important for lasting humor memories to form. Thus, we tested memory for 27 cartoons across 12-h delay periods containing either sleep or wakefulness. Results indicate that humor's enhancing effect on recall memory is robust across a 12-h delay and that a period of sleep facilitates this effect over wakefulness when cartoons are novel to participants and ranked based on subjective emotional ratings. Further, in accordance with previous studies that reveal diminished emotional reactivity to stimuli following sleep, in a supplemental experiment, we found that sleep reduced subjective ratings of humor, arousal, and positivity of humorous cartoons. These findings provide preliminary evidence that sleep's impact on negative emotional memory consolidation and emotional reactivity can be extended to positive stimuli as well.

  15. 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

  16. 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.

  17. 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.

  18. Drug enhancement of memory consolidation: historical perspective and neurobiological implications.

    Science.gov (United States)

    McGaugh, James L; Roozendaal, Benno

    2009-01-01

    Studies of drug enhancement of cognition began with Lashley's (Psychobiology 1:141-170, 1917) report that strychnine administered before daily training trials enhanced rats' maze learning. Many subsequent studies confirmed that finding and found that stimulant drugs also enhance the learning of a wide range of tasks. A central problem in interpreting such findings is that of distinguishing the drug effects on brain processes underlying memory formation from many other possible effects of the drugs on the behavior used to assess learning. The subsequent finding that comparable learning enhancement can be obtained by posttraining drug administration provided compelling evidence that drugs can enhance memory by acting on memory consolidation processes. Such evidence stimulated the investigation of endogenous regulation of memory consolidation by arousal-released adrenal stress hormones. Considerable evidence now indicates that such hormones regulate memory consolidation via activation of the basolateral amygdala and subsequent influences on many efferent brain regions involved in processing recent experiences. The implications of these findings for the development of cognitive enhancing drugs are discussed.

  19. 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.

  20. Is sleep-related verbal memory consolidation impaired in sleepwalkers?

    Science.gov (United States)

    Uguccioni, Ginevra; Pallanca, Olivier; Golmard, Jean-Louis; Leu-Semenescu, Smaranda; Arnulf, Isabelle

    2015-04-01

    In order to evaluate verbal memory consolidation during sleep in subjects experiencing sleepwalking or sleep terror, 19 patients experiencing sleepwalking/sleep terror and 19 controls performed two verbal memory tasks (16-word list from the Free and Cued Selective Reminding Test, and a 220- and 263-word modified story recall test) in the evening, followed by nocturnal video polysomnography (n = 29) and morning recall (night-time consolidation after 14 h, n = 38). The following morning, they were given a daytime learning task using the modified story recall test in reverse order, followed by an evening recall test after 9 h of wakefulness (daytime consolidation, n = 38). The patients experiencing sleepwalking/sleep terror exhibited more frequent awakenings during slow-wave sleep and longer wakefulness after sleep onset than the controls. Despite this reduction in sleep quality among sleepwalking/sleep terror patients, they improved their scores on the verbal tests the morning after sleep compared with the previous evening (+16 ± 33%) equally well as the controls (+2 ± 13%). The performance of both groups worsened during the daytime in the absence of sleep (-16 ± 15% for the sleepwalking/sleep terror group and -14 ± 11% for the control group). There was no significant correlation between the rate of memory consolidation and any of the sleep measures. Seven patients experiencing sleepwalking also sleep-talked during slow-wave sleep, but their sentences were unrelated to the tests or the list of words learned during the evening. In conclusion, the alteration of slow-wave sleep during sleepwalking/sleep terror does not noticeably impact on sleep-related verbal memory consolidation. © 2014 European Sleep Research Society.

  1. 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...

  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. Encoding of Fear Memory in High and Low Fear Mice

    Science.gov (United States)

    2013-11-18

    response to  masked   facial  stimuli in posttraumatic stress disorder: a  functional MRI study. Biological psychiatry 47:769‐76  105.  Repa JC, Muller J...none Developed a tissue or serum repository none Developed a data registry none Principal Investigator (Last, First, Middle) Coyner...of tissue . RESULTS We find in a mouse line of high and low Pavlovian conditioned fear that inhibition of the phosphorylation of MAPK with the MEK

  4. 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....

  5. Memory Consolidation and Neural Substrate of Reward

    Directory of Open Access Journals (Sweden)

    Mañas, Mauro

    2012-08-01

    Full Text Available Prematurity is one of the most relevant health problems among children in the developed countries. Around 8 to 10% of children birth before the 37 week and/or with a very low birth weight (VLBW (1500 g. This causes 75% of the prenatal mortality and the 50% of the children disability. The aim of this study was to assess neuropsychological and emotional impairments in 7 year old children who were born VLBW. A clinical interview, the Children Neuropsychological Assessment Battery, and the Behavioral Assessment System for Children (BASC were administrated. VLBW children showed memory and executive function deficits, as well as, behavioral and attention problems. These results highlight the importance of long term follow up of the VLBW children and point out the necessity of developing adequate neuropsychological and emotional treatment program for these children.

  6. 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

  7. Effects of sleep deprivation on different phases of memory in the rat: dissociation between contextual and tone fear conditioning tasks

    Directory of Open Access Journals (Sweden)

    Vanessa C Rossi

    2014-11-01

    Full Text Available Numerous studies show that sleep deprivation (SD impacts negatively on cognitive processes, including learning and memory. Memory formation encompasses distinct phases of which acquisition, consolidation and retrieval are better known. Previous studies with pre-training SD induced by the platform method have shown impairment in fear conditioning tasks. Nonetheless, pre-training manipulations do not allow the distinction between effects on acquisition and/or consolidation, interfering, ultimately, on recall of/performance in the task. In the present study, animals were first trained in contextual and tone fear conditioning tasks and then submitted to SD with the purpose to evaluate the effect of this manipulation on different stages of the learning process, e.g. in the uptake of (new information during learning, its encoding and stabilization, and the recall of stored memories. Besides, we also investigated the effect of SD in the extinction of fear memory and a possible state-dependent learning induced by this manipulation. For each task (contextual or tone fear conditioning, animals were trained and then distributed into control, not sleep-deprived (CTL and SD groups, the latter being submitted to the modified multiple platform paradigm for 96 h. Subsets of eight rats in each group/experiment were submitted to the test of the tasks, either immediately or at different time intervals after SD. The results indicated that a pre-, but not post-training SD impaired recall in the contextual and tone fear conditioning; b this impairment was not state-dependent; c in the contextual fear conditioning, pre-test SD prevented extinction of the learned task. Overall, these results suggest that SD interferes with acquisition, recall and extinction, but not necessarily with consolidation of emotional memory.

  8. Sleep-dependent consolidation in multiple memory systems

    OpenAIRE

    Schönauer, Monika

    2014-01-01

    Before newly formed memories can last for the long-term, they must undergo a period of consolidation. It has been shown that sleep facilitates this process. One hypothesis about how this may occur is that learning-related neuronal activity is replayed during following sleep periods. Such a reactivation of neural activity patterns has been repeatedly shown in the hippocampal formation in animals. Hippocampally-induced reactivation can also be observed in other brain areas like the neocortex an...

  9. Additive Expression of Consolidated Memory through Drosophila Mushroom Body Subsets.

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    Chu-Huai Yang

    2016-05-01

    Full Text Available Associative olfactory memory in Drosophila has two components called labile anesthesia-sensitive memory and consolidated anesthesia-resistant memory (ARM. Mushroom body (MB is a brain region critical for the olfactory memory and comprised of 2000 neurons that can be classified into αβ, α'β', and γ neurons. Previously we demonstrated that two parallel pathways mediated ARM consolidation: the serotonergic dorsal paired medial (DPM-αβ neurons and the octopaminergic anterior paired lateral (APL-α'β' neurons. This finding prompted us to ask how this composite ARM is retrieved. Here, we showed that blocking the output of αβ neurons and that of α'β' neurons each impaired ARM retrieval, and blocking both simultaneously had an additive effect. Knockdown of radish and octβ2R in αβ and α'β' neurons, respectively, impaired ARM. A combinatorial assay of radish mutant background rsh1 and neurotransmission blockade confirmed that ARM retrieved from α'β' neuron output is independent of radish. We identified MBON-β2β'2a and MBON-β'2mp as the MB output neurons downstream of αβ and α'β' neurons, respectively, whose glutamatergic transmissions also additively contribute to ARM retrieval. Finally, we showed that α'β' neurons could be functionally subdivided into α'β'm neurons required for ARM retrieval, and α'β'ap neurons required for ARM consolidation. Our work demonstrated that two parallel neural pathways mediating ARM consolidation in Drosophila MB additively contribute to ARM expression during retrieval.

  10. Delayed effects of cortisol enhance fear memory of trace conditioning.

    Science.gov (United States)

    Cornelisse, Sandra; van Ast, Vanessa A; Joëls, Marian; Kindt, Merel

    2014-02-01

    Corticosteroids induce rapid non-genomic effects followed by slower genomic effects that are thought to modulate cognitive function in opposite and complementary ways. It is presently unknown how these time-dependent effects of cortisol affect fear memory of delay and trace conditioning. This distinction is of special interest because the neural substrates underlying these types of conditioning may be differently affected by time-dependent cortisol effects. Delay conditioning is predominantly amygdala-dependent, while trace conditioning additionally requires the hippocampus. Here, we manipulated the timing of cortisol action during acquisition of delay and trace fear conditioning, by randomly assigning 63 men to one of three possible groups: (1) receiving 10mg hydrocortisone 240 min (slow cort) or (2) 60 min (rapid cort) before delay and trace acquisition, or (3) placebo at both times, in a double-blind design. The next day, we tested memory for trace and delay conditioning. Fear potentiated startle responses, skin conductance responses and unconditioned stimulus expectancy scores were measured throughout the experiment. The fear potentiated startle data show that cortisol intake 240 min before actual fear acquisition (slow cort) uniquely strengthened subsequent trace conditioned memory. No effects of cortisol delivery 60 min prior to fear acquisition were found on any measure of fear memory. Our findings emphasize that slow, presumably genomic, but not more rapid effects of corticosteroids enhance hippocampal-dependent fear memories. On a broader level, our findings underline that basic experimental research and clinically relevant pharmacological treatments employing corticosteroids should acknowledge the timing of corticosteroid administration relative to the learning phase, or therapeutic intervention. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. REGULAR REHEARSAL HELPS IN CONSOLIDATION OF LONG TERM MEMORY

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    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

  12. 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.

  13. 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

  14. Systems consolidation revisited, but not revised: The promise and limits of optogenetics in the study of memory.

    Science.gov (United States)

    Hardt, Oliver; Nadel, Lynn

    2017-12-05

    Episodic memories (in humans) and event-like memories (in non-human animals) require the hippocampus for some time after acquisition, but at remote points seem to depend more on cortical areas instead. Systems consolidation refers to the process that promotes this reorganization of memory. Various theoretical frameworks accounting for this process have been proposed, but clear evidence favoring one or another of these positions has been lacking. Addressing this issue, a recent study deployed some of the most advanced neurobiological technologies - optogenetics and calcium imaging - and provided high resolution, precise observations regarding brain systems involved in recent and remote contextual fear memories. We critically review these findings within their historical context and conclude that they do not resolve the debate concerning systems consolidation. This is because the relevant question concerning the quality of memory at recent and remote time points has not been answered: Does the memory reorganization taking place during systems consolidation result in changes to the content of memory? Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Daytime naps, motor memory consolidation and regionally specific sleep spindles.

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    Masaki Nishida

    Full Text Available BACKGROUND: Increasing evidence demonstrates that motor-skill memories improve across a night of sleep, and that non-rapid eye movement (NREM sleep commonly plays a role in orchestrating these consolidation enhancements. Here we show the benefit of a daytime nap on motor memory consolidation and its relationship not simply with global sleep-stage measures, but unique characteristics of sleep spindles at regionally specific locations; mapping to the corresponding memory representation. METHODOLOGY/PRINCIPAL FINDINGS: Two groups of subjects trained on a motor-skill task using their left hand - a paradigm known to result in overnight plastic changes in the contralateral, right motor cortex. Both groups trained in the morning and were tested 8 hr later, with one group obtaining a 60-90 minute intervening midday nap, while the other group remained awake. At testing, subjects that did not nap showed no significant performance improvement, yet those that did nap expressed a highly significant consolidation enhancement. Within the nap group, the amount of offline improvement showed a significant correlation with the global measure of stage-2 NREM sleep. However, topographical sleep spindle analysis revealed more precise correlations. Specifically, when spindle activity at the central electrode of the non-learning hemisphere (left was subtracted from that in the learning hemisphere (right, representing the homeostatic difference following learning, strong positive relationships with offline memory improvement emerged-correlations that were not evident for either hemisphere alone. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that motor memories are dynamically facilitated across daytime naps, enhancements that are uniquely associated with electrophysiological events expressed at local, anatomically discrete locations of the brain.

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

    NARCIS (Netherlands)

    Zhou, M.; Kindt, M.; Joëls, M.; Krugers, H.J.

    2011-01-01

    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

  17. 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.

  18. 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.

  19. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Does sleep benefit memory consolidation in children with focal epilepsy?

    Science.gov (United States)

    Chan, Samantha; Pressler, Ronit; Boyd, Stewart G; Baldeweg, Torsten; Cross, J Helen

    2017-03-01

    Children with epilepsy have high rates of both cognitive impairment and sleep disruption. It is thus assumed that sleep-dependent memory consolidation is vulnerable to ongoing epileptic activity, but direct evidence of this is limited. We performed a within-subject comparison of memory retention across intervals of wake or overnight sleep. Healthy children (n = 21, 6-16 years, 12 female) and children with focal epilepsy (n = 22, 6-16 years, 9 female) performed verbal and visuospatial memory tasks under each condition. Sleep was assessed with electroencephalography (EEG) polysomnography during the overnight interval. Interictal discharges were quantified manually. Memory retention was greater in the sleep condition in both the verbal (F 1,39 = 10.8, p = 0.002, Cohen's d = 0.67) and the visuospatial (F 1,36 = 4.23, p = 0.05, Cohen's d = 0.40) tasks, with no significant interaction of group by condition in either task. Across the total sample, gain in memory retention with sleep in the verbal task correlated with duration of slow wave sleep (r = 0.4, p = 0.01). In patients, sleep-dependent memory consolidation was negatively correlated with interictal discharge rate in both the verbal (ρ = -0.49, p = 0.04) and visuospatial (ρ = -0.45, p = 0.08) tasks. On post hoc analysis, a longer history of epilepsy (r = 0.53, p = 0.01) and a temporal (t 10 = 1.8, p = 0.1, Cohen's d = 0.86) rather than an extratemporal seizure focus (t 10 = 0.8, p = 0.4, Cohen's d = 0.30) was associated with greater contribution of sleep to verbal memory retention. We have demonstrated that memory consolidation in children with focal epilepsy benefits from sleep, showing the same correlation with slow wave sleep as in healthy children, but an inverse relationship with the interictal discharge load during sleep. This mechanism appears to be increasingly recruited with longer duration of illness, indicating a resilient homeostatic function which may be harnessed to aid learning. Wiley Periodicals

  2. The consolidation of implicit sequence memory in obstructive sleep apnea.

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    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.

  3. Consolidation of human somatosensory memory during motor learning.

    Science.gov (United States)

    Cuppone, Anna Vera; Semprini, Marianna; Konczak, Jürgen

    2018-03-13

    Sensorimotor learning is a bidirectional process associated with concurrent neuroplastic changes in the motor and somatosensory system. While motor memory consolidation and retention have been extensively studied during skill acquisition, little is known about the formation and consolidation of somatosensory memory associated with motor learning. Using a robotic exoskeleton, we tracked markers of somatosensory and motor learning while healthy participants trained to make goal-directed wrist reaching movements over five days and evaluated retention for up to 10 days after practice. Markers of somatosensory learning were changes in wrist position sense bias (systematic error) and precision (random error). The main results are as follows: First, somatosensory (proprioceptive) memory consolidation shows signs of cost savings with repeated sensorimotor training - the same feature is known for motor memory formation. Moreover, somatosensory learning generalized to untrained workspace. Second, somatosensory learning over days can be characterized as an early improvement in sensory precision and a later improvement in sensory bias. Third, the time course of learning gains in position sense acuity coincided with improvements in spatial movement accuracy. Finally, the gains of somatosensory learning were retained for several days. Improvements in position sense bias were still visible up to 3 days after the end of practice for the trained workspace positions, but decayed faster in the untrained workspace. Improvements in position sense precision were retained for up to 10 days and were workspace independent. The findings are consistent with the view that an internal model of somatosensory joint space is formed during motor learning. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Sensory memory consolidation observed: increased specificity of detail over days.

    Science.gov (United States)

    Weinberger, Norman M; Miasnikov, Alexandre A; Chen, Jemmy C

    2009-03-01

    Memories are usually multidimensional, including contents such as sensory details, motivational state and emotional overtones. Memory contents generally change over time, most often reported as a loss in the specificity of detail. To study the temporal changes in the sensory contents of associative memory without motivational and emotional contents, we induced memory for acoustic frequency by pairing a tone with stimulation of the cholinergic nucleus basalis. Adult male rats were first tested for behavioral responses (disruption of ongoing respiration) to tones (1-15 kHz), yielding pre-training behavioral frequency generalization gradients (BFGG). They next received three days of training consisting of a conditioned stimulus (CS) tone (8.00 kHz, 70 dB, 2 s) either Paired (n=5) or Unpaired (n=5) with weak electrical stimulation (approximately 48 microA) of the nucleus basalis (100 Hz, 0.2 s, co-terminating with CS offset). Testing for behavioral memory was performed by obtaining post-training BFGGs at two intervals, 24 and 96 h after training. At 24 h post-training, the Paired group exhibited associative behavioral memory manifested by significantly larger responses to tone than the Unpaired group. However, they exhibited no specificity in memory for the frequency of the tonal CS, as indexed by a flat BFGG. In contrast, after 96 h post-training the Paired group did exhibit specificity of memory as revealed by tuned BFGGs with a peak at the CS-band of frequencies. This increased detail of memory developed due to a loss of response to lower and higher frequency side-bands, without any change in the absolute magnitude of response to CS-band frequencies. These findings indicate that the sensory contents of associative memory can be revealed to become more specific, through temporal consolidation in the absence of non-sensory factors such as motivation and emotion.

  5. 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

    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...... 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...

  6. 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.

  7. 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

  8. 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

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Zhaohui Liao

    2017-11-01

    Full Text Available 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.

  11. Memory consolidation in children with epilepsy: does sleep matter?

    Science.gov (United States)

    Sud, Shama; Sadaka, Yair; Massicotte, Colin; Smith, Mary Lou; Bradbury, Laura; Go, Cristina; Weiss, Shelly K

    2014-02-01

    Children with epilepsy have frequent sleep disturbance and challenges in learning and memory. There is little research on the consolidation of memory during sleep in this population. The goal of this pilot study was to determine whether children with epilepsy are able to consolidate memories better after a sleep versus wake period as has been demonstrated in typically developing children. This study was a prospective evaluation of children with epilepsy to determine if sleep improved episodic memory (using word lists) as compared with memory following a wake period of similar duration. The study was conducted in patients in the Epilepsy Monitoring Unit at a single academic health science center. In the sleep recall condition, the learning trials were presented in the evening, and delayed recall of the words was tested in the morning. In the wake condition, the learning took place in the morning, and the delayed recall took place later in the day. Subjects wore an actigraph to evaluate sleep/wake patterns. Data regarding the children's epilepsy, antiepileptic medications, and frequency of interictal epileptiform discharges were also documented. Ten children (agd 8-17years) participated in the study. For the entire sample, recall after sleep was better than recall after awake (p=0.03), and 7 of the 10 children showed this effect. However, reanalyses removing an outlier showed no difference between the two recall conditions. The mean number of interictal epileptiform discharges was 8.8 during the recall after sleep and 7.8 during the recall after awake. Three children had seizures during the evaluation. In this pilot study, we demonstrated that a small cohort of children with epilepsy, with similar interictal epileptiform discharges during sleep and wake, showed no advantage in memory for a word list after a period of sleep than after a period of being awake. This finding requires further study in a larger cohort. Poor memory consolidation during sleep may contribute

  12. Age-related differences in sleep-based memory consolidation: A meta-analysis.

    Science.gov (United States)

    Gui, Wen-Jun; Li, Hui-Jie; Guo, Yu-Hua; Peng, Peng; Lei, Xu; Yu, Jing

    2017-03-01

    A period of post-learning sleep benefits memory consolidation compared with an equal-length wake interval. However, whether this sleep-based memory consolidation changes as a function of age remains controversial. Here we report a meta-analysis that investigates the age differences in the sleep-based memory consolidation in two types of memory: declarative memory and procedural memory. The meta-analysis included 22 comparisons of the performance between young adults (N =640) and older adults (N =529) on behavioral tasks measuring sleep-based memory consolidation. Our results showed a significant overall sleep-based beneficial effect in young adults but not in older adults. However, further analyses suggested that the age differences were mainly manifested in sleep-based declarative memory consolidation but not in procedural memory consolidation. We discussed the possible underlying mechanisms for the age-related degradation in sleep-based memory consolidation. Further research is needed to determine the crucial components for sleep-related memory consolidation in older adults such as age-related changes in neurobiological and cardiovascular functions, which may play an important role in this context and have the potential to delineate the interrelationships between age-related changes in sleep and memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. 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…

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Autonomic activity during sleep predicts memory consolidation in humans.

    Science.gov (United States)

    Whitehurst, Lauren N; Cellini, Nicola; McDevitt, Elizabeth A; Duggan, Katherine A; Mednick, Sara C

    2016-06-28

    Throughout history, psychologists and philosophers have proposed that good sleep benefits memory, yet current studies focusing on the relationship between traditionally reported sleep features (e.g., minutes in sleep stages) and changes in memory performance show contradictory findings. This discrepancy suggests that there are events occurring during sleep that have not yet been considered. The autonomic nervous system (ANS) shows strong variation across sleep stages. Also, increases in ANS activity during waking, as measured by heart rate variability (HRV), have been correlated with memory improvement. However, the role of ANS in sleep-dependent memory consolidation has never been examined. Here, we examined whether changes in cardiac ANS activity (HRV) during a daytime nap were related to performance on two memory conditions (Primed and Repeated) and a nonmemory control condition on the Remote Associates Test. In line with prior studies, we found sleep-dependent improvement in the Primed condition compared with the Quiet Wake control condition. Using regression analyses, we compared the proportion of variance in performance associated with traditionally reported sleep features (model 1) vs. sleep features and HRV during sleep (model 2). For both the Primed and Repeated conditions, model 2 (sleep + HRV) predicted performance significantly better (73% and 58% of variance explained, respectively) compared with model 1 (sleep only, 46% and 26% of variance explained, respectively). These findings present the first evidence, to our knowledge, that ANS activity may be one potential mechanism driving sleep-dependent plasticity.

  17. Peri-encoding predictors of memory encoding and consolidation.

    Science.gov (United States)

    Cohen, Noga; Pell, Liat; Edelson, Micah G; Ben-Yakov, Aya; Pine, Alex; Dudai, Yadin

    2015-03-01

    We review reports of brain activations that occur immediately prior to the onset or following the offset of to-be-remembered information and can predict subsequent mnemonic success. Memory-predictive pre-encoding processes, occurring from fractions of a second to minutes prior to event onset, are mainly associated with activations in the medial temporal lobe (MTL), amygdala and midbrain, and with enhanced theta oscillations. These activations may be considered as the neural correlates of one or more cognitive operations, including contextual processing, attention, and the engagement of distinct computational modes associated with prior encoding or retrieval. Post-encoding activations that correlate with subsequent memory performance are mainly observed in the MTL, sensory cortices and frontal regions. These activations may reflect binding of elements of the encoded information and initiation of memory consolidation. In all, the findings reviewed here illustrate the importance of brain states in the immediate peri-encoding time windows in determining encoding success. Understanding these brain states and their specific effects on memory may lead to optimization of the encoding of desired memories and mitigation of undesired ones. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. The Origins of Fears of Compassion: Shame and Lack of Safeness Memories, Fears of Compassion and Psychopathology.

    Science.gov (United States)

    Matos, Marcela; Duarte, Joana; Pinto-Gouveia, José

    2017-11-17

    Empirical and clinical research suggests that some individuals find self-generating compassion and receiving compassion from others difficult and aversive. However, it is unclear how these fears of compassion are linked to early experiences and to psychopathological symptoms. This study explores the relationship between shame traumatic memories, centrality of shame memories, early memories of warmth and safeness, fears of compassion, and depression, anxiety and paranoid symptoms. Participants were 302 individuals from the general community population, who completed self-report measures of fears of compassion, shame memories, early affiliative memories, and psychopathology. Shame traumatic and central memories were positively associated with fears of compassion for self, for others and from others, whereas early memories of warmth and safeness were negatively related to such fears. Path analyses revealed that fears of compassion for self and of receiving compassion from others mediated the effects of shame traumatic memory, centrality of shame memory and early memories of warmth and safeness on depressive, anxious and paranoid symptoms. These findings have implications for therapeutic interventions as these fears, as well as the negative shame-based emotional memories fuelling them, may need to be addressed in therapy to assist patients in self-generating and receiving compassion.

  19. 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...

  20. 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 ...

  1. 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.

  2. 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…

  3. Transient disruption of fear-related memory by post-retrieval inactivation of gastrin-releasing peptide or N-methyl-D-aspartate receptors in the hippocampus.

    Science.gov (United States)

    Luft, Tatiana; Amaral, Olavo B; Schwartsmann, Gilberto; Roesler, Rafael

    2008-02-01

    Molecular accounts of memory consolidation suggest that new learning generates persistent synaptic modifications through activation of an extensive set of neuronal receptors and intracellular signal transduction pathways, accompanied by RNA and protein synthesis. This traditional cellular consolidation theory has been challenged by evidence that reactivation of a previously consolidated memory might render this memory again susceptible to disruption by amnesic treatments, a process generally referred to as reconsolidation. Current evidence indicates that reconsolidation can be disrupted by administration of a variety of pharmacological agents after memory reactivation. Previous studies have indicated that the gastrin-releasing preferring type of bombesin receptor (GRPR) and the N-methyl-D-aspartate glutamate receptor (NMDAR) in the rat hippocampus are involved in consolidation of inhibitory avoidance (IA), a fear-related memory task. We show here that blockade of hippocampal GRPRs or NMDARs after memory reactivation temporarily disrupts memory retention. Post-retrieval intra-hippocampal infusion of the GRPR antagonist RC-3095 or the NMDAR antagonist aminophosphonopentanoic acid (AP5) produced an impairment of IA performance tested 2 days after training in rats. However, this impairment was transient and recovered to levels of control rats in a subsequent test 3 days after training. The drug effects were only present after memory reactivation and not in its absence. These findings provide evidence that GRPR or NMDAR inactivation after retrieval can impair fear memory.

  4. 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.

  5. Sleep restriction can attenuate prioritization benefits on declarative memory consolidation.

    Science.gov (United States)

    Lo, June C; Bennion, Kelly A; Chee, Michael W L

    2016-12-01

    As chronic sleep restriction is a widespread problem among adolescents, the present study investigated the effects of a 1-week sleep restriction (SR) versus control period on the consolidation of long-term memory for prose passages. We also determined whether the benefit of prioritization on memory is modulated by adequate sleep occurring during consolidation. Fifty-six healthy adolescents (25 male, aged 15-19 years) were instructed to remember a prose passage in which half of the content was highlighted (prioritized), and were told that they would receive an additional bonus for remembering highlighted content. Following an initial free recall test, participants underwent a 7-night period in which they received either a 5-h (SR) or 9-h (control) nightly sleep opportunity, monitored by polysomnography on selected nights. Free recall of the passage was tested at the end of the sleep manipulation period (1 week after encoding), and again 6 weeks after encoding. Recall of highlighted content was superior to that of non-highlighted content at all three time-points (initial, 1 week, 6 weeks). This beneficial effect of prioritization on memory was stronger 1 week relative to a few minutes after encoding for the control, but not the SR group. N3 duration was similar in the control and SR groups. Overall, the present study shows that the benefits of prioritization on memory are enhanced over time, requiring time and sleep to unfold fully. Partial sleep deprivation (i.e. 5-h nocturnal sleep opportunity) may attenuate such benefits, but this may be offset by preservation of N3 sleep duration. © 2016 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

  6. Memory consolidation and inducible nitric oxide synthase expression during different sleep stages in Parkinson disease.

    Science.gov (United States)

    Wu, Dean; Tseng, Ing-Jy; Yuan, Rey-Yue; Hsieh, Chia-Yu; Hu, Chaur-Jong

    2014-01-01

    Parkinson disease (PD) is a neurodegenerative disease characterized by motor and nonmotor dysfunctions, which include sleep disturbances. Rapid eye movement (REM) sleep is associated with numerous physiologic changes such as memory consolidation. Compelling evidence suggests that nitric oxide (NO) is crucial to both sleep regulation and memory consolidation. In our study, we explored changes in biologic molecules during various sleep stages and the effects of sleep on memory consolidation in PD. Ten PD patients and 14 volunteers without PD participated in our study. The gene expression of inducible NO synthase (iNOS) in all sleep stages was measured using realtime polymerase chain reaction (PCR) based on polysomnography (PSG)-guided peripheral blood sampling. In addition, the efficiency of memory consolidation during the sleep of the participants was measured using the Wechsler Memory Scale, third edition (WMS-III). The iNOS expression increased in all sleep stages among the PD patients compared to the control participants, in whom iNOS expression decreased during REM sleep. Regarding memory consolidation, the performance of the controls in logic memory and the patients in visual reproduction tasks improved after sleep. The iNOS synthase expression was different from control participants among PD patients, and the expression was dissimilar in various sleep stages. Sleep might enhance memory consolidation and there are different memory consolidation profiles between PD and control participants demonstrating distinct memory consolidation profiles. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. 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

  8. Acute Exercise Improves Motor Memory Consolidation in Preadolescent Children.

    Science.gov (United States)

    Lundbye-Jensen, Jesper; Skriver, Kasper; Nielsen, Jens B; Roig, Marc

    2017-01-01

    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 results also

  9. Effects of sleep deprivation on different phases of memory in the rat: dissociation between contextual and tone fear conditioning tasks.

    Science.gov (United States)

    Rossi, Vanessa Contatto; Tiba, Paula Ayako; Moreira, Karin Di Monteiro; Ferreira, Tatiana Lima; Oliveira, Maria Gabriela Menezes; Suchecki, Deborah

    2014-01-01

    Numerous studies show that sleep deprivation (SD) impacts negatively on cognitive processes, including learning and memory. Memory formation encompasses distinct phases of which acquisition, consolidation and retrieval are better known. Previous studies with pre-training SD induced by the platform method have shown impairment in fear conditioning tasks. Nonetheless, pre-training manipulations do not allow the distinction between effects on acquisition and/or consolidation, interfering, ultimately, on recall of/performance in the task. In the present study, animals were first trained in contextual and tone fear conditioning (TFC) tasks and then submitted to SD with the purpose to evaluate the effect of this manipulation on different stages of the learning process, e.g., in the uptake of (new) information during learning, its encoding and stabilization, and the recall of stored memories. Besides, we also investigated the effect of SD in the extinction of fear memory and a possible state-dependent learning induced by this manipulation. For each task (contextual or TFC), animals were trained and then distributed into control, not sleep-deprived (CTL) and SD groups, the latter being submitted to the modified multiple platform paradigm for 96 h. Subsets of eight rats in each group/experiment were submitted to the test of the tasks, either immediately or at different time intervals after SD. The results indicated that (a) pre- but not post-training SD impaired recall in the contextual and TFC; (b) this impairment was not state-dependent; and (c) in the contextual fear conditioning (CFC), pre-test SD prevented extinction of the learned task. Overall, these results suggest that SD interferes with acquisition, recall and extinction, but not necessarily with consolidation of emotional memory.

  10. Acute exposure to blue wavelength light during memory consolidation improves verbal memory performance.

    Science.gov (United States)

    Alkozei, Anna; Smith, Ryan; Dailey, Natalie S; Bajaj, Sahil; Killgore, William D S

    2017-01-01

    Acute exposure to light within the blue wavelengths has been shown to enhance alertness and vigilance, and lead to improved speed on reaction time tasks, possibly due to activation of the noradrenergic system. It remains unclear, however, whether the effects of blue light extend beyond simple alertness processes to also enhance other aspects of cognition, such as memory performance. The aim of this study was to investigate the effects of a thirty minute pulse of blue light versus placebo (amber light) exposure in healthy normally rested individuals in the morning during verbal memory consolidation (i.e., 1.5 hours after memory acquisition) using an abbreviated version of the California Verbal Learning Test (CVLT-II). At delayed recall, individuals who received blue light (n = 12) during the consolidation period showed significantly better long-delay verbal recall than individuals who received amber light exposure (n = 18), while controlling for the effects of general intelligence, depressive symptoms and habitual wake time. These findings extend previous work demonstrating the effect of blue light on brain activation and alertness to further demonstrate its effectiveness at facilitating better memory consolidation and subsequent retention of verbal material. Although preliminary, these findings point to a potential application of blue wavelength light to optimize memory performance in healthy populations. It remains to be determined whether blue light exposure may also enhance performance in clinical populations with memory deficits.

  11. 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,

  12. Reciprocal Interaction of Dendrite Geometry and Nuclear Calcium-VEGFD Signaling Gates Memory Consolidation and Extinction.

    Science.gov (United States)

    Hemstedt, Thekla J; Bengtson, C Peter; Ramírez, Omar; Oliveira, Ana M M; Bading, Hilmar

    2017-07-19

    Nuclear calcium is an important signaling end point in synaptic excitation-transcription coupling that is critical for long-term neuroadaptations. Here, we show that nuclear calcium acting via a target gene, VEGFD, is required for hippocampus-dependent fear memory consolidation and extinction in mice. Nuclear calcium-VEGFD signaling upholds the structural integrity and complexity of the dendritic arbor of CA1 neurons that renders those cells permissive for the efficient generation of synaptic input-evoked nuclear calcium transients driving the expression of plasticity-related genes. Therefore, the gating of memory functions rests on the reciprocally reinforcing maintenance of an intact dendrite geometry and a functional synapse-to-nucleus communication axis. In psychiatric and neurodegenerative disorders, therapeutic application of VEGFD may help to stabilize dendritic structures and network connectivity, which may prevent cognitive decline and could boost the efficacy of extinction-based exposure therapies. SIGNIFICANCE STATEMENT This study uncovers a reciprocal relationship between dendrite geometry, the ability to generate nuclear calcium transients in response to synaptic inputs, and the subsequent induction of expression of plasticity-related and dendritic structure-preserving genes. Insufficient nuclear calcium signaling in CA1 hippocampal neurons and, consequently, reduced expression of the nuclear calcium target gene VEGFD, a dendrite maintenance factor, leads to reduced-complexity basal dendrites of CA1 neurons, which severely compromises the animals' consolidation of both memory and extinction memory. The structure-protective function of VEGFD may prove beneficial in psychiatric disorders as well as neurodegenerative and aging-related conditions that are associated with loss of neuronal structures, dysfunctional excitation-transcription coupling, and cognitive decline. Copyright © 2017 the authors 0270-6474/17/376946-10$15.00/0.

  13. Are fear memories erasable?–reconsolidation of learned fear with fear-relevant and fear-irrelevant stimuli

    OpenAIRE

    Golkar, Armita; Bellander, Martin; Olsson, Andreas; Öhman, Arne

    2012-01-01

    Recent advances in the field of fear learning have demonstrated that a single reminder exposure prior to extinction training can prevent the return of extinguished fear by disrupting the process of reconsolidation. These findings have however proven hard to replicate in humans. Given the significant implications of preventing the return of fear, the purpose of the present study was to further study the prerequisites for the putative effects of disrupting reconsolidation. In two experiments, w...

  14. 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

  15. Diminished nap effects on memory consolidation are seen under oral contraceptive use

    NARCIS (Netherlands)

    Genzel, L.K.E.; Baurle, A.; Potyka, A.; Wehrle, R.; Adamczyk, M.; Friess, E.; Steiger, A.; Dresler, M.

    2014-01-01

    Many young females take exogenous hormones as oral contraceptive (OC), a condition rarely controlled for in studies on sleep and memory consolidation even though sex hormones influence consolidation. This study investigated the effects of OCs on sleep-related consolidation of a motor and declarative

  16. The endocannabinoid system in anxiety, fear memory and habituation

    Science.gov (United States)

    Ruehle, S; Rey, A Aparisi; Remmers, F

    2012-01-01

    Evidence for the involvement of the endocannabinoid system (ECS) in anxiety and fear has been accumulated, providing leads for novel therapeutic approaches. In anxiety, a bidirectional influence of the ECS has been reported, whereby anxiolytic and anxiogenic responses have been obtained after both increases and decreases of the endocannabinoid tone. The recently developed genetic tools have revealed different but complementary roles for the cannabinoid type 1 (CB1) receptor on GABAergic and glutamatergic neuronal populations. This dual functionality, together with the plasticity of CB1 receptor expression, particularly on GABAergic neurons, as induced by stressful and rewarding experiences, gives the ECS a unique regulatory capacity for maintaining emotional homeostasis. However, the promiscuity of the endogenous ligands of the CB1 receptor complicates the interpretation of experimental data concerning ECS and anxiety. In fear memory paradigms, the ECS is mostly involved in the two opposing processes of reconsolidation and extinction of the fear memory. Whereas ECS activation deteriorates reconsolidation, proper extinction depends on intact CB1 receptor signalling. Thus, both for anxiety and fear memory processing, endocannabinoid signalling may ensure an appropriate reaction to stressful events. Therefore, the ECS can be considered as a regulatory buffer system for emotional responses. PMID:21768162

  17. Are fear memories erasable? –reconsolidation of learned fear with fear relevant and fear-irrelevant stimuli

    Directory of Open Access Journals (Sweden)

    Armita eGolkar

    2012-11-01

    Full Text Available Recent advances in the field of fear learning have demonstrated that a single reminder exposure prior to extinction training can prevent the return of extinguished fear by disrupting the process of reconsolidation. These findings have however proven hard to replicate in humans. Given the significant implications of preventing the return of fear, the purpose of the present study was to further study the prerequisites for the putative effects of disrupting reconsolidation. In two experiments, we assessed whether extinction training initiated within the reconsolidation time window could abolish the return of fear using fear-relevant (experiment 1 or fear-irrelevant (experiment 2 conditioned stimuli (CS. In both experiments, participants went through conditioning, extinction and reinstatement testing on three consecutive days, with one of two reinforced CS being reactivated 10 minutes prior to extinction. We found that a single reminder exposure prior to extinction training did not prevent the return of extinguished fear responding using either fear-relevant or fear-irrelevant CSs. Our findings point to the need to further study the specific parameters that enable disruption of reconsolidation.

  18. Interaction between N-ethylmaleimide-sensitive factor and GluR2 is essential for fear memory formation in lateral amygdala.

    Science.gov (United States)

    Joels, Gil; Lamprecht, Raphael

    2010-11-24

    Long-term memory formation is believed to involve alterations of synaptic efficacy. It has been shown that GluR1-containing AMPA receptors are inserted into synapses following stimuli leading to plasticity and that GluR2/GluR3-containing receptors replace existing synaptic AMPA receptors continuously and may act to maintain synaptic efficacy. Maintaining GluR2/GluR3 receptors level in synapse requires interactions of N-ethylmaleimide-sensitive factor (NSF) with GluR2. To assess possible roles of NSF-GluR2 interaction in rat lateral amygdala (LA) in fear memory formation we used a specific GluR2-NSF interaction inhibitory peptide (pep-R845A). This inhibitory peptide, composed of a modified NSF binding site of GluR2, was previously shown to interact specifically with NSF and to affect AMPA-mediated synaptic efficacy. The inhibitory peptide was linked to a TAT peptide (TAT-pep-R845A) to facilitate internalization into LA cells. Infusion of the TAT-pep-R845A inhibitory peptide into LA 30 min before fear conditioning led to a significant impairment of long-term fear memory formation. In contrast, the control TAT peptide alone had no effect on fear memory. Injection of TAT-pep-R845A peptide into LA had no effect on short-term fear memory. In addition, the inhibitory peptide had no effect on memory retrieval when injected into LA 30 min before fear memory test. Furthermore, maintenance of memory was not impaired when the peptide was injected 24 h after fear conditioning and fear memory was tested 48 h afterward. These results show that GluR2-NSF interaction in LA is necessary for fear memory consolidation but not retrieval or persistence.

  19. 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

  20. Involvement of Spindles in Memory Consolidation Is Slow Wave Sleep-Specific

    Science.gov (United States)

    Cox, Roy; Hofman, Winni F.; Talamini, Lucia M.

    2012-01-01

    Both sleep spindles and slow oscillations have been implicated in sleep-dependent memory consolidation. Whereas spindles occur during both light and deep sleep, slow oscillations are restricted to deep sleep, raising the possibility of greater consolidation-related spindle involvement during deep sleep. We assessed declarative memory retention…

  1. 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

  2. Spicatoside A enhances memory consolidation through the brain-derived neurotrophic factor in mice.

    Science.gov (United States)

    Kwon, Guyoung; Lee, Hyung Eun; Lee, Dong Hwa; Woo, Hyun; Park, Se Jin; Gao, Qingtao; Ahn, Young Je; Son, Kun Ho; Ryu, Jong Hoon

    2014-06-20

    Brain-derived neurotrophic factor (BDNF) plays a pivotal role in memory consolidation. Previously, we found that the increased mature BDNF (mBDNF) levels in the hippocampal region at a specific time window after the acquisition trial are required for memory consolidation. In the present study, we investigated whether spicatoside A enhances memory consolidation, and whether its effects on memory consolidation are related to hippocampal mBDNF levels. Spicatoside A (2.5, 5, 10 or 20mg/kg) enhanced memory consolidation in a dose-dependent manner, and enhanced memory consolidation was also observed when spicatoside A was administered 1h after the acquisition trial. Concurrently, when spicatoside A was administered immediately or 1h after the acquisition trial, hippocampal mBDNF levels were similar or significantly increased at 9h after the acquisition trial compared to levels at 6h. These results suggest that increased mBDNF levels in the hippocampal region at 9h after the acquisition trial might play a pivotal role in memory consolidation and that spicatoside A might enhance memory consolidation by increasing hippocampal mBDNF levels. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. 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'

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Competition between engrams influences fear memory formation and recall.

    Science.gov (United States)

    Rashid, Asim J; Yan, Chen; Mercaldo, Valentina; Hsiang, Hwa-Lin Liz; Park, Sungmo; Cole, Christina J; De Cristofaro, Antonietta; Yu, Julia; Ramakrishnan, Charu; Lee, Soo Yeun; Deisseroth, Karl; Frankland, Paul W; Josselyn, Sheena A

    2016-07-22

    Collections of cells called engrams are thought to represent memories. Although there has been progress in identifying and manipulating single engrams, little is known about how multiple engrams interact to influence memory. In lateral amygdala (LA), neurons with increased excitability during training outcompete their neighbors for allocation to an engram. We examined whether competition based on neuronal excitability also governs the interaction between engrams. Mice received two distinct fear conditioning events separated by different intervals. LA neuron excitability was optogenetically manipulated and revealed a transient competitive process that integrates memories for events occurring closely in time (coallocating overlapping populations of neurons to both engrams) and separates memories for events occurring at distal times (disallocating nonoverlapping populations to each engram). Copyright © 2016, American Association for the Advancement of Science.

  9. 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.

  10. 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.…

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

    Science.gov (United States)

    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.

  12. 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

  13. [Current understanding of sleep, dreaming and related memory consolidation].

    Science.gov (United States)

    Han, Victor Z; Shi, Jun-Han

    2013-12-01

    Sleep is a naturally recurring state found throughout the animal kingdom and characterized by a reversible loss of consciousness. Although in humans the daily amount of sleep decreases with aging, the total amount of time spent for sleep is estimated as up to one-third of one's lifetime. In mammals, sleep shows a clear daily rhythmicity as well as nightly phases, which are strongly controlled by the circadian clock located in the hypothalamic suprachiasmatic nuclei and are also regulated by ambient light. While it is certain that sleep is critical for survival in general, the functional significance of sleep is still under investigation. Dreaming is a common psychological phenomenon occurring during human sleep, yet its content and natural function, if any, are still a matter of debate. In recent years, accumulated evidence strongly supports the notion that new information acquired during the day time is processed and transformed into long-term memory in a complicated and sophisticated way during sleeping. Such information processing is commonly referred to as memory consolidation.

  14. 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.

  15. Selective REM-Sleep Deprivation Does Not Diminish Emotional Memory Consolidation in Young Healthy Subjects

    OpenAIRE

    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 ...

  16. 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 ...

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

    OpenAIRE

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

    2015-01-01

    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 stre...

  18. Autobiographical memory and hyperassociativity in the dreaming brain: implications for memory consolidation in sleep

    Science.gov (United States)

    Horton, Caroline L.; Malinowski, Josie E.

    2015-01-01

    In this paper we argue that autobiographical memory (AM) 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-contextualizing 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 AM 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 AM during sleep. PMID:26191010

  19. Autobiographical memory and hyperassociativity in the dreaming brain: implications for memory consolidation in sleep.

    Science.gov (United States)

    Horton, Caroline L; Malinowski, Josie E

    2015-01-01

    In this paper we argue that autobiographical memory (AM) 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-contextualizing 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 AM 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 AM during sleep.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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.

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

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    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.

  4. Circadian Modulation of Consolidated Memory Retrieval Following Sleep Deprivation in Drosophila

    Science.gov (United States)

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

    2012-01-01

    Objectives: 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. Design: 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. Results 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. Conclusions 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. Citation: Le Glou E; Seugnet L; Shaw PJ; Preat T; Goguel V. Circadian modulation of consolidated memory retrieval following sleep deprivation in Drosophila. SLEEP 2012;35(10):1377-1384. PMID:23024436

  5. Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation

    Directory of Open Access Journals (Sweden)

    Inoue Naoko

    2009-03-01

    Full Text Available Abstract Background The formation of long-term memory (LTM and the late phase of long-term potentiation (L-LTP depend on macromolecule synthesis, translation, and transcription in neurons. vesl-1S (VASP/Ena-related gene upregulated during seizure and LTP, also known as homer-1a is an LTP-induced immediate early gene. The short form of Vesl (Vesl-1S is an alternatively spliced isoform of the vesl-1 gene, which also encodes the long form of the Vesl protein (Vesl-1L. Vesl-1L is a postsynaptic scaffolding protein that binds to and modulates the metabotropic glutamate receptor 1/5 (mGluR1/5, the IP3 receptor, and the ryanodine receptor. Vesl-1 null mutant mice show abnormal behavior, which includes anxiety- and depression-related behaviors, and an increase in cocaine-induced locomotion; however, the function of the short form of Vesl in behavior is poorly understood because of the lack of short-form-specific knockout mice. Results In this study, we generated short-form-specific gene targeting (KO mice by knocking in part of vesl-1L/homer-1c cDNA. Homozygous KO mice exhibited normal spine number and morphology. Using the contextual fear conditioning test, we demonstrated that memory acquisition and short-term memory were normal in homozygous KO mice. In contrast, these mice showed impairment in fear memory consolidation. Furthermore, the process from recent to remote memory was affected in homozygous KO mice. Interestingly, reactivation of previously consolidated fear memory attenuated the conditioning-induced freezing response in homozygous KO mice, which suggests that the short form plays a role in fear memory reconsolidation. General activity, emotional performance, and sensitivity to electrofootshock were normal in homozygous KO mice. Conclusion These results indicate that the short form of the Vesl family of proteins plays a role in multiple steps of long-term, but not short-term, fear memory formation.

  6. Offline consolidation of memory varies with time in slow wave sleep and can be accelerated by cuing memory reactivations.

    Science.gov (United States)

    Diekelmann, Susanne; Biggel, Simon; Rasch, Björn; Born, Jan

    2012-09-01

    Memory representations are reactivated during slow-wave sleep (SWS) after learning, and these reactivations cause a beneficial effect of sleep for memory consolidation. Memory reactivations can also be externally triggered during sleep by associated cues which enhance the sleep-dependent memory consolidation process. Here, we compared in humans the influence of sleep periods (i) of 40min and (ii) of 90min without externally triggered reactivations and (iii) of externally triggered reactivations by an associated odor cue during a 40-min sleep period on the consolidation of previously learned hippocampus-dependent visuo-spatial memories. We show that external reactivation by an odor cue during the 40-min sleep period enhanced memory stability to the same extent as 90min of sleep without odor reactivation. In contrast, 40min of sleep without external reactivations were not sufficient to benefit memory. In the 90-min sleep condition, memory enhancements were associated with time spent in SWS and were independent of the presence or absence of REM sleep. These results suggest that the efficacy of hippocampus-dependent memory consolidation depends on the duration of sleep and particularly SWS. External reactivation cues can accelerate the consolidation process even during shorter sleep episodes. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. Distinct effects of estrogen receptor antagonism on object recognition and spatial memory consolidation in ovariectomized mice.

    Science.gov (United States)

    Kim, Jaekyoon; Frick, Karyn M

    2017-11-01

    Exogenous treatment with the potent estrogen 17β-estradiol (E 2 ) or selective estrogen receptor α/β (ERα/β) agonists enhances the consolidation of hippocampal-dependent object recognition (OR) and object placement (OP) memories in ovariectomized rodents. Although such data suggest that individual ERs are sufficient for memory consolidation, the necessity of a given ER for memory consolidation can only be demonstrated by blocking receptor function, for example with an ER antagonist. However, the effects on memory of antagonizing ERα or ERβ function are not well understood. Moreover, ER antagonism in ovariectomized subjects also provides indirect information about the role of individual ERs in the memory-enhancing effects of local hippocampal E 2 synthesis. Therefore, this study used pharmacological inhibition of ERα and ERβ to elucidate the importance of each ER to memory consolidation. Specifically, we examined effects on OR and OP memory consolidation of immediate post-training dorsal hippocampal (DH) infusion of MPP and PHTPP, selective antagonists for ERα and ERβ, respectively. Each drug exhibited a distinct effect on OR and OP. DH infusion of MPP (0.28 or 2.78ng/hemisphere) impaired memory in OP, but not OR. However, DH infusion of PHTPP (0.21 or 2.12ng/hemisphere) impaired memory in both OR and OP. Neither drug affected the elapsed time to accumulate object exploration in either task, suggesting a specific effect on memory. These results indicate that activation of either classical ER within the dorsal hippocampus is important for hippocampal memory consolidation in ovariectomized mice, but suggest that specific ER involvement is memory- or task-specific. The findings also indirectly support a role for ERα and ERβ in mediating the memory-enhancing effects of hippocampally-synthesized E 2 . Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Possible role of cholinesterase inhibitors on memory consolidation following hypobaric hypoxia of rats.

    Science.gov (United States)

    Muthuraju, Sangu; Maiti, Panchanan; Solanki, Preeti; Sharma, Alpesh Kumar; Pati, Soumya; Singh, Shashi Bala; Prasad, Dipti; Ilavazhagan, Govindasamy

    2011-05-01

    High altitude (HA) generates a deleterious effect known as hypobaric hypoxia (HBH). This causes severe physiological and psychological changes such as acute mountain sickness (AMS) and cognitive functions in terms of learning and memory. The present study has evaluated the effect of cholinesterase inhibitors on memory consolidation following HBH. Adult male Sprague Dawley rats (80-90 days old) with an average body weight of 250 ± 25 g were used. Rats were assessed memory consolidation by using Morris water maze (MWM) for 8 days. After assessment of memory consolidation, rats were then exposed to HBH in stimulated chamber for 7 days at 6,100 m. After exposure to HBH, the memory consolidation of rats has been assessed in MWM. The results showed that there was memory consolidation impairment in HBH-exposed rats as compared to normoxic rats in terms of time spent in quaradents, rings, and counters. The rats which have been treated with physostigmine (PHY) and galantamine (GAL) showed better time spent in quaradents, rings, and counters as compared with hypoxic rats. In conclusion, the cholinesterase inhibitors could ameliorate the impairment of memory consolidation following HBH.

  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. 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...... (ILC) cortices 36 d following contextual fear conditioning. Upon extinction, aCC spine density returned to baseline, but the enhanced proportion of large spines did not. Differently, ILC spine density remained elevated, but the size of spines decreased dramatically. Thus, extinction partially erases...

  16. Attenuating fearful memories: effect of cued extinction on intrusions.

    Science.gov (United States)

    Marks, Elizabeth H; Zoellner, Lori A

    2014-12-01

    Exposure-based therapies for posttraumatic stress disorder are thought to reduce intrusive memories through extinction processes. Methods that enhance extinction may translate to improved treatment. Rat research suggests retrieving a memory via a conditioned stimulus (CS) cue, and then modifying the retrieved memory within a specific reconsolidation window may enhance extinction. In humans, studies (e.g., Kindt & Soeter, 2013; Schiller et al., 2010) using basic learning paradigms show discrepant findings. Using a distressing film paradigm, participants (N = 148) completed fear acquisition and extinction. At extinction, they were randomized to 1 of 3 groups: CS cue within reconsolidation window, CS cue outside window, or non-CS cue within window. Intrusions were assessed 24 hr after extinction. Participants receiving the CS cue and completing extinction within the reconsolidation window had more intrusions (M = 2.40, SD = 2.54) than those cued outside (M = 1.65, SD = 1.70) or those receiving a non-CS cue (M = 1.24, SD = 1.26), F(2, 145) = 4.52, p = .01, d = 0.55. Consistent with the reconsolidation hypothesis, presenting a CS cue does appear to activate a specific period of time during which a memory can be updated. However, the CS cue caused increased, rather than decreased, frequency of intrusions. Understanding parameters of preextinction cueing may help us better understand reconsolidation as a potential memory updating mechanism.

  17. 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

  18. 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.

  19. Declarative memory consolidation in humans: a prospective functional magnetic resonance imaging study.

    NARCIS (Netherlands)

    Takashima, A.; Petersson, K.M.; Rutters, F.; Tendolkar, I.; Jensen, O.; Zwarts, M.J.; McNaughton, B.L.; Fernandez, G.S.E.

    2006-01-01

    Retrieval of recently acquired declarative memories depends on the hippocampus, but with time, retrieval is increasingly sustainable by neocortical representations alone. This process has been conceptualized as system-level consolidation. Using functional magnetic resonance imaging, we assessed over

  20. 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.

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

    Science.gov (United States)

    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.

  2. 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.

  3. Gender differences in the effects of post-learning emotion on consolidation of item memory and source memory.

    Science.gov (United States)

    Wang, Bo; Fu, Xiaolan

    2010-05-01

    Item memory and source memory are two integral elements of episodic memory. Although many studies have examined the effect of emotion on item memory, little research has simultaneously taken into account item memory and source memory. In addition, in the majority of previous studies, learning stimuli are used as the source of emotion, making it difficult to understand whether emotion has an effect on encoding or on consolidation of episodic memory. Furthermore, although gender differences exist in neurophysiological responses to emotional stimuli, in many studies gender differences were neglected and this leaves the picture incomplete regarding the effect of emotion on episodic memory. In this study, we examined gender differences in the effects of post-learning emotion on consolidation of item memory and source memory. Participants learned neutral Chinese nouns, took a memory pretest, and were then randomly assigned to three conditions, in which they either watched a 3-min negative video clip, or watched a 3-min positive video clip, or remained calm and relaxed for 3 min. Thirty minutes after the initial learning, participants took a memory posttest. We found that: (1) For females, post-learning negative emotion enhanced consolidation of item memory; however, neither negative emotion nor positive emotion had a significant effect on consolidation of source memory; (2) For males, neither negative nor positive emotion after learning had a significant effect on either item memory or source memory. Possible reasons for the gender differences, as well as the theoretical significance and practical implications of this study were discussed. Copyright 2010 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Jarste Morgenthaler

    Full Text Available 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.

  7. 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.

  8. 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.

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

    Science.gov (United States)

    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.

  10. 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.

  11. 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

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

    Directory of Open Access Journals (Sweden)

    Kara A Kittelberger

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

  13. Memory Consolidation Is Linked to Spindle-Mediated Information Processing during Sleep.

    Science.gov (United States)

    Cairney, Scott A; Guttesen, Anna Á Váli; El Marj, Nicole; Staresina, Bernhard P

    2018-03-02

    How are brief encounters transformed into lasting memories? Previous research has established the role of non-rapid eye movement (NREM) sleep, along with its electrophysiological signatures of slow oscillations (SOs) and spindles, for memory consolidation [1-4]. In related work, experimental manipulations have demonstrated that NREM sleep provides a window of opportunity to selectively strengthen particular memory traces via the delivery of auditory cues [5-10], a procedure known as targeted memory reactivation (TMR). It has remained unclear, however, whether TMR triggers the brain's endogenous consolidation mechanisms (linked to SOs and/or spindles) and whether those mechanisms in turn mediate effective processing of mnemonic information. We devised a novel paradigm in which associative memories (adjective-object and adjective-scene pairs) were selectively cued during a post-learning nap, successfully stabilizing next-day retention relative to non-cued memories. First, we found that, compared to novel control adjectives, memory cues evoked an increase in fast spindles. Critically, during the time window of cue-induced spindle activity, the memory category linked to the verbal cue (object or scene) could be reliably decoded, with the fidelity of this decoding predicting the behavioral consolidation benefits of TMR. These results provide correlative evidence for an information processing role of sleep spindles in service of memory consolidation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (United States)

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

    2016-03-30

    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. 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. Copyright © 2016 Hennies et al.

  15. Acute exercise and motor memory consolidation: The role of exercise intensity and timing

    DEFF Research Database (Denmark)

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

    2015-01-01

    that exercise intensity plays an important role for motor memory consolidation in favour of higher intensity aerobic exercise, while Experiment B indicates that timing of exercise is also important, with exercise immediately following motor skill learning being more efficient. Motor performance in retention......Background A single bout of high intensity cycling (~90% VO2peak) immediately after motor skill training enhances motor memory consolidation. It is unclear how different parameters of exercise may influence this process and the underlying mechanisms are poorly understood. We hypothesize...... that the effects of exercise on consolidation are time-dependent with a decreasing positive effect of exercise post acquisition and investigate the role of exercise intensity and timing on motor memory consolidation. Furthermore, we explore the potential role of transient changes in corticospinal excitability (CSE...

  16. Blurring Aversive Memory: Exploring a Novel Route to Fear Reduction

    NARCIS (Netherlands)

    Leer, A.

    2015-01-01

    Treatment of pathological fear typically involves exposure to the feared stimulus. This procedure is effective in reducing fear in the short term. However, many patients relapse, i.e. show a return of fear. The present thesis explored a novel route to counter the renewal of fear. Previous research

  17. Blurring Aversive Memory : Exploring a Novel Route to Fear Reduction

    NARCIS (Netherlands)

    Leer, Arne|info:eu-repo/dai/nl/381059650

    2015-01-01

    Treatment of pathological fear typically involves exposure to the feared stimulus. This procedure is effective in reducing fear in the short term. However, many patients relapse, i.e. show a return of fear. The present thesis explored a novel route to counter the renewal of fear. Previous research

  18. Inactivation of the Infralimbic but Not the Prelimbic Cortex Impairs Consolidation and Retrieval of Fear Extinction

    Science.gov (United States)

    Laurent, Vincent; Westbrook, R. Frederick

    2009-01-01

    Rats were subjected to one or two cycles of context fear conditioning and extinction to study the roles of the prelimbic cortex (PL) and infralimbic cortex (IL) in learning and relearning to inhibit fear responses. Inactivation of the PL depressed fear responses across the first or second extinction but did not impair learning or relearning fear…

  19. 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.

  20. 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.

  1. 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.

  2. 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…

  3. Midlife Decline in Declarative Memory Consolidation Is Correlated with a Decline in Slow Wave Sleep

    Science.gov (United States)

    Backhaus, Jutta; Born, Jan; Hoeckesfeld, Ralf; Fokuhl, Sylvia; Hohagen, Fritz; Junghanns, Klaus

    2007-01-01

    Sleep architecture as well as memory function are strongly age dependent. Slow wave sleep (SWS), in particular, decreases dramatically with increasing age, starting already beyond the age of 30. SWS normally predominates during early nocturnal sleep and is implicated in declarative memory consolidation. However, the consequences of changes in…

  4. 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

  5. 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…

  6. The effect of two benzodiazepine receptor agonist hypnotics on sleep-dependent memory consolidation.

    Science.gov (United States)

    Hall-Porter, Janine M; Schweitzer, Paula K; Eisenstein, Rhody D; Ahmed, Hasan Ali H; Walsh, James K

    2014-01-15

    Numerous studies have demonstrated that sleep promotes memory consolidation, but there is little research on the effect of hypnotics on sleep-dependent memory consolidation. We compared bedtime administration of zolpidem-ER 12.5 mg (6- to 8-h duration of action), middle-of-the-night administration of zaleplon 10 mg (3- to 4-h duration of action), and placebo to examine the effect of different durations of hypnotic drug exposure on memory consolidation during sleep. Twenty-two participants with no sleep complaints underwent 3 conditions in a counterbalanced crossover study: (1) zolpidem-ER 12.5 mg (bedtime dosing), (2) zaleplon 10 mg (middle-of-the-night dosing), and (3) placebo. Memory testing was conducted before and after an 8-h sleep period, using a word pair association task (WPT; declarative memory) and a finger-tapping task (FTT; procedural memory). ANOVA revealed a significant condition effect for the WPT (p = 0.025) and a trend for the FTT (p = 0.067), which was significant when sex was added to the model (p = 0.014). Improvement in memory performance following sleep was lower with bedtime dosing of zolpidem-ER compared to placebo and middle-of-the-night dosing of zaleplon. There were no differences between placebo and zaleplon. The results suggest that in some circumstances hypnotics may have the potential to reduce the degree of sleep-dependent memory consolidation and that drug-free sleep early in the night may ameliorate this effect.

  7. 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.

  8. Possible Overlapping Time Frames of Acquisition and Consolidation Phases in Object Memory Processes: A Pharmacological Approach

    Science.gov (United States)

    Akkerman, Sven; Blokland, Arjan; Prickaerts, Jos

    2016-01-01

    In previous studies, we have shown that acetylcholinesterase inhibitors and phosphodiesterase inhibitors (PDE-Is) are able to improve object memory by enhancing acquisition processes. On the other hand, only PDE-Is improve consolidation processes. Here we show that the cholinesterase inhibitor donepezil also improves memory performance when…

  9. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  12. Cerebral Activation During Initial Motor Learning Forecasts Subsequent Sleep-Facilitated Memory Consolidation in Older Adults.

    Science.gov (United States)

    King, Bradley R; Saucier, Philippe; Albouy, Genevieve; Fogel, Stuart M; Rumpf, Jost-Julian; Klann, Juliane; Buccino, Giovanni; Binkofski, Ferdinand; Classen, Joseph; Karni, Avi; Doyon, Julien

    2017-02-01

    Older adults exhibit deficits in motor memory consolidation; however, little is known about the cerebral correlates of this impairment. We thus employed fMRI to investigate the neural substrates underlying motor sequence memory consolidation, and the modulatory influence of post-learning sleep, in healthy older adults. Participants were trained on a motor sequence and retested following an 8-h interval including wake or diurnal sleep as well as a 22-h interval including a night of sleep. Results demonstrated that a post-learning nap improved offline consolidation across same- and next-day retests. This enhanced consolidation was reflected by increased activity in the putamen and the medial temporal lobe, including the hippocampus, regions that have previously been implicated in sleep-dependent neural plasticity in young adults. Moreover, for the first time in older adults, the neural substrates subserving initial motor learning, including the putamen, cerebellum, and parietal cortex, were shown to forecast subsequent consolidation depending on whether a post-learning nap was afforded. Specifically, sufficient activation in a motor-related network appears to be necessary to trigger sleep-facilitated consolidation in older adults. Our findings not only demonstrate that post-learning sleep can enhance motor memory consolidation in older adults, but also provide the system-level neural correlates of this beneficial effect. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. 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.

  14. Sleep-dependent memory consolidation in the epilepsy monitoring unit: A pilot study.

    Science.gov (United States)

    Sarkis, Rani A; Alam, Javad; Pavlova, Milena K; Dworetzky, Barbara A; Pennell, Page B; Stickgold, Robert; Bubrick, Ellen J

    2016-08-01

    We sought to examine whether patients with focal epilepsy exhibit sleep dependent memory consolidation, whether memory retention rates correlated with particular aspects of sleep physiology, and how the process was affected by seizures. We prospectively recruited patients with focal epilepsy and assessed declarative memory using a task consisting of 15 pairs of colored pictures on a 5×6 grid. Patients were tested 12h after training, once after 12h of wakefulness and once after 12h that included sleep. EMG chin electrodes were placed to enable sleep scoring. The number and density of sleep spindles were assessed using a wavelet-based algorithm. Eleven patients were analyzed age 21-56years. The percentage memory retention over 12h of wakefulness was 62.7% and over 12h which included sleep 83.6% (p=0.04). Performance on overnight testing correlated with the duration of slow wave sleep (SWS) (r=+0.63, psleep dependent memory consolidation in patients with epilepsy which mostly correlates with the amount of SWS. Our preliminary findings suggest that nocturnal seizures likely disrupt sleep dependent memory consolidation. Findings highlight the importance of SWS in sleep dependent memory consolidation and the adverse impact of nocturnal seizures on this process. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  16. Sleep, dreams, and memory consolidation: The role of the stress hormone cortisol

    OpenAIRE

    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 influence on many of the brain systems involved in memory. The concentration of cortisol escalates over the course of the night's sleep, in ways that we ...

  17. Top-down cortical input during NREM sleep consolidates perceptual memory.

    Science.gov (United States)

    Miyamoto, D; Hirai, D; Fung, C C A; Inutsuka, A; Odagawa, M; Suzuki, T; Boehringer, R; Adaikkan, C; Matsubara, C; Matsuki, N; Fukai, T; McHugh, T J; Yamanaka, A; Murayama, M

    2016-06-10

    During tactile perception, long-range intracortical top-down axonal projections are essential for processing sensory information. Whether these projections regulate sleep-dependent long-term memory consolidation is unknown. We altered top-down inputs from higher-order cortex to sensory cortex during sleep and examined the consolidation of memories acquired earlier during awake texture perception. Mice learned novel textures and consolidated them during sleep. Within the first hour of non-rapid eye movement (NREM) sleep, optogenetic inhibition of top-down projecting axons from secondary motor cortex (M2) to primary somatosensory cortex (S1) impaired sleep-dependent reactivation of S1 neurons and memory consolidation. In NREM sleep and sleep-deprivation states, closed-loop asynchronous or synchronous M2-S1 coactivation, respectively, reduced or prolonged memory retention. Top-down cortical information flow in NREM sleep is thus required for perceptual memory consolidation. Copyright © 2016, American Association for the Advancement of Science.

  18. 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.

  19. 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

  20. Reward retroactively enhances memory consolidation for related items

    OpenAIRE

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

    2017-01-01

    Reward motivation has been shown to modulate episodic memory processes in order to support future adaptive behavior. However, for a memory system to be truly adaptive, it should enhance memory for rewarded events as well as for neutral events that may seem inconsequential at the time of encoding but can gain importance later. Here, we investigated the influence of reward motivation on retroactive memory enhancement selectively for conceptually related information. We found behavioral evidence...

  1. Reward Retroactively Enhances Memory Consolidation for Related Items

    Science.gov (United States)

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

    2017-01-01

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

  2. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Procedural Memory Consolidation in the Performance of Brief Keyboard Sequences

    Science.gov (United States)

    Duke, Robert A.; Davis, Carla M.

    2006-01-01

    Using two sequential key press sequences, we tested the extent to which subjects' performance on a digital piano keyboard changed between the end of training and retest on subsequent days. We found consistent, significant improvements attributable to sleep-based consolidation effects, indicating that learning continued after the cessation of…

  7. 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

    Objectives 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...... 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...... 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...

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

    Science.gov (United States)

    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

  9. Diminished nap effects on memory consolidation are seen under oral contraceptive use.

    Science.gov (United States)

    Genzel, Lisa; Bäurle, Anna; Potyka, Alina; Wehrle, Renate; Adamczyk, Marek; Friess, Elisabeth; Steiger, Axel; Dresler, Martin

    2014-01-01

    Many young females take exogenous hormones as oral contraceptive (OC), a condition rarely controlled for in studies on sleep and memory consolidation even though sex hormones influence consolidation. This study investigated the effects of OCs on sleep-related consolidation of a motor and declarative task, utilizing a daytime nap protocol. Fifteen healthy, young females taking OCs came to the sleep lab for three different conditions: nap with previous learning, wake with previous learning and nap without learning. They underwent each condition twice, once during the "pill-active" weeks and once during the "pill-free" week, resulting in 6 visits. In all conditions, participants showed a significant off-line consolidation effect, independent of pill week or nap/wake condition. There were no significant differences in sleep stage duration, spindle activity or spectral EEG frequency bands between naps with or without the learning condition. The present data showed a significant off-line enhancement in memory irrespective of potential beneficial effects of a nap. In comparison to previous studies, this may suggest that the use of OCs may enhance off-line memory consolidation in motor and verbal tasks per se. These results stress the importance to control for the use of OCs in studies focusing on memory performance. © 2015 S. Karger AG, Basel

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

    Science.gov (United States)

    Nishida, Masaki; Nakashima, Yusaku; Nishikawa, Toru

    2016-01-01

    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. 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). 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. Because the changes in slow-frequency spindle activity affected the thalamocortical network dysfunction in patients medicated for depression, dysregulated spindle generation may impair sleep-dependent memory consolidation. Our findings may help to elucidate the cognitive deficits that occur in patients with major depression both in the waking state and during sleep.

  11. Forming Competing Fear Learning and Extinction Memories in Adolescence Makes Fear Difficult to Inhibit

    Science.gov (United States)

    Baker, Kathryn D.; Richardson, Rick

    2015-01-01

    Fear inhibition is markedly impaired in adolescent rodents and humans. The present experiments investigated whether this impairment is critically determined by the animal's age at the time of fear learning or their age at fear extinction. Male rats (n = 170) were tested for extinction retention after conditioning and extinction at different ages.…

  12. A novel form of memory for auditory fear conditioning at a low-intensity unconditioned stimulus.

    Directory of Open Access Journals (Sweden)

    Ayumi Kishioka

    Full Text Available Fear is one of the most potent emotional experiences and is an adaptive component of response to potentially threatening stimuli. On the other hand, too much or inappropriate fear accounts for many common psychiatric problems. Cumulative evidence suggests that the amygdala plays a central role in the acquisition, storage and expression of fear memory. Here, we developed an inducible striatal neuron ablation system in transgenic mice. The ablation of striatal neurons in the adult brain hardly affected the auditory fear learning under the standard condition in agreement with previous studies. When conditioned with a low-intensity unconditioned stimulus, however, the formation of long-term fear memory but not short-tem memory was impaired in striatal neuron-ablated mice. Consistently, the ablation of striatal neurons 24 h after conditioning with the low-intensity unconditioned stimulus, when the long-term fear memory was formed, diminished the retention of the long-term memory. Our results reveal a novel form of the auditory fear memory depending on striatal neurons at the low-intensity unconditioned stimulus.

  13. Coordination of Slow Waves With Sleep Spindles Predicts Sleep-Dependent Memory Consolidation in Schizophrenia.

    Science.gov (United States)

    Demanuele, Charmaine; Bartsch, Ullrich; Baran, Bengi; Khan, Sheraz; Vangel, Mark G; Cox, Roy; Hämäläinen, Matti; Jones, Matthew W; Stickgold, Robert; Manoach, Dara S

    2017-01-01

    Schizophrenia patients have correlated deficits in sleep spindle density and sleep-dependent memory consolidation. In addition to spindle density, memory consolidation is thought to rely on the precise temporal coordination of spindles with slow waves (SWs). We investigated whether this coordination is intact in schizophrenia and its relation to motor procedural memory consolidation. Twenty-one chronic medicated schizophrenia patients and 17 demographically matched healthy controls underwent two nights of polysomnography, with training on the finger tapping motor sequence task (MST) on the second night and testing the following morning. We detected SWs (0.5-4 Hz) and spindles during non-rapid eye movement (NREM) sleep. We measured SW-spindle phase-amplitude coupling and its relation with overnight improvement in MST performance. Patients did not differ from controls in the timing of SW-spindle coupling. In both the groups, spindles peaked during the SW upstate. For patients alone, the later in the SW upstate that spindles peaked and the more reliable this phase relationship, the greater the overnight MST improvement. Regression models that included both spindle density and SW-spindle coordination predicted overnight improvement significantly better than either parameter alone, suggesting that both contribute to memory consolidation. Schizophrenia patients show intact spindle-SW temporal coordination, and these timing relationships, together with spindle density, predict sleep-dependent memory consolidation. These relations were seen only in patients suggesting that their memory is more dependent on optimal spindle-SW timing, possibly due to reduced spindle density. Interventions to improve memory may need to increase spindle density while preserving or enhancing the coordination of NREM oscillations. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e

  14. 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.

  15. 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.

  16. Declarative Memory Consolidation: Mechanisms Acting during Human Sleep

    Science.gov (United States)

    Gais, Steffen; Born, Jan

    2004-01-01

    Of late, an increasing number of studies have shown a strong relationship between sleep and memory. Here we summarize a series of our own studies in humans supporting a beneficial influence of slow-wave sleep (SWS) on declarative memory formation, and try to identify some mechanisms that might underlie this influence. Specifically, these…

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

    NARCIS (Netherlands)

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

    2008-01-01

    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

  18. Locus coeruleus and dopaminergic consolidation of everyday memory

    NARCIS (Netherlands)

    Takeuchi, T.; Duszkiewicz, A.J.; Sonneborn, A.; Spooner, P.A.; Yamasaki, M.; Watanabe, M.; Smith, C.C.; Fernandez, G.S.E.; Deisseroth, K.; Greene, R.W.; Morris, R.G.

    2016-01-01

    The retention of episodic-like memory is enhanced, in humans and animals, when something novel happens shortly before or after encoding. Using an everyday memory task in mice, we sought the neurons mediating this dopamine-dependent novelty effect, previously thought to originate exclusively from the

  19. Money Enhances Memory Consolidation--But Only for Boring Material

    Science.gov (United States)

    Murayama, Kou; Kuhbandner, Christof

    2011-01-01

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

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

    NARCIS (Netherlands)

    Talamini, L.M.; Nieuwenhuis, I.L.C.; Takashima, A.; Jensen, O.

    2008-01-01

    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

  1. 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.

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

    Science.gov (United States)

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

    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.

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

    Science.gov (United States)

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

    2012-03-20

    Recent research investigating Pavlovian fear conditioning and fear extinction has elucidated the neurocircuitry involved in acquisition and inhibition of fear responses. Modulatory factors that may underlie individual differences in fear acquisition and inhibition, however, are not well understood. Testosterone is known to affect anxiety-like behavior and cognitive processing. In this study, we hypothesized that castration would increase anxiety and reduce memory for contextual fear conditioning in an age-dependent manner. In addition, castration would reduce the rate of extinction to context, as high levels of testosterone correlate with reduced PTSD-like symptoms. We compared behaviors in male mice that were castrated at one of two different time points, either before puberty (at 4 weeks) or after puberty (at 10 weeks) to sham-operated control mice. The behaviors investigated included: anxiety, cued and contextual fear conditioning, and extinction of the fear memory. An interaction of hormone status and age and a significant effect of age were measured in the elevated plus maze, a measure of anxiety. Castration caused a significant reduction of contextual fear memory, but no effect on cued fear memory. There was no significant effect of castration on extinction. Interestingly, a significant effect of age of the mouse at the time of testing was observed on extinction. These results suggest that endogenous androgens during puberty are important for anxiety and fear memory formation. In addition, these results define a late post-adolescent developmental time point for changes in anxiety and fear extinction. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. A Cross-Syndrome Study of the Differential Effects of Sleep on Declarative Memory Consolidation in Children with Neurodevelopmental Disorders

    Science.gov (United States)

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

    2017-01-01

    Sleep plays an active role in memory consolidation. Because children with Down syndrome (DS) and Williams syndrome (WS) experience significant problems with sleep and also with learning, we predicted that sleep-dependent memory consolidation would be impaired in these children when compared to typically developing (TD) children. This is the first…

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

    Directory of Open Access Journals (Sweden)

    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

  6. Relationship between Fear Conditionability and Aversive Memories: Evidence from a Novel Conditioned-Intrusion Paradigm

    Science.gov (United States)

    Wegerer, Melanie; Blechert, Jens; Kerschbaum, Hubert; Wilhelm, Frank H.

    2013-01-01

    Intrusive memories – a hallmark symptom of posttraumatic stress disorder (PTSD) – are often triggered by stimuli possessing similarity with cues that predicted or accompanied the traumatic event. According to learning theories, intrusive memories can be seen as a conditioned response to trauma reminders. However, direct laboratory evidence for the link between fear conditionability and intrusive memories is missing. Furthermore, fear conditioning studies have predominantly relied on standardized aversive stimuli (e.g. electric stimulation) that bear little resemblance to typical traumatic events. To investigate the general relationship between fear conditionability and aversive memories, we tested 66 mentally healthy females in a novel conditioned-intrusion paradigm designed to model real-life traumatic experiences. The paradigm included a differential fear conditioning procedure with neutral sounds as conditioned stimuli and short violent film clips as unconditioned stimuli. Subsequent aversive memories were assessed through a memory triggering task (within 30 minutes, in the laboratory) and ambulatory assessment (involuntary aversive memories in the 2 days following the experiment). Skin conductance responses and subjective ratings demonstrated successful differential conditioning indicating that naturalistic aversive film stimuli can be used in a fear conditioning experiment. Furthermore, aversive memories were elicited in response to the conditioned stimuli during the memory triggering task and also occurred in the 2 days following the experiment. Importantly, participants who displayed higher conditionability showed more aversive memories during the memory triggering task and during ambulatory assessment. This suggests that fear conditioning constitutes an important source of persistent aversive memories. Implications for PTSD and its treatment are discussed. PMID:24244407

  7. 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

  8. 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…

  9. 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…

  10. Sleep-mediated memory consolidation depends on the level of integration at encoding.

    Science.gov (United States)

    Himmer, Lea; Müller, Elias; Gais, Steffen; Schönauer, Monika

    2017-01-01

    There is robust evidence that sleep facilitates declarative memory consolidation. Integration of newly acquired memories into existing neocortical knowledge networks has been proposed to underlie this effect. Here, we test whether sleep affects memory retention for word-picture associations differently when it was learned explicitly or using a fast mapping strategy. Fast mapping is an incidental form of learning that references new information to existing knowledge and possibly allows neocortical integration already during encoding. If the integration of information into neocortical networks is a main function of sleep-dependent memory consolidation, material learned via fast mapping should therefore benefit less from sleep. Supporting this idea, we find that sleep has a protective effect on explicitly learned associations. In contrast, memory for associations learned by fast mapping does not benefit from sleep and remains stable regardless of whether sleep or wakefulness follows learning. Our results thus indicate that the need for sleep-mediated consolidation depends on the strategy used for learning and might thus be related to the level of integration of newly acquired memory achieved during encoding. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Impairment of sleep-related memory consolidation in schizophrenia: relevance of sleep spindles?

    Science.gov (United States)

    Göder, Robert; Graf, Anna; Ballhausen, Felix; Weinhold, Sara; Baier, Paul Christian; Junghanns, Klaus; Prehn-Kristensen, Alexander

    2015-05-01

    Deficits in declarative memory performance are among the most severe neuropsychological impairments in schizophrenia and contribute to poor clinical outcomes. The importance of sleep for brain plasticity and memory consolidation is widely accepted, and sleep spindles seem to play an important role in these processes. The aim of this study was to test the associations of sleep spindles and picture memory consolidation in patients with schizophrenia and healthy controls. We studied 16 patients with schizophrenia on stable antipsychotic medication (mean age ± standard deviation, 29.4 ± 6.4 years) and 16 healthy controls matched for age and educational level. Sleep was recorded and scored according to American Academy of Sleep Medicine (AASM) standard criteria. We performed a picture recognition paradigm and compared recognition performance for neutral and emotional pictures in sleep and wake conditions. Recognition accuracy was better in healthy controls than in patients with schizophrenia in the sleep and wake conditions. However, the memory-promoting effect of sleep was significantly lower in schizophrenia patients than in controls. Sleep spindle activity was reduced in patients, and sleep spindle density was correlated with sleep-associated facilitation of recognition accuracy for neutral pictures. Reduced sleep spindles seem to play an important role as a possible mechanism or biomarker for impaired sleep-related memory consolidation in patients with schizophrenia, and are a new target for treatment to improve memory functions and clinical outcomes in these patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. 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…

  13. 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

  14. A single pair of neurons links sleep to memory consolidation in Drosophila melanogaster.

    Science.gov (United States)

    Haynes, Paula R; Christmann, Bethany L; Griffith, Leslie C

    2015-01-07

    Sleep promotes memory consolidation in humans and many other species, but the physiological and anatomical relationships between sleep and memory remain unclear. Here, we show the dorsal paired medial (DPM) neurons, which are required for memory consolidation in Drosophila, are sleep-promoting inhibitory neurons. DPMs increase sleep via release of GABA onto wake-promoting mushroom body (MB) α'/β' neurons. Functional imaging demonstrates that DPM activation evokes robust increases in chloride in MB neurons, but is unable to cause detectable increases in calcium or cAMP. Downregulation of α'/β' GABAA and GABABR3 receptors results in sleep loss, suggesting these receptors are the sleep-relevant targets of DPM-mediated inhibition. Regulation of sleep by neurons necessary for consolidation suggests that these brain processes may be functionally interrelated via their shared anatomy. These findings have important implications for the mechanistic relationship between sleep and memory consolidation, arguing for a significant role of inhibitory neurotransmission in regulating these processes.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Involvement of the insular cortex in regulating glucocorticoid effects on memory consolidation of inhibitory avoidance training

    NARCIS (Netherlands)

    Fornari, R.V.; Wichmann, R.; Atucha Trevino, E.; Desprez, T.; Eggens-Meijer, E.; Roozendaal, B.

    2012-01-01

    Glucocorticoids are known to enhance the consolidation of memory of emotionally arousing experiences by acting upon a network of interconnected brain regions. Although animal studies typically do not consider the insular cortex (IC) to be part of this network, the present findings indicate that the

  17. 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

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

    NARCIS (Netherlands)

    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

  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. 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…

  1. Activation of MAPK Is Necessary for Long-Term Memory Consolidation Following Food-Reward Conditioning

    Science.gov (United States)

    Ribeiro, Maria J.; Schofield, Michael G.; Kemenes, Ildiko; O'Shea, Michael; Kemenes, Gyorgy; Benjamin, Paul R.

    2005-01-01

    Although an important role for the mitogen-activated protein kinase (MAPK) has been established for memory consolidation in a variety of learning paradigms, it is not known if this pathway is also involved in appetitive classical conditioning. We address this question by using a single-trial food-reward conditioning paradigm in the freshwater…

  2. Surface Expression of NMDA Receptor Changes during Memory Consolidation in the Crab "Neohelice granulata"

    Science.gov (United States)

    Hepp, Yanil; Salles, Angeles; Carbo-Tano, Martin; Pedreira, Maria Eugenia; Freudenthal, Ramiro

    2016-01-01

    The aim of the present study was to analyze the surface expression of the NMDA-like receptors during the consolidation of contextual learning in the crab "Neohelice granulata". Memory storage is based on alterations in the strength of synaptic connections between neurons. The glutamatergic synapses undergo various forms of…

  3. 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

  4. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. [Sleep deprivation effect upon spatial memory consolidation in rats after one-day learning in a Morris water maze].

    Science.gov (United States)

    Dorokhov, V B; Kozhedub, R G; Arsen'ev, G N; Kozhechkin, S N; Ukraintseva, Iu V; Kulikov, M A; Manolov, A I; Koval'zon, V M

    2011-01-01

    The effect of sleep deprivation by 'carousel' method on spatial memory consolidation in a Morris water maze was studied in Wistar male rats after one-day learning (in accordance to a protocol by Frick et al., 2000). It was found that after fast 3-hr learning the memory trace retains during 24-hr. Twenty four hour sleep deprivation followed learning impaired consolidation of spatial memory. So the rat model of a one-day learning is suitable for the studying of neurophysiological mechanisms of sleep deprivation effects on spatial memory consolidation.

  8. Forming competing fear learning and extinction memories in adolescence makes fear difficult to inhibit

    OpenAIRE

    Baker, Kathryn D.; Richardson, Rick

    2015-01-01

    Fear inhibition is markedly impaired in adolescent rodents and humans. The present experiments investigated whether this impairment is critically determined by the animal's age at the time of fear learning or their age at fear extinction. Male rats (n = 170) were tested for extinction retention after conditioning and extinction at different ages. We examined neural correlates of impaired extinction retention by detection of phosphorylated mitogen-activated protein kinase immunoreactivity (pMA...

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

    Science.gov (United States)

    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

  10. 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.

  11. 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

  12. Locus coeruleus and dopaminergic consolidation of everyday memory

    Science.gov (United States)

    Takeuchi, Tomonori; Duszkiewicz, Adrian J.; Sonneborn, Alex; Spooner, Patrick A.; Yamasaki, Miwako; Watanabe, Masahiko; Smith, Caroline C.; Fernández, Guillén; Deisseroth, Karl; Greene, Robert W.; Morris, Richard G. M.

    2016-01-01

    Summary The retention of episodic-like memory is enhanced, in humans and animals, when something novel happens shortly before or after encoding. Using an everyday memory task in mice, we sought the neurons mediating this dopamine-dependent novelty effect, previously thought to originate exclusively from the tyrosine hydroxylase-expressing (TH+) neurons in the ventral tegmental area (VTA). We report that neuronal firing in the locus coeruleus (LC) is especially sensitive to environmental novelty, LC-TH+ neurons project more profusely than VTA-TH+ neurons to the hippocampus, optogenetic activation of LC-TH+ neurons mimics the novelty effect, and this novelty-associated memory enhancement is unaffected by VTA inactivation. Surprisingly, two effects of LC-TH+ photoactivation are sensitive to hippocampal D1/D5 receptor blockade and resistant to adrenoceptors blockade – memory enhancement and long lasting potentiation of synaptic transmission in CA1 ex vivo. Thus, LC-TH+ neurons can mediate post-encoding memory enhancement in a manner consistent with possible co-release of dopamine in hippocampus. PMID:27602521

  13. mTOR Is Essential for Corticosteroid Effects on Hippocampal AMPA Receptor Function and Fear Memory

    Science.gov (United States)

    Xiong, Hui; Casse, Frédéric; Zhou, Yang; Zhou, Ming; Xiong, Zhi-Qi; Joëls, Marian; Martin, Stéphane; Krugers, Harm J.

    2015-01-01

    Glucocorticoid hormones, via activation of their receptors, promote memory consolidation, but the exact underlying mechanisms remain elusive. We examined how corticosterone regulates AMPA receptors (AMPARs), which are crucial for synaptic plasticity and memory formation. Combining a live imaging fluorescent recovery after photobleaching approach…

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Post-reexposure administration of riluzole attenuates the reconsolidation of conditioned fear memory in rats.

    Science.gov (United States)

    Akagi, Kie; Yamada, Misa; Saitoh, Akiyoshi; Oka, Jun-Ichiro; Yamada, Mitsuhiko

    2018-03-15

    Recently, we demonstrated that riluzole, which has been shown to block the glutamatergic system, facilitates fear extinction in rats. Here, we undertook experiments on contextual fear conditioning to clarify the actions of riluzole on the reconsolidation of fear memory in rats. We used the fast-acting benzodiazepine midazolam as a reconsolidation-inhibiting control drug. We demonstrated that riluzole (3 mg/kg) and midazolam (1 mg/kg) impaired the reconsolidation of contextual fear memory. Results from spontaneous recovery experiments also suggested that riluzole attenuated reconsolidation. Indeed, conditioned fear did not recover spontaneously 4 weeks after a short (3 min) reexposure and riluzole administration, whereas it recovered after a long (10 min) reexposure. Using western blotting, we demonstrated that a short reexposure increased the phosphorylation of cyclic adenosine monophosphate response element binding protein significantly in the dorsal part of hippocampus, but not in the medial prefrontal cortex. Interestingly, this phosphorylation was attenuated by riluzole with short reexposure. In addition, bilateral microinjection of riluzole (2 μM/0.2 μl/side) directly into the dorsal hippocampus clearly attenuated the reconsolidation. These findings suggested that the attenuating effect of riluzole on the reconsolidation of fear memory involves, at least in part, the dorsal part of the hippocampus. In conclusion, we demonstrated that riluzole attenuates the reconsolidation of fear memory in rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Declarative and procedural memory consolidation during sleep in patients with borderline personality disorder.

    Science.gov (United States)

    Hornung, Orla P; Regen, Francesca; Warnstedt, Claudia; Anghelescu, Ion; Danker-Hopfe, Heidi; Heuser, Isabella; Lammers, Claas-Hinrich

    2008-07-01

    Borderline personality disorder (BPD) is characterized by changes in subjective and objective measures of sleep quality. As recent findings point to the importance of sleep in memory consolidation, sleep-related memory consolidation was investigated in 15 female BPD patients (mean age 26.1+/-6.1 years) and 15 female healthy controls (mean age 25.6+/-6.8 years). Before and after the study night, declarative and procedural memory performance was tested by a paired associate list and a mirror tracing task. Subjective sleep quality was assessed by a sleep questionnaire, objective sleep quality was measured by a portable sleep recording device. During the study night the restorative value of sleep was significantly reduced in BPD patients (psleep quality showed a trend for longer REM sleep duration (p=0.054). No significant differences were found regarding overnight performance improvement in the declarative and procedural memory tasks. Present findings suggest that declarative and procedural memory consolidation during sleep is intact in BPD patients.

  20. Slow wave sleep induced by GABA agonist tiagabine fails to benefit memory consolidation.

    Science.gov (United States)

    Feld, Gordon B; Wilhelm, Ines; Ma, Ying; Groch, Sabine; Binkofski, Ferdinand; Mölle, Matthias; Born, Jan

    2013-09-01

    Slow wave sleep (SWS) plays a pivotal role in consolidating memories. Tiagabine has been shown to increase SWS in favor of REM sleep without impacting subjective sleep. However, it is unknown whether this effect is paralleled by an improved sleep-dependent consolidation of memory. This double-blind within-subject crossover study tested sensitivity of overnight retention of declarative neutral and emotional materials (word pairs, pictures) as well as a procedural memory task (sequence finger tapping) to oral administration of placebo or 10 mg tiagabine (at 22:30). Fourteen healthy young men aged 21.9 years (range 18-28 years). Tiagabine significantly increased the time spent in SWS and decreased REM sleep compared to placebo. Tiagabine also enhanced slow wave activity (0.5-4.0 Hz) and density of sleep. Fast (12-15 Hz) and slow (9-12 Hz) spindle activity, in particular that occurring phase-locked to the slow oscillation cycle, was decreased following tiagabine. Despite signs of deeper and more SWS, overnight retention of memory tested after sleep the next evening (19:30) was generally not improved after tiagabine, but on average even lower than after placebo, with this impairing effect reaching significance for procedural sequence finger tapping. Our data show that increasing slow wave sleep with tiagabine does not improve memory consolidation. Possibly this is due to functional differences from normal slow wave sleep, i.e., the concurrent suppressive influence of tiagabine on phase-locked spindle activity.

  1. Cerebral Asymmetries in Sleep-Dependent Processes of Memory Consolidation

    Science.gov (United States)

    Peigneux, Philippe; Schmitz, Remy; Willems, Sylvie

    2007-01-01

    Preference for previously seen, unfamiliar objects reflects a memory bias on affective judgment, known as the "mere exposure effect" (MEE). Here, we investigated the effect of time, post-exposure sleep, and the brain hemisphere solicited on preference generalization toward objects viewed in different perspectives. When presented in the right…

  2. 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 influence on many of the brain systems involved in memory. The concentration of cortisol escalates over the course of the night's sleep, in ways that we propose can help explain the changing nature of dreams across the sleep cycle.

  3. 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 influence on many of the brain systems involved in memory. The concentration of cortisol escalates over the course of the night's sleep, in ways that we propose can help explain the changing nature of dreams across the sleep cycle. PMID:15576884

  4. 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.

  5. Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia

    NARCIS (Netherlands)

    Telch, M.J.; Bruchey, A.K.; Rosenfield, D.; Cobb, A.R.; Smits, J.A.J.; Pahl, S.; Gonzalez-Lima, F.

    2014-01-01

    Administering methylene blue, a memory-enhancing agent, after successful exposure therapy promoted the retention of fear extinction in claustrophobic patients, but clinicians should carefully consider what level of fear reduction was achieved in session to avoid harmful

  6. Effects of Post-Session Administration of Methylene Blue on Fear Extinction and Contextual Memory in Adults With Claustrophobia

    NARCIS (Netherlands)

    Telch, M.J.; Bruchey, A.K.; Rosenfield, D.; Cobb, A.R.; Smits, J.A.J.; Pahl, S.; Gonzalez-Lima, F.

    2014-01-01

    Administering methylene blue, a memory-enhancing agent, after successful exposure therapy promoted the retention of fear extinction in claustrophobic patients, but clinicians should carefully consider what level of fear reduction was achieved in session to avoid harmful

  7. Role of oxytocin receptors in modulation of fear by social memory.

    Science.gov (United States)

    Guzmán, Yomayra F; Tronson, Natalie C; Sato, Keisuke; Mesic, Ivana; Guedea, Anita L; Nishimori, Katsuhiko; Radulovic, Jelena

    2014-05-01

    Oxytocin receptors (Oxtr) are important mediators of social learning and emotion, with bidirectional effects on fear and anxiety. Contrary to the anxiolytic actions of Oxtr in the amygdala, we recently showed that Oxtr in the lateral septum mediate the enhancement of fear conditioning by social defeat in mice. Using positive social interactions, which impair fear conditioning, here we attempted to delineate whether the role of septal Oxtr in fear regulation depends on the valence of the social memory. Pharmacological and genetic manipulations of lateral septal Oxtr were combined with the social buffering of fear paradigm, in which pre-exposure to nonfearful conspecifics reduces subsequent contextual fear conditioning, as revealed by decreased freezing behavior. Antagonism and down-regulation of Oxtr in the lateral septum abolished, while oxytocin (Oxt) administration before pre-exposure to nonfearful conspecifics facilitated the decrease of freezing behavior. The septal oxytocin system enhances memory of social interactions regardless of their valence, reducing fear after positive and enhancing fear after negative social encounters. These findings explain, at least in part, the seemingly bidirectional role of Oxt in fear regulation.

  8. Familiarity Speeds Up Visual Short-term Memory Consolidation: Electrophysiological Evidence from Contralateral Delay Activities.

    Science.gov (United States)

    Xie, Weizhen; Zhang, Weiwei

    2018-01-01

    To test how preexisting long-term memory influences visual STM, this study takes advantage of individual differences in participants' prior familiarity with Pokémon characters and uses an ERP component, the contralateral delay activity (CDA), to assess whether observers' prior stimulus familiarity affects STM consolidation and storage capacity. In two change detection experiments, consolidation speed, as indexed by CDA fractional area latency and/or early-window (500-800 msec) amplitude, was significantly associated with individual differences in Pokémon familiarity. In contrast, the number of remembered Pokémon stimuli, as indexed by Cowan's K and late-window (1500-2000 msec) CDA amplitude, was significantly associated with individual differences in Pokémon familiarity when STM consolidation was incomplete because of a short presentation of Pokémon stimuli (500 msec, Experiment 2), but not when STM consolidation was allowed to complete given sufficient encoding time (1000 msec, Experiment 1). Similar findings were obtained in between-group analyses when participants were separated into high-familiarity and low-familiarity groups based on their Pokémon familiarity ratings. Together, these results suggest that stimulus familiarity, as a proxy for the strength of preexisting long-term memory, primarily speeds up STM consolidation, which may subsequently lead to an increase in the number of remembered stimuli if consolidation is incomplete. These findings thus highlight the importance of research assessing how effects on representations (e.g., STM capacity) are in general related to (or even caused by) effects on processes (e.g., STM consolidation) in cognition.

  9. Temporal dynamics of immediate early gene expression during cellular consolidation of spatial memory.

    Science.gov (United States)

    Barry, Daniel N; Commins, Sean

    2017-06-01

    The consolidation of newly acquired memories on a cellular level is thought to take place in the first few hours following learning. This process is dependent on de novo protein synthesis during this time, which ultimately leads to long-term structural and functional neuronal changes and the stabilisation of a memory trace. Immediate early genes (IEGs) are rapidly expressed in neurons following learning, and previous research has suggested more than one wave of IEG expression facilitates consolidation in the hours following learning. We analysed the expression of Zif268, c-Fos and Arc protein in a number of brain regions involved in spatial learning either 90min, 4h or 8h following training in the Morris water maze task. Consistent with the role of IEGs in the earliest stages of consolidation, a single wave of expression was observed in most brain regions at 90min, however a subsequent wave of expression was not observed at 8h. In fact, Zif268 expression was observed to fall below the levels of naïve controls at this time-point in the medial prefrontal and perirhinal cortices. This may be indicative of synaptic downscaling in these regions in the hours following learning, and an important marker of the consolidation of spatial memory. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Reactivation or transformation? Motor memory consolidation associated with cerebral activation time-locked to sleep spindles.

    Science.gov (United States)

    Fogel, Stuart; Albouy, Genevieve; King, Bradley R; Lungu, Ovidiu; Vien, Catherine; Bore, Arnaud; Pinsard, Basile; Benali, Habib; Carrier, Julie; Doyon, Julien

    2017-01-01

    Motor memory consolidation is thought to depend on sleep-dependent reactivation of brain areas recruited during learning. However, up to this point, there has been no direct evidence to support this assertion in humans, and the physiological processes supporting such reactivation are unknown. Here, simultaneous electroencephalographic and functional magnetic resonance imaging (EEG-fMRI) recordings were conducted during post-learning sleep to directly investigate the spindle-related reactivation of a memory trace formed during motor sequence learning (MSL), and its relationship to overnight enhancement in performance (reflecting consolidation). We show that brain regions within the striato-cerebello-cortical network recruited during training on the MSL task, and in particular the striatum, were also activated during sleep, time-locked to spindles. Interestingly, the consolidated trace in the striatum was not simply strengthened, but was transformed/reorganized from rostrodorsal (associative) to caudoventral (sensorimotor) subregions. Moreover, the degree of the reactivation was correlated with overnight improvements in performance. Altogether, the present findings demonstrate that striatal reactivation linked to sleep spindles in the post-learning night, is related to motor memory consolidation.

  11. The Influence of Sleep on the Consolidation of Positive Emotional Memories: Preliminary Evidence

    Directory of Open Access Journals (Sweden)

    Alexis M. Chambers

    2014-05-01

    Full Text Available Studies have not only shown that a period of sleep following learning offers greater benefits to later memory than a period of wakefulness, but also that sleep actively promotes those components of memories that are emotionally salient. However, sleep's role in emotional memory consolidation has largely been investigated with memories that are specifically negative in content, such as memory for negative images or texts, leaving open the question of whether sleep influences positive memories in a similar manner. The current study investigated the emotional memory trade-off effect for positive versus neutral information. Scenes in which a positive or neutral object was placed on a neutral background were encoded prior to a period of polysomnographically-monitored nocturnal sleep or daytime wakefulness. Recognition memory was tested for the objects and backgrounds separately following the delay using the Remember/Know paradigm. Compared to wake participants, those who slept during the delay had increased recollection memory performance for positive objects, but not the neutral components of the studied scenes. Further, familiarity of positive objects was negatively correlated with REM latency. These results provide preliminary evidence that sleep contributes to the selective processing of positive memories, and point toward a role for REM sleep in positive memory formation.

  12. 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.

  13. 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

    2017-06-26

    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 CO 2 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 CO 2 inhalation to retrieval increased activation of amygdala neurons bearing the memory trace and increased the synaptic exchange from Ca 2+ -impermeable to Ca 2+ -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.

  14. 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

  15. 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.

  16. Transcranial electrical currents to probe EEG brain rhythms and memory consolidation during sleep in humans.

    Directory of Open Access Journals (Sweden)

    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.

  17. NREM2 and Sleep Spindles Are Instrumental to the Consolidation of Motor Sequence Memories

    Science.gov (United States)

    Laventure, Samuel; Fogel, Stuart; Lungu, Ovidiu; Albouy, Geneviève; Sévigny-Dupont, Pénélope; Vien, Catherine; Sayour, Chadi; Carrier, Julie; Benali, Habib; Doyon, Julien

    2016-01-01

    Although numerous studies have convincingly demonstrated that sleep plays a critical role in motor sequence learning (MSL) consolidation, the specific contribution of the different sleep stages in this type of memory consolidation is still contentious. To probe the role of stage 2 non-REM sleep (NREM2) in this process, we used a conditioning protocol in three different groups of participants who either received an odor during initial training on a motor sequence learning task and were re-exposed to this odor during different sleep stages of the post-training night (i.e., NREM2 sleep [Cond-NREM2], REM sleep [Cond-REM], or were not conditioned during learning but exposed to the odor during NREM2 [NoCond]). Results show that the Cond-NREM2 group had significantly higher gains in performance at retest than both the Cond-REM and NoCond groups. Also, only the Cond-NREM2 group yielded significant changes in sleep spindle characteristics during cueing. Finally, we found that a change in frequency of sleep spindles during cued-memory reactivation mediated the relationship between the experimental groups and gains in performance the next day. These findings strongly suggest that cued-memory reactivation during NREM2 sleep triggers an increase in sleep spindle activity that is then related to the consolidation of motor sequence memories. PMID:27032084

  18. 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.

  19. 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.

  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. 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.…

  2. Effect of conditioned stimulus exposure during slow wave sleep on fear memory extinction in humans.

    Science.gov (United States)

    He, Jia; Sun, Hong-Qiang; Li, Su-Xia; Zhang, Wei-Hua; Shi, Jie; Ai, Si-Zhi; Li, Yun; Li, Xiao-Jun; Tang, Xiang-Dong; Lu, Lin

    2015-03-01

    Repeated exposure to a neutral conditioned stimulus (CS) in the absence of a noxious unconditioned stimulus (US) elicits fear memory extinction. The aim of the current study was to investigate the effects of mild tone exposure (CS) during slow wave sleep (SWS) on fear memory extinction in humans. The healthy volunteers underwent an auditory fear conditioning paradigm on the experimental night, during which tones served as the CS, and a mild shock served as the US. They were then randomly assigned to four groups. Three groups were exposed to the CS for 3 or 10 min or an irrelevant tone (control stimulus, CtrS) for 10 min during SWS. The fourth group served as controls and was not subjected to any interventions. All of the subjects completed a memory test 4 h after SWS-rich stage to evaluate the effect on fear extinction. Moreover, we conducted similar experiments using an independent group of subjects during the daytime to test whether the memory extinction effect was specific to the sleep condition. Ninety-six healthy volunteers (44 males) aged 18-28 y. Participants exhibited undisturbed sleep during 2 consecutive nights, as assessed by sleep variables (all P > 0.05) from polysomnographic recordings and power spectral analysis. Participants who were re-exposed to the 10 min CS either during SWS and wakefulness exhibited attenuated fear responses (wake-10 min CS, P memory extinction without altering sleep profiles. © 2015 Associated Professional Sleep Societies, LLC.

  3. 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.

  4. 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.

  5. 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

  6. Sleep-dependent motor sequence memory consolidation in individuals with periodic limb movements.

    Science.gov (United States)

    Sergeeva, Valya; Viczko, Jeremy; Ray, Laura B; Owen, Adrian M; Fogel, Stuart M

    2017-12-01

    Periodic limb movements (PLMs) during sleep increase with age and are associated with striatal neurodegeneration and dopamine deficiency. Limb movements are often associated with disruptions to non-rapid eye movement (NREM) sleep. Motor skill memory consolidation recruits the striatum, and learning-dependent striatal activation is associated with NREM sleep. Therefore, we investigated whether de novo individuals who significantly experience elevated levels of PLMs but have not been formally diagnosed with periodic limb movement disorder had learning and sleep-related memory deficits and whether these deficits were related to sleep quality and symptom severity. In total, 14 adults with significantly elevated PLMs (PLM condition), 15 age-matched controls (CTRL), and 14 age-matched "disturbed" sleep (through induced leg movements) controls (CTRL-ES) participated. The participants were trained (PM) and retested (AM) on procedural motor sequence learning (MSL) and declarative paired associates memory tasks. Baseline sleep quality was significantly worse in PLM than in CTRL. Despite the continued presence of PLMs in the PLM condition on the experimental night, remarkably, sleep quality improved and arousals decreased, vs. baseline, and did not differ from CTRL. MSL was significantly slower in the PLM condition than in CTRL at training but surprisingly exhibited overnight performance gains, which correlated with reduced arousals. As predicted, CTRL but not CTRL-ES had overnight gains in MSL. Taken together, this suggests that in the PLM condition, sleep quality was normalized following MSL, where they derived the same benefit of sleep to procedural memory consolidation as in CTRL. Sleep did not benefit declarative memory. Although preliminary, these results suggest that MSL in individuals with PLMs may provide a benefit to sleep, which in turn may benefit memory consolidation. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. The Multidimensional Aspects of Sleep Spindles and Their Relationship to Word-Pair Memory Consolidation.

    Science.gov (United States)

    Lustenberger, Caroline; Wehrle, Flavia; Tüshaus, Laura; Achermann, Peter; Huber, Reto

    2015-07-01

    Several studies proposed a link between sleep spindles and sleep dependent memory consolidation in declarative learning tasks. In addition to these state-like aspects of sleep spindles, they have also trait-like characteristics, i.e., were related to general cognitive performance, an important distinction that has often been neglected in correlative studies. Furthermore, from the multitude of different sleep spindle measures, often just one specific aspect was analyzed. Thus, we aimed at taking multidimensional aspects of sleep spindles into account when exploring their relationship to word-pair memory consolidation. Each subject underwent 2 study nights with all-night high-density electroencephalographic (EEG) recordings. Sleep spindles were automatically detected in all EEG channels. Subjects were trained and tested on a word-pair learning task in the evening, and retested in the morning to assess sleep related memory consolidation (overnight retention). Trait-like aspects refer to the mean of both nights and state-like aspects were calculated as the difference between night 1 and night 2. Sleep laboratory. Twenty healthy male subjects (age: 23.3 ± 2.1 y). Overnight retention was negatively correlated with trait-like aspects of fast sleep spindle density and positively with slow spindle density on a global level. In contrast, state-like aspects were observed for integrated slow spindle activity, which was positively related to the differences in overnight retention in specific regions. Our results demonstrate the importance of a multidimensional approach when investigating the relationship between sleep spindles and memory consolidation and thereby provide a more complete picture explaining divergent findings in the literature. © 2015 Associated Professional Sleep Societies, LLC.

  8. Reduced sleep spindles and spindle coherence in schizophrenia: mechanisms of impaired memory consolidation?

    Science.gov (United States)

    Wamsley, Erin J; Tucker, Matthew A; Shinn, Ann K; Ono, Kim E; McKinley, Sophia K; Ely, Alice V; Goff, Donald C; Stickgold, Robert; Manoach, Dara S

    2012-01-15

    Sleep spindles are thought to induce synaptic changes and thereby contribute to memory consolidation during sleep. Patients with schizophrenia show dramatic reductions of both spindles and sleep-dependent memory consolidation, which may be causally related. To examine the relations of sleep spindle activity to sleep-dependent consolidation of motor procedural memory, 21 chronic, medicated schizophrenia outpatients and 17 healthy volunteers underwent polysomnography on two consecutive nights. On the second night, participants were trained on the finger-tapping motor sequence task (MST) at bedtime and tested the following morning. The number, density, frequency, duration, amplitude, spectral content, and coherence of stage 2 sleep spindles were compared between groups and examined in relation to overnight changes in MST performance. Patients failed to show overnight improvement on the MST and differed significantly from control participants who did improve. Patients also exhibited marked reductions in the density (reduced 38% relative to control participants), number (reduced 36%), and coherence (reduced 19%) of sleep spindles but showed no abnormalities in the morphology of individual spindles or of sleep architecture. In patients, reduced spindle number and density predicted less overnight improvement on the MST. In addition, reduced amplitude and sigma power of individual spindles correlated with greater severity of positive symptoms. The observed sleep spindle abnormalities implicate thalamocortical network dysfunction in schizophrenia. In addition, the findings suggest that abnormal spindle generation impairs sleep-dependent memory consolidation in schizophrenia, contributes to positive symptoms, and is a promising novel target for the treatment of cognitive deficits in schizophrenia. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. 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.

  10. Acute exercise and motor memory consolidation: Does exercise type play a role?

    DEFF Research Database (Denmark)

    Thomas, Richard; Flindtgaard, Mads; Skriver, Kasper Christen

    2017-01-01

    following visuomotor skill acquisition on the retention of motor memory in 40 young (25.3 ±3.6 years), able-bodied male participants randomly assigned to one of four groups either performing strength training (STR), circuit training (CT), indoor hockey (HOC) or rest (CON). Retention tests of the motor skill......-line effects on motor memory, we conclude that exercise-induced effects beneficial to consolidation appear to depend primarily on the physiological stimulus rather than type of exercise and movements employed....

  11. 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.

  12. Elevation of hippocampal neurogenesis induces a temporally-graded pattern of forgetting of contextual fear memories.

    Science.gov (United States)

    Gao, Aijing; Xia, Frances; Guskjolen, Axel; Ramsaran, Adam I; Santoro, Adam; Josselyn, Sheena A; Frankland, Paul W

    2018-02-16

    Throughout life neurons are continuously generated in the subgranular zone of the hippocampus. The subsequent integration of newly-generated neurons alters patterns of dentate gyrus input and output connectivity, potentially rendering memories already stored in those circuits harder to access. Consistent with this prediction, we previously showed that increasing hippocampal neurogenesis after training induces forgetting of hippocampus-dependent memories, including contextual fear memory. However, the brain regions supporting contextual fear memories change with time, and this time-dependent memory reorganization might regulate the sensitivity of contextual fear memories to fluctuations in hippocampal neurogenesis. By virally expressing the inhibitory DREADD hM4Di we first confirmed that chemogenetic inhibition of dorsal hippocampal neurons impairs retrieval of recent (day-old) but not remote (month-old) contextual fear memories in male mice. We then contrasted the effects of increasing hippocampal neurogenesis at recent vs remote time points after contextual fear conditioning in male and female mice. Increasing hippocampal neurogenesis immediately following training reduced conditioned freezing when mice were replaced in the context one month later. In contrast, when hippocampal neurogenesis was increased time points remote to training, conditioned freezing levels were unaltered when mice were subsequently tested. These temporally-graded forgetting effects were observed using both environmental and genetic interventions to increase hippocampal neurogenesis. Our experiments identify memory age as a boundary condition for neurogenesis-mediated forgetting and suggest that as contextual fear memories mature they become less sensitive to changes in hippocampal neurogenesis levels because they no longer depend on the hippocampus for their expression. Significance statement: New neurons are generated in the hippocampus throughout life. As they integrate into the

  13. Relaxing music counters heightened consolidation of emotional memory.

    Science.gov (United States)

    Rickard, Nikki S; Wong, Wendy Wing; Velik, Lauren

    2012-02-01

    Emotional events tend to be retained more strongly than other everyday occurrences, a phenomenon partially regulated by the neuromodulatory effects of arousal. Two experiments demonstrated the use of relaxing music as a means of reducing arousal levels, thereby challenging heightened long-term recall of an emotional story. In Experiment 1, participants (N=84) viewed a slideshow, during which they listened to either an emotional or neutral narration, and were exposed to relaxing or no music. Retention was tested 1 week later via a forced choice recognition test. Retention for both the emotional content (Phase 2 of the story) and material presented immediately after the emotional content (Phase 3) was enhanced, when compared with retention for the neutral story. Relaxing music prevented the enhancement for material presented after the emotional content (Phase 3). Experiment 2 (N=159) provided further support to the neuromodulatory effect of music by post-event presentation of both relaxing music and non-relaxing auditory stimuli (arousing music/background sound). Free recall of the story was assessed immediately afterwards and 1 week later. Relaxing music significantly reduced recall of the emotional story (Phase 2). The findings provide further insight into the capacity of relaxing music to attenuate the strength of emotional memory, offering support for the therapeutic use of music for such purposes. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. fMRI and sleep correlates of the age-related impairment in motor memory consolidation.

    Science.gov (United States)

    Fogel, Stuart M; Albouy, Genevieve; Vien, Catherine; Popovicci, Romana; King, Bradley R; Hoge, Rick; Jbabdi, Saad; Benali, Habib; Karni, Avi; Maquet, Pierre; Carrier, Julie; Doyon, Julien

    2014-08-01

    Behavioral studies indicate that older adults exhibit normal motor sequence learning (MSL), but paradoxically, show impaired consolidation of the new memory trace. However, the neural and physiological mechanisms underlying this impairment are entirely unknown. Here, we sought to identify, through functional magnetic resonance imaging during MSL and electroencephalographic (EEG) recordings during daytime sleep, the functional correlates and physiological characteristics of this age-related motor memory deficit. As predicted, older subjects did not exhibit sleep-dependent gains in performance (i.e., behavioral changes that reflect consolidation) and had reduced sleep spindles compared with young subjects. Brain imaging analyses also revealed that changes in activity across the retention interval in the putamen and related brain regions were associated with sleep spindles. This change in striatal activity was increased in young subjects, but reduced by comparison in older subjects. These findings suggest that the deficit in sleep-dependent motor memory consolidation in elderly individuals is related to a reduction in sleep spindle oscillations and to an associated decrease of activity in the cortico-striatal network. Copyright © 2013 Wiley Periodicals, Inc.

  15. Evidence for two distinct sleep-related long-term memory consolidation processes.

    Science.gov (United States)

    Schönauer, Monika; Grätsch, Melanie; Gais, Steffen

    2015-02-01

    Numerous studies examine the effect of a night's sleep on memory consolidation, but few go beyond this short time-scale to test long-lasting effects of sleep on memory. We investigated long-term effects of sleep on typical memory tasks. During the hours following learning, participants slept or stayed awake. We compared recall performance between wake and sleep conditions after delays of up to 6 days. Performance develops in two distinct ways. Word pair, syllable, and motor sequence learning tasks benefit from sleep during the first day after encoding, when compared with daytime or nighttime wakefulness. However, performance in the wake conditions recovers after another night of sleep, so that we observe no lasting effect of sleep. Sleep deprivation before recall does not impair performance. Thus, fatigue cannot adequately explain the lack of long-term effects. We suggest that the hippocampus might serve as a buffer during the retention interval, and consolidation occurs during delayed sleep. In contrast, a non-hippocampal mirror-tracing task benefits significantly from sleep, even when tested after a 4-day delay including recovery sleep. This indicates a dissociation between two sleep-related consolidation mechanisms, which could rely on distinct neuronal processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Real-World-Time Simulation of Memory Consolidation in a Large-Scale Cerebellar Model.

    Science.gov (United States)

    Gosui, Masato; Yamazaki, Tadashi

    2016-01-01

    We report development of a large-scale spiking network model of the cerebellum composed of more than 1 million neurons. The model is implemented on graphics processing units (GPUs), which are dedicated hardware for parallel computing. Using 4 GPUs simultaneously, we achieve realtime simulation, in which computer simulation of cerebellar activity for 1 s completes within 1 s in the real-world time, with temporal resolution of 1 ms. This allows us to carry out a very long-term computer simulation of cerebellar activity in a practical time with millisecond temporal resolution. Using the model, we carry out computer simulation of long-term gain adaptation of optokinetic response (OKR) eye movements for 5 days aimed to study the neural mechanisms of posttraining memory consolidation. The simulation results are consistent with animal experiments and our theory of posttraining memory consolidation. These results suggest that realtime computing provides a useful means to study a very slow neural process such as memory consolidation in the brain.

  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. Unconditioned stimulus revaluation to promote conditioned fear extinction in the memory reconsolidation window.

    Directory of Open Access Journals (Sweden)

    Xiang-Xing Zeng

    Full Text Available The retrieval-extinction paradigm, which disrupts the reconsolidation of fear memories in humans, is a non-invasive technique that can be used to prevent the return of fear in humans. In the present study, unconditioned stimulus revaluation was applied in the retrieval-extinction paradigm to investigate its promotion of conditioned fear extinction in the memory reconsolidation window after participants acquired conditioned fear. This experiment comprised three stages (acquisition, unconditioned stimulus revaluation, retrieval-extinction and three methods for indexing fear (unconditioned stimulus expectancy, skin conductance response, conditioned stimulus pleasure rating. After the acquisition phase, we decreased the intensity of the unconditioned stimulus in one group (devaluation and maintained constant for the other group (control. The results indicated that both groups exhibited similar levels of unconditioned stimulus expectancy, but the devaluation group had significantly smaller skin conductance responses and exhibited a growth in conditioned stimulus + pleasure. Thus, our findings indicate unconditioned stimulus revaluation effectively promoted the extinction of conditioned fear within the memory reconsolidation window.

  19. Influence of the anteromedial thalamus on social defeat-associated contextual fear memory.

    Science.gov (United States)

    Rangel, Miguel J; Baldo, Marcus Vinicius C; Canteras, Newton Sabino

    2018-02-26

    The ventral part of the anteromedial thalamic nucleus (AMv) is heavily targeted by the dorsal premammillary nucleus (PMd), which is the main hypothalamic site that is responsive to both predator and conspecific aggressor threats. This PMd-AMv pathway is likely involved in modulating memory processing, and previous findings from our group have shown that cytotoxic lesions or pharmacological inactivation of the AMv drastically reduced contextual fear responses to predator-associated environments. In the present study, we investigated the role of the AMv in both unconditioned (i.e., fear responses during social defeat) and contextual fear responses (i.e., during exposure to a social defeat-associated context). We addressed this question by placing N-methyl-d-aspartate (NMDA) lesions in the AMv and testing unconditioned fear responses during social defeat and contextual fear responses during exposure to a social defeat-associated context. Accordingly, bilateral AMv lesions did not change unconditioned responses, but decreased contextual conditioning related to social defeat. Notably, our bilateral AMv lesions also included, to a certain degree, the nucleus reuniens (RE), but single RE lesions did not affect innate or contextual fear responses. Overall, our results support the idea that the AMv works as a critical hub, receiving massive inputs from a hypothalamic site that is largely responsive to social threats and transferring social threat information to circuits involved in the processing of contextual fear memories. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. 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

  1. 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

  2. Affecting long-term fear memory formation through optical control of Rac1 GTPase and PAK activity in lateral amygdala.

    Science.gov (United States)

    Das, Aniruddha; Dines, Monica; Alapin, Jessica M; Lamprecht, Raphael

    2017-10-24

    Fear conditioning, a behavioral model for studying fear-related disorders, is believed to be formed by alterations of synaptic efficacy mediated by changes in synaptic transmission and neuronal morphology in lateral amygdala (LA). Rac GTPase and its downstream effector p21-activated kinase (PAK) are involved in such key neuronal functions. Here we show that optical activation of Rac1 GTPase using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation of PAK and inhibition of long-term but not short-term auditory fear conditioning memory formation. Activation of PA-Rac1 in LA one day after fear conditioning had no effect on long-term fear memory tested 24 hrs after PA-Rac1 activation. Inhibition of PAK in LA by microinjection of the PAK inhibitor IPA-3 30 minutes before fear conditioning enhanced long-term but not short-term fear memory formation. Our results demonstrate that photoactivation of Rac1 GTPase in lateral amygdala impairs fear memory formation. Moreover, Rac1 effector PAK activity during fear conditioning constrains the formation of fear memory in LA. Thus, Rac GTPase and PAK proteins may serve as targets for treatment of fear and anxiety disorders.

  3. 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.

  4. Involvement of the insular cortex in regulating glucocorticoid effects on memory consolidation of inhibitory avoidance training.

    Science.gov (United States)

    Fornari, Raquel V; Wichmann, Romy; Atucha, Erika; Desprez, Tifany; Eggens-Meijer, Ellie; Roozendaal, Benno

    2012-01-01

    Glucocorticoids are known to enhance the consolidation of memory of emotionally arousing experiences by acting upon a network of interconnected brain regions. Although animal studies typically do not consider the insular cortex (IC) to be part of this network, the present findings indicate that the IC is importantly involved in regulating glucocorticoid effects on memory consolidation of emotionally arousing inhibitory avoidance training. The specific glucocorticoid receptor (GR) agonist RU 28362 (3 or 10 ng in 0.5 μl) infused bilaterally into the IC of male Sprague-Dawley rats immediately after one-trial inhibitory avoidance training dose-dependently enhanced 48 h retention performance. Moreover, training on the inhibitory avoidance task increased neuronal activity of the IC, as assessed by an increased number of cells expressing immunoreactivity for phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). However, systemic administration of a memory-enhancing dose of corticosterone (1 mg/kg) after inhibitory avoidance training rapidly reduced the number of pERK1/2-positive cells in the IC, suggesting that glucocorticoid administration reduces overall neuronal activity of the IC. To investigate which components of the inhibitory avoidance training experience were influenced by the intra-IC glucocorticoid administration, in the last experiment rats were trained on a modified inhibitory avoidance task in which context exposure and footshock training occur on two sequential days. RU 28362 administration into the IC enhanced later retention when infused immediately after either the context or footshock training. Thus, these findings indicate that the IC mediates glucocorticoid effects on the consolidation of memory of different components of inhibitory avoidance training and suggest that the IC might be an important element of the rodent brain network involved in emotional regulation of learning and memory.

  5. Involvement of the insular cortex in regulating glucocorticoid effects on memory consolidation of inhibitory avoidance training

    Directory of Open Access Journals (Sweden)

    Raquel eFornari

    2012-03-01

    Full Text Available Glucocorticoids are known to enhance the consolidation of memory of emotionally arousing experiences by acting upon a network of interconnected brain regions. Although animal studies typically do not consider the insular cortex (IC to be part of this network, the present findings indicate that the IC is importantly involved in regulating glucocorticoid effects on memory consolidation of emotionally arousing inhibitory avoidance training. The specific glucocorticoid receptor agonist RU 28362 (3 or 10 ng in 0.5 l infused bilaterally into the IC of male Sprague-Dawley rats immediately after one-trial inhibitory avoidance training dose-dependently enhanced 48-h retention performance. Moreover, training on the inhibitory avoidance task increased neuronal activity of the IC, as assessed by an increased number of cells expressing immunoreactivity for phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2. However, systemic administration of a memory-enhancing dose of corticosterone (1 mg/kg after inhibitory avoidance training rapidly reduced the number of pERK1/2-positive cells in the IC, suggesting that glucocorticoid administration reduces overall neuronal activity of the IC. To investigate which components of the inhibitory avoidance training experience were influenced by the intra-IC glucocorticoid administration, in the last experiment rats were trained on a modified inhibitory avoidance task in which context exposure and footshock training occur on two sequential days. RU 28362 administration into the IC enhanced later retention when infused immediately after either the context or footshock training. Thus, these findings indicate that the IC mediates glucocorticoid effects on the consolidation of memory of different components of inhibitory avoidance training and suggest that the IC might be an important element of the rodent brain network involved in emotional regulation of learning and memory.

  6. 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

  7. The Relative Impact of Sleep and Circadian Drive on Motor Skill Acquisition and Memory Consolidation.

    Science.gov (United States)

    Tucker, Matthew A; Morris, Christopher J; Morgan, Alexandra; Yang, Jessica; Myers, Samantha; Pierce, Joanna Garcia; Stickgold, Robert; Scheer, Frank A J L

    2017-04-01

    Sleep during the biological night facilitates memory consolidation. Here we determined the impact of sleep and wake on motor skill learning (acquisition) and subsequent off-line skill improvement (memory consolidation), independent of circadian phase, and compared this to the impact of the endogenous circadian system, independent of whether sleep occurred during the biological night or day. Participants completed two 8-day sleep laboratory visits, adhering on one visit to a circadian aligned ("normal") sleep schedule for the full duration of the protocol, and on the other to a circadian misaligned (12-hour inverted) schedule, with alignment during the first 3 days, a 12-hour 'slam shift' on Day 4, followed by circadian misalignment during the last 4 days of the protocol. Participants were repeatedly trained and tested on different versions of the finger-tapping motor sequence task across each visit. Sleep facilitated offline memory consolidation regardless of whether it occurred during the biological day or night, while circadian phase had no significant impact. These sleep-related benefits remained after accounting for general motor speed, measured in the absence of learning. In addition, motor skill acquisition was facilitated when the training session followed shortly after sleep, without significant impact of circadian phase (biological morning vs. evening). This effect was largely driven by heightened acquisition in participants who slept during the day and were trained shortly thereafter, that is, when acquisition occurred during the biological evening. These benefits were also retained after controlling for general motor speed. Sleep benefits both the acquisition and consolidation of motor skill regardless of whether they occur during the biological day or night. After controlling for general motor speed, a critical adjustment that few studies perform, these sleep benefits remain intact. Our findings have clear implications for night shift workers who obtain

  8. An overview of the neuro-cognitive processes involved in the encoding, consolidation, and retrieval of true and false memories

    OpenAIRE

    Straube Benjamin

    2012-01-01

    Abstract 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...

  9. Visual working memory encoding in schizophrenia and first-degree relatives: neurofunctional abnormalities and impaired consolidation.

    Science.gov (United States)

    Stäblein, Michael; Storchak, Helena; Ghinea, Denisa; Kraft, Dominik; Knöchel, Christian; Prvulovic, David; Bittner, Robert A; Reif, Andreas; Oertel-Knöchel, Viola

    2018-03-09

    Working memory (WM) deficits in schizophrenia (SCZ) have been linked to impairments in the encoding phase that are associated with aberrant neuronal functioning. Similar abnormalities have been observed in unaffected first-degree relatives (REL) and are thus discussed as candidate endophenotypes. The process of WM consolidation - i.e. the formation of durable WM representations - is assumed to be impaired in SCZ, but no study has investigated WM consolidation and neuronal correlates of visual WM encoding in REL before. We examined whole-brain activation during the encoding phase with an event-related functional magnetic resonance imaging study design in 25 SCZ subjects, 22 REL subjects, and 25 healthy controls. Subjects performed a visual masked change detection task that assessed WM performance and consolidation. SCZ showed deficient WM performance indicating an impairment consolidation process, accompanied by broad neuronal hypoactivation, most prominently in frontal brain regions, as well as increased activity of the anterior cingulate during the encoding phase. REL showed decreased neuronal activity in the middle and medial frontal gyrus and increased activity in the precentral gyrus and insula during encoding, but no significant behavioral deficits were observed. In respect of given consolidation times, REL showed a shift from decreased frontal activity at short time intervals to increased frontal activity at longer time intervals. Findings suggest WM consolidation may be slowed in REL so that the deployment of compensatory neuronal resources during encoding is needed to assure proper WM performance. This supports the view of WM-related neuronal dysfunctions as a potential endophenotypic marker.

  10. 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...... 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...... in the exercise condition showed larger (∼24%) improvements in procedural memory through consolidation although differences between groups did not reach statistical significance. Exercise promoted an increase in CSE, which remained elevated 2h after exercise. More importantly, global increases in CSE following...

  11. Dreaming of a learning task is associated with enhanced sleep-dependent memory consolidation.

    Science.gov (United States)

    Wamsley, Erin J; Tucker, Matthew; Payne, Jessica D; Benavides, Joseph A; Stickgold, Robert

    2010-05-11

    It is now well established that postlearning sleep is beneficial for human memory performance. Meanwhile, human and animal studies have demonstrated that learning-related neural activity is re-expressed during posttraining nonrapid eye movement (NREM) sleep. NREM sleep processes appear to be particularly beneficial for hippocampus-dependent forms of memory. These observations suggest that learning triggers the reactivation and reorganization of memory traces during sleep, a systems-level process that in turn enhances behavioral performance. Here, we hypothesized that dreaming about a learning experience during NREM sleep would be associated with improved performance on a hippocampus-dependent spatial memory task. Subjects were trained on a virtual navigation task and then retested on the same task 5 hr after initial training. Improved performance at retest was strongly associated with task-related dream imagery during an intervening afternoon nap. Task-related thoughts during wakefulness, in contrast, did not predict improved performance. These observations suggest that sleep-dependent memory consolidation in humans is facilitated by the offline reactivation of recently formed memories, and furthermore that dream experiences reflect this memory processing. That similar effects were not observed during wakefulness suggests that these mnemonic processes are specific to the sleep state. (c) 2010 Elsevier Ltd. All rights reserved.

  12. 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.

  13. 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.

  14. Effects of Aging on Slow Wave Sleep Dynamics and Human Spatial Navigational Memory Consolidation

    Science.gov (United States)

    Varga, Andrew W.; Ducca, Emma L.; Kishi, Akifumi; Fischer, Esther; Parekh, Ankit; Koushyk, Viachaslau; Yau, Po Lai; Gumb, Tyler; Leibert, David P.; Wohlleber, Margaret E.; Burschtin, Omar E.; Convit, Antonio; Rapoport, David M.

    2016-01-01

    The consolidation of spatial navigational memory during sleep is supported by electrophysiological and behavioral evidence. The features of sleep that mediate this ability may change with aging, as percentage of slow wave sleep is canonically thought to decrease with age, and slow waves are thought to help orchestrate hippocampal-neocortical dialogue that supports systems level consolidation. In this study, groups of younger and older subjects performed timed trials before and after polysomnographically recorded sleep on a 3D spatial maze navigational task. Although younger subjects performed better than older subjects at baseline, both groups showed similar improvement across pre-sleep trials. However, younger subjects experienced significant improvement in maze performance during sleep that was not observed in older subjects, without differences in morning psychomotor vigilance between groups. Older subjects had sleep quality marked by decreased amount of slow wave sleep and increased fragmentation of slow wave sleep, resulting in decreased slow wave activity. Across all subjects, frontal slow wave activity was positively correlated with both overnight change in maze performance and medial prefrontal cortical volume, illuminating a potential neuroanatomical substrate for slow wave activity changes with aging and underscoring the importance of slow wave activity in sleep-dependent spatial navigational memory consolidation. PMID:27143431

  15. Effects of aging on slow-wave sleep dynamics and human spatial navigational memory consolidation.

    Science.gov (United States)

    Varga, Andrew W; Ducca, Emma L; Kishi, Akifumi; Fischer, Esther; Parekh, Ankit; Koushyk, Viachaslau; Yau, Po Lai; Gumb, Tyler; Leibert, David P; Wohlleber, Margaret E; Burschtin, Omar E; Convit, Antonio; Rapoport, David M; Osorio, Ricardo S; Ayappa, Indu

    2016-06-01

    The consolidation of spatial navigational memory during sleep is supported by electrophysiological and behavioral evidence. The features of sleep that mediate this ability may change with aging, as percentage of slow-wave sleep is canonically thought to decrease with age, and slow waves are thought to help orchestrate hippocampal-neocortical dialog that supports systems level consolidation. In this study, groups of younger and older subjects performed timed trials before and after polysomnographically recorded sleep on a 3D spatial maze navigational task. Although younger subjects performed better than older subjects at baseline, both groups showed similar improvement across presleep trials. However, younger subjects experienced significant improvement in maze performance during sleep that was not observed in older subjects, without differences in morning psychomotor vigilance between groups. Older subjects had sleep quality marked by decreased amount of slow-wave sleep and increased fragmentation of slow-wave sleep, resulting in decreased slow-wave activity. Across all subjects, frontal slow-wave activity was positively correlated with both overnight change in maze performance and medial prefrontal cortical volume, illuminating a potential neuroanatomical substrate for slow-wave activity changes with aging and underscoring the importance of slow-wave activity in sleep-dependent spatial navigational memory consolidation. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Assessing the Effect of Early Visual Cortex Transcranial Magnetic Stimulation on Working Memory Consolidation.

    Science.gov (United States)

    van Lamsweerde, Amanda E; Johnson, Jeffrey S

    2017-07-01

    Maintaining visual working memory (VWM) representations recruits a network of brain regions, including the frontal, posterior parietal, and occipital cortices; however, it is unclear to what extent the occipital cortex is engaged in VWM after sensory encoding is completed. Noninvasive brain stimulation data show that stimulation of this region can affect working memory (WM) during the early consolidation time period, but it remains unclear whether it does so by influencing the number of items that are stored or their precision. In this study, we investigated whether single-pulse transcranial magnetic stimulation (spTMS) to the occipital cortex during VWM consolidation affects the quantity or quality of VWM representations. In three experiments, we disrupted VWM consolidation with either a visual mask or spTMS to retinotopic early visual cortex. We found robust masking effects on the quantity of VWM representations up to 200 msec poststimulus offset and smaller, more variable effects on WM quality. Similarly, spTMS decreased the quantity of VWM representations, but only when it was applied immediately following stimulus offset. Like visual masks, spTMS also produced small and variable effects on WM precision. The disruptive effects of both masks and TMS were greatly reduced or entirely absent within 200 msec of stimulus offset. However, there was a reduction in swap rate across all time intervals, which may indicate a sustained role of the early visual cortex in maintaining spatial information.

  17. Background matters: Minor vibratory stimulation during motor skill acquisition selectively reduces off-line memory consolidation.

    Science.gov (United States)

    Korman, Maria; Herling, Zohar; Levy, Ishay; Egbarieh, Nebal; Engel-Yeger, Batya; Karni, Avi

    2017-04-01

    Although a ubiquitous situation, it is not clear how effective is a learning experience when task-irrelevant, sensory noise occurs in the background. Here, young adults were trained on the finger opposition sequence task, in a well-established training and testing protocol affording measures for online as well as off-line learning. During the training session, one group experienced a minor background vibratory stimulation to the trunk by the means of vibrating cushion, while the second group experienced recorded sound vibrations. A control group was trained with no extra sensory stimulation. Sensory stimulation during training had no effect on the online within-session gains, but dampened the expression of the off-line, consolidation phase, gains in the two sensory stimulation groups. These results suggest that background sensory stimulation can selectively modify off-line, procedural memory consolidation processes, despite well-preserved on-line learning. Classical studies have shown that neural plasticity in sensory systems is modulated by motor input. The current results extend this notion and suggest that some types of task-irrelevant sensory stimulation, concurrent with motor training, may constitute a 'gating' factor - modulating the triggering of long-term procedural memory consolidation processes. Thus, vibratory stimulation may be considered as a behavioral counterpart of pharmacological interventions that do not interfere with short term neural plasticity but block long-term plasticity. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. The Effect of Acute Exercise on Consolidation and Retention of Motor Memory

    DEFF Research Database (Denmark)

    Skriver, Kasper Christen

    . Hence, the overall aim of the present thesis was to investigate the relationship between acute exercise and motor memory, with special interest in investigating if exercise performed after motor skill learning could improve skill retention. Study I was designed to assess if a single bout of exercise....... Additionally, POST outperformed PRE after seven days, thus indicating that exercise affects the process during which the memory is consolidated more than learning itself. In order to investigate if the behavioral effects of exercise could be demonstrated in school children, we conducted Study II, partially......There is substantial evidence that a single bout of exercise can improve cognitive functions and retention of certain types of declarative memory. However, it is unclear if a similar effect can be demonstrated when coupling physical activity with the acquisition and retention of a motor skill...

  19. Transcranial electrical stimulation during sleep enhances declarative (but not procedural) memory consolidation: Evidence from a meta-analysis.

    Science.gov (United States)

    Barham, Michael P; Enticott, Peter G; Conduit, Russell; Lum, Jarrad A G

    2016-04-01

    This meta-analysis summarizes research examining whether transcranial electrical stimulation (transcranial direct current stimulation with oscillating and constant currents; transcranial alternating current stimulation), administered during sleep, can modulate declarative and procedural memory consolidation. Included in the meta-analysis were 13 experiments that represented data from 179 participants. Study findings were summarized using standardized mean difference (SMD) which is an effect size that summarizes differences in standard deviation units. Results showed electrical stimulation during sleep could enhance (SMD=0.447; p=.003) or disrupt (SMD=-0.476, p=.030) declarative memory consolidation. However, transcranial electric stimulation does not appear to be able to enhance (SMD=0.154, p=.279) or disrupt (SMD=0.076, p=.675) procedural memory consolidation. This meta-analysis provides strong evidence that TES is able to modulate some consolidation processes. Additional research is required to determine the mechanisms by which transcranial electrical stimulation is able to influence declarative memory consolidation. Finally, it is yet to be determined whether transcranial electrical stimulation can modulate procedural memory consolidation. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  20. 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.

  1. 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.

  2. 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.

  3. Autobiographical memory and hyperassociativity in the dreaming brain: implications for memory consolidation in sleep

    OpenAIRE

    Horton, Caroline L.; Malinowski, Josie E.

    2015-01-01

    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 mor...

  4. Role of the somatostatin system in contextual fear memory and hippocampal synaptic plasticity.

    Science.gov (United States)

    Kluge, Christian; Stoppel, Christian; Szinyei, Csaba; Stork, Oliver; Pape, Hans-Christian

    2008-04-01

    Somatostatin has been implicated in various cognitive and emotional functions, but its precise role is still poorly understood. Here, we have made use of mice with somatostatin deficiency, based upon genetic invalidation or pharmacologically induced depletion, and Pavlovian fear conditioning in order to address the contribution of the somatostatin system to associative fear memory. The results demonstrate an impairment of foreground and background contextual but not tone fear conditioning in mice with targeted ablation of the somatostatin gene. These deficits were associated with a decrease in long-term potentiation in the CA1 area of the hippocampus. Both the behavioral and the electrophysiological phenotypes were mimicked in wild-type mice through application of the somatostatin-depleting substance cysteamine prior to fear training, whereas no further deficits were observed upon application in the somatostatin null mutants. These results suggest that the somatostatin system plays a critical role in the acquisition of contextual fear memory, but not tone fear learning, and further highlights the role of hippocampal synaptic plasticity for information processing concerning contextual information.

  5. 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.

  6. 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…

  7. 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.

  8. 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.

  9. Differences between Presentation Methods in Working Memory Procedures: A Matter of Working Memory Consolidation

    Science.gov (United States)

    Ricker, Timothy J.; Cowan, Nelson

    2014-01-01

    Understanding forgetting from working memory, the memory used in ongoing cognitive processing, is critical to understanding human cognition. In the past decade, a number of conflicting findings have been reported regarding the role of time in forgetting from working memory. This has led to a debate concerning whether longer retention intervals…

  10. 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

  11. NF-κB Transcription Factor Role in Consolidation and Reconsolidation of Persistent Memories

    Directory of Open Access Journals (Sweden)

    Verónica ede la Fuente

    2015-09-01

    Full Text Available Transcriptional regulation is an important molecular process required for long-term neural plasticity and long-term memory formation. Thus, one main interest in molecular neuroscience in the last decades has been the identification of transcription factors that are involved in memory processes. Among them, the NF-κB family of transcription factors has gained interest due to a significant body of evidence that supports a key role of these proteins in synaptic plasticity and memory. In recent years, the interest was particularly reinforced because NF-κB was characterized as an important regulator of synaptogenesis. This function may be explained by its participation in synapse to nucleus communication, as well as a possible local role at the synapse. This review provides an overview of experimental work obtained in the last years, showing the essential role of this transcription factor in memory processes in different learning tasks in mammals. We focus the review on the consolidation and reconsolidation memory phases as well as on the regulation of immediate-early and late genes by epigenetic mechanisms that determine enduring forms of memories.

  12. NF-κB transcription factor role in consolidation and reconsolidation of persistent memories

    Science.gov (United States)

    de la Fuente, Verónica; Federman, Noel; Zalcman, Gisela; Salles, Angeles; Freudenthal, Ramiro; Romano, Arturo

    2015-01-01

    Transcriptional regulation is an important molecular process required for long-term neural plasticity and long-term memory (LTM) formation. Thus, one main interest in molecular neuroscience in the last decades has been the identification of transcription factors that are involved in memory processes. Among them, the nuclear factor κB (NF-κB) family of transcription factors has gained interest due to a significant body of evidence that supports a key role of these proteins in synaptic plasticity and memory. In recent years, the interest was particularly reinforced because NF-κB was characterized as an important regulator of synaptogenesis. This function may be explained by its participation in synapse to nucleus communication, as well as a possible local role at the synapse. This review provides an overview of experimental work obtained in the last years, showing the essential role of this transcription factor in memory processes in different learning tasks in mammals. We focus the review on the consolidation and reconsolidation memory phases as well as on the regulation of immediate-early and late genes by epigenetic mechanisms that determine enduring forms of memories. PMID:26441513

  13. Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia.

    Science.gov (United States)

    Telch, Michael J; Bruchey, Aleksandra K; Rosenfield, David; Cobb, Adam R; Smits, Jasper; Pahl, Sandra; Gonzalez-Lima, F

    2014-10-01

    Preclinical studies have shown that low-dose methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. The authors report on the first controlled experiment to examine the memory-enhancing effects of posttraining methylene blue administration on retention of fear extinction and contextual memory following fear extinction training. Adult participants displaying marked claustrophobic fear were randomly assigned to double-blind administration of 260 mg of methylene blue (N=23) or administration of placebo (N=19) immediately following six 5-minute extinction trials in an enclosed chamber. Retesting occurred 1 month later to assess fear renewal as indexed by peak fear during exposure to a nontraining chamber, with the prediction that the effects of methylene blue would vary as a function of fear reduction achieved during extinction training. Incidental contextual memory was assessed 1 and 30 days after training to assess the cognitive-enhancing effects of methylene blue independent of its effects on fear attenuation. Consistent with predictions, participants displaying low end fear posttraining showed significantly less fear at the 1-month follow-up if they received methylene blue posttraining compared with placebo. In contrast, participants displaying moderate to high levels of posttraining fear tended to fare worse at the follow-up if they received methylene blue posttraining. Methylene blue's enhancement of contextual memory was unrelated to initial or posttraining claustrophobic fear. Methylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session but may have a deleterious effect on extinction when administered after an unsuccessful exposure session.

  14. Differential Involvement of Amygdala and Cortical NMDA Receptors Activation upon Encoding in Odor Fear Memory

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    Hegoburu, Chloé; Parrot, Sandrine; Ferreira, Guilaume; Mouly, Anne-Marie

    2014-01-01

    Although the basolateral amygdala (BLA) plays a crucial role for the acquisition of fear memories, sensory cortices are involved in their long-term storage in rats. However, the time course of their respective involvement has received little investigation. Here we assessed the role of the glutamatergic N-methyl-D-aspartate (NMDA) receptors in the…

  15. Hippocampus and Medial Prefrontal Cortex Contributions to Trace and Contextual Fear Memory Expression over Time

    Science.gov (United States)

    Beeman, Christopher L.; Bauer, Philip S.; Pierson, Jamie L.; Quinn, Jennifer J.

    2013-01-01

    Previous work has shown that damage to the dorsal hippocampus (DH) occurring at recent, but not remote, timepoints following acquisition produces a deficit in trace conditioned fear memory expression. The opposite pattern has been observed with lesions to the medial prefrontal cortex (mPFC). The present studies address: (1) whether these lesion…

  16. 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...

  17. Interleukin-1 receptor null mutant mice show decreased anxiety-like behavior and enhanced fear memory

    Science.gov (United States)

    Koo, Ja Wook; Duman, Ronald S.

    2013-01-01

    IL-1β is a proinflammatory cytokine that contributes to psychological stress responses and has been implicated in various psychiatric disorders most notably depression. Preclinical studies also demonstrate that IL-1β modulates anxiety- and fear-related behaviors, although these findings are difficult to assess because IL-1β infusions influence locomotor activity and nociception. Here we demonstrate that IL-1RI null mice exhibit a behavioral phenotype consistent with a decrease in anxiety-related behaviors. This includes significant effects in the elevated plus maze, light–dark, and novelty-induced hypophagia tests compared to wild-type mice, with no differences in locomotor activity. With regard to fear conditioning, IL-1RI null mice showed more freezing in auditory and contextual fear conditioning tests, and there was no effect on pain sensitivity. Taken together, the results indicate that the IL-1β/IL-1RI signaling pathway induces anxiety-related behaviors and impairs fear memory. PMID:19429130

  18. The influence of catch trials on the consolidation of motor memory in force field adaptation tasks

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    Anne eFocke

    2013-07-01

    Full Text Available In computational neuroscience it is generally accepted that human motor memory contains neural representations of the physics of the musculoskeletal system and the objects in the environment. These representations are called internal models. Force field studies, in which subjects have to adapt to dynamic perturbations induced by a robotic manipulandum, are an established tool to analyze the characteristics of such internal models. The aim of the current study was to investigate whether catch trials during force field learning could influence the consolidation of motor memory in more complex tasks. Thereby, the force field was more than double the force field of previous studies (35 Ns/m. Moreover, the arm of the subjects was not supported. A total of forty-six subjects participated in this study and performed center-out movements at a robotic manipulandum in two different force fields. Two control groups learned force field A on day 1 and were retested in the same force field on day 3 (AA. Two test groups additionally learned an interfering force field B (=-A on day 2 (ABA. The difference between the two test and control groups, respectively, was the absence (0% or presence (19% of catch trials, in which the force field was turned off suddenly. The results showed consolidation of force field A on day 3 for both control groups. Test groups showed no consolidation of force field A (19% catch trials and even poorer performance on day 3 (0% catch trials. In conclusion, it can be stated that catch trials seem to have a positive effect on the performance on day 3 but do not trigger a consolidation process as shown in previous studies that used a lower force field viscosity with supported arm. These findings indicate that the results of previous studies in which less complex tasks were analyzed, cannot be fully transferred to more complex tasks. Moreover, the effects of catch trials in these situations are insufficiently understood and further research

  19. Estradiol-Induced Object Recognition Memory Consolidation Is Dependent on Activation of mTOR Signaling in the Dorsal Hippocampus

    Science.gov (United States)

    Fortress, Ashley M.; Fan, Lu; Orr, Patrick T.; Zhao, Zaorui; Frick, Karyn M.

    2013-01-01

    The mammalian target of rapamycin (mTOR) signaling pathway is an important regulator of protein synthesis and is essential for various forms of hippocampal memory. Here, we asked whether the enhancement of object recognition memory consolidation produced by dorsal hippocampal infusion of 17[Beta]-estradiol (E[subscript 2]) is dependent on mTOR…

  20. Sleep promotes consolidation of emotional memory in healthy children but not in children with attention-deficit hyperactivity disorder.

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    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.

  1. Sleep promotes consolidation of emotional memory in healthy children but not in children with attention-deficit hyperactivity disorder.

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    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.

  2. Fact retrieval and memory consolidation for a movement sequence: bidirectional effects of 'unrelated' cognitive tasks on procedural memory.

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    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.

  3. Loss of Ensemble Segregation in Dentate Gyrus, but Not in Somatosensory Cortex, during Contextual Fear Memory Generalization

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    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.

  4. Low levels of estradiol are associated with elevated conditioned responding during fear extinction and with intrusive memories in daily life

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    Wegerer, Melanie; Kerschbaum, Hubert; Blechert, Jens; Wilhelm, Frank H.

    2014-01-01

    Posttraumatic stress disorder (PTSD) can be conceptualized as a disorder of emotional memory showing strong (conditioned) responses to trauma reminders and intrusive memories among other symptoms. Women are at greater risk of developing PTSD than men. Recent studies have demonstrated an influence of ovarian steroid hormones in both fear conditioning and intrusive memory paradigms. However, although intrusive memories are considered non-extinguished emotional reactions to trauma reminders, none of the previous studies has investigated effects of ovarian hormones on fear conditioning mechanisms and intrusive memories in conjunction. This may have contributed to an overall inconsistent picture of the role of these hormones in emotional learning and memory. To remedy this, we exposed 37 healthy women with a natural menstrual cycle (during early follicular or luteal cycle phase) to a novel conditioned-intrusion paradigm designed to model real-life traumatic experiences. The paradigm included a differential fear conditioning procedure with short violent film clips as unconditioned stimuli. Intrusive memories about the film clips were assessed ambulatorily on subsequent days. Women with lower levels of estradiol displayed elevated differential conditioned skin conductance responding during fear extinction and showed stronger intrusive memories. The inverse relationship between estradiol and intrusive memories was at least partially accounted for by the conditioned responding observed during fear extinction. Progesterone levels were not associated with either fear acquisition/extinction or with intrusive memories. This suggests that lower levels of estradiol might promote stronger symptoms of PTSD through associative processes. PMID:25463649

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

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    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.

  6. Interaction between episodic and semantic memory networks in the acquisition and consolidation of novel spoken words.

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    Takashima, Atsuko; Bakker, Iske; van Hell, Janet G; Janzen, Gabriele; McQueen, James M

    2017-04-01

    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 again after a delay of one week. Words learned with meanings were remembered better than those learned without meanings. Both episodic (hippocampus-dependent) and semantic (dependent on distributed neocortical areas) memory systems were utilised during recognition of the novel words. The extent to which the two systems were involved changed as a function of time and the amount of associated information, with more involvement of both systems for the meaningful words than for the form-only words after the one-week delay. These results suggest that the reason the meaningful words were remembered better is that their retrieval can benefit more from these two complementary memory systems. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Does sleep play a role in memory consolidation? A comparative test.

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    Isabella Capellini

    Full Text Available Sleep is a pervasive characteristic of mammalian species, yet its purpose remains obscure. It is often proposed that 'sleep is for the brain', a view that is supported by experimental studies showing that sleep improves cognitive processes such as memory consolidation. Some comparative studies have also reported that mammalian sleep durations are higher among more encephalized species. However, no study has assessed the relationship between sleep and the brain structures that are implicated in specific cognitive processes across species. The hippocampus, neocortex and amygdala are important for memory consolidation and learning and are also in a highly actived state during sleep. We therefore investigated the evolutionary relationship between mammalian sleep and the size of these brain structures using phylogenetic comparative methods. We found that evolutionary increases in the size of the amygdala are associated with corresponding increases in NREM sleep durations. These results are consistent with the hypothesis that NREM sleep is functionally linked with specializations of the amygdala, including perhaps memory processing.

  8. Identification of a functional connectome for long-term fear memory in mice.

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    Anne L Wheeler

    Full Text Available Long-term memories are thought to depend upon the coordinated activation of a broad network of cortical and subcortical brain regions. However, the distributed nature of this representation has made it challenging to define the neural elements of the memory trace, and lesion and electrophysiological approaches provide only a narrow window into what is appreciated a much more global network. Here we used a global mapping approach to identify networks of brain regions activated following recall of long-term fear memories in mice. Analysis of Fos expression across 84 brain regions allowed us to identify regions that were co-active following memory recall. These analyses revealed that the functional organization of long-term fear memories depends on memory age and is altered in mutant mice that exhibit premature forgetting. Most importantly, these analyses indicate that long-term memory recall engages a network that has a distinct thalamic-hippocampal-cortical signature. This network is concurrently integrated and segregated and therefore has small-world properties, and contains hub-like regions in the prefrontal cortex and thalamus that may play privileged roles in memory expression.

  9. Serotonergic Modulation of Conditioned Fear

    OpenAIRE

    Homberg, Judith R.

    2012-01-01

    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...

  10. On Disruption of Fear Memory by Reconsolidation Blockade: Evidence from Cannabidiol Treatment

    Science.gov (United States)

    Stern, Cristina A J; Gazarini, Lucas; Takahashi, Reinaldo N; Guimarães, Francisco S; Bertoglio, Leandro J

    2012-01-01

    The search for reconsolidation blockers may uncover clinically relevant drugs for disrupting memories of significant stressful life experiences, such as those underlying the posttraumatic stress disorder. Considering the safety of systemically administered cannabidiol (CBD), the major non-psychotomimetic component of Cannabis sativa, to animals and humans, the present study sought to investigate whether and how this phytocannabinoid (3–30 mg/kg intraperitoneally; i.p.) could mitigate an established memory, by blockade of its reconsolidation, evaluated in a contextual fear-conditioning paradigm in rats. We report that CBD is able to disrupt 1- and 7-days-old memories when administered immediately, but not 6 h, after their retrieval for 3 min, with the dose of 10 mg/kg being the most effective. This effect persists in either case for at least 1 week, but is prevented when memory reactivation was omitted, or when the cannabinoid type-1 receptors were antagonized selectively with AM251 (1.0 mg/kg). Pretreatment with the serotonin type-1A receptor antagonist WAY100635, however, failed to block CBD effects. These results highlight that recent and older fear memories are equally vulnerable to disruption induced by CBD through reconsolidation blockade, with a consequent long-lasting relief in contextual fear-induced freezing. Importantly, this CBD effect is dependent on memory reactivation, restricted to time window of <6 h, and is possibly dependent on cannabinoid type-1 receptor-mediated signaling mechanisms. We also observed that the fear memories disrupted by CBD treatment do not show reinstatement or spontaneous recovery over 22 days. These findings support the view that reconsolidation blockade, rather than facilitated extinction, accounts for the aforementioned CBD results in our experimental conditions. PMID:22549120

  11. Evaluation Effects of Verapamil as a Calcium Channel Blocker on Acquisition, Consolidation and Retrieval of Memory in Mice

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    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

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

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    Fatemeh Taherian

    2014-07-01

    Full Text Available Introduction: Previous studies have demonstrated that the &beta-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.

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

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    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.

  14. "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.

  15. 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.

  16. Modulating influences of memory strength and sensitivity of the retrieval test on the detectability of the sleep consolidation effect.

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    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. Cronobacter sakazakii infection alters serotonin transporter and improved fear memory retention in the rats

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    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. Cronobacter sakazakii