Sample records for defective contextual memory
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Wang, Zhenshan; Phan, Trongha; Storm, Daniel R.
2011-01-01
Although primary cilia are found on neurons throughout the brain, their physiological function remains elusive. Human ciliopathies are associated with cognition defects and transgenic mice lacking proteins expressed in primary cilia exhibit defects in learning and memory. Recently, it was reported that mice lacking the G-protein coupling receptor somatostatin receptor-3 (SSTR3), a protein expressed predominately in the primary cilia of neurons, have defective memory for novel object recognition and lower cAMP levels in the brain. Since SSTR3 is coupled to regulation of adenylyl cyclase this suggests that adenylyl cyclase activity in primary cilia of CNS neurons may be critical for some forms of learning and memory. Because the type 3 adenylyl cyclase (AC3) is expressed in primary cilia of hippocampal neurons, we examined AC3−/− mice for several forms of learning and memory. Here, we report that AC3−/− mice show no short-term memory for novel objects and fail to exhibit extinction of contextual fear conditioning. They also show impaired learning and memory for temporally dissociated passive avoidance (TDPA). Since AC3 is exclusively expressed in primary cilia we conclude that cAMP signals generated within primary cilia contribute to some forms of learning and memory including extinction of contextual fear conditioning. PMID:21490195
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Wang, Zhenshan; Phan, Trongha; Storm, Daniel R
2011-04-13
Although primary cilia are found on neurons throughout the brain, their physiological function remains elusive. Human ciliopathies are associated with cognition defects, and transgenic mice lacking proteins expressed in primary cilia exhibit defects in learning and memory. Recently, it was reported that mice lacking the G-protein-coupling receptor somatostatin receptor-3 (SSTR3), a protein expressed predominately in the primary cilia of neurons, have defective memory for novel object recognition and lower cAMP levels in the brain. Since SSTR3 is coupled to regulation of adenylyl cyclase, this suggests that adenylyl cyclase activity in primary cilia of CNS neurons may be critical for some forms of learning and memory. Because the type 3 adenylyl cyclase (AC3) is expressed in primary cilia of hippocampal neurons, we examined AC3(-/-) mice for several forms of learning and memory. Here, we report that AC3(-/-) mice show no short-term memory for novel objects and fail to exhibit extinction of contextual fear conditioning. They also show impaired learning and memory for temporally dissociative passive avoidance. Since AC3 is exclusively expressed in primary cilia, we conclude that cAMP signals generated within primary cilia contribute to some forms of learning and memory, including extinction of contextual fear conditioning.
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Genetic disruption of the core circadian clock impairs hippocampus-dependent memory.
Wardlaw, Sarah M; Phan, Trongha X; Saraf, Amit; Chen, Xuanmao; Storm, Daniel R
2014-08-01
Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1-/- mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippocampus. Bmal1-/- mice exhibit impaired contextual fear and spatial memory. Furthermore, LTP in hippocampal slices from Bmal1-/- mice is also significantly decreased relative to that from wild-type mice. Activation of Erk1,2 MAP kinase (MAPK) during training for contextual fear memory and diurnal oscillation of MAPK activity and cAMP in the hippocampus is also lost in Bmal1-/- mice, suggesting that the memory defects are due to reduction of the memory consolidation pathway in the hippocampus. We conclude that critical signaling events in the hippocampus required for memory depend on BMAL1. © 2014 Wardlaw et al.; Published by Cold Spring Harbor Laboratory Press.
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Dominance of objects over context in a mediotemporal lobe model of schizophrenia.
Talamini, Lucia M; Meeter, Martijn
2009-08-04
A large body of evidence suggests impaired context processing in schizophrenia. Here we propose that this impairment arises from defective integration of mediotemporal 'what' and 'where' routes, carrying object and spatial information to the hippocampus. We have previously shown, in a mediotemporal lobe (MTL) model, that the abnormal connectivity between MTL regions observed in schizophrenia can explain the episodic memory deficits associated with the disorder. Here we show that the same neuropathology leads to several context processing deficits observed in patients with schizophrenia: 1) failure to choose subordinate stimuli over dominant ones when the former fit the context, 2) decreased contextual constraints in memory retrieval, as reflected in increased false alarm rates and 3) impaired retrieval of contextual information in source monitoring. Model analyses show that these deficits occur because the 'schizophrenic MTL' forms fragmented episodic representations, in which objects are overrepresented at the expense of spatial contextual information. These findings highlight the importance of MTL neuropathology in schizophrenia, demonstrating that it may underlie a broad spectrum of deficits, including context processing and memory impairments. It is argued that these processing deficits may contribute to central schizophrenia symptoms such as contextually inappropriate behavior, associative abnormalities, conversational drift, concreteness and delusions.
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Dominance of Objects over Context in a Mediotemporal Lobe Model of Schizophrenia
Talamini, Lucia M.; Meeter, Martijn
2009-01-01
Background A large body of evidence suggests impaired context processing in schizophrenia. Here we propose that this impairment arises from defective integration of mediotemporal ‘what’ and ‘where’ routes, carrying object and spatial information to the hippocampus. Methodology and Findings We have previously shown, in a mediotemporal lobe (MTL) model, that the abnormal connectivity between MTL regions observed in schizophrenia can explain the episodic memory deficits associated with the disorder. Here we show that the same neuropathology leads to several context processing deficits observed in patients with schizophrenia: 1) failure to choose subordinate stimuli over dominant ones when the former fit the context, 2) decreased contextual constraints in memory retrieval, as reflected in increased false alarm rates and 3) impaired retrieval of contextual information in source monitoring. Model analyses show that these deficits occur because the ‘schizophrenic MTL’ forms fragmented episodic representations, in which objects are overrepresented at the expense of spatial contextual information. Conclusions and Significance These findings highlight the importance of MTL neuropathology in schizophrenia, demonstrating that it may underlie a broad spectrum of deficits, including context processing and memory impairments. It is argued that these processing deficits may contribute to central schizophrenia symptoms such as contextually inappropriate behavior, associative abnormalities, conversational drift, concreteness and delusions. PMID:19652706
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Preserved memory-based orienting of attention with impaired explicit memory in healthy ageing
Salvato, Gerardo; Patai, Eva Z.; Nobre, Anna C.
2016-01-01
It is increasingly recognised that spatial contextual long-term memory (LTM) prepares neural activity for guiding visuo-spatial attention in a proactive manner. In the current study, we investigated whether the decline in explicit memory observed in healthy ageing would compromise this mechanism. We compared the behavioural performance of younger and older participants on learning new contextual memories, on orienting visual attention based on these learnt contextual associations, and on explicit recall of contextual memories. We found a striking dissociation between older versus younger participants in the relationship between the ability to retrieve contextual memories versus the ability to use these to guide attention to enhance performance on a target-detection task. Older participants showed significant deficits in the explicit retrieval task, but their behavioural benefits from memory-based orienting of attention were equivalent to those in young participants. Furthermore, memory-based orienting correlated significantly with explicit contextual LTM in younger adults but not in older adults. These results suggest that explicit memory deficits in ageing might not compromise initial perception and encoding of events. Importantly, the results also shed light on the mechanisms of memory-guided attention, suggesting that explicit contextual memories are not necessary. PMID:26649914
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Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory
Ko, Hyoung-Gon; Jang, Deok-Jin; Son, Junehee; Kwak, Chuljung; Choi, Jun-Hyeok; Ji, Young-Hoon; Lee, Yun-Sil; Son, Hyeon; Kaang, Bong-Kiun
2009-01-01
Newborn neurons in the subgranular zone (SGZ) of the hippocampus incorporate into the dentate gyrus and mature. Numerous studies have focused on hippocampal neurogenesis because of its importance in learning and memory. However, it is largely unknown whether hippocampal neurogenesis is involved in memory extinction per se. Here, we sought to examine the possibility that hippocampal neurogenesis may play a critical role in the formation and extinction of hippocampus-dependent contextual fear memory. By methylazoxymethanol acetate (MAM) or gamma-ray irradiation, hippocampal neurogenesis was impaired in adult mice. Under our experimental conditions, only a severe impairment of hippocampal neurogenesis inhibited the formation of contextual fear memory. However, the extinction of contextual fear memory was not affected. These results suggest that although adult newborn neurons contribute to contextual fear memory, they may not be involved in the extinction or erasure of hippocampus-dependent contextual fear memory. PMID:19138433
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Yu, Sarah S; Johnson, Jeffrey D; Rugg, Michael D
2012-06-01
It has been proposed that the hippocampus selectively supports retrieval of contextual associations, but an alternative view holds that the hippocampus supports strong memories regardless of whether they contain contextual information. We employed a memory test that combined the 'Remember/Know' and source memory procedures, which allowed test items to be segregated both by memory strength (recognition accuracy) and, separately, by the quality of the contextual information that could be retrieved (indexed by the accuracy/confidence of a source memory judgment). As measured by fMRI, retrieval-related hippocampal activity tracked the quality of retrieved contextual information and not memory strength. These findings are consistent with the proposal that the hippocampus supports contextual recollection rather than recognition memory more generally. Copyright © 2011 Wiley Periodicals, Inc.
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Chronic fluoxetine dissociates contextual from auditory fear memory.
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.
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Unilateral hippocampal inactivation or lesion selectively impairs remote contextual fear memory.
Zhou, Heng; Zhou, Qixin; Xu, Lin
2016-10-01
Contextual fear memory depends on the hippocampus, but the role of unilateral hippocampus in this type of memory remains unclear. Herein, pharmacological inactivation or excitotoxic lesions were used to study the role of unilateral hippocampus in the stages of contextual fear memory. The pharmacological experiments revealed that compared with the control groups, unilateral hippocampal blockade did not impair 1-day recent memory following learning, whereas bilateral hippocampal blockade significantly impaired this memory. The lesion experiments showed that compared with the control groups, the formed contextual fear memory was retained for 7 days and that 30-day remote memory was markedly reduced in unilateral hippocampal lesion groups. These results indicate that an intact bilateral hippocampus is required for the formation of remote memory and that unilateral hippocampus is sufficient for recent contextual fear memory.
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Preserved memory-based orienting of attention with impaired explicit memory in healthy ageing.
Salvato, Gerardo; Patai, Eva Z; Nobre, Anna C
2016-01-01
It is increasingly recognised that spatial contextual long-term memory (LTM) prepares neural activity for guiding visuo-spatial attention in a proactive manner. In the current study, we investigated whether the decline in explicit memory observed in healthy ageing would compromise this mechanism. We compared the behavioural performance of younger and older participants on learning new contextual memories, on orienting visual attention based on these learnt contextual associations, and on explicit recall of contextual memories. We found a striking dissociation between older versus younger participants in the relationship between the ability to retrieve contextual memories versus the ability to use these to guide attention to enhance performance on a target-detection task. Older participants showed significant deficits in the explicit retrieval task, but their behavioural benefits from memory-based orienting of attention were equivalent to those in young participants. Furthermore, memory-based orienting correlated significantly with explicit contextual LTM in younger adults but not in older adults. These results suggest that explicit memory deficits in ageing might not compromise initial perception and encoding of events. Importantly, the results also shed light on the mechanisms of memory-guided attention, suggesting that explicit contextual memories are not necessary. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
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An update on contextual fear memory mechanisms: Transition between Amygdala and Hippocampus.
Chaaya, Nicholas; Battle, Andrew R; Johnson, Luke R
2018-05-09
Context is an ever-present combination of discrete environmental elements capable of influencing many psychological processes. When context is associated with an aversive stimulus, a permanent contextual fear memory is formed. Context is hypothesized to greatly influence the treatability of various fear-based pathologies, in particular, post-traumatic stress disorder (PTSD). In order to understand how contextual fear memories are encoded and impact underlying fear pathology, delineation of the underlying neural circuitry of contextual fear memory consolidation and maintenance is essential. Past understandings of contextual fear suggest that the hippocampus only creates a unitary, or single, representation of context. This representation is sent to the amygdala, which creates the associative contextual fear memory. In contrast, here we review new evidence from the literature showing contextual fear memories to be consolidated and maintained by both amygdala and hippocampus. Based on this evidence, we revise the current model of contextual fear memory consolidation, highlighting a larger role for hippocampus. This new model may better explain the role of the hippocampus in PTSD. Copyright © 2018 Elsevier Ltd. All rights reserved.
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The roles of Eph receptors in contextual fear conditioning memory formation.
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.
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Einarsson, Einar Ö; Pors, Jennifer; Nader, Karim
2015-01-01
After acquisition, hippocampus-dependent memories undergo a systems consolidation process, during which they become independent of the hippocampus and dependent on the anterior cingulate cortex (ACC) for memory expression. However, consolidated remote memories can become transiently hippocampus-dependent again following memory reactivation. How this systems reconsolidation affects the role of the ACC in remote memory expression is not known. Using contextual fear conditioning, we show that the expression of 30-day-old remote memory can transiently be supported by either the ACC or the dorsal hippocampus following memory reactivation, and that the ACC specifically mediates expression of remote generalized contextual fear memory. We found that suppression of neural activity in the ACC with the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) impaired the expression of remote, but not recent, contextual fear memory. Fear expression was not affected by this treatment if preceded by memory reactivation 6 h earlier, nor was it affected by suppression of neural activity in the dorsal hippocampus with the GABA-receptor agonist muscimol. However, simultaneous targeting of both the ACC and the dorsal hippocampus 6 h after memory reactivation disrupted contextual fear memory expression. Second, we observed that expression of a 30-day-old generalized contextual fear memory in a novel context was not affected by memory reactivation 6 h earlier. However, intra-ACC CNQX infusion before testing impaired contextual fear expression in the novel context, but not the original training context. Together, these data suggest that although the dorsal hippocampus may be recruited during systems reconsolidation, the ACC remains necessary for the expression of generalized contextual fear memory. PMID:25091528
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Einarsson, Einar Ö; Pors, Jennifer; Nader, Karim
2015-01-01
After acquisition, hippocampus-dependent memories undergo a systems consolidation process, during which they become independent of the hippocampus and dependent on the anterior cingulate cortex (ACC) for memory expression. However, consolidated remote memories can become transiently hippocampus-dependent again following memory reactivation. How this systems reconsolidation affects the role of the ACC in remote memory expression is not known. Using contextual fear conditioning, we show that the expression of 30-day-old remote memory can transiently be supported by either the ACC or the dorsal hippocampus following memory reactivation, and that the ACC specifically mediates expression of remote generalized contextual fear memory. We found that suppression of neural activity in the ACC with the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) impaired the expression of remote, but not recent, contextual fear memory. Fear expression was not affected by this treatment if preceded by memory reactivation 6 h earlier, nor was it affected by suppression of neural activity in the dorsal hippocampus with the GABA-receptor agonist muscimol. However, simultaneous targeting of both the ACC and the dorsal hippocampus 6 h after memory reactivation disrupted contextual fear memory expression. Second, we observed that expression of a 30-day-old generalized contextual fear memory in a novel context was not affected by memory reactivation 6 h earlier. However, intra-ACC CNQX infusion before testing impaired contextual fear expression in the novel context, but not the original training context. Together, these data suggest that although the dorsal hippocampus may be recruited during systems reconsolidation, the ACC remains necessary for the expression of generalized contextual fear memory.
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TBI-Induced Formation of Toxic Tau and Its Biochemical Similarities to Tau in AD Brains
2016-10-01
onto wild-type mice markedly reduces 1) memory including contextual fear memory and spatial memory, and 2) long-term potentiation, a type of...TERMS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s disease 16. SECURITY CLASSIFICATION OF: 17...mechanism leading to TBI and AD. 2 KEYWORDS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s
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Time-dependent effects of cortisol on the contextualization of emotional memories.
van Ast, Vanessa A; Cornelisse, Sandra; Meeter, Martijn; Joëls, Marian; Kindt, Merel
2013-12-01
The inability to store fearful memories into their original encoding context is considered to be an important vulnerability factor for the development of anxiety disorders like posttraumatic stress disorder. Altered memory contextualization most likely involves effects of the stress hormone cortisol, acting via receptors located in the memory neurocircuitry. Cortisol via these receptors induces rapid nongenomic effects followed by slower genomic effects, which are thought to modulate cognitive function in opposite, complementary ways. Here, we targeted these time-dependent effects of cortisol during memory encoding and tested subsequent contextualization of emotional and neutral memories. In a double-blind, placebo-controlled design, 64 men were randomly assigned to one of three groups: 1) received 10 mg hydrocortisone 30 minutes (rapid cortisol effects) before a memory encoding task; 2) received 10 mg hydrocortisone 210 minutes (slow cortisol) before a memory encoding task; or 3) received placebo at both times. During encoding, participants were presented with neutral and emotional words in unique background pictures. Approximately 24 hours later, context dependency of their memories was assessed. Recognition data revealed that cortisol's rapid effects impair emotional memory contextualization, while cortisol's slow effects enhance it. Neutral memory contextualization remained unaltered by cortisol, irrespective of the timing of the drug. This study shows distinct time-dependent effects of cortisol on the contextualization of specifically emotional memories. The results suggest that rapid effects of cortisol may lead to impaired emotional memory contextualization, while slow effects of cortisol may confer protection against emotional memory generalization. © 2013 Society of Biological Psychiatry.
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The importance of context: evidence that contextual representations increase intrusive memories.
Pearson, David G; Ross, Fiona D C; Webster, Victoria L
2012-03-01
Intrusive memories appear to enter consciousness via involuntary rather than deliberate recollection. Some clinical accounts of PTSD seek to explain this phenomenon by making a clear distinction between the encoding of sensory-based and contextual representations. Contextual representations have been claimed to actively reduce intrusions by anchoring encoded perceptual data for an event in memory. The current analogue trauma study examined this hypothesis by manipulating contextual information independently from encoded sensory-perceptual information. Participants' viewed images selected from the International Affective Picture System that depicted scenes of violence and bodily injury. Images were viewed either under neutral conditions or paired with contextual information. Two experiments revealed a significant increase in memory intrusions for images paired with contextual information in comparison to the same images viewed under neutral conditions. In contrast to the observed increase in intrusion frequency there was no effect of contextual representations on voluntary memory for the images. The vividness and emotionality of memory intrusions were also unaffected. The analogue trauma paradigm may fail to replicate the effect of extreme stress on encoding postulated to occur during PTSD. These findings question the assertion that intrusive memories develop from a lack of integration between sensory-based and contextual representations in memory. Instead it is argued contextual representations play a causal role in increasing the frequency of intrusions by increasing the sensitivity of memory to involuntary retrieval by associated internal and external cues. Copyright © 2011 Elsevier Ltd. All rights reserved.
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ERIC Educational Resources Information Center
Tendolkar, Indira; Arnold, Jennifer; Petersson, Karl Magnus; Weis, Susanne; Brockhaus-Dumke, Anke; van Eijndhoven, Philip; Buitelaar, Jan; Fernandez, Guillen
2008-01-01
We investigated how the hippocampus and its adjacent mediotemporal structures contribute to contextual and noncontextual declarative memory retrieval by manipulating the amount of contextual information across two levels of the same contextual dimension in a source memory task. A first analysis identified medial temporal lobe (MTL) substructures…
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Cortisol mediates the effects of stress on the contextual dependency of memories.
van Ast, Vanessa A; Cornelisse, Sandra; Meeter, Martijn; Kindt, Merel
2014-03-01
Stress is known to exert considerable impact on learning and memory processes. Typically, human studies have investigated memory for single items (e.g., pictures, words), but it remains unresolved how exactly stress may alter the storage of memories into their original encoding context (i.e., memory contextualization). Since neurocircuitry underlying memory contextualization processes is sensitive to the well-known stress hormone cortisol, we here investigated whether cortisol mediates stress effects on memory contextualization. Forty healthy young men were randomly assigned to a psychosocial stress or control group. Ten minutes after stress manipulation offset, participants were instructed to learn and remember neutral and negative words, each of which was depicted against a unique background picture. Approximately 24h later, memory was tested by means of cued retrieval and recognition tasks. To assess memory contextualization half of the words were tested in intact item-contexts pairs, and half in rearranged item-context combinations. Recognition data showed that cortisol, but no other indices of stress such as heart rate or subjective stress, mediated the effects of stress on contextualization of neutral and negative memories. The mediation analysis further showed that stress resulted in increases in cortisol and that cortisol was positively related to memory contextualization, but unrelated to other measures of memory. Thus, there seems to be a specific role for cortisol in the integration of a central memory into its surrounding context. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Stability of Recent and Remote Contextual Fear Memory
ERIC Educational Resources Information Center
Frankland, Paul W.; Ding, Hoi-Ki; Takahashi, Eiki; Suzuki, Akinobu; Kida, Satoshi; Silva, Alcino J.
2006-01-01
Following initial encoding, memories undergo a prolonged period of reorganization. While such reorganization may occur in many different memory systems, its purpose is not clear. Previously, we have shown that recall of recent contextual fear memories engages the dorsal hippocampus (dHPC). In contrast, recall of remote contextual fear memories…
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Type 1 Adenylyl Cyclase is Essential for Maintenance of Remote Contextual Fear Memory
Shan, Qiang; Chan, Guy C.-K.; Storm, Daniel R.
2008-01-01
Although molecular mechanisms for hippocampus-dependent memory have been extensively studied, much less is known about signaling events important for remote memory. Here we report that mice lacking type 1 adenylyl cyclase (AC1) are able to establish and retrieve remote contextual memory but unable to sustain it as long as wild type mice. Interestingly, mice over-expressing AC1 show superior remote contextual memory even though they exhibit normal hippocampus-dependent contextual memory. These data illustrate that calcium coupling to cAMP contributes to the stability of remote memory and identifies AC1 as a potential drug target site to improve long-term remote memory. PMID:19036980
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Prefrontal neuronal circuits of contextual fear conditioning.
Rozeske, R R; Valerio, S; Chaudun, F; Herry, C
2015-01-01
Over the past years, numerous studies have provided a clear understanding of the neuronal circuits and mechanisms involved in the formation, expression and extinction phases of conditioned cued fear memories. Yet, despite a strong clinical interest, a detailed understanding of these memory phases for contextual fear memories is still missing. Besides the well-known role of the hippocampus in encoding contextual fear behavior, growing evidence indicates that specific regions of the medial prefrontal cortex differentially regulate contextual fear acquisition and storage in both animals and humans that ultimately leads to expression of contextual fear memories. In this review, we provide a detailed description of the recent literature on the role of distinct prefrontal subregions in contextual fear behavior and provide a working model of the neuronal circuits involved in the acquisition, expression and generalization of contextual fear memories. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
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Heath, Florence C; Jurkus, Regimantas; Bast, Tobias; Pezze, Marie A; Lee, Jonathan L C; Voigt, J Peter; Stevenson, Carl W
2015-07-01
Dopamine D1-like receptor signalling is involved in contextual fear conditioning, but the brain regions involved and its role in other contextual fear memory processes remain unclear. The objective of this study was to investigate (1) the effects of SCH 23390, a dopamine D1/D5 receptor antagonist, on contextual fear memory encoding, retrieval and reconsolidation, and (2) if the effects of SCH 23390 on conditioning involve the dorsal hippocampus (DH) and/or basolateral amygdala (BLA). Rats were used to examine the effects of systemically administering SCH 23390 on the acquisition, consolidation, retrieval and reconsolidation of contextual fear memory, and on locomotor activity and shock sensitivity. We also determined the effects of MK-801, an NMDA receptor antagonist, on contextual fear memory reconsolidation. The effects of infusing SCH 23390 locally into DH or BLA on contextual fear conditioning and locomotor activity were also examined. Systemic administration of SCH 23390 impaired contextual fear conditioning but had no effects on fear memory consolidation, retrieval or reconsolidation. MK-801 was found to impair reconsolidation, suggesting that the behavioural parameters used allowed for the pharmacological disruption of memory reconsolidation. The effects of SCH 23390 on conditioning were unlikely the result of any lasting drug effects on locomotor activity at memory test or any acute drug effects on shock sensitivity during conditioning. SCH 23390 infused into either DH or BLA impaired contextual fear conditioning and decreased locomotor activity. These findings suggest that dopamine D1-like receptor signalling in DH and BLA contributes to the acquisition of contextual fear memory.
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TRPC3 channels critically regulate hippocampal excitability and contextual fear memory.
Neuner, Sarah M; Wilmott, Lynda A; Hope, Kevin A; Hoffmann, Brian; Chong, Jayhong A; Abramowitz, Joel; Birnbaumer, Lutz; O'Connell, Kristen M; Tryba, Andrew K; Greene, Andrew S; Savio Chan, C; Kaczorowski, Catherine C
2015-03-15
Memory formation requires de novo protein synthesis, and memory disorders may result from misregulated synthesis of critical proteins that remain largely unidentified. Plasma membrane ion channels and receptors are likely candidates given their role in regulating neuron excitability, a candidate memory mechanism. Here we conduct targeted molecular monitoring and quantitation of hippocampal plasma membrane proteins from mice with intact or impaired contextual fear memory to identify putative candidates. Here we report contextual fear memory deficits correspond to increased Trpc3 gene and protein expression, and demonstrate TRPC3 regulates hippocampal neuron excitability associated with memory function. These data provide a mechanistic explanation for enhanced contextual fear memory reported herein following knockdown of TRPC3 in hippocampus. Collectively, TRPC3 modulates memory and may be a feasible target to enhance memory and treat memory disorders. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
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On the role of working memory in spatial contextual cueing.
Travis, Susan L; Mattingley, Jason B; Dux, Paul E
2013-01-01
The human visual system receives more information than can be consciously processed. To overcome this capacity limit, we employ attentional mechanisms to prioritize task-relevant (target) information over less relevant (distractor) information. Regularities in the environment can facilitate the allocation of attention, as demonstrated by the spatial contextual cueing paradigm. When observers are exposed repeatedly to a scene and invariant distractor information, learning from earlier exposures enhances the search for the target. Here, we investigated whether spatial contextual cueing draws on spatial working memory resources and, if so, at what level of processing working memory load has its effect. Participants performed 2 tasks concurrently: a visual search task, in which the spatial configuration of some search arrays occasionally repeated, and a spatial working memory task. Increases in working memory load significantly impaired contextual learning. These findings indicate that spatial contextual cueing utilizes working memory resources.
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How does intentionality of encoding affect memory for episodic information?
Craig, Michael; Butterworth, Karla; Nilsson, Jonna; Hamilton, Colin J.; Gallagher, Peter
2016-01-01
Episodic memory enables the detailed and vivid recall of past events, including target and wider contextual information. In this paper, we investigated whether/how encoding intentionality affects the retention of target and contextual episodic information from a novel experience. Healthy adults performed (1) a What-Where-When (WWW) episodic memory task involving the hiding and delayed recall of a number of items (what) in different locations (where) in temporally distinct sessions (when) and (2) unexpected tests probing memory for wider contextual information from the WWW task. Critically, some participants were informed that memory for WWW information would be subsequently probed (intentional group), while this came as a surprise for others (incidental group). The probing of contextual information came as a surprise for all participants. Participants also performed several measures of episodic and nonepisodic cognition from which common episodic and nonepisodic factors were extracted. Memory for target (WWW) and contextual information was superior in the intentional group compared with the incidental group. Memory for target and contextual information was unrelated to factors of nonepisodic cognition, irrespective of encoding intentionality. In addition, memory for target information was unrelated to factors of episodic cognition. However, memory for wider contextual information was related to some factors of episodic cognition, and these relationships differed between the intentional and incidental groups. Our results lead us to propose the hypothesis that intentional encoding of episodic information increases the coherence of the representation of the context in which the episode took place. This hypothesis remains to be tested. PMID:27918286
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False memory for context and true memory for context similarly activate the parahippocampal cortex.
Karanian, Jessica M; Slotnick, Scott D
2017-06-01
The role of the parahippocampal cortex is currently a topic of debate. One view posits that the parahippocampal cortex specifically processes spatial layouts and sensory details (i.e., the visual-spatial processing view). In contrast, the other view posits that the parahippocampal cortex more generally processes spatial and non-spatial contexts (i.e., the general contextual processing view). A large number of studies have found that true memories activate the parahippocampal cortex to a greater degree than false memories, which would appear to support the visual-spatial processing view as true memories are typically associated with greater visual-spatial detail than false memories. However, in previous studies, contextual details were also greater for true memories than false memories. Thus, such differential activity in the parahippocampal cortex may have reflected differences in contextual processing, which would challenge the visual-spatial processing view. In the present functional magnetic resonance imaging (fMRI) study, we employed a source memory paradigm to investigate the functional role of the parahippocampal cortex during true memory and false memory for contextual information to distinguish between the visual-spatial processing view and the general contextual processing view. During encoding, abstract shapes were presented to the left or right of fixation. During retrieval, old shapes were presented at fixation and participants indicated whether each shape was previously on the "left" or "right" followed by an "unsure", "sure", or "very sure" confidence rating. The conjunction of confident true memories for context and confident false memories for context produced activity in the parahippocampal cortex, which indicates that this region is associated with contextual processing. Furthermore, the direct contrast of true memory and false memory produced activity in the visual cortex but did not produce activity in the parahippocampal cortex. The present evidence suggests that the parahippocampal cortex is associated with general contextual processing rather than only being associated with visual-spatial processing. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Working memory dependence of spatial contextual cueing for visual search.
Pollmann, Stefan
2018-05-10
When spatial stimulus configurations repeat in visual search, a search facilitation, resulting in shorter search times, can be observed that is due to incidental learning. This contextual cueing effect appears to be rather implicit, uncorrelated with observers' explicit memory of display configurations. Nevertheless, as I review here, this search facilitation due to contextual cueing depends on visuospatial working memory resources, and it disappears when visuospatial working memory is loaded by a concurrent delayed match to sample task. However, the search facilitation immediately recovers for displays learnt under visuospatial working memory load when this load is removed in a subsequent test phase. Thus, latent learning of visuospatial configurations does not depend on visuospatial working memory, but the expression of learning, as memory-guided search in repeated displays, does. This working memory dependence has also consequences for visual search with foveal vision loss, where top-down controlled visual exploration strategies pose high demands on visuospatial working memory, in this way interfering with memory-guided search in repeated displays. Converging evidence for the contribution of working memory to contextual cueing comes from neuroimaging data demonstrating that distinct cortical areas along the intraparietal sulcus as well as more ventral parieto-occipital cortex are jointly activated by visual working memory and contextual cueing. © 2018 The British Psychological Society.
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ERIC Educational Resources Information Center
Zhang, Wei-Ping; Guzowski, John F.; Thomas, Steven A.
2005-01-01
We recently described a critical role for adrenergic signaling in the hippocampus during contextual and spatial memory retrieval. To determine which neurons are activated by contextual memory retrieval and its sequelae in the presence and absence of adrenergic signaling, transcriptional imaging for the immediate-early gene "Arc" was used in…
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A Key Role for Nectin-1 in the Ventral Hippocampus in Contextual Fear Memory
Grosse, Jocelyn; Krummenacher, Claude; Sandi, Carmen
2013-01-01
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 amygdala and dorsal hippocampus, respectively, thus opening new venues for the development of treatments to psychopathological alterations linked to impaired contextualization of emotions. PMID:23418609
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Law, L. Matthew; Smith, David M.
2012-01-01
The anterior thalamus (AT) is anatomically interconnected with the hippocampus and other structures known to be involved in memory, and the AT is involved in many of the same learning and memory functions as the hippocampus. For example, like the hippocampus, the AT is involved in spatial cognition and episodic memory. The hippocampus also has a well-documented role in contextual memory processes, but it is not known whether the AT is similarly involved in contextual memory. In the present study, we assessed the role of the AT in contextual memory processes by temporarily inactivating the AT and training rats on a recently developed context-based olfactory list learning task, which was designed to assess the use of contextual information to resolve interference. Rats were trained on one list of odor discrimination problems, followed by training on a second list in either the same context or a different context. In order to induce interference, some of the odors appeared on both lists with their predictive value reversed. Control rats that learned the two lists in different contexts performed significantly better than rats that learned the two lists in the same context. However, AT lesions completely abolished this contextual learning advantage, a result that is very similar to the effects of hippocampal inactivation. These findings demonstrate that the AT, like the hippocampus, is involved in contextual memory and suggest that the hippocampus and AT are part of a functional circuit involved in contextual memory. PMID:23025833
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Context controls access to working and reference memory in the pigeon (Columba livia).
Roberts, William A; Macpherson, Krista; Strang, Caroline
2016-01-01
The interaction between working and reference memory systems was examined under conditions in which salient contextual cues were presented during memory retrieval. Ambient colored lights (red or green) bathed the operant chamber during the presentation of comparison stimuli in delayed matching-to-sample training (working memory) and during the presentation of the comparison stimuli as S+ and S- cues in discrimination training (reference memory). Strong competition between memory systems appeared when the same contextual cue appeared during working and reference memory training. When different contextual cues were used, however, working memory was completely protected from reference memory interference. © 2016 Society for the Experimental Analysis of Behavior.
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Reconsolidation and update of morphine-associated contextual memory in mice.
Escosteguy-Neto, Joao Carlos; Varela, Patricia; Correa-Neto, Nelson Francisco; Coelho, Laura Segismundo; Onaivi, Emmanuel S; Santos-Junior, Jair Guilherme
2016-04-01
Drug addiction can be viewed as a pathological memory that is constantly retrieved and reconsolidated. Since drug abuse takes place in different contexts, it could be considered that reconsolidation plays a role in memory updating. There is consistent evidence supporting the role of reconsolidation in the strength and maintenance of contextual memories induced by drugs of abuse. However, this role is not well established in memory update. The purpose of the current study was to assess the reconsolidation process over memory update. C57BL6 mice were subjected to a morphine-induced, conditioned place preference (CPP) paradigm. Based on CPP results, animals were divided into distinct experimental groups, according to the contextual characteristics of the re-exposure and a second CPP Test. Re-exposure in the original context was important for memory maintenance and re-exposure under discrete contextual changes resulted in memory updating, although original memory was maintained. Interestingly, cycloheximide, an inhibitor of protein synthesis, had different outcomes in our protocol. When the re-exposure was done under discrete contextual changes, cycloheximide treatment just after re-exposure blocked memory updating, without changes in memory maintenance. When re-exposure was done under the original context, only two subsequent cycloheximide injections (3 and 6h) disrupted later CPP expression. Considering the temporal window of protein synthesis in consolidation and reconsolidation, these findings suggest that re-exposure, according to the contextual characteristics in our protocol, could trigger both phenomena. Furthermore, when new information is present on retrieval, reconsolidation plays a pivotal role in memory updating. Copyright © 2016 Elsevier Inc. All rights reserved.
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How does intentionality of encoding affect memory for episodic information?
Craig, Michael; Butterworth, Karla; Nilsson, Jonna; Hamilton, Colin J; Gallagher, Peter; Smulders, Tom V
2016-11-01
Episodic memory enables the detailed and vivid recall of past events, including target and wider contextual information. In this paper, we investigated whether/how encoding intentionality affects the retention of target and contextual episodic information from a novel experience. Healthy adults performed (1) a What-Where-When (WWW) episodic memory task involving the hiding and delayed recall of a number of items (what) in different locations (where) in temporally distinct sessions (when) and (2) unexpected tests probing memory for wider contextual information from the WWW task. Critically, some participants were informed that memory for WWW information would be subsequently probed (intentional group), while this came as a surprise for others (incidental group). The probing of contextual information came as a surprise for all participants. Participants also performed several measures of episodic and nonepisodic cognition from which common episodic and nonepisodic factors were extracted. Memory for target (WWW) and contextual information was superior in the intentional group compared with the incidental group. Memory for target and contextual information was unrelated to factors of nonepisodic cognition, irrespective of encoding intentionality. In addition, memory for target information was unrelated to factors of episodic cognition. However, memory for wider contextual information was related to some factors of episodic cognition, and these relationships differed between the intentional and incidental groups. Our results lead us to propose the hypothesis that intentional encoding of episodic information increases the coherence of the representation of the context in which the episode took place. This hypothesis remains to be tested. © 2016 Craig et al.; Published by Cold Spring Harbor Laboratory Press.
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Daumas, Stéphanie; Halley, Hélène; Francés, Bernard; Lassalle, Jean-Michel
2005-01-01
Studies on human and animals shed light on the unique hippocampus contributions to relational memory. However, the particular role of each hippocampal subregion in memory processing is still not clear. Hippocampal computational models and theories have emphasized a unique function in memory for each hippocampal subregion, with the CA3 area acting as an autoassociative memory network and the CA1 area as a critical output structure. In order to understand the respective roles of the CA3- and CA1-hippocampal areas in the formation of contextual memory, we studied the effects of the reversible inactivation by lidocaine of the CA3 or CA1 areas of the dorsal hippocampus on acquisition, consolidation, and retrieval of a contextual fear conditioning. Whereas infusions of lidocaine never impaired elementary tone conditioning, their effects on contextual conditioning provided interesting clues about the role of these two hippocampal regions. They demonstrated first that the CA3 area is necessary for the rapid elaboration of a unified representation of the context. Secondly, they suggested that the CA1 area is rather involved in the consolidation process of contextual memory. Third, they showed that CA1 or CA3 inactivation during retention test has no effect on contextual fear retrieval when a recognition memory procedure is used. In conclusion, our findings point as evidence that CA1 and CA3 subregions of the dorsal hippocampus play important and different roles in the acquisition and consolidation of contextual fear memory, whereas they are not required for context recognition.
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ERIC Educational Resources Information Center
Robin, Jessica; Moscovitch, Morris
2014-01-01
Several recent studies have explored the effect of contextual familiarity on remembered and imagined events. The aim of this study was to examine the extent of this effect by comparing the effect of cuing spatial memories, episodic memories, and imagined future events with spatial contextual cues of varying levels of familiarity. We used…
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Differential patterns of contextual organization of memory in first-episode psychosis.
Murty, Vishnu P; McKinney, Rachel A; DuBrow, Sarah; Jalbrzikowski, Maria; Haas, Gretchen L; Luna, Beatriz
2018-02-15
Contextual information is used to support and organize episodic memory. Prior research has reliably shown memory deficits in psychosis; however, little research has characterized how this population uses contextual information during memory recall. We employed an approach founded in a computational framework of free recall to quantify how individuals with first episode of psychosis (FEP, N = 97) and controls (CON, N = 55) use temporal and semantic context to organize memory recall. Free recall was characterized using the Hopkins Verbal Learning Test-Revised (HVLT-R). We compared FEP and CON on three measures of free recall: proportion recalled, temporal clustering, and semantic clustering. Measures of temporal/semantic clustering quantified how individuals use contextual information to organize memory recall. We also assessed to what extent these measures relate to antipsychotic use and differentiated between different types of psychosis. We also explored the relationship between these measures and intelligence. In comparison to CON, FEP had reduced recall and less temporal clustering during free recall (p < 0.05, Bonferroni-corrected), and showed a trend towards greater semantic clustering (p = 0.10, Bonferroni-corrected). Within FEP, antipsychotic use and diagnoses did not differentiate between free recall accuracy or contextual organization of memory. IQ was related to free recall accuracy, but not the use of contextual information during recall in either group (p < 0.05, Bonferroni-corrected). These results show that in addition to deficits in memory recall, FEP differed in how they organize memories compared to CON.
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Nakayama, Kei; Ohashi, Rie; Shinoda, Yo; Yamazaki, Maya; Abe, Manabu; Fujikawa, Akihiro; Shigenobu, Shuji; Futatsugi, Akira; Noda, Masaharu; Mikoshiba, Katsuhiko; Furuichi, Teiichi; Sakimura, Kenji; Shiina, Nobuyuki
2017-11-21
Local regulation of synaptic efficacy is thought to be important for proper networking of neurons and memory formation. Dysregulation of global translation influences long-term memory in mice, but the relevance of the regulation specific for local translation by RNA granules remains elusive. Here, we demonstrate roles of RNG105/caprin1 in long-term memory formation. RNG105 deletion in mice impaired synaptic strength and structural plasticity in hippocampal neurons. Furthermore, RNG105-deficient mice displayed unprecedentedly severe defects in long-term memory formation in spatial and contextual learning tasks. Genome-wide profiling of mRNA distribution in the hippocampus revealed an underlying mechanism: RNG105 deficiency impaired the asymmetric somato-dendritic localization of mRNAs. Particularly, RNG105 deficiency reduced the dendritic localization of mRNAs encoding regulators of AMPAR surface expression, which was consistent with attenuated homeostatic AMPAR scaling in dendrites and reduced synaptic strength. Thus, RNG105 has an essential role, as a key regulator of dendritic mRNA localization, in long-term memory formation.
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Manginelli, Angela A; Baumgartner, Florian; Pollmann, Stefan
2013-02-15
Behavioral evidence suggests that the use of implicitly learned spatial contexts for improved visual search may depend on visual working memory resources. Working memory may be involved in contextual cueing in different ways: (1) for keeping implicitly learned working memory contents available during search or (2) for the capture of attention by contexts retrieved from memory. We mapped brain areas that were modulated by working memory capacity. Within these areas, activation was modulated by contextual cueing along the descending segment of the intraparietal sulcus, an area that has previously been related to maintenance of explicit memories. Increased activation for learned displays, but not modulated by the size of contextual cueing, was observed in the temporo-parietal junction area, previously associated with the capture of attention by explicitly retrieved memory items, and in the ventral visual cortex. This pattern of activation extends previous research on dorsal versus ventral stream functions in memory guidance of attention to the realm of attentional guidance by implicit memory. Copyright © 2012 Elsevier Inc. All rights reserved.
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Abdullahi, Payman Rasise; Eskandarian, Sharaf; Ghanbari, Ali; Rashidy-Pour, Ali
2018-05-23
There is increasing evidence that oxytocin is involved in learning and memory process. This study investigated the effects of blockade of oxytocin receptors using the selective oxytocin receptor antagonist atosiban (ATO) on contextual fear memory consolidation and reconsolidation in male rats. Post-training injections of different doses of ATO (1, 10, 100 or 1000 µg/kg) impaired the 48 h retention performance in a dose-dependent manner. The same doses of ATO following memory reactivation did not impair subsequent expression of contextual fear memories which formed under low or high shock intensities and tested 24 h or one week following memory reactivation. Also, no effect was found when ATO was administrated in the absence of memory reactivation. Our finding is the first report that indicates endogenous oxytocin released during training play an important role in the consolidation, but not reconsolidation of contextual fear memory in rats. Copyright © 2018. Published by Elsevier B.V.
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Wetherill, Reagan R.; Fromme, Kim
2011-01-01
The present study examined the effects of alcohol consumption on narrative recall and contextual memory among individuals with and without a history of fragmentary blackouts in an attempt to better understand why some individuals experience alcohol-induced memory impairments whereas others do not, even at comparable blood alcohol concentrations (BACs). Standardized beverage (alcohol, no alcohol) administration procedures and neuropsychological assessments measured narrative recall and context memory performance before and after alcohol consumption in individuals with (n = 44) and without (n = 44) a history of fragmentary blackouts. Findings indicate acute alcohol intoxication led to impairments in free recall, but not next-day cued recall. Further, participants showed similar memory performance when sober, but individuals who consumed alcohol and had a positive history of fragmentary blackouts showed greater contextual memory impairments than those who had not previously experienced a fragmentary blackout. Thus, it appears that some individuals may have an inherent vulnerability to alcohol-induced memory impairments due to alcohol’s effects on contextual memory processes. PMID:21497445
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Contextual Information Drives the Reconsolidation-Dependent Updating of Retrieved Fear Memories
Jarome, Timothy J; Ferrara, Nicole C; Kwapis, Janine L; Helmstetter, Fred J
2015-01-01
Stored memories enter a temporary state of vulnerability following retrieval known as ‘reconsolidation', a process that can allow memories to be modified to incorporate new information. Although reconsolidation has become an attractive target for treatment of memories related to traumatic past experiences, we still do not know what new information triggers the updating of retrieved memories. Here, we used biochemical markers of synaptic plasticity in combination with a novel behavioral procedure to determine what was learned during memory reconsolidation under normal retrieval conditions. We eliminated new information during retrieval by manipulating animals' training experience and measured changes in proteasome activity and GluR2 expression in the amygdala, two established markers of fear memory lability and reconsolidation. We found that eliminating new contextual information during the retrieval of memories for predictable and unpredictable fear associations prevented changes in proteasome activity and glutamate receptor expression in the amygdala, indicating that this new information drives the reconsolidation of both predictable and unpredictable fear associations on retrieval. Consistent with this, eliminating new contextual information prior to retrieval prevented the memory-impairing effects of protein synthesis inhibitors following retrieval. These results indicate that under normal conditions, reconsolidation updates memories by incorporating new contextual information into the memory trace. Collectively, these results suggest that controlling contextual information present during retrieval may be a useful strategy for improving reconsolidation-based treatments of traumatic memories associated with anxiety disorders such as post-traumatic stress disorder. PMID:26062788
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Zhao, Yan; Liu, Peng; Chu, Zheng; Liu, Fei; Han, Wei; Xun, Xi; Dang, Yong-Hui
2015-10-22
The memories that are formed between rewarding and drug-associated contextual cues have been suggested to contribute to drug addiction relapse. Recent evidence has indicated that the ventrolateral orbital cortex (VLO) plays important roles in reward-based learning and reversal learning. However, whether the VLO is required for methamphetamine-induced contextual memory formation is not well understood. In the present study, a three-phase methamphetamine-induced conditioned place preference (CPP) model was used to investigate the effects of VLO lesions on the formation of drug-associated contextual memories in rats. We found that the VLO lesions themselves elicited no observable effects on place preferences. However, the VLO lesions delayed the acquisition and extinction phases of CPP without affecting the expression level. Furthermore, the VLO lesions did not have an obvious influence on CPP reinstatement. These results indicate that electrolytic lesions of the bilateral ventrolateral orbital cortex can inhibit the formation of methamphetamine-induced contextual memories in rats. Moreover, VLO may not be critically involved in memory storage and retrieval. Copyright © 2015 Elsevier B.V. All rights reserved.
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Schlagbauer, Bernhard; Mink, Maurice; Müller, Hermann J; Geyer, Thomas
2017-02-01
Observers are able to resume an interrupted search trial faster relative to responding to a new, unseen display. This finding of rapid resumption is attributed to short-term perceptual hypotheses generated on the current look and confirmed upon subsequent looks at the same display. It has been suggested that the contents of perceptual hypotheses are similar to those of other forms of memory acquired long-term through repeated exposure to the same search displays over the course of several trials, that is, the memory supporting "contextual cueing." In three experiments, we investigated the relationship between short-term perceptual hypotheses and long-term contextual memory. The results indicated that long-term, contextual memory of repeated displays neither affected the generation nor the confirmation of short-term perceptual hypotheses for these displays. Furthermore, the analysis of eye movements suggests that long-term memory provides an initial benefit in guiding attention to the target, whereas in subsequent looks guidance is entirely based on short-term perceptual hypotheses. Overall, the results reveal a picture of both long- and short-term memory contributing to reliable performance gains in interrupted search, while exerting their effects in an independent manner.
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Generation and Memory for Contextual Detail
ERIC Educational Resources Information Center
Mulligan, Neil W.
2004-01-01
Generation enhances item memory but may not enhance other aspects of memory. In 12 experiments, the author investigated the effect of generation on context memory, motivated in part by the hypothesis that generation produces a trade-off in encoding item and contextual information. Participants generated some study words (e.g., hot-___) and read…
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Gulick, Danielle; Gould, Thomas J.
2009-01-01
Background Ethanol is a frequently abused, addictive drug that impairs cognitive function. Ethanol may disrupt cognitive processes by altering attention, short-term memory, and/ or long-term memory. Interestingly, some research suggests that ethanol may enhance cognitive processes at lower doses. The current research examined the dose-dependent effects of ethanol on contextual and cued fear conditioning. In addition, the present studies assessed the importance of stimulus salience in the effects of ethanol and directly compared the effects of ethanol on short-term and long-term memory. Methods This study employed both foreground and background fear conditioning, which differ in the salience of contextual stimuli, and tested conditioning at 4 hours, 24 hours, and 1 week in order to assess the effects of ethanol on short-term and long-term memory. Foreground conditioning consisted of 2 presentations of a foot shock unconditioned stimulus (US) (2 seconds, 0.57 mA). Background conditioning consisted of 2 auditory conditioned stimulus (30 seconds, 85 dB white noise)–foot shock (US; 2 seconds, 0.57 mA) pairings. Results For both foreground and background conditioning, ethanol enhanced short-term and long-term memory for contextual and cued conditioning at a low dose (0.25 g/kg) and impaired short-term and long-term memory for contextual and cued conditioning at a high dose (1.0 g/kg). Conclusions These results suggest that ethanol has long-lasting, biphasic effects on short-term and long-term memory for contextual and cued conditioning. Furthermore, the effects of ethanol on contextual fear conditioning are independent of the salience of the context. PMID:17760787
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Inhibition of Rac1 Activity in the Hippocampus Impairs the Forgetting of Contextual Fear Memory.
Jiang, Lizhu; Mao, Rongrong; Zhou, Qixin; Yang, Yuexiong; Cao, Jun; Ding, Yuqiang; Yang, Yuan; Zhang, Xia; Li, Lingjiang; Xu, Lin
2016-03-01
Fear is crucial for survival, whereas hypermnesia of fear can be detrimental. Inhibition of the Rac GTPase is recently reported to impair the forgetting of initially acquired memory in Drosophila. Here, we investigated whether inhibition of Rac1 activity in rat hippocampus could contribute to the hypermnesia of contextual fear. We found that spaced but not massed training of contextual fear conditioning caused inhibition of Rac1 activity in the hippocampus and heightened contextual fear. Furthermore, intrahippocampal injection of the Rac1 inhibitor NSC23766 heightened contextual fear in massed training, while Rac1 activator CN04-A weakened contextual fear in spaced training rats. Our study firstly demonstrates that contextual fear memory in rats is actively regulated by Rac1 activity in the hippocampus, which suggests that the forgetting impairment of traumatic events in posttraumatic stress disorder may be contributed to the pathological inhibition of Rac1 activity in the hippocampus.
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Generation and memory for contextual detail.
Mulligan, Neil W
2004-07-01
Generation enhances item memory but may not enhance other aspects of memory. In 12 experiments, the author investigated the effect of generation on context memory, motivated in part by the hypothesis that generation produces a trade-off in encoding item and contextual information. Participants generated some study words (e.g., hot-c__) and read others (e.g., hot-cold). Generation consistently enhanced item memory but did not enhance context memory. More specifically, generation disrupted context memory for the color of the target word but did not affect context memory for location, background color, and cue-word color. The specificity of the negative generation effect in context memory argues against a general item-context trade-off. A processing account of generation meets greater success. In addition, the results provide no evidence that generation enhances recollection of contextual details. Copyright 2004 APA, all rights reserved
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ERIC Educational Resources Information Center
Raj, Vinaya; Bell, Martha Ann
2010-01-01
Episodic memories contain various forms of contextual detail (e.g., perceptual, emotional, cognitive details) that need to become integrated. Each of these contextual features can be used to attribute a memory episode to its source, or origin of information. Memory for source information is one critical component in the formation of episodic…
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Wetherill, Reagan R; Fromme, Kim
2011-08-01
The present study examined the effects of alcohol consumption on narrative recall and contextual memory among individuals with and without a history of fragmentary blackouts in an attempt to better understand why some individuals experience alcohol-induced memory impairments whereas others do not, even at comparable blood alcohol concentrations (BACs). Standardized beverage (alcohol and no alcohol) administration procedures and neuropsychological assessments measured narrative recall and context memory performance before and after alcohol consumption in individuals with (n=44) and without (n=44) a history of fragmentary blackouts. Findings indicate that acute alcohol intoxication led to impairments in free recall, but not next-day cued recall. Further, participants showed similar memory performance when sober, but individuals who consumed alcohol and had a positive history of fragmentary blackouts showed greater contextual memory impairments than those who had not previously experienced a fragmentary blackout. Thus, it appears that some individuals may have an inherent vulnerability to alcohol-induced memory impairments due to alcohol's effects on contextual memory processes. Copyright © 2011 Elsevier Ltd. All rights reserved.
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False memory for context activates the parahippocampal cortex.
Karanian, Jessica M; Slotnick, Scott D
2014-01-01
Previous studies have reported greater activity in the parahippocampal cortex during true memory than false memory, which has been interpreted as reflecting greater sensory processing during true memory. However, in these studies, sensory detail and contextual information were confounded. In the present fMRI study, we employed a novel paradigm to dissociate these factors. During encoding, abstract shapes were presented in one of two contexts (i.e., moving or stationary). During retrieval, participants classified shapes as previously "moving" or "stationary." Critically, contextual processing was relatively greater during false memory ("moving" responses to stationary items), while sensory processing was relatively greater during true memory ("moving" responses to moving items). Within the medial temporal lobe, false memory versus true memory produced greater activity in the parahippocampal cortex, whereas true memory versus false memory produced greater activity in the hippocampus. The present results indicate that the parahippocampal cortex mediates contextual processing rather than sensory processing.
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Contextual Fear Memories Formed in the Absence of the Dorsal Hippocampus Decay Across Time
Zelikowsky, Moriel; Bissiere, Stephanie; Fanselow, Michael S.
2012-01-01
Mammals suffering damage to the hippocampus display a dramatic loss of explicit, recently formed memories (retrograde amnesia). In contrast, deficits in the ability to form new memories following hippocampal damage (anterograde amnesia) can be overcome with sufficient training. By combining contextual fear conditioning with lesions of the dorsal hippocampus in rats, we discovered that while animals can form long-term contextual fear memories in the absence of the hippocampus, these memories decay with time, lacking the permanence that is a hallmark characteristic of normal fear memories. These findings indicate that while it is initially possible to acquire explicit memories when the hippocampus is compromised, these memories cannot transfer from a recent to remote state. This suggests that memories formed outside the hippocampus may nevertheless require the hippocampus to undergo systems consolidation, which has important clinical implications for the treatment of memory disorders. PMID:22399761
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Wheelan, Nicola; Webster, Scott P.; Kenyon, Christopher J.; Caughey, Sarah; Walker, Brian R.; Holmes, Megan C.; Seckl, Jonathan R.; Yau, Joyce L.W.
2015-01-01
High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11β-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11β-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11β-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals. PMID:25497454
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Wheelan, Nicola; Webster, Scott P; Kenyon, Christopher J; Caughey, Sarah; Walker, Brian R; Holmes, Megan C; Seckl, Jonathan R; Yau, Joyce L W
2015-04-01
High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11β-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11β-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11β-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Gao, Aijing; Xia, Frances; Guskjolen, Axel J; Ramsaran, Adam I; Santoro, Adam; Josselyn, Sheena A; Frankland, Paul W
2018-03-28
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 designer receptor exclusively activated by designer drugs, 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 versus 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 1 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 hippocampus, they remodel neural circuitry, potentially making information stored in those circuits harder to access. Consistent with this, increasing hippocampal neurogenesis after learning induces forgetting of the learnt information. The current study in mice asks whether these forgetting effects depend on the age of the memory. We found that post-training increases in hippocampal neurogenesis only impacted recently acquired, and not remotely acquired, hippocampal memories. These experiments identify memory age as a boundary condition for neurogenesis-mediated forgetting, and suggest remote memories are less sensitive to changes in hippocampal neurogenesis levels because they no longer depend critically on the hippocampus for their expression. Copyright © 2018 the authors 0270-6474/18/383190-09$15.00/0.
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Long-term consolidation of declarative memory: insight from temporal lobe epilepsy.
Tramoni, Eve; Felician, Olivier; Barbeau, Emmanuel J; Guedj, Eric; Guye, Maxime; Bartolomei, Fabrice; Ceccaldi, Mathieu
2011-03-01
Several experiments carried out with a subset of patients with temporal lobe epilepsy have demonstrated normal memory performance at standard delays of recall (i.e. minutes to hours) but impaired performance over longer delays (i.e. days or weeks), suggesting altered long-term consolidation mechanisms. These mechanisms were specifically investigated in a group of five adult-onset pharmaco-sensitive patients with temporal lobe epilepsy, exhibiting severe episodic memory complaints despite normal performance at standardized memory assessment. In a first experiment, the magnitude of autobiographical memory loss was evaluated using retrograde personal memory tasks based on verbal and visual cues. In both conditions, results showed an unusual U-shaped pattern of personal memory impairment, encompassing most of the patients' life, sparing however, periods of the childhood, early adulthood and past several weeks. This profile was suggestive of a long-term consolidation impairment of personal episodes, adequately consolidated over 'short-term' delays but gradually forgotten thereafter. Therefore, in a subsequent experiment, patients were submitted to a protocol specifically devised to investigate short and long-term consolidation of contextually-bound experiences (episodic memory) and context-free information (semantic knowledge and single-items). In the short term (1 h), performance at both contextually-free and contextually-bound memory tasks was intact. After a 6-week delay, however, contextually-bound memory performance was impaired while contextually-free memory performance remained preserved. This effect was independent of task difficulty and the modality of retrieval (recall and recognition). Neuroimaging studies revealed the presence of mild metabolic changes within medial temporal lobe structures. Taken together, these results show the existence of different consolidation systems within declarative memory. They suggest that mild medial temporal lobe dysfunction can impede the building and stabilization of episodic memories but leaves long-term semantic and single-items mnemonic traces intact.
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Emotion’s Influence on Memory for Spatial and Temporal Context
Schmidt, Katherine; Patnaik, Pooja; Kensinger, Elizabeth A.
2010-01-01
Individuals report remembering emotional items vividly. It is debated whether this report reflects enhanced memory accuracy or a bias to believe emotional memories are vivid. We hypothesized emotion would enhance memory accuracy, improving memory for contextual details. The hallmark of episodic memory is that items are remembered in a spatial and temporal context, so we examined whether an item’s valence (positive, negative) or arousal (high, low) would influence its ability to be remembered with those contextual details. Across two experiments, high-arousal items were remembered with spatial and temporal context more often than low-arousal items. Item valence did not influence memory for those details, although positive high-arousal items were recognized or recalled more often than negative items. These data suggest that emotion does not just bias participants to believe they have a vivid memory; rather, the arousal elicited by an event can benefit memory for some types of contextual details. PMID:21379376
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Contextualization: Memory Formation and Retrieval in a Nested Environment
NASA Astrophysics Data System (ADS)
Piefke, Martina; Markowitsch, Hans J.
Episodic memory functions are highly context-dependent. This is true for both experimental and autobiographical episodic memory. We here review neuropsychological and neuroimaging evidence for effects of differential encoding and retrieval contexts on episodic memory performance as well as the underlying neurofunctional mechanisms. In studies of laboratory episodic memory, the influence of context parameters can be assessed by experimental manipulations. Such experiments suggest that contextual variables mainly affect prefrontal functions supporting executive processes involved in episodic learning and retrieval. Context parameters affecting episodic autobiographical memory are far more complex and cannot easily be controlled. Data support the view that not only prefrontal, but also further medial temporal and posterior parietal regions mediating the re-experience and emotional evaluation of personal memories are highly influenced by changing contextual variables of memory encoding and retrieval. Based on our review of available data, we thus suggest that experimental and autobiographical episodic memories are influenced by both overlapping and differential context parameters.
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Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano; Alviña, Karina; Zhang, Yuxiang; Dushko, Margaret; Ku, Taeyun; Zemoura, Khaled; Rich, David; Garcia-Dominguez, Dario; Hung, Matthew; Yelhekar, Tushar D; Sørensen, Andreas Toft; Xu, Weifeng; Chung, Kwanghun; Castillo, Pablo E; Lin, Yingxi
2018-03-07
Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report that the activity-dependent transcription factor Npas4 selectively regulates the structure and strength of MF-CA3 synapses by restricting the number of their functional synaptic contacts without affecting the other synaptic inputs onto CA3 pyramidal neurons. Using an activity-dependent reporter, we identified CA3 pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation. Copyright © 2018 Elsevier Inc. All rights reserved.
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Time, Not Sleep, Unbinds Contexts from Item Memory
Cox, Roy; Tijdens, Ron R.; Meeter, Martijn M.; Sweegers, Carly C. G.; Talamini, Lucia M.
2014-01-01
Contextual cues are known to benefit memory retrieval, but whether and how sleep affects this context effect remains unresolved. We manipulated contextual congruence during memory retrieval in human volunteers across 12 h and 24 h intervals beginning with either sleep or wakefulness. Our data suggest that whereas contextual cues lose their potency with time, sleep does not modulate this process. Furthermore, our results are consistent with the idea that sleep's beneficial effect on memory retention depends on the amount of waking time that has passed between encoding and sleep onset. The findings are discussed in the framework of competitive consolidation theory. PMID:24498441
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The cortical underpinnings of context-based memory distortion.
Aminoff, Elissa; Schacter, Daniel L; Bar, Moshe
2008-12-01
Everyday contextual settings create associations that later afford generating predictions about what objects to expect in our environment. The cortical network that takes advantage of such contextual information is proposed to connect the representation of associated objects such that seeing one object (bed) will activate the visual representations of other objects sharing the same context (pillow). Given this proposal, we hypothesized that the cortical activity elicited by seeing a strong contextual object would predict the occurrence of false memories whereby one erroneously "remembers" having seen a new object that is related to a previously presented object. To test this hypothesis, we used functional magnetic resonance imaging during encoding of contextually related objects, and later tested recognition memory. New objects that were contextually related to previously presented objects were more often falsely judged as "old" compared with new objects that were contextually unrelated to old objects. This phenomenon was reflected by activity in the cortical network mediating contextual processing, which provides a better understanding of how the brain represents and processes context.
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Contextually Mediated Spontaneous Retrieval Is Specific to the Hippocampus
Long, Nicole M.; Sperling, Michael R.; Worrell, Gregory A.; Davis, Kathryn A.; Gross, Robert E.; Lega, Bradley C.; Jobst, Barbara C.; Sheth, Sameer A.; Zaghloul, Kareem; Stein, Joel M.; Kahana, Michael J.
2018-01-01
SUMMARY Although it is now well established that the hippocampus supports memory encoding [1, 2], little is known about hippocampal activity during spontaneous memory retrieval. Recent intracranial electroencephalographic (iEEG) work has shown that hippocampal activity during encoding predicts subsequent temporal organization of memories [3], supporting a role in contextual binding. It is an open question, however, whether the hippocampus similarly supports contextually mediated processes during retrieval. Here, we analyzed iEEG recordings obtained from 215 epilepsy patients as they performed a free recall task. To identify neural activity specifically associated with contextual retrieval, we compared correct recalls, intrusions (incorrect recall of either items from prior lists or items not previously studied), and deliberations (matched periods during recall when no items came to mind). Neural signals that differentiate correct recalls from both other retrieval classes reflect contextual retrieval, as correct recalls alone arise from the correct context. We found that in the hippocampus, high-frequency activity (HFA, 44–100 Hz), a proxy for neural activation [4], was greater prior to correct recalls relative to the other retrieval classes, with no differentiation between intrusions and deliberations. This pattern was not observed in other memory-related cortical regions, including DLPFC, thus supporting a specific hippocampal contribution to contextually mediated memory retrieval. PMID:28343962
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Hein, A.M.; Stutzman, D.L.; Bland, S.T.; Barrientos, R.M.; Watkins, L.R.; Rudy, J.W.; Maier, S.F.
2008-01-01
The intra-hippocampal administration of interleukin-1β (IL-1β) as well as the induction of elevated but physiological levels of IL-1β within the hippocampus interferes with the formation of long-term memory. There is evidence suggesting that the induction of prostaglandin (PG) formation by IL-1β is involved in impairments in working and spatial memory following IL-1β. The present experiments extend these findings by showing that PGs are responsible for memory deficits in contextual fear conditioning that occur following IL-1β injection into the dorsal hippocampus. Cyclooxygenase (COX) inhibition blocked the disruption in contextual fear conditioning produced by IL-1β and COX inhibition alone also disrupted contextual memory, suggesting an inverted U-shaped relationship between PG levels and memory. In addition to demonstrating the necessity of PGs in IL-1β mediated memory deficits, we also show that PGs injected directly into the dorsal hippocampus are sufficient to impair context memory and significantly reduce post-conditioning levels of BDNF within the hippocampus, suggesting a possible mechanism for the memory-impairing effects of PGs. PMID:18035502
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Strekalova, T; Zörner, B; Zacher, C; Sadovska, G; Herdegen, T; Gass, P
2003-02-01
Using specific polyclonal antisera against c-Fos, JunB, c-Jun and JunD, we tried to identify the candidate transcription factors of the immediate early gene family which may contribute to the molecular processes during contextual memory reconsolidation. For that purpose we analyzed the expression of these proteins in the hippocampus after contextual memory retrieval in a mouse model of fear conditioning. A single exposure to a foot shock of 0.8 mA was sufficient to induce robust contextual fear conditioning in C57BI/6N mice. In these mice context dependent memory retrieval evoked a marked induction of c-Fos and JunB, but not of c-Jun and JunD, in pyramidal CA1 neurons of the dorsal hippocampus. In contrast, mice exposed and re-exposed only to the context, without foot shock, did not show behavioral signs of contextual fear conditioning and exhibited significantly less expression of c-Fos and JunB in CA1 neurons. Mice which received a foot shock but were not re-exposed to the context revealed no immediate early gene induction. These results demonstrate that contextual memory retrieval is associated with de novo synthesis of specific members of the Fos/Jun transcription factor family. Therefore we suggest that these genes may contribute to plasticity and reconsolidation accompanying the retrieval process. The specific activation of CA1 neurons during the retrieval of contextual fear associations supports the postulated concept of a mnemonic role of this hippocampal subsector during the retrieval of contextual informations.
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Contextual consistency facilitates long-term memory of perceptual detail in barely seen images.
Gronau, Nurit; Shachar, Meytal
2015-08-01
It is long known that contextual information affects memory for an object's identity (e.g., its basic level category), yet it is unclear whether schematic knowledge additionally enhances memory for the precise visual appearance of an item. Here we investigated memory for visual detail of merely glimpsed objects. Participants viewed pairs of contextually related and unrelated stimuli, presented for an extremely brief duration (24 ms, masked). They then performed a forced-choice memory-recognition test for the precise perceptual appearance of 1 of 2 objects within each pair (i.e., the "memory-target" item). In 3 experiments, we show that memory-target stimuli originally appearing within contextually related pairs are remembered better than targets appearing within unrelated pairs. These effects are obtained whether the target is presented at test with its counterpart pair object (i.e., when reiterating the original context at encoding) or whether the target is presented alone, implying that the contextual consistency effects are mediated predominantly by processes occurring during stimulus encoding, rather than during stimulus retrieval. Furthermore, visual detail encoding is improved whether object relations involve implied action or not, suggesting that, contrary to some prior suggestions, action is not a necessary component for object-to-object associative "grouping" processes. Our findings suggest that during a brief glimpse, but not under long viewing conditions, contextual associations may play a critical role in reducing stimulus competition for attention selection and in facilitating rapid encoding of sensory details. Theoretical implications with respect to classic frame theories are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
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Evidence for Hippocampus-Dependent Contextual Learning at Postnatal Day 17 in the Rat
ERIC Educational Resources Information Center
Foster, Jennifer A.; Burman, Michael A.
2010-01-01
Long-term memory for fear of an environment (contextual fear conditioning) emerges later in development (postnatal day; PD 23) than long-term memory for fear of discrete stimuli (PD 17). As contextual, but not explicit cue, fear conditioning relies on the hippocampus; this has been interpreted as evidence that the hippocampus is not fully…
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Yin, Xi; Gao, Yuan; Shi, Hai-Shui; Song, Li; Wang, Jie-Chao; Shao, Juan; Geng, Xu-Hong; Xue, Gai; Li, Jian-Li; Hou, Yan-Ning
2016-01-01
Histone modifications have been implicated in learning and memory. Our previous transcriptome data showed that expression of sirtuins 6 (SIRT6), a member of Histone deacetylases (HDACs) family in the hippocampal cornu ammonis 1 (CA1) was decreased after contextual fear conditioning. However, the role of SIRT6 in the formation of memory is still elusive. In the present study, we found that contextual fear conditioning inhibited translational expression of SIRT6 in the CA1. Microinfusion of lentiviral vector-expressing SIRT6 into theCA1 region selectively enhanced the expression of SIRT6 and impaired the formation of long-term contextual fear memory without affecting short-term fear memory. The overexpression of SIRT6 in the CA1 had no effect on anxiety-like behaviors or locomotor activity. Also, we also found that SIRT6 overexpression significantly inhibited the expression of insulin-like factor 2 (IGF2) and amounts of proteins and/or phosphoproteins (e.g. Akt, pAkt, mTOR and p-mTOR) related to the IGF2 signal pathway in the CA1. These results demonstrate that the overexpression of SIRT6 in the CA1 impaired the formation of long-term fear memory, and SIRT6 in the CA1 may negatively modulate the formation of contextual fear memory via inhibiting the IGF signaling pathway. PMID:26732053
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Zeitlin, Ross; Patel, Sagar; Solomon, Rosalynn; Tran, John; Weeber, Edwin J; Echeverria, Valentina
2012-03-17
Posttraumatic stress disorder (PTSD) is an anxiety disorder triggered by traumatic events. Symptoms include anxiety, depression and deficits in fear memory extinction (FE). PTSD patients show a higher prevalence of cigarette smoking than the general population. The present study investigated the effects of cotinine, a tobacco-derived compound, over anxiety and contextual fear memory after fear conditioning (FC) in mice, a model for inducing PTSD-like symptoms. Two-month-old C57BL/6J mice were separated into three experimental groups. These groups were used to investigate the effect of pretreatment with cotinine on contextual fear memory and posttreatment on extinction and stability or retrievability of the fear memory. Also, changes induced by cotinine on the expression of extracellular signal-regulated kinase (ERK)1/2 were assessed after extinction in the hippocampus. An increase in anxiety and corticosterone levels were found after fear conditioning. Cotinine did not affect corticosterone levels but enhanced the extinction of contextual fear, decreased anxiety and the stability and/or retrievability of contextual fear memory. Cotinine-treated mice showed higher levels of the active forms of ERK1/2 than vehicle-treated mice after FC. This evidence suggests that cotinine is a potential new pharmacological treatment to reduce symptoms in individuals with PTSD. Published by Elsevier B.V.
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Davies, M Frances; Tsui, Janet; Flannery, Judy A; Li, Xiangqi; DeLorey, Timothy M; Hoffman, Brian B
2004-02-01
alpha(2) adrenergic agonists such as dexmedetomidine generally suppress noradrenergic transmission and have sedative, analgesic, and antihypertensive properties. Considering the importance of the neurotransmitter norepinephrine in forming memories for fearful events, we have investigated the acute and chronic effects of dexmedetomidine on discrete cue and contextual fear conditioning in mice. When administered before training, dexmedetomidine (10-20 microg/kg, i.p.) selectively suppressed discrete cue fear conditioning without affecting contextual memory. This behavioral change was associated with a decrease in memory retrieval-induced expression of c-Fos and P-CREB in the lateral, basolateral, and central nuclei of the amygdala. Dexmedetomidine's action on discrete cue memory did not occur in alpha(2A) adrenoceptor knockout (KO) mice. When dexmedetomidine was administered after training, it suppressed contextual memory, an effect that did not occur in alpha(2A) adrenoceptor KO mice. We conclude that dexmedetomidine, acting at alpha(2A) adrenoceptors, must be present during the encoding process to decrease discrete cue fear memory; however, its ability to suppress contextual memory is likely the result of blocking the consolidation process. The ability of alpha(2) agonists to suppress fear memory may be a valuable property clinically in order to suppress the formation of memories during stressful situations.
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Poppenk, Jordan; Norman, Kenneth A.
2012-01-01
Recent cognitive research has revealed better source memory performance for familiar relative to novel stimuli. Here we consider two possible explanations for this finding. The source memory advantage for familiar stimuli could arise because stimulus novelty induces attention to stimulus features at the expense of contextual processing, resulting in diminished overall levels of contextual processing at study for novel (vs. familiar) stimuli. Another possibility is that stimulus information retrieved from long-term memory (LTM) provides scaffolding that facilitates the formation of item-context associations. If contextual features are indeed more effectively bound to familiar (vs. novel) items, the relationship between contextual processing at study and subsequent source memory should be stronger for familiar items. We tested these possibilities by applying multi-voxel pattern analysis (MVPA) to a recently collected functional magnetic resonance imaging (fMRI) dataset, with the goal of measuring contextual processing at study and relating it to subsequent source memory performance. Participants were scanned with fMRI while viewing novel proverbs, repeated proverbs (previously novel proverbs that were shown in a pre-study phase), and previously known proverbs in the context of one of two experimental tasks. After scanning was complete, we evaluated participants’ source memory for the task associated with each proverb. Drawing upon fMRI data from the study phase, we trained a classifier to detect on-task processing (i.e., how strongly was the correct task set activated). On-task processing was greater for previously known than novel proverbs and similar for repeated and novel proverbs. However, both within- and across participants, the relationship between on-task processing and subsequent source memory was stronger for repeated than novel proverbs and similar for previously known and novel proverbs. Finally, focusing on the repeated condition, we found that higher levels of hippocampal activity during the pre-study phase, which we used as an index of episodic encoding, led to a stronger relationship between on-task processing at study and subsequent memory. Together, these findings suggest different mechanisms may be primarily responsible for superior source memory for repeated and previously known stimuli. Specifically, they suggest that prior stimulus knowledge enhances memory by boosting the overall level of contextual processing, whereas stimulus repetition enhances the probability that contextual features will be successfully bound to item features. Several possible theoretical explanations for this pattern are discussed. PMID:22820636
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Emotion's influence on memory for spatial and temporal context.
Schmidt, Katherine; Patnaik, Pooja; Kensinger, Elizabeth A
2011-02-01
Individuals report remembering emotional items vividly. It is debated whether this report reflects enhanced memory accuracy or a bias to believe emotional memories are vivid. We hypothesized emotion would enhance memory accuracy, improving memory for contextual details. The hallmark of episodic memory is that items are remembered in a spatial and temporal context, so we examined whether an item's valence (positive, negative) or arousal (high, low) would influence its ability to be remembered with those contextual details. Across two experiments, high-arousal items were remembered with spatial and temporal context more often than low-arousal items. Item valence did not influence memory for those details, although positive high-arousal items were recognized or recalled more often than negative items. These data suggest that emotion does not just bias participants to believe they have a vivid memory; rather, the arousal elicited by an event can benefit memory for some types of contextual details. © 2010 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business
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Age-related changes in neural oscillations supporting context memory retrieval
Strunk, Jonathan; James, Taylor; Arndt, Jason; Duarte, Audrey
2018-01-01
Recent evidence suggests that directing attention toward single item-context associations during encoding improves young and older adults’ context memory performance and reduces demands on executive functions during retrieval. In everyday situations, there are many event features competing for our attention, and our ability to successfully recover those details may depend on our ability to ignore others. Failures of selective attention may contribute to older adults’ context memory impairments. In the current electroencephalogram (EEG) study, we assessed the effects of age on processes supporting successful context memory retrieval of selectively attended features as indexed by neural oscillations. During encoding, young and older adults were directed to attend to a picture of an object and its relationship to one of two concurrently presented contextual details: a color or scene. At retrieval, we tested their memory for the object, its attended and unattended context features, and their confidence for both the attended and unattended features. Both groups showed greater memory for attended than unattended contextual features. However, older adults showed evidence of hyper-binding between attended and unattended context features while the young adults did not. EEG results in the theta band suggest that young and older adults recollect similar amounts of information but brain-behavior correlations suggest that this information was supportive of contextual memory performance, particularly for young adults. By contrast, sustained beta desynchronization, indicative of sensory reactivation and episodic reconstruction, was correlated with contextual memory performance for older adults only. We conclude that older adults’ inhibition deficits during encoding reduced the selectivity of their contextual memories, which led to reliance on executive functions like episodic reconstruction to support successful memory retrieval. PMID:28237686
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Age-related changes in neural oscillations supporting context memory retrieval.
Strunk, Jonathan; James, Taylor; Arndt, Jason; Duarte, Audrey
2017-06-01
Recent evidence suggests that directing attention toward single item-context associations during encoding improves young and older adults' context memory performance and reduces demands on executive functions during retrieval. In everyday situations, there are many event features competing for our attention, and our ability to successfully recover those details may depend on our ability to ignore others. Failures of selective attention may contribute to older adults' context memory impairments. In the current electroencephalogram (EEG) study, we assessed the effects of age on processes supporting successful context memory retrieval of selectively attended features as indexed by neural oscillations. During encoding, young and older adults were directed to attend to a picture of an object and its relationship to one of two concurrently presented contextual details: a color or scene. At retrieval, we tested their memory for the object, its attended and unattended context features, and their confidence for both the attended and unattended features. Both groups showed greater memory for attended than unattended contextual features. However, older adults showed evidence of hyper-binding between attended and unattended context features while the young adults did not. EEG results in the theta band suggest that young and older adults recollect similar amounts of information but brain-behavior correlations suggest that this information was supportive of contextual memory performance, particularly for young adults. By contrast, sustained beta desynchronization, indicative of sensory reactivation and episodic reconstruction, was correlated with contextual memory performance for older adults only. We conclude that older adults' inhibition deficits during encoding reduced the selectivity of their contextual memories, which led to reliance on executive functions like episodic reconstruction to support successful memory retrieval. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Wang, Yunpeng; Zhang, Hongying; Cui, Jingjing; Zhang, Jing; Yin, Fangyuan; Guo, Hao; Lai, Jianghua; Xing, Bo
2018-04-17
Contextual memory driven by abused drugs such as opiates has a central role in maintenance and relapse of drug-taking behaviors. Although dopamine (DA) signaling favors memory storage and retrieval via regulation of hippocampal-prefrontal connectivity, its role in modulating opiate-associated contextual memory is largely unknown. Here, we report roles of DA signaling within the hippocampal-prefrontal circuit for opiate-related memories. Combining-conditioned place preference (CPP) with molecular analyses, we investigated the DA D1 receptor (D1R) and extracellular signal-regulated kinase (ERK)-cAMP-response element binding protein (CREB) signaling, as well as DA D2 receptor (D2R) and protein kinase B (PKB or Akt)/glycogen synthase kinase 3 (GSK3) signaling in the ventral hippocampus (vHip) and medial prefrontal cortex (mPFC) during the formation of opiate-related associative memories. Morphine-CPP acquisition increased the activity of the D1R-ERK-CREB pathway in both the vHip and mPFC. Morphine-CPP reinstatement was associated with the D2R-mediated hyperactive GSK3 via Akt inhibition in the vHip and PFC. Furthermore, integrated D1R-ERK-CREB and D2R-Akt-GSK3 pathways in the vHip-mPFC circuit are required for the acquisition and retrieval of the morphine contextual memory, respectively. Moreover, blockage of D1R or D2R signaling could alleviate normal Hip-dependent spatial memory. These results suggest that D1R and D2R signaling are differentially involved in the acquisition and retrieval of morphine contextual memory, and DA signaling in the vHip-mPFC connection contributes to morphine-associated and normal memory, largely depending on opiate exposure states.
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Gil, N; Josman, N
2001-08-01
The purpose of the present study was to examine the ability of the Contextual Memory Test (CMT) to differentiate between elderly people suffering from Alzheimer's disease (AD) in comparison to healthy elderly people. Specifically, the objectives were to compare for differences between and within the groups on components of memory, including immediate and delayed recall as well as recognition. In addition, parameters of metamemory skills, such as general awareness, self-prediction of memory capacity, self-estimation, strategy use and use of contextual information, as well as the correlation between self-awareness and actual performance in both groups, were investigated. The sample consisted of 60 elderly participants, including 30 people diagnosed with AD who were assigned to the research group and 30 people matched for age, gender and educational level who were assigned to the control group. The results provide support for the hypothesis positing differences in memory performance between healthy elderly participants and those suffering from AD, particularly in immediate and delayed recall as well as in recognition. Moreover, findings indicate an improvement in memory performance under the cued condition (contextual), whereas improvement in the AD group proved to be significant only for immediate recall. The findings point to a distinct overestimation of memory ability predicted by both the AD and control groups. Following the memory task, however, the participants accurately estimated the number of items they remembered. In addition, significant correlations between the use of contextual and association strategies and the number of items remembered by both groups were obtained, in immediate as well as in delayed recall. Therefore, these findings support the CMT as a valuable memory and metamemory assessment tool for use with the AD population.
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Hypobaric hypoxia impairs cued and contextual fear memory in rats.
Kumari, Punita; Kauser, Hina; Wadhwa, Meetu; Roy, Koustav; Alam, Shahnawaz; Sahu, Surajit; Kishore, Krishna; Ray, Koushik; Panjwani, Usha
2018-04-26
Fear memory is essential for survival, and its dysregulation leads to disorders. High altitude hypobaric hypoxia (HH) is known to induce cognitive decline. However, its effect on fear memory is still an enigma. We aimed to investigate the temporal effect of HH on fear conditioning and the underlying mechanism. Adult male Sprague-Dawley rats were trained for fear conditioning and exposed to simulated HH equivalent to 25,000 ft for different durations (1, 3, 7, 14 and 21 days). Subsequently, rats were tested for cued and contextual fear conditioning. Neuronal morphology, apoptosis and DNA fragmentation were studied in the medial prefrontal cortex (mPFC), hippocampus and basolateral amygdala (BLA). We observed significant deficit in cued and contextual fear acquisition (at 1, 3 and 7 days) and consolidation (cued at 1 and 3 days and contextual fear at 1, 3 and 7 days) under HH. HH exposure with retraining showed the earlier restoration of contextual fear memory. Further, we found a gradual increase in the number of pyknotic and apoptotic neurons together with the increase in DNA fragmentation in mPFC, hippocampus, and BLA up to 7 days of HH exposure. The present study concludes that HH exposure equivalent to 25000 ft induced cued and contextual fear memory deficit (acquisition and consolidation) which is found to be correlated with the neurodegenerative changes in the limbic brain regions. Copyright © 2018. Published by Elsevier B.V.
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Inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear.
Jiang, Lizhu; Mao, Rongrong; Tong, Jianbin; Li, Jinnan; Chai, Anping; Zhou, Qixin; Yang, Yuexiong; Wang, Liping; Li, Lingjiang; Xu, Lin
2016-10-01
Promoting extinction of fear memory is the main treatment of fear disorders, especially post-traumatic stress disorder (PTSD). However, fear extinction is often incomplete in these patients. Our previous study had shown that Rac1 activity in hippocampus plays a crucial role in the learning of contextual fear memory in rats. Here, we further investigated whether Rac1 activity also modulated the extinction of contextual fear memory. We found that massed extinction obviously upregulated hippocampal Rac1 activity and induced long-term extinction of contextual fear in rats. Intrahippocampal injection of the Rac1 inhibitor NSC23766 prevents extinction of contextual fear in massed extinction training rats. In contrast, long-spaced extinction downregulated Rac1 activity and caused less extinction. And Rac1 activator CN04-A promotes extinction of contextual fear in long-spaced extinction rats. Our study demonstrates that inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear, suggesting that modulating Rac1 activity of the hippocampus may be promising therapy of fear disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Fernandez Espejo, Emilio
2003-03-01
Prefrontal dopamine loss delays extinction of cued fear conditioning responses, but its role in contextual fear conditioning has not been explored. Medial prefrontal lesions also enhance social interaction in rats, but the role of prefrontal dopamine loss on social interaction memory is not known. Besides, a role for subcortical accumbal dopamine on mnesic changes after prefrontal dopamine manipulation has been proposed but not explored. The objective was to study the involvement of dopaminergic neurotransmission in the medial prefrontal cortex (mPFC) and nucleus accumbens in two mnesic tasks: contextual fear conditioning and social interaction memory. For contextual fear conditioning, short- and long-term freezing responses after an electric shock were studied, as well as extinction retention. Regarding social interaction memory, the recognition of a juvenile, a very sensitive short-term memory test, was used. Dopamine loss was carried out by injection of 6-hydroxydopamine, and postmortem catecholamine levels were analyzed by high-performance liquid chromatography. Prefrontocortical dopamine loss (>76%) led to a reactive enhancement of accumbal dopamine content (p<0.01), supporting the hypothesis that a hyperdopaminergic tone emerges in the nucleus accumbens after prefrontocortical dopamine loss. In lesioned rats, long-term extinction of contextual fear conditioning was significantly delayed and extinction retention was impaired without changes in acquisition and short-term contextual fear conditioning and, on the other hand, acquisition and short-term social interaction memory were not affected, although time spent on social interaction was significantly reduced. Added dopamine loss in the nucleus accumbens (>76%) did not alter these behavioral changes. In summary, the results of the present study indicate that the dopaminergic network in the mPFC (but not in the nucleus accumbens) coordinates the normal long-term extinction of contextual fear conditioning responses without affecting their acquisition, and it is involved in time spent on social interaction, but not acquisition and short-term social interaction memory.
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Pearson, David G
2012-12-01
Information processing accounts of post-traumatic stress disorder (PTSD) state that intrusive memories emerge due to a lack of integration between perceptual and contextual trauma representations in autobiographical memory. This hypothesis was tested experimentally using an analogue trauma paradigm in which participants viewed an aversive film designed to elicit involuntary recollections. Participants viewed scenes from the film either paired with contextual information or with the contextual information omitted. After viewing the film participants were asked to record for one week any involuntary intrusions for the film using a provided intrusions diary. The results revealed a significant increase in analogue intrusions for the film when viewed with contextual information in comparison to when the film was viewed with the contextual information omitted. In contrast there was no effect of contextual information on valence ratings or voluntary memory for the film, or on the reported vividness and emotionality of the intrusions. The analogue trauma paradigm may have failed to reproduce the effect of extreme stress on encoding that is postulated to occur during PTSD. The findings have potential implications for trauma intervention as they suggest that the contextual understanding of a scene during encoding can be integral to the subsequent occurrence of traumatic intrusions. The pattern of results found in the study are inconsistent with dual-representation accounts of intrusive memory formation, and instead provide new evidence that contextual representations play a casual role in increasing the frequency of involuntary intrusions for traumatic material. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Transfer of Old "Reactivated" Memory Retrieval Cues in Rats
ERIC Educational Resources Information Center
Briggs, James F.; Riccio, David C.
2008-01-01
The present studies examined whether the retrieval of an old "reactivated" memory could be brought under the control of new contextual cues. In Experiment 1 rats trained in one context were exposed to different contextual cues either immediately, 60 or 120 min after a cued reactivation of the training memory. When tested in the shifted context,…
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Mosaic expression of Atrx in the mouse central nervous system causes memory deficits
Tamming, Renee J.; Siu, Jennifer R.; Jiang, Yan; Prado, Marco A. M.; Beier, Frank
2017-01-01
ABSTRACT The rapid modulation of chromatin organization is thought to play a crucial role in cognitive processes such as memory consolidation. This is supported in part by the dysregulation of many chromatin-remodelling proteins in neurodevelopmental and psychiatric disorders. A key example is ATRX, an X-linked gene commonly mutated in individuals with syndromic and nonsyndromic intellectual disability. The consequences of Atrx inactivation for learning and memory have been difficult to evaluate because of the early lethality of hemizygous-null animals. In this study, we evaluated the outcome of brain-specific Atrx deletion in heterozygous female mice. These mice exhibit a mosaic pattern of ATRX protein expression in the central nervous system attributable to the location of the gene on the X chromosome. Although the hemizygous male mice die soon after birth, heterozygous females survive to adulthood. Body growth is stunted in these animals, and they have low circulating concentrations of insulin growth factor 1. In addition, they are impaired in spatial, contextual fear and novel object recognition memory. Our findings demonstrate that mosaic loss of ATRX expression in the central nervous system leads to endocrine defects and decreased body size and has a negative impact on learning and memory. PMID:28093507
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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 consolidation as well as persistence of conditioned fear memory. In addition, rats submitted to swimming exercise over six weeks showed an improved performance in the test of auditory-cued fear memory persistence, but not in the test of contextual fear memory persistence. Moreover, no significant effect from swimming exercise was observed on consolidation of both contextual and auditory fear memory. So, our study, revealing the effect of the swimming exercise on different stages of implicit memory of tone/foot shock conditioning, contributes to and complements the current knowledge about the environmental modulation of memory process. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Encoding of contextual fear memory requires de novo proteins in the prelimbic cortex
Rizzo, Valerio; Touzani, Khalid; Raveendra, Bindu L.; Swarnkar, Supriya; Lora, Joan; Kadakkuzha, Beena M.; Liu, Xin-An; Zhang, Chao; Betel, Doron; Stackman, Robert W.; Puthanveettil, Sathyanarayanan V.
2016-01-01
Background Despite our understanding of the significance of the prefrontal cortex in the consolidation of long-term memories (LTM), its role in the encoding of LTM remains elusive. Here we investigated the role of new protein synthesis in the mouse medial prefrontal cortex (mPFC) in encoding contextual fear memory. Methods Because a change in the association of mRNAs to polyribosomes is an indicator of new protein synthesis, we assessed the changes in polyribosome-associated mRNAs in the mPFC following contextual fear conditioning (CFC) in the mouse. Differential gene expression in mPFC was identified by polyribosome profiling (n = 18). The role of new protein synthesis in mPFC was determined by focal inhibition of protein synthesis (n = 131) and by intra-prelimbic cortex manipulation (n = 56) of Homer 3, a candidate identified from polyribosome profiling. Results We identified several mRNAs that are differentially and temporally recruited to polyribosomes in the mPFC following CFC. Inhibition of protein synthesis in the prelimbic (PL), but not in the anterior cingulate cortex (ACC) region of the mPFC immediately after CFC disrupted encoding of contextual fear memory. Intriguingly, inhibition of new protein synthesis in the PL 6 hours after CFC did not impair encoding. Furthermore, expression of Homer 3, an mRNA enriched in polyribosomes following CFC, in the PL constrained encoding of contextual fear memory. Conclusions Our studies identify several molecular substrates of new protein synthesis in the mPFC and establish that encoding of contextual fear memories require new protein synthesis in PL subregion of mPFC. PMID:28503670
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Kathirvelu, Balachandar; Colombo, Paul J
2013-11-01
Neural systems specialized for memory may interact during memory formation or recall, and the results of interactions are important determinants of how systems control behavioral output. In two experiments, we used lentivirus-mediated expression of the transcription factor CREB (LV-CREB) to test if localized manipulations of cellular plasticity influence interactions between the hippocampus and dorsolateral striatum. In Experiment 1, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for response learning, and impairs memory for place learning. LV-CREB in the dorsolateral striatum had no effect on response learning, but impaired place memory; a finding consistent with competition between the striatum and hippocampus. In Experiment 2, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for cue learning, and impairs memory for contextual fear conditioning. LV-CREB in the dorsolateral striatum enhanced memory for cue learning and, in contrast to our prediction, also enhanced memory for contextual fear conditioning, consistent with a cooperative interaction between the striatum and hippocampus. Overall, the current experiments demonstrate that infusion of LV-CREB in the dorsolateral striatum (1) increases levels of CREB protein locally, (2) does not alter acquisition of place, response, cue, or contextual fear conditioning, (3) facilitates memory for cue learning and contextual fear conditioning, and (4) impairs memory for place learning. Taken together, the present results provide evidence that LV-CREB in the dorsolateral striatum can enhance memory formation and cause both competitive and cooperative interactions with the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.
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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.
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El Haj, Mohamad; Kessels, Roy P C; Allain, Philippe
2016-01-01
Source memory is a core component of episodic recall as it allows for the reconstruction of contextual details characterizing the acquisition of episodic events. Unlike episodic memory, little is known about source memory rehabilitation. Our review addresses this issue by emphasizing several strategies as useful tools in source memory rehabilitation programs. Four main strategies are likely to improve source recall in amnesic patients-namely, (a) contextual cueing, (b) unitization, (c) errorless learning, and (d) executive function programs. The rationale behind our suggestion is that: (a) reinstating contextual cues during retrieval can serve as retrieval cues and enhance source memory; (b) unitization as an encoding process allows for the integration of several pieces of contextual information into a new single entity; (c) errorless learning may prevent patients from making errors during source learning; and (d) as source memory deteriorations have been classically attributed to executive dysfunction, the rehabilitation of the latter ability is likely to maintain the former ability. Besides these four strategies, our review suggests several additional rehabilitation techniques such as the vanishing cues and spaced retrieval methods. Another additional strategy is the use of electronic devices. By gathering these strategies, our review provides a helpful guideline for clinicians dealing with source memory impairments. Our review further highlights the lack of randomized and controlled studies in the field of source memory rehabilitation.
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Atsak, Piray; Hauer, Daniela; Campolongo, Patrizia; Schelling, Gustav; McGaugh, James L.; Roozendaal, Benno
2012-01-01
There is extensive evidence that glucocorticoid hormones impair the retrieval of memory of emotionally arousing experiences. Although it is known that glucocorticoid effects on memory retrieval impairment depend on rapid interactions with arousal-induced noradrenergic activity, the exact mechanism underlying this presumably nongenomically mediated glucocorticoid action remains to be elucidated. Here, we show that the hippocampal endocannabinoid system, a rapidly activated retrograde messenger system, is involved in mediating glucocorticoid effects on retrieval of contextual fear memory. Systemic administration of corticosterone (0.3–3 mg/kg) to male Sprague–Dawley rats 1 h before retention testing impaired the retrieval of contextual fear memory without impairing the retrieval of auditory fear memory or directly affecting the expression of freezing behavior. Importantly, a blockade of hippocampal CB1 receptors with AM251 prevented the impairing effect of corticosterone on retrieval of contextual fear memory, whereas the same impairing dose of corticosterone increased hippocampal levels of the endocannabinoid 2-arachidonoylglycerol. We also found that antagonism of hippocampal β-adrenoceptor activity with local infusions of propranolol blocked the memory retrieval impairment induced by the CB receptor agonist WIN55,212–2. Thus, these findings strongly suggest that the endocannabinoid system plays an intermediary role in regulating rapid glucocorticoid effects on noradrenergic activity in impairing memory retrieval of emotionally arousing experiences. PMID:22331883
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Phan, Trongha X; Phan, Trongha H; Chan, Guy C-K; Sindreu, Carlos B; Eckel-Mahan, Kristin L; Storm, Daniel R
2011-07-20
Consolidation of hippocampus-dependent memory is dependent on activation of the cAMP/Erk/MAPK (mitogen-activated protein kinase) signal transduction pathway in the hippocampus. Recently, we discovered that adenylyl cyclase and MAPK activities undergo a circadian oscillation in the hippocampus and that inhibition of this oscillation impairs contextual memory. This suggests the interesting possibility that the persistence of hippocampus-dependent memory depends upon the reactivation of MAPK in the hippocampus during the circadian cycle. A key unanswered question is whether the circadian oscillation of this signaling pathway is intrinsic to the hippocampus or is driven by the master circadian clock in the suprachiasmatic nucleus (SCN). To address this question, we ablated the SCN of mice by electrolytic lesion and examined hippocampus-dependent memory as well as adenylyl cyclase and MAPK activities. Electrolytic lesion of the SCN 2 d after training for contextual fear memory reduced contextual memory measured 2 weeks after training, indicating that maintenance of contextual memory depends on the SCN. Spatial memory was also compromised in SCN-lesioned mice. Furthermore, the diurnal oscillation of adenylyl cyclase and MAPK activities in the hippocampus was destroyed by lesioning of the SCN. These data suggest that hippocampus-dependent long-term memory is dependent on the SCN-controlled oscillation of the adenylyl cyclase/MAPK pathway in the hippocampus.
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Phan, Trongha; Chan, Guy; Sindreu, Carlos; Eckel-Mahan, Kristin; Storm, Daniel R.
2011-01-01
Consolidation of hippocampus dependent memory is dependent on activation of the cAMP/ Erk/MAPK signal transduction pathway in the hippocampus. Recently, we discovered that adenylyl cyclase and MAPK activities undergo a circadian oscillation in the hippocampus and that inhibition of this oscillation impairs contextual memory. This suggests the interesting possibility that the persistence of hippocampus-dependent memory depends upon the reactivation of MAPK in the hippocampus during the circadian cycle. A key unanswered question is whether the circadian oscillation of this signaling pathway is intrinsic to the hippocampus or is driven by the master circadian clock in the suprachiasmatic nucleus (SCN). To address this question, we ablated the SCN of mice by electrolytic lesion and examined hippocampus-dependent memory as well as adenylyl cyclase and MAPK activities. Electrolytic lesion of the SCN two days after training for contextual fear memory reduced contextual memory measured two weeks after training indicating that maintenance of contextual memory depends on the SCN. Spatial memory was also compromised in SCN-lesioned mice. Furthermore, the diurnal oscillation of adenylyl cyclase and MAPK activities in the hippocampus was destroyed by lesioning of the SCN. These data suggest that hippocampus-dependent long-term memory is dependent on the SCN-controlled oscillation of the adenylyl cyclase/MAPK pathway in the hippocampus. PMID:21775607
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Chen, Weihai; Yan, Minmin; Wang, Yan; Wang, Xiaqing; Yuan, Jiajin; Li, Ming
2016-10-01
Nitric oxide (NO) is an important retrograde neuronal intracellular messenger which plays an important role in synaptic plasticity and is involved in learning and memory. However, evidence that NO is particularly important for the acquisition of contextual fear conditioning is mixed. Also, little is known about at which stages of the contextual fear conditioning does NO make its contribution. In the present study, we used 7-nitroindazole to temporarily inhibit neural nitric oxide synthase at either the pre-exposure stage or conditioning stage in a two-process paradigm and examined the potential contribution that NO makes to the contextually conditioned fear. Results showed that the expression of contextual fear memory was significantly impaired in rats treated with 7-nitroindazole (30mg/kg, i.p.) prior to the pairing of context-shock (p=0.034, n=8), but not after the conditioning phase (p=0.846, n=8). In addition, the expression of contextual fear memory and reconsolidation was not significantly impaired by 7-nitroindazole administered prior to the context pre-exposure stage or prior to another context-shock learning. These findings suggest that NO is specifically involved in the acquisition but not the consolidation, retrieval or reconsolidation of contextual fear memory. Copyright © 2016 Elsevier Inc. All rights reserved.
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Beracochea, Daniel; Krazem, Ali; Henkouss, Nadia; Haccard, Guillaume; Roller, Marc; Fromentin, Emilie
2016-08-01
The number of Americans older than 65 years old is projected to more than double in the next 40 years. Cognitive changes associated to aging can affect an adult's day-to-day functioning. Among these cognitive changes, reasoning, episodic memory, working memory, and processing speed decline gradually over time. Early memory changes include a decline in both working and episodic memory. The aim of the present study was to determine whether chronic (up to 75 days) daily administration of wild blueberry extract or a wild blueberry full spectrum powder would help prevent memory failure associated with aging in tasks involving various forms of memory. Both blueberry ingredients were used in a study comparing young mice (6 months old) to aged mice (18 months old). At this age, mice exhibit memory decline due to aging, which is exacerbated first by a loss in working and contextual (episodic-like) memory. Contextual memory (episodic-like memory) was evaluated using the contextual serial discrimination test. Working and spatial memory were evaluated using the Morris-Water maze test and the sequential alternation test. Statistical analysis was performed using an ANOVA with the Bonferroni post-hoc test. Supplementation with wild blueberry full spectrum powder and wild blueberry extract resulted in significant improvement of contextual memory, while untreated aged mice experienced a decline in such memory. Only the wild blueberry full spectrum powder significantly contributed to an improvement of spatial and working memory versus untreated aged mice. These improvements of cognitive performance may be related to brain oxidative status, acetylcholinesterase activity, neuroprotection, or attenuation of immunoreactivity. Georg Thieme Verlag KG Stuttgart · New York.
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Temporal context and the organisational impairment of memory search in schizophrenia.
Polyn, Sean M; McCluey, Joshua D; Morton, Neal W; Woolard, Austin A; Luksik, Andrew S; Heckers, Stephan
2015-01-01
An influential theory of schizophrenic deficits in executive function suggests that patients have difficulty maintaining and utilising an internal contextual representation, whose function is to ensure that stimuli are processed in a task-appropriate manner. In basic research on episodic memory, retrieved-context theories propose that an internal contextual representation is critically involved in memory search, facilitating the retrieval of task-appropriate memories. This contextual machinery is thought to give rise to temporal organisation during free recall: the tendency for successive recall responses to correspond to items from nearby positions on the study list. If patients with schizophrenia have a generalised contextual deficit, then this leads to the prediction that these patients will exhibit reduced temporal organisation in free recall. Using a combination of classic and recently developed organisational measures, we characterised recall organisation in 75 patients with schizophrenia and 72 nondisordered control participants performing a multi-trial free-recall task. Patients with schizophrenia showed diminished temporal organisation, as well as diminished subjective organisation of their recall sequences relative to control participants. The two groups showed similar amounts of semantic organisation during recall. The observation of reduced temporal organisation in the patient group is consistent with the proposal that the memory deficit in schizophrenia can be characterised as a deficit in contextual processing.
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ERIC Educational Resources Information Center
Ball, B. Hunter; DeWitt, Michael R.; Knight, Justin B.; Hicks, Jason L.
2014-01-01
The current study sought to examine the relative contributions of encoding and retrieval processes in accessing contextual information in the absence of item memory using an extralist cuing procedure in which the retrieval cues used to query memory for contextual information were "related" to the target item but never actually studied.…
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ERIC Educational Resources Information Center
Einarsson, Einar O.; Nader, Karim
2012-01-01
It has been suggested that memories become more stable and less susceptible to the disruption of reconsolidation over weeks after learning. Here, we test this by targeting the anterior cingulate cortex (ACC) and test its involvement in the formation, consolidation, and reconsolidation of recent and remote contextual fear memory. We found that…
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Sol Fustiñana, María; de la Fuente, Verónica; Federman, Noel; Freudenthal, Ramiro
2014-01-01
The ubiquitin–proteasome system (UPS) of protein degradation has been evaluated in different forms of neural plasticity and memory. The role of UPS in such processes is controversial. Several results support the idea that the activation of this system in memory consolidation is necessary to overcome negative constrains for plasticity. In this case, the inhibition of the UPS during consolidation impairs memory. Similar results were reported for memory reconsolidation. However, in other cases, the inhibition of UPS had no effect on memory consolidation and reconsolidation but impedes the amnesic action of protein synthesis inhibition after retrieval. The last finding suggests a specific action of the UPS inhibitor on memory labilization. However, another interpretation is possible in terms of the synthesis/degradation balance of positive and negative elements in neural plasticity, as was found in the case of long-term potentiation. To evaluate these alternative interpretations, other reconsolidation-interfering drugs than translation inhibitors should be tested. Here we analyzed initially the UPS inhibitor effect in contextual conditioning in crabs. We found that UPS inhibition during consolidation impaired long-term memory. In contrast, UPS inhibition did not affect memory reconsolidation after contextual retrieval but, in fact, impeded memory labilization, blocking the action of drugs that does not affect directly the protein synthesis. To extend these finding to vertebrates, we performed similar experiments in contextual fear memory in mice. We found that the UPS inhibitor in hippocampus affected memory consolidation and blocked memory labilization after retrieval. These findings exclude alternative interpretations to the requirement of UPS in memory labilization and give evidence of this mechanism in both vertebrates and invertebrates. PMID:25135196
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Poppenk, Jordan; Norman, Kenneth A
2012-11-01
Recent cognitive research has revealed better source memory performance for familiar relative to novel stimuli. Here we consider two possible explanations for this finding. The source memory advantage for familiar stimuli could arise because stimulus novelty induces attention to stimulus features at the expense of contextual processing, resulting in diminished overall levels of contextual processing at study for novel (vs. familiar) stimuli. Another possibility is that stimulus information retrieved from long-term memory (LTM) provides scaffolding that facilitates the formation of item-context associations. If contextual features are indeed more effectively bound to familiar (vs. novel) items, the relationship between contextual processing at study and subsequent source memory should be stronger for familiar items. We tested these possibilities by applying multi-voxel pattern analysis (MVPA) to a recently collected functional magnetic resonance imaging (fMRI) dataset, with the goal of measuring contextual processing at study and relating it to subsequent source memory performance. Participants were scanned with fMRI while viewing novel proverbs, repeated proverbs (previously novel proverbs that were shown in a pre-study phase), and previously known proverbs in the context of one of two experimental tasks. After scanning was complete, we evaluated participants' source memory for the task associated with each proverb. Drawing upon fMRI data from the study phase, we trained a classifier to detect on-task processing (i.e., how strongly was the correct task set activated). On-task processing was greater for previously known than novel proverbs and similar for repeated and novel proverbs. However, both within and across participants, the relationship between on-task processing and subsequent source memory was stronger for repeated than novel proverbs and similar for previously known and novel proverbs. Finally, focusing on the repeated condition, we found that higher levels of hippocampal activity during the pre-study phase, which we used as an index of episodic encoding, led to a stronger relationship between on-task processing at study and subsequent memory. Together, these findings suggest different mechanisms may be primarily responsible for superior source memory for repeated and previously known stimuli. Specifically, they suggest that prior stimulus knowledge enhances memory by boosting the overall level of contextual processing, whereas stimulus repetition enhances the probability that contextual features will be successfully bound to item features. Several possible theoretical explanations for this pattern are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Kugelman, Tara; Zuloaga, Damian G; Weber, Sydney; Raber, Jacob
2016-02-01
The brain might be exposed to irradiation under a variety of situations, including clinical treatments, nuclear accidents, dirty bomb scenarios, and military and space missions. Correctly recalling tasks learned prior to irradiation is important but little is known about post-learning effects of irradiation. It is not clear whether exposure to X-ray irradiation during memory consolidation, a few hours following training, is associated with altered contextual fear conditioning 24h after irradiation and which brain region(s) might be involved in these effects. Brain immunoreactivity patterns of the immediately early gene c-Fos, a marker of cellular activity was used to determine which brain areas might be altered in post-training irradiation memory retention tasks. In this study, we show that post-training gamma irradiation exposure (1 Gy) enhanced contextual fear memory 24h later and is associated with reduced cellular activation in the infralimbic cortex. Reduced GABA-ergic neurotransmission in parvalbumin-positive cells in the infralimbic cortex might play a role in this post-training radiation-enhanced contextual fear memory. Copyright © 2015 Elsevier B.V. All rights reserved.
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Kugelman, Tara; Zuloaga, Damian G.; Weber, Sydney; Raber, Jacob
2015-01-01
The brain might be exposed to irradiation under a variety of situations, including clinical treatments, nuclear accidents, dirty bomb scenarios, and military and space missions. Correctly recalling tasks learned prior to irradiation is important but little is known about post-learning effects of irradiation. It is not clear whether exposure to X-ray irradiation during memory consolidation, a few hours following training, is associated with altered contextual fear conditioning 24 hours after irradiation and which brain region(s) might be involved in these effects. Brain immunoreactivity patterns of the immediately early gene c-Fos, a marker of cellular activity was used to determine which brain areas might be altered in post-training irradiation memory retention tasks. In this study, we show that post-training gamma irradiation exposure (1 Gy) enhanced contextual fear memory 24 hours later and is associated with reduced cellular activation in the infralimbic cortex. Reduced GABA-ergic neurotransmission in parvalbumin-positive cells in the infralimbic cortex might play a role in this post-training radiation-enhanced contextual fear memory. PMID:26522840
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Taherian, Fatemeh; Vafaei, Abbas Ali; Vaezi, Gholam Hassan; Eskandarian, Sharaf; Kashef, Adel; Rashidy-Pour, Ali
2014-01-01
Introduction Previous studies have demonstrated that the β-adrenergic receptor antagonist propranolol impairs fear memory reconsolidation in experimental animals. There are experimental parameters such as the age and the strength of memory that can interact with pharmacological manipulations of memory reconsolidation. In this study, we investigated the ability of the age and the strength of memory to influence the disrupting effects of propranolol on fear memory reconsolidation in rats. Methods The rats were trained in a contextual fear conditioning using two (weak training) or five (strong training) footshocks (1mA). Propranolol (10mg/kg) injection was immediately followed retrieval of either a one-day recent (weak or strong) or 36-day remote (weak or strong) contextual fear memories. Results We found that propranolol induced a long-lasting impairment of subsequent expression of recent and remote memories with either weak or strong strength. We also found no memory recovery after a weak reminder shock. Furthermore, no significant differences were found on the amount of memory deficit induced by propranolol among memories with different age and strength. Discussion Our data suggest that the efficacy of propranolol in impairing fear memory reconsolidation is not limited to the age or strength of the memory. PMID:25337385
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The Role Of Basal Forebrain Cholinergic Neurons In Fear and Extinction Memory
Knox, Dayan
2016-01-01
Cholinergic input to the neocortex, dorsal hippocampus (dHipp), and basolateral amygdala (BLA) is critical for neural function and synaptic plasticity in these brain regions. Synaptic plasticity in the neocortex, dHipp, ventral Hipp (vHipp), and BLA has also been implicated in fear and extinction memory. This finding raises the possibility that basal forebrain (BF) cholinergic neurons, the predominant source of acetylcholine in these brain regions, have an important role in mediating fear and extinction memory. While empirical studies support this hypothesis, there are interesting inconsistencies among these studies that raise questions about how best to define the role of BF cholinergic neurons in fear and extinction memory. Nucleus basalis magnocellularis (NBM) cholinergic neurons that project to the BLA are critical for fear memory and contextual fear extinction memory. NBM cholinergic neurons that project to the neocortex are critical for cued and contextual fear conditioned suppression, but are not critical for fear memory in other behavioral paradigms and in the inhibitory avoidance paradigm may even inhibit contextual fear memory formation. Medial septum and diagonal band of Broca cholinergic neurons are critical for contextual fear memory and acquisition of cued fear extinction. Thus, even though the results of previous studies suggest BF cholinergic neurons modulate fear and extinction memory, inconsistent findings among these studies necessitates more research to better define the neural circuits and molecular processes through which BF cholinergic neurons modulate fear and extinction memory. Furthermore, studies determining if BF cholinergic neurons can be manipulated in such a manner so as to treat excessive fear in anxiety disorders are needed. PMID:27264248
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Manenti, Rosa; Sandrini, Marco; Gobbi, Elena; Cobelli, Chiara; Brambilla, Michela; Binetti, Giuliano; Cotelli, Maria
2017-01-01
Episodic memory is critical to daily life functioning. This type of declarative memory declines with age and is the earliest cognitive function to be compromised in Alzheimer’s disease (AD). Subjective memory complaints are commonly reported by older adults and have been considered a risk factor for developing AD. The possibilities for prevention of memory disorders in older adults have increased substantially in recent years. Previous studies have shown that anodal transcranial Direct Current Stimulation (tDCS) applied over the left lateral prefrontal cortex (PFC) after a contextual reminder strengthened existing verbal episodic memories, conceivably through reconsolidation, in elderly people. In this study, we hypothesized that anodal tDCS applied over the left lateral PFC after a contextual reminder would improve delayed memory retrieval relative to placebo (sham) stimulation in elderly individuals with SMC. Twenty-two subjects learned a list of words. Twenty-four hour later, tDCS (anodal or placebo) was applied over the left lateral PFC after a contextual reminder. Memory retrieval was tested 48h and 30 days later. These findings showed that anodal tDCS over the left lateral PFC strengthened existing episodic memories, a behavioral effect documented by improved recognition up to 30 days, relative to placebo stimulation. This study suggests that tDCS after a contextual reminder can induce long-lasting beneficial effects by facilitating the consolidation processes and opens up the possibility to design specific non-invasive interventions aimed at preventing memory decline in this at-risk population. PMID:29259554
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Nasehi, Mohammad; Soltanpour, Reyhaneh; Ebrahimi-Ghiri, Mohaddeseh; Zarrabian, Shahram; Zarrindast, Mohammad-Reza
2017-11-01
The effects of pharmacological interventions on fear memory have widely been studied, but there are very few studies about the effects of brain electrical stimulation on fear memory function. Therefore, our aim was to determine whether anodal/cathodal transcranial direct current stimulation (tDCS) over the right frontal cortex would modify propranolol-induced contextual and auditory fear memory deficits, before or after training. The adult NMRI male mice were randomly assigned into three groups: the sham group, the anodal tDCS group, and the cathodal tDCS group. Fear memories were evaluated using a classical fear conditioning apparatus. While the anodal stimulation did not affect fear retrieval, post-training cathodal stimulation improved fear memory retrieval. Regardless of when propranolol (0.1 mg/kg) was administered, it impaired fear memory retrieval. However, when anodal stimulation and propranolol were applied prior to the training, contextual fear memory retrieval was increased and auditory fear memory was reversed. An enhanced contextual retrieval was also observed when propranolol was administered prior to the training and stimulation occurred after the training. Only when the stimulation occurred prior to the training and propranolol was administered after the training was there a selective improvement in contextual fear memory retrieval, leaving the auditory fear memory retrieval impaired. Interestingly, cathodal stimulation improved the effects of propranolol on auditory fear memory only when it occurred prior to the training. The results highlight possible improving effects for anodal/cathodal tDCS on propranolol-induced deficits on fear memories. The timing of the interventions related to the specific phases of memory formation is important in modulating fear behaviors.
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Contextual cuing: the effects of stimulus variation, intentionality, and aging.
Lyon, John; Scialfa, Charles; Cordazzo, Scheila; Bubric, Katherine
2014-06-01
Three experiments investigated the generalisation of contextual cuing and whether the effect is incidental or intentional in nature. Experiment 1 assessed contextual cuing across variations in display contrast, homogeneity, and spatial separation. Cuing effects were found with all display types and reaction-time disruption was manifested for repeated displays when consistent configurations had their target locations altered. Recognition memory for repeated displays was at chance levels. Experiment 2 showed that contextual cuing was insensitive to instructions to search for and remember repeated displays. Experiment 2A found that there were no age differences in contextual cuing or effects of intentional instructions, and no memory for repeated displays. Future research questions concern the generalisation of contextual cuing to a wider variety of display conditions and naturalistic tasks.
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Kasper, Ryan W; Grafton, Scott T; Eckstein, Miguel P; Giesbrecht, Barry
2015-03-01
Visual search can be facilitated by the learning of spatial configurations that predict the location of a target among distractors. Neuropsychological and functional magnetic resonance imaging (fMRI) evidence implicates the medial temporal lobe (MTL) memory system in this contextual cueing effect, and electroencephalography (EEG) studies have identified the involvement of visual cortical regions related to attention. This work investigated two questions: (1) how memory and attention systems are related in contextual cueing; and (2) how these systems are involved in both short- and long-term contextual learning. In one session, EEG and fMRI data were acquired simultaneously in a contextual cueing task. In a second session conducted 1 week later, EEG data were recorded in isolation. The fMRI results revealed MTL contextual modulations that were correlated with short- and long-term behavioral context enhancements and attention-related effects measured with EEG. An fMRI-seeded EEG source analysis revealed that the MTL contributed the most variance to the variability in the attention enhancements measured with EEG. These results support the notion that memory and attention systems interact to facilitate search when spatial context is implicitly learned. © 2015 New York Academy of Sciences.
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Vlachos, Ioannis; Herry, Cyril; Lüthi, Andreas; Aertsen, Ad; Kumar, Arvind
2011-01-01
The basal nucleus of the amygdala (BA) is involved in the formation of context-dependent conditioned fear and extinction memories. To understand the underlying neural mechanisms we developed a large-scale neuron network model of the BA, composed of excitatory and inhibitory leaky-integrate-and-fire neurons. Excitatory BA neurons received conditioned stimulus (CS)-related input from the adjacent lateral nucleus (LA) and contextual input from the hippocampus or medial prefrontal cortex (mPFC). We implemented a plasticity mechanism according to which CS and contextual synapses were potentiated if CS and contextual inputs temporally coincided on the afferents of the excitatory neurons. Our simulations revealed a differential recruitment of two distinct subpopulations of BA neurons during conditioning and extinction, mimicking the activation of experimentally observed cell populations. We propose that these two subgroups encode contextual specificity of fear and extinction memories, respectively. Mutual competition between them, mediated by feedback inhibition and driven by contextual inputs, regulates the activity in the central amygdala (CEA) thereby controlling amygdala output and fear behavior. The model makes multiple testable predictions that may advance our understanding of fear and extinction memories. PMID:21437238
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Transfer of Old ‘Reactivated’ Memory Retrieval Cues in Rats
Briggs, James F.; Riccio, David C.
2008-01-01
The present studies examined whether the retrieval of an old ‘reactivated’ memory could be brought under the control of new contextual cues. In Experiment 1 rats trained in one context were exposed to different contextual cues either immediately, 60 min, or 120 min after a cued reactivation of the training memory. When tested in the shifted context, subjects exposed shortly after reactivation treated the shifted context as the original context. This transfer diminished with longer post-reactivation delays. Experiment 2 replicated the basic finding and demonstrated that the transfer of the old retrieval cues was specific to the contextual cues present during exposure. These findings are consistent with previous research (i.e., Briggs, Fitz, & Riccio, in press) showing the transfer of retrieval cues for a new memory, and demonstrating a similarity (in this case) between newly acquired and old reactivated memories. PMID:19190707
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Choi, Koeun; Kirkorian, Heather L; Pempek, Tiffany A
2017-04-17
Researchers tested the impact of contextual mismatch, proactive interference, and working memory (WM) on toddlers' transfer across contexts. Forty-two toddlers (27-34 months) completed four object-retrieval trials, requiring memory updating on Trials 2-4. Participants watched hiding events on a tablet computer. Search performance was tested using another tablet (match) or a felt board (mismatch). WM was assessed. On earlier search trials, WM predicted transfer in both conditions, and toddlers in the match condition outperformed those in the mismatch condition; however, the benefit of contextual match and WM decreased over trials. Contextual match apparently increased proactive interference on later trials. Findings are interpreted within existing accounts of the transfer deficit, and a combined account is proposed. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.
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Riaz, Sadia; Schumacher, Anett; Sivagurunathan, Seyon; Van Der Meer, Matthijs; Ito, Rutsuko
2017-07-01
The hippocampus (HPC) has been widely implicated in the contextual control of appetitive and aversive conditioning. However, whole hippocampal lesions do not invariably impair all forms of contextual processing, as in the case of complex biconditional context discrimination, leading to contention over the exact nature of the contribution of the HPC in contextual processing. Moreover, the increasingly well-established functional dissociation between the dorsal (dHPC) and ventral (vHPC) subregions of the HPC has been largely overlooked in the existing literature on hippocampal-based contextual memory processing in appetitively motivated tasks. Thus, the present study sought to investigate the individual roles of the dHPC and the vHPC in contextual biconditional discrimination (CBD) performance and memory retrieval. To this end, we examined the effects of transient post-acquisition pharmacological inactivation (using a combination of GABA A and GABA B receptor agonists muscimol and baclofen) of functionally distinct subregions of the HPC (CA1/CA3 subfields of the dHPC and vHPC) on CBD memory retrieval. Additional behavioral assays including novelty preference, light-dark box and locomotor activity test were also performed to confirm that the respective sites of inactivation were functionally silent. We observed robust deficits in CBD performance and memory retrieval following inactivation of the vHPC, but not the dHPC. Our data provides novel insight into the differential roles of the ventral and dorsal HPC in reward contextual processing, under conditions in which the context is defined by proximal cues. © 2017 Wiley Periodicals, Inc.
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Kutlu, Munir Gunes; Garrett, Brendan; Gadiwalla, Sana; Tumolo, Jessica M; Gould, Thomas J
2017-11-01
Previous research has shown that acute nicotine, an agonist of nAChRs, impaired fear extinction. However, the effects of acute nicotine on consolidation of contextual fear extinction memories and associated cell signaling cascades are unknown. Therefore, we examined the effects of acute nicotine injections before (pre-extinction) and after (post-extinction) contextual fear extinction on behavior and the phosphorylation of dorsal and ventral hippocampal ERK1/2 and JNK1 and protein levels on the 1st and 3rd day of extinction. Our results showed that acute nicotine administered prior to extinction sessions downregulated the phosphorylated forms of ERK1/2 in the ventral hippocampus, but not dorsal hippocampus, and JNK1 in both dorsal and ventral hippocampus on the 3rd extinction day. These effects were absent on the 1st day of extinction. We also showed that acute nicotine administered immediately and 30 min, but not 6 h, following extinction impaired contextual fear extinction suggesting that acute nicotine disrupts consolidation of contextual fear extinction memories. Finally, acute nicotine injections immediately after extinction sessions upregulated the phosphorylated forms of ERK1/2 in the ventral hippocampus, but did not affect JNK1. These results show that acute nicotine impairs contextual fear extinction potentially by altering molecular processes responsible for the consolidation of extinction memories. Copyright © 2017 Elsevier Inc. All rights reserved.
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Vetere, Gisella; Restivo, Leonardo; Cole, Christina J.; Ross, P. Joel; Ammassari-Teule, Martine; Josselyn, Sheena A.; Frankland, Paul W.
2011-01-01
Remodeling of cortical connectivity is thought to allow initially hippocampus-dependent memories to be expressed independently of the hippocampus at remote time points. Consistent with this, consolidation of a contextual fear memory is associated with dendritic spine growth in neurons of the anterior cingulate cortex (aCC). To directly test whether such cortical structural remodeling is necessary for memory consolidation, we disrupted spine growth in the aCC at different times following contextual fear conditioning in mice. We took advantage of previous studies showing that the transcription factor myocyte enhancer factor 2 (MEF2) negatively regulates spinogenesis both in vitro and in vivo. We found that increasing MEF2-dependent transcription in the aCC during a critical posttraining window (but not at later time points) blocked both the consolidation-associated dendritic spine growth and subsequent memory expression. Together, these data strengthen the causal link between cortical structural remodeling and memory consolidation and, further, identify MEF2 as a key regulator of these processes. PMID:21531906
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Bos, Marieke G N; Jacobs van Goethem, Tessa H; Beckers, Tom; Kindt, Merel
2014-12-01
Retrieval of traumatic experiences is often accompanied by strong feelings of distress. Here, we examined in healthy participants whether post-reactivation stress experience affects the context-dependency of emotional memory. First, participants studied words from two distinctive emotional categories (i.e., war and disease) presented against a category-related background picture. One day later, participants returned to the lab and received a reminder of the words of one emotional category followed by exposure to a stress task (Stress group, n=22) or a control task (Control group, n=24). Six days later, memory contextualization was tested using a word stem completion task. Half of the word stems were presented against the encoding context (i.e., congruent context) and the other half of the word stems were presented against the other context (i.e., incongruent context). The results showed that participants recalled more words in the congruent context than in the incongruent context. Interestingly, cortisol mediated the effect of stress exposure on memory contextualization. The stronger the post-reactivation cortisol response, the more memory performance relied on the contextual embedding of the words. Taken together, the current findings suggest that a moderate cortisol response after memory reactivation might serve an adaptive function in preventing generalization of emotional memories over contexts. Copyright © 2014 Elsevier Ltd. All rights reserved.
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The role of basal forebrain cholinergic neurons in fear and extinction memory.
Knox, Dayan
2016-09-01
Cholinergic input to the neocortex, dorsal hippocampus (dHipp), and basolateral amygdala (BLA) is critical for neural function and synaptic plasticity in these brain regions. Synaptic plasticity in the neocortex, dHipp, ventral Hipp (vHipp), and BLA has also been implicated in fear and extinction memory. This finding raises the possibility that basal forebrain (BF) cholinergic neurons, the predominant source of acetylcholine in these brain regions, have an important role in mediating fear and extinction memory. While empirical studies support this hypothesis, there are interesting inconsistencies among these studies that raise questions about how best to define the role of BF cholinergic neurons in fear and extinction memory. Nucleus basalis magnocellularis (NBM) cholinergic neurons that project to the BLA are critical for fear memory and contextual fear extinction memory. NBM cholinergic neurons that project to the neocortex are critical for cued and contextual fear conditioned suppression, but are not critical for fear memory in other behavioral paradigms and in the inhibitory avoidance paradigm may even inhibit contextual fear memory formation. Medial septum and diagonal band of Broca cholinergic neurons are critical for contextual fear memory and acquisition of cued fear extinction. Thus, even though the results of previous studies suggest BF cholinergic neurons modulate fear and extinction memory, inconsistent findings among these studies necessitates more research to better define the neural circuits and molecular processes through which BF cholinergic neurons modulate fear and extinction memory. Furthermore, studies determining if BF cholinergic neurons can be manipulated in such a manner so as to treat excessive fear in anxiety disorders are needed. Copyright © 2016 Elsevier Inc. All rights reserved.
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Rapid, experience-dependent translation of neurogranin enables memory encoding.
Jones, Kendrick J; Templet, Sebastian; Zemoura, Khaled; Kuzniewska, Bozena; Pena, Franciso X; Hwang, Hongik; Lei, Ding J; Haensgen, Henny; Nguyen, Shannon; Saenz, Christopher; Lewis, Michael; Dziembowska, Magdalena; Xu, Weifeng
2018-06-19
Experience induces de novo protein synthesis in the brain and protein synthesis is required for long-term memory. It is important to define the critical temporal window of protein synthesis and identify newly synthesized proteins required for memory formation. Using a behavioral paradigm that temporally separates the contextual exposure from the association with fear, we found that protein synthesis during the transient window of context exposure is required for contextual memory formation. Among an array of putative activity-dependent translational neuronal targets tested, we identified one candidate, a schizophrenia-associated candidate mRNA, neurogranin (Ng, encoded by the Nrgn gene) responding to novel-context exposure. The Ng mRNA was recruited to the actively translating mRNA pool upon novel-context exposure, and its protein levels were rapidly increased in the hippocampus. By specifically blocking activity-dependent translation of Ng using virus-mediated molecular perturbation, we show that experience-dependent translation of Ng in the hippocampus is required for contextual memory formation. We further interrogated the molecular mechanism underlying the experience-dependent translation of Ng, and found that fragile-X mental retardation protein (FMRP) interacts with the 3'UTR of the Nrgn mRNA and is required for activity-dependent translation of Ng in the synaptic compartment and contextual memory formation. Our results reveal that FMRP-mediated, experience-dependent, rapid enhancement of Ng translation in the hippocampus during the memory acquisition enables durable context memory encoding. Copyright © 2018 the Author(s). Published by PNAS.
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Rapid, experience-dependent translation of neurogranin enables memory encoding
Jones, Kendrick J.; Templet, Sebastian; Zemoura, Khaled; Pena, Franciso X.; Hwang, Hongik; Lei, Ding J.; Haensgen, Henny; Nguyen, Shannon; Saenz, Christopher; Lewis, Michael; Dziembowska, Magdalena
2018-01-01
Experience induces de novo protein synthesis in the brain and protein synthesis is required for long-term memory. It is important to define the critical temporal window of protein synthesis and identify newly synthesized proteins required for memory formation. Using a behavioral paradigm that temporally separates the contextual exposure from the association with fear, we found that protein synthesis during the transient window of context exposure is required for contextual memory formation. Among an array of putative activity-dependent translational neuronal targets tested, we identified one candidate, a schizophrenia-associated candidate mRNA, neurogranin (Ng, encoded by the Nrgn gene) responding to novel-context exposure. The Ng mRNA was recruited to the actively translating mRNA pool upon novel-context exposure, and its protein levels were rapidly increased in the hippocampus. By specifically blocking activity-dependent translation of Ng using virus-mediated molecular perturbation, we show that experience-dependent translation of Ng in the hippocampus is required for contextual memory formation. We further interrogated the molecular mechanism underlying the experience-dependent translation of Ng, and found that fragile-X mental retardation protein (FMRP) interacts with the 3′UTR of the Nrgn mRNA and is required for activity-dependent translation of Ng in the synaptic compartment and contextual memory formation. Our results reveal that FMRP-mediated, experience-dependent, rapid enhancement of Ng translation in the hippocampus during the memory acquisition enables durable context memory encoding. PMID:29880715
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How Does Intentionality of Encoding Affect Memory for Episodic Information?
ERIC Educational Resources Information Center
Craig, Michael; Butterworth, Karla; Nilsson, Jonna; Hamilton, Colin J.; Gallagher, Peter; Smulders, Tom V.
2016-01-01
Episodic memory enables the detailed and vivid recall of past events, including target and wider contextual information. In this paper, we investigated whether/how encoding intentionality affects the retention of target and contextual episodic information from a novel experience. Healthy adults performed (1) a "What-Where-When"…
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Modulation of cannabinoid signaling by amygdala α2-adrenergic system in fear conditioning.
Nasehi, Mohammad; Zamanparvar, Majid; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza
2016-03-01
The noradrenergic system plays a critical role in the modulation of emotional state, primarily related to anxiety, arousal, and stress. Growing evidence suggests that the endocannabinoid system mediates stress responses and emotional homeostasis, in part, by targeting noradrenergic circuits. In addition, there is an interaction between the cannabinoid and noradrenergic system that has significant functional and behavioral implications. Considering the importance of these systems in forming memories for fearful events, we have investigated the involvement of basolateral amygdala (BLA) α2-adrenoceptors on ACPA (as selective cannabinoid CB1 agonist)-induced inhibition of the acquisition of contextual and auditory conditioned fear. A contextual and auditory fear conditioning apparatus for assess fear memory in adult male NMRI mice was used. Pre-training, intraperitoneal administration of ACPA decreased the percentage freezing time in contextual (at doses of 0.05 and 0.1mg/kg) and auditory (at dose of 0.1 mg/kg) in the fear conditioning task, indicating memory acquisition deficit. The same result was observed with intra-BLA microinjection of clonidine (0.001-0.5 μg/mouse, for both memories), as α2-adrenoceptor agonist and yohimbine (at doses of 0.005 and 0.05 for contextual and at dose of 0.05 μg/mouse for auditory fear memory), as α2-adrenoceptor antagonist. In addition, intra-BLA microinjection of clonidine (0.0005 μg/mouse) did not alter ACPA response in both conditions, while the same dose of yohimbine potentiated ACPA response at the lower dose on contextual fear memory. It is concluded that BLA α2-adrenergic receptors may be involved in context- but not tone-dependent fear memory impairment induced by activation of CB1 receptors. Copyright © 2015. Published by Elsevier B.V.
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Chen, Yan-Chu; Ma, Yun-Li; Lin, Cheng-Hsiung; Cheng, Sin-Jhong; Hsu, Wei-Lun; Lee, Eminy H.-Y.
2017-01-01
Galectin-3, a member of the galectin protein family, has been found to regulate cell proliferation, inhibit apoptosis and promote inflammatory responses. Galectin-3 is also expressed in the adult rat hippocampus, but its role in learning and memory function is not known. Here, we found that contextual fear-conditioning training, spatial training or injection of NMDA into the rat CA1 area each dramatically decreased the level of endogenous galectin-3 expression. Overexpression of galectin-3 impaired fear memory, whereas galectin-3 knockout (KO) enhanced fear retention, spatial memory and hippocampal long-term potentiation. Galectin-3 was further found to associate with integrin α3, an association that was decreased after fear-conditioning training. Transfection of the rat CA1 area with small interfering RNA against galectin-3 facilitated fear memory and increased phosphorylated focal adhesion kinase (FAK) levels, effects that were blocked by co-transfection of the FAK phosphorylation-defective mutant Flag-FAKY397F. Notably, levels of serine-phosphorylated galectin-3 were decreased by fear conditioning training. In addition, blockade of galectin-3 phosphorylation at Ser-6 facilitated fear memory, whereas constitutive activation of galectin-3 at Ser-6 impaired fear memory. Interestingly galectin-1 plays a role in fear-memory formation similar to that of galectin-3. Collectively, our data provide the first demonstration that galectin-3 is a novel negative regulator of memory formation that exerts its effects through both extracellular and intracellular mechanisms. PMID:28744198
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Mosaic expression of Atrx in the mouse central nervous system causes memory deficits.
Tamming, Renee J; Siu, Jennifer R; Jiang, Yan; Prado, Marco A M; Beier, Frank; Bérubé, Nathalie G
2017-02-01
The rapid modulation of chromatin organization is thought to play a crucial role in cognitive processes such as memory consolidation. This is supported in part by the dysregulation of many chromatin-remodelling proteins in neurodevelopmental and psychiatric disorders. A key example is ATRX, an X-linked gene commonly mutated in individuals with syndromic and nonsyndromic intellectual disability. The consequences of Atrx inactivation for learning and memory have been difficult to evaluate because of the early lethality of hemizygous-null animals. In this study, we evaluated the outcome of brain-specific Atrx deletion in heterozygous female mice. These mice exhibit a mosaic pattern of ATRX protein expression in the central nervous system attributable to the location of the gene on the X chromosome. Although the hemizygous male mice die soon after birth, heterozygous females survive to adulthood. Body growth is stunted in these animals, and they have low circulating concentrations of insulin growth factor 1. In addition, they are impaired in spatial, contextual fear and novel object recognition memory. Our findings demonstrate that mosaic loss of ATRX expression in the central nervous system leads to endocrine defects and decreased body size and has a negative impact on learning and memory. © 2017. Published by The Company of Biologists Ltd.
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Contextual knowledge reduces demands on working memory during reading.
Miller, Lisa M Soederberg; Cohen, Jason A; Wingfield, Arthur
2006-09-01
An experiment is reported in which young, middle-aged, and older adults read and recalled ambiguous texts either with or without the topic title that supplied contextual knowledge. Within each of the age groups, the participants were divided into those with high or low working memory (WM) spans, with available WM capacity further manipulated by the presence or absence of an auditory target detection task concurrent with the reading task. Differences in reading efficiency (reading time per proposition recalled) between low WM span and high WM span groups were greater among readers who had access to contextual knowledge relative to those who did not, suggesting that contextual knowledge reduces demands on WM capacity. This position was further supported by the finding that increased age and attentional demands, two factors associated with reduced WM capacity, exaggerated the benefits of contextual knowledge on reading efficiency. The relative strengths of additional potential predictors of reading efficiency (e.g., interest, effort, and memory beliefs), along with knowledge, WM span, and age, are reported. Findings showed that contextual knowledge was the strongest predictor of reading efficiency even after controlling for the effects of all of the other predictors.
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Bar, Moshe; Aminoff, Elissa; Schacter, Daniel L.
2009-01-01
The parahippocampal cortex (PHC) has been implicated both in episodic memory and in place/scene processing. We proposed that this region should instead be seen as intrinsically mediating contextual associations, and not place/scene processing or episodic memory exclusively. Given that place/scene processing and episodic memory both rely on associations, this modified framework provides a platform for reconciling what seemed like different roles assigned to the same region. Comparing scenes with scenes, we show here that the PHC responds significantly more strongly to scenes with rich contextual associations compared with scenes of equal visual qualities but less associations. This result provides the strongest support to the view that the PHC mediates contextual associations in general, rather than places or scenes proper, and necessitates a revision of current views such as that the PHC contains a dedicated place/scenes “module.” PMID:18716212
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Patai, Eva Zita; Buckley, Alice; Nobre, Anna Christina
2013-01-01
A popular model of visual perception states that coarse information (carried by low spatial frequencies) along the dorsal stream is rapidly transmitted to prefrontal and medial temporal areas, activating contextual information from memory, which can in turn constrain detailed input carried by high spatial frequencies arriving at a slower rate along the ventral visual stream, thus facilitating the processing of ambiguous visual stimuli. We were interested in testing whether this model contributes to memory-guided orienting of attention. In particular, we asked whether global, low-spatial frequency (LSF) inputs play a dominant role in triggering contextual memories in order to facilitate the processing of the upcoming target stimulus. We explored this question over four experiments. The first experiment replicated the LSF advantage reported in perceptual discrimination tasks by showing that participants were faster and more accurate at matching a low spatial frequency version of a scene, compared to a high spatial frequency version, to its original counterpart in a forced-choice task. The subsequent three experiments tested the relative contributions of low versus high spatial frequencies during memory-guided covert spatial attention orienting tasks. Replicating the effects of memory-guided attention, pre-exposure to scenes associated with specific spatial memories for target locations (memory cues) led to higher perceptual discrimination and faster response times to identify targets embedded in the scenes. However, either high or low spatial frequency cues were equally effective; LSF signals did not selectively or preferentially contribute to the memory-driven attention benefits to performance. Our results challenge a generalized model that LSFs activate contextual memories, which in turn bias attention and facilitate perception.
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Patai, Eva Zita; Buckley, Alice; Nobre, Anna Christina
2013-01-01
A popular model of visual perception states that coarse information (carried by low spatial frequencies) along the dorsal stream is rapidly transmitted to prefrontal and medial temporal areas, activating contextual information from memory, which can in turn constrain detailed input carried by high spatial frequencies arriving at a slower rate along the ventral visual stream, thus facilitating the processing of ambiguous visual stimuli. We were interested in testing whether this model contributes to memory-guided orienting of attention. In particular, we asked whether global, low-spatial frequency (LSF) inputs play a dominant role in triggering contextual memories in order to facilitate the processing of the upcoming target stimulus. We explored this question over four experiments. The first experiment replicated the LSF advantage reported in perceptual discrimination tasks by showing that participants were faster and more accurate at matching a low spatial frequency version of a scene, compared to a high spatial frequency version, to its original counterpart in a forced-choice task. The subsequent three experiments tested the relative contributions of low versus high spatial frequencies during memory-guided covert spatial attention orienting tasks. Replicating the effects of memory-guided attention, pre-exposure to scenes associated with specific spatial memories for target locations (memory cues) led to higher perceptual discrimination and faster response times to identify targets embedded in the scenes. However, either high or low spatial frequency cues were equally effective; LSF signals did not selectively or preferentially contribute to the memory-driven attention benefits to performance. Our results challenge a generalized model that LSFs activate contextual memories, which in turn bias attention and facilitate perception. PMID:23776509
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Contextual cueing: implicit learning and memory of visual context guides spatial attention.
Chun, M M; Jiang, Y
1998-06-01
Global context plays an important, but poorly understood, role in visual tasks. This study demonstrates that a robust memory for visual context exists to guide spatial attention. Global context was operationalized as the spatial layout of objects in visual search displays. Half of the configurations were repeated across blocks throughout the entire session, and targets appeared within consistent locations in these arrays. Targets appearing in learned configurations were detected more quickly. This newly discovered form of search facilitation is termed contextual cueing. Contextual cueing is driven by incidentally learned associations between spatial configurations (context) and target locations. This benefit was obtained despite chance performance for recognizing the configurations, suggesting that the memory for context was implicit. The results show how implicit learning and memory of visual context can guide spatial attention towards task-relevant aspects of a scene.
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Gruenenfelder, Thomas M; Recchia, Gabriel; Rubin, Tim; Jones, Michael N
2016-08-01
We compared the ability of three different contextual models of lexical semantic memory (BEAGLE, Latent Semantic Analysis, and the Topic model) and of a simple associative model (POC) to predict the properties of semantic networks derived from word association norms. None of the semantic models were able to accurately predict all of the network properties. All three contextual models over-predicted clustering in the norms, whereas the associative model under-predicted clustering. Only a hybrid model that assumed that some of the responses were based on a contextual model and others on an associative network (POC) successfully predicted all of the network properties and predicted a word's top five associates as well as or better than the better of the two constituent models. The results suggest that participants switch between a contextual representation and an associative network when generating free associations. We discuss the role that each of these representations may play in lexical semantic memory. Concordant with recent multicomponent theories of semantic memory, the associative network may encode coordinate relations between concepts (e.g., the relation between pea and bean, or between sparrow and robin), and contextual representations may be used to process information about more abstract concepts. Copyright © 2015 Cognitive Science Society, Inc.
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Repeated Recall and PKM? Maintain Fear Memories in Juvenile Rats
ERIC Educational Resources Information Center
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…
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ERIC Educational Resources Information Center
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…
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Sauvage, M; Brabet, P; Holsboer, F; Bockaert, J; Steckler, T
2000-12-08
Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor subtype 1 (PAC1) have been suggested to play a role in the modulation of learning and memory. However, behavioral evidence for altered mnemonic function due to altered PAC1 activity is missing. Therefore, the role of PAC1 in learning and memory was studied in mouse mutants lacking this receptor (PAC1 knock-out mice), tested in water maze two-choice spatial discrimination, one-trial contextual and cued fear conditioning, and multiple-session contextual discrimination. Water maze spatial discrimination was unaffected in PAC1 mutants, while a mild deficit was observed in multiple session contextual discrimination in PAC1 knock-out mice. Furthermore, PAC1 knock-out mice were able to learn the association between context and shock in one-trial contextual conditioning, but showed faster return to baseline than wild-type mice. Thus, the effects of PAC1 knock-out on modulating performance in these tasks were subtle and suggest that PAC1 only plays a limited role in learning and memory.
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Chang, Shih-Dar; Liang, K C
2017-02-01
Contextual fear conditioning involves forming a representation for the context and associating it with a shock, which were attributed by the prevailing view to functions of the hippocampus and amygdala, respectively. Yet our recent evidence suggested that both processes require integrity of the dorsal hippocampus (DH). In view of the DH involvement in uniting multiple stimuli into a configuration, this study examined whether the DH would integrate context and shock into a shocked-context representation. Male Wistar rats were trained on a two-phase training paradigm of contextual fear conditioning. They explored a novel context on the first day to acquire a contextual representation, and received a shock in that context on the second day to form the context-shock memory. Tests of conditioned freezing given on the following days revealed two properties of configural memory-direct and mediated pattern completion: First, the contextual fear memory was retrieved in a novel context by a cue embedded in the configural set-a shock that did not elicit significant freezing on its own. Second, freezing was also elicited in a novel context by a transportation chamber that was not directly paired with the shock but could activate the fear memory inferentially. The effects were specific to the cue and not due to context generalization. Infusion of lidocaine into the DH, but not the amygdala, immediately after context-shock training impaired conditioned freezing elicited through either type of pattern completion. Our data suggest that the DH in contextual fear conditioning associates context and shock in parallel with the amygdala by incorporating the shock into an otherwise neutral context representation and turning it into a shocked-context representation. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Disruption of hippocampal CA3 network: effects on episodic-like memory processing in C57BL/6J mice.
Daumas, Stéphanie; Halley, Hélène; Lassalle, Jean-Michel
2004-07-01
Lesion studies have demonstrated the prominent role of the hippocampus in spatial and contextual learning. To better understand how contextual information is processed in the CA3 region during learning, we focused on the CA3 autoassociative network hypothesis. We took advantage of a particularity of the mossy fibre (MF) synapses, i.e. their high zinc concentration, to reversibly disrupt the afferent MF pathway by microinfusions of an intracellular (DEDTC) or an extracellular (CaEDTA) zinc chelator into the CA3 area of the dorsal hippocampus of mice. Disruption of the CA3 network significantly impaired the acquisition and the consolidation of contextual fear conditioning, whereas contextual retrieval was unaffected. These results also suggest a heterogeneity between the cognitive processes underlying spatial and contextual memory that might be linked to the specific involvement of free zinc in contextual information processing.
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Effects of normal aging on memory for multiple contextual features.
Gagnon, Sylvain; Soulard, Kathleen; Brasgold, Melissa; Kreller, Joshua
2007-08-01
Twenty-four younger (18-35 years) and 24 older adult participants (65 or older) were exposed to three experimental conditions involving the memorization words and their associated contextual features, with contextual feature complexity increasing from Conditions 1 to 3. In Condition 1, words presented varied only on one binary feature (color, size, or character), while in Conditions 2 and 3, words presented varied on two and three binary features, respectively. Each condition was carried out as follows: (1) learning of a word list; (2) encoding of words and their contextual features; (3) delay; and (4) memory for contextual features through a discrimination task. Results indicated that young adults discriminated more features than older adults on all conditions. In both age groups, contextual feature discrimination accuracy decreased as the number of features increased. Moreover, older adults demonstrated near floor performance when tested with two or more binary features. We conclude that increasing context complexity strains attentional resources.
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Graham, Bronwyn M; Richardson, Rick
2010-06-01
Fibroblast growth factor-2 (FGF2) is a potent neurotrophic factor that is involved in brain development and the formation of long-term memory. It has recently been shown that acute FGF2, administered at the time of learning, enhances long-term memory for contextual fear conditioning as well as extinction of conditioned fear in developing rats. As other research has shown that administering FGF2 on the first day of life leads to long-term morphological changes in the hippocampus, in the present study we investigated whether early life exposure to FGF2 affects contextual fear conditioning, and renewal following extinction, later in life. Experiment 1 demonstrated that a single injection of FGF2 on Postnatal Day (PND) 1 did not lead to any detectable changes in contextual fear conditioning in PND 16 or PND 23 rats. Experiments 2 and 3 demonstrated that 5 days of injections of FGF2 (from PND 1-5) facilitated contextual fear conditioning in PND 16 and PND 23 rats. Experiment 4 demonstrated that the observed facilitation of memory was not due to FGF2 increasing rats' sensitivity to foot shock. Experiment 5 showed that early life exposure to FGF2 did not affect learning about a discrete conditioned stimulus, but did allow PND 16 rats to use contextual information in more complex ways, leading to context-dependent extinction of conditioned fear. These results further implicate FGF2 as a critical signal involved in the development of learning and memory.
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Sparks, Fraser T.; Lehmann, Hugo; Hernandez, Khadaryna; Sutherland, Robert J.
2011-01-01
Damage to the hippocampus (HPC) using the excitotoxin N-methyl-D-aspartate (NMDA) can cause retrograde amnesia for contextual fear memory. This amnesia is typically attributed to loss of cells in the HPC. However, NMDA is also known to cause intense neuronal discharge (seizure activity) during the hours that follow its injection. These seizures may have detrimental effects on retrieval of memories. Here we evaluate the possibility that retrograde amnesia is due to NMDA-induced seizure activity or cell damage per se. To assess the effects of NMDA induced activity on contextual memory, we developed a lesion technique that utilizes the neurotoxic effects of NMDA while at the same time suppressing possible associated seizure activity. NMDA and tetrodotoxin (TTX), a sodium channel blocker, are simultaneously infused into the rat HPC, resulting in extensive bilateral damage to the HPC. TTX, co-infused with NMDA, suppresses propagation of seizure activity. Rats received pairings of a novel context with foot shock, after which they received NMDA-induced, TTX+NMDA-induced, or no damage to the HPC at a recent (24 hours) or remote (5 weeks) time point. After recovery, the rats were placed into the shock context and freezing was scored as an index of fear memory. Rats with an intact HPC exhibited robust memory for the aversive context at both time points, whereas rats that received NMDA or NMDA+TTX lesions showed a significant reduction in learned fear of equal magnitude at both the recent and remote time points. Therefore, it is unlikely that observed retrograde amnesia in contextual fear conditioning are due to disruption of non-HPC networks by propagated seizure activity. Moreover, the memory deficit observed at both time points offers additional evidence supporting the proposition that the HPC has a continuing role in maintaining contextual memories. PMID:22110648
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Sexual behavior modulates contextual fear memory through dopamine D1/D5 receptors.
Bai, Hua-Yi; Cao, Jun; Liu, Na; Xu, Lin; Luo, Jian-Hong
2009-03-01
Traumatic events always lead to aversive emotional memory, i.e., fear memory. In contrast, positive events in daily life such as sex experiences seem to reduce aversive memory after aversive events. Thus, we hypothesized that post-traumatic pleasurable experiences, especially instinctive behaviors such as sex, might modulate traumatic memory through a memory competition mechanism. Here, we first report that male rats persistently expressed much lower fear responses when exposed to females, but not when exposed to males, for 24 h immediately after contextual fear conditioning. Remarkably, this effect of sexual behavior was blocked by either systemic or intrahippocampal injection of the dopamine D1/D5 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) and was mimicked by systemic but not intrahippocampal injection of the D1/D5 receptor agonist R(+)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol hydrochloride (SKF39393). Furthermore, as a candidate mechanism underlying contextual fear memory, the impaired induction of hippocampal long-term potentiation (LTP) elicited by conditioned fear was rescued in male rats immediately exposed to female but not male rats for 24 h. Systemic injection of the dopamine D1/D5 receptor antagonist SCH23390 or agonist SKF38393 prevented or mimicked the effect of sexual behavior on the impaired induction of hippocampal LTP. Thus, our finding suggests that dopaminergic functions may, at least partially, govern competition between contextual fear and enjoyable memories through the modulation of hippocampal LTP.
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A shared neural ensemble links distinct contextual memories encoded close in time
NASA Astrophysics Data System (ADS)
Cai, Denise J.; Aharoni, Daniel; Shuman, Tristan; Shobe, Justin; Biane, Jeremy; Song, Weilin; Wei, Brandon; Veshkini, Michael; La-Vu, Mimi; Lou, Jerry; Flores, Sergio E.; Kim, Isaac; Sano, Yoshitake; Zhou, Miou; Baumgaertel, Karsten; Lavi, Ayal; Kamata, Masakazu; Tuszynski, Mark; Mayford, Mark; Golshani, Peyman; Silva, Alcino J.
2016-06-01
Recent studies suggest that a shared neural ensemble may link distinct memories encoded close in time. According to the memory allocation hypothesis, learning triggers a temporary increase in neuronal excitability that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Here we show in mice that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week. Several findings indicate that this overlap of neuronal ensembles links two contextual memories. First, fear paired with one context is transferred to a neutral context when the two contexts are acquired within a day but not across a week. Second, the first memory strengthens the second memory within a day but not across a week. Older mice, known to have lower CA1 excitability, do not show the overlap between ensembles, the transfer of fear between contexts, or the strengthening of the second memory. Finally, in aged mice, increasing cellular excitability and activating a common ensemble of CA1 neurons during two distinct context exposures rescued the deficit in linking memories. Taken together, these findings demonstrate that contextual memories encoded close in time are linked by directing storage into overlapping ensembles. Alteration of these processes by ageing could affect the temporal structure of memories, thus impairing efficient recall of related information.
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A new mouse model of ARX dup24 recapitulates the patients' behavioral and fine motor alterations.
Dubos, Aline; Meziane, Hamid; Iacono, Giovanni; Curie, Aurore; Riet, Fabrice; Martin, Christelle; Loaëc, Nadège; Birling, Marie-Christine; Selloum, Mohammed; Normand, Elisabeth; Pavlovic, Guillaume; Sorg, Tania; Stunnenberg, Henk G; Chelly, Jamel; Humeau, Yann; Friocourt, Gaëlle; Hérault, Yann
2018-06-15
The aristaless-related homeobox (ARX) transcription factor is involved in the development of GABAergic and cholinergic neurons in the forebrain. ARX mutations have been associated with a wide spectrum of neurodevelopmental disorders in humans, among which the most frequent, a 24 bp duplication in the polyalanine tract 2 (c.428_451dup24), gives rise to intellectual disability, fine motor defects with or without epilepsy. To understand the functional consequences of this mutation, we generated a partially humanized mouse model carrying the c.428_451dup24 duplication (Arxdup24/0) that we characterized at the behavior, neurological and molecular level. Arxdup24/0 males presented with hyperactivity, enhanced stereotypies and altered contextual fear memory. In addition, Arxdup24/0 males had fine motor defects with alteration of reaching and grasping abilities. Transcriptome analysis of Arxdup24/0 forebrains at E15.5 showed a down-regulation of genes specific to interneurons and an up-regulation of genes normally not expressed in this cell type, suggesting abnormal interneuron development. Accordingly, interneuron migration was altered in the cortex and striatum between E15.5 and P0 with consequences in adults, illustrated by the defect in the inhibitory/excitatory balance in Arxdup24/0 basolateral amygdala. Altogether, we showed that the c.428_451dup24 mutation disrupts Arx function with a direct consequence on interneuron development, leading to hyperactivity and defects in precise motor movement control and associative memory. Interestingly, we highlighted striking similarities between the mouse phenotype and a cohort of 33 male patients with ARX c.428_451dup24, suggesting that this new mutant mouse line is a good model for understanding the pathophysiology and evaluation of treatment.
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A new mouse model of ARX dup24 recapitulates the patients’ behavioral and fine motor alterations
Dubos, Aline; Meziane, Hamid; Iacono, Giovanni; Curie, Aurore; Riet, Fabrice; Martin, Christelle; Loaëc, Nadège; Birling, Marie-Christine; Selloum, Mohammed; Normand, Elisabeth; Pavlovic, Guillaume; Sorg, Tania; Stunnenberg, Henk G; Chelly, Jamel; Humeau, Yann; Friocourt, Gaëlle; Hérault, Yann
2018-01-01
Abstract The aristaless-related homeobox (ARX) transcription factor is involved in the development of GABAergic and cholinergic neurons in the forebrain. ARX mutations have been associated with a wide spectrum of neurodevelopmental disorders in humans, among which the most frequent, a 24 bp duplication in the polyalanine tract 2 (c.428_451dup24), gives rise to intellectual disability, fine motor defects with or without epilepsy. To understand the functional consequences of this mutation, we generated a partially humanized mouse model carrying the c.428_451dup24 duplication (Arxdup24/0) that we characterized at the behavior, neurological and molecular level. Arxdup24/0 males presented with hyperactivity, enhanced stereotypies and altered contextual fear memory. In addition, Arxdup24/0 males had fine motor defects with alteration of reaching and grasping abilities. Transcriptome analysis of Arxdup24/0 forebrains at E15.5 showed a down-regulation of genes specific to interneurons and an up-regulation of genes normally not expressed in this cell type, suggesting abnormal interneuron development. Accordingly, interneuron migration was altered in the cortex and striatum between E15.5 and P0 with consequences in adults, illustrated by the defect in the inhibitory/excitatory balance in Arxdup24/0 basolateral amygdala. Altogether, we showed that the c.428_451dup24 mutation disrupts Arx function with a direct consequence on interneuron development, leading to hyperactivity and defects in precise motor movement control and associative memory. Interestingly, we highlighted striking similarities between the mouse phenotype and a cohort of 33 male patients with ARX c.428_451dup24, suggesting that this new mutant mouse line is a good model for understanding the pathophysiology and evaluation of treatment. PMID:29659809
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Kanatsou, Sofia; Ter Horst, Judith P.; Harris, Anjanette P.; Seckl, Jonathan R.; Krugers, Harmen J.; Joëls, Marian
2016-01-01
Early-life stress (ELS) is a risk factor for the development of psychopathology, particularly in women. Human studies have shown that certain haplotypes of NR3C2, encoding the mineralocorticoid receptor (MR), that result in gain of function, may protect against the consequences of stress exposure, including childhood trauma. Here, we tested the hypothesis that forebrain-specific overexpression of MR in female mice would ameliorate the effects of ELS on anxiety and memory in adulthood. We found that ELS increased anxiety, did not alter spatial discrimination and reduced contextual fear memory in adult female mice. Transgenic overexpression of MR did not alter anxiety but affected spatial memory performance and enhanced contextual fear memory formation. The effects of ELS on anxiety and contextual fear were not affected by transgenic overexpression of MR. Thus, MR overexpression in the forebrain does not represent a major resilience factor to early life adversity in female mice. PMID:26858618
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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.
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Cullen, Patrick K; Gilman, T Lee; Winiecki, Patrick; Riccio, David C; Jasnow, Aaron M
2015-10-01
Memories for context become less specific with time resulting in animals generalizing fear from training contexts to novel contexts. Though much attention has been given to the neural structures that underlie the long-term consolidation of a context fear memory, very little is known about the mechanisms responsible for the increase in fear generalization that occurs as the memory ages. Here, we examine the neural pattern of activation underlying the expression of a generalized context fear memory in male C57BL/6J mice. Animals were context fear conditioned and tested for fear in either the training context or a novel context at recent and remote time points. Animals were sacrificed and fluorescent in situ hybridization was performed to assay neural activation. Our results demonstrate activity of the prelimbic, infralimbic, and anterior cingulate (ACC) cortices as well as the ventral hippocampus (vHPC) underlie expression of a generalized fear memory. To verify the involvement of the ACC and vHPC in the expression of a generalized fear memory, animals were context fear conditioned and infused with 4% lidocaine into the ACC, dHPC, or vHPC prior to retrieval to temporarily inactivate these structures. The results demonstrate that activity of the ACC and vHPC is required for the expression of a generalized fear memory, as inactivation of these regions returned the memory to a contextually precise form. Current theories of time-dependent generalization of contextual memories do not predict involvement of the vHPC. Our data suggest a novel role of this region in generalized memory, which should be incorporated into current theories of time-dependent memory generalization. We also show that the dorsal hippocampus plays a prolonged role in contextually precise memories. Our findings suggest a possible interaction between the ACC and vHPC controls the expression of fear generalization. Copyright © 2015 Elsevier Inc. All rights reserved.
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On the transition from reconsolidation to extinction of contextual fear memories
Flavell, Charlotte R.; Lee, Jonathan L.C.
2017-01-01
Retrieval of an associative memory can lead to different phenomena. Brief reexposure sessions tend to trigger reconsolidation, whereas more extended ones trigger extinction. In appetitive and fear cued Pavlovian memories, an intermediate “null point” period has been observed where neither process seems to be engaged. Here we investigated whether this phenomenon extends to contextual fear memory. Adult rats were subjected to a contextual fear conditioning paradigm, reexposed to the context 2 d later for 3, 5, 10, 20, or 30 min, with immediate injections of MK-801 or saline following reexposure, and tested on the following day. We observed a significant effect of MK-801 with the 3- and 30-min sessions, impairing reconsolidation and extinction, respectively. However, it did not have significant effects with 5-, 10-, or 20-min sessions, even though freezing decreased from reexposure to test. Further analyses indicated that this is not likely to be due to a variable transition point at the population level. In conclusion, the results show that in contextual fear memories there is a genuine “null point” between the parameters that induce reconsolidation and extinction, as defined by the effects of MK-801, although NMDA receptor-independent decreases in freezing can still occur in these conditions. PMID:28814464
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Selective inhibition of miR-92 in hippocampal neurons alters contextual fear memory.
Vetere, Gisella; Barbato, Christian; Pezzola, Silvia; Frisone, Paola; Aceti, Massimiliano; Ciotti, MariaTeresa; Cogoni, Carlo; Ammassari-Teule, Martine; Ruberti, Francesca
2014-12-01
Post-transcriptional gene regulation mediated by microRNAs (miRNAs) is implicated in memory formation; however, the function of miR-92 in this regulation is uncharacterized. The present study shows that training mice in contextual fear conditioning produces a transient increase in miR-92 levels in the hippocampus and decreases several miR-92 gene targets, including: (i) the neuronal Cl(-) extruding K(+) Cl(-) co-transporter 2 (KCC2) protein; (ii) the cytoplasmic polyadenylation protein (CPEB3), an RNA-binding protein regulator of protein synthesis in neurons; and (iii) the transcription factor myocyte enhancer factor 2D (MEF2D), one of the MEF2 genes which negatively regulates memory-induced structural plasticity. Selective inhibition of endogenous miR-92 in CA1 hippocampal neurons, by a sponge lentiviral vector expressing multiple sequences imperfectly complementary to mature miR-92 under the control of the neuronal specific synapsin promoter, leads to up-regulation of KCC2, CPEB3 and MEF2D, impairs contextual fear conditioning, and prevents a memory-induced increase in the spine density. Taken together, the results indicate that neuronal-expressed miR-92 is an endogenous fine regulator of contextual fear memory in mice. © 2014 Wiley Periodicals, Inc.
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The Influence of Contextual Change on Remembering in Short-Term Memory. Final Report.
ERIC Educational Resources Information Center
Falkenberg, Philippe R.
If the contextual similarity between learning and recall within a single trial in a short-term memory (STM) paradigm is varied, recall varies proportionately. This context effect was demonstrated using variations of the Peterson-Peterson (1959) paradigm for both aurally and visually presented material, verbal and arithmetic context, and within and…
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The Role of Working Memory and Contextual Constraints in Children's Processing of Relative Clauses
ERIC Educational Resources Information Center
Wieghall, Anna R.; Altmann, Gerry T. M.
2011-01-01
An auditory sentence comprehension task investigated the extent to which the integration of contextual and structural cues was mediated by verbal memory span with 32 English-speaking six- to eight-year-old children. Spoken relative clause sentences were accompanied by visual context pictures which fully (depicting the actions described within the…
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ERIC Educational Resources Information Center
Sharot, Tali; Yonelinas, Andrew P.
2008-01-01
Emotion has been suggested to slow forgetting via a mechanism that enhances memory consolidation. Here, we investigate whether this time dependent process influences the subjective experience of recollection as well as the ability to retrieve specific contextual details of the study event. To do so we examined recognition for emotional and neutral…
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Rimmele, Ulrike; Davachi, Lila; Petrov, Radoslav; Dougal, Sonya; Phelps, Elizabeth A.
2013-01-01
Emotion strengthens the subjective experience of recollection. However, these vivid and confidently remembered emotional memories may not necessarily be more accurate. We investigated whether the subjective sense of recollection for negative stimuli is coupled with enhanced memory accuracy for contextual details using the remember/know paradigm. Our results indicate a double-dissociation between the subjective feeling of remembering, and the objective memory accuracy for details of negative and neutral scenes. “Remember” judgments were boosted for negative relative to neutral scenes. In contrast, memory for contextual details and associative binding was worse for negative compared to neutral scenes given a “remember” response. These findings show that the enhanced subjective recollective experience for negative stimuli does not reliably indicate greater objective recollection, at least of the details tested, and thus may be driven by a different mechanism than the subjective recollective experience for neutral stimuli. PMID:21668106
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People, clothing, music, and arousal as contextual retrieval cues in verbal memory.
Standing, Lionel G; Bobbitt, Kristin E; Boisvert, Kathryn L; Dayholos, Kathy N; Gagnon, Anne M
2008-10-01
Four experiments (N = 164) on context-dependent memory were performed to explore the effects on verbal memory of incidental cues during the test session which replicated specific features of the learning session. These features involved (1) bystanders, (2) the clothing of the experimenter, (3) background music, and (4) the arousal level of the subject. Social contextual cues (bystanders or experimenter clothing) improved verbal recall or recognition. However, recall decreased when the contextual cue was a different stimulus taken from the same conceptual category (piano music by Chopin) that was heard during learning. Memory was unaffected by congruent internal cues, produced by the same physiological arousal level (low, moderate, or high heart rate) during the learning and test sessions. However, recall increased with the level of arousal across the three congruent conditions. The results emphasize the effectiveness as retrieval cues of stimuli which are socially salient, concrete, and external.
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Revest, J-M; Le Roux, A; Roullot-Lacarrière, V; Kaouane, N; Vallée, M; Kasanetz, F; Rougé-Pont, F; Tronche, F; Desmedt, A; Piazza, P V
2014-01-01
Activation of glucocorticoid receptors (GR) by glucocorticoid hormones (GC) enhances contextual fear memories through the activation of the Erk1/2MAPK signaling pathway. However, the molecular mechanism mediating this effect of GC remains unknown. Here we used complementary molecular and behavioral approaches in mice and rats and in genetically modified mice in which the GR was conditionally deleted (GRNesCre). We identified the tPA-BDNF-TrkB signaling pathway as the upstream molecular effectors of GR-mediated phosphorylation of Erk1/2MAPK responsible for the enhancement of contextual fear memory. These findings complete our knowledge of the molecular cascade through which GC enhance contextual fear memory and highlight the role of tPA-BDNF-TrkB-Erk1/2MAPK signaling pathways as one of the core effectors of stress-related effects of GC. PMID:24126929
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Social Relevance Enhances Memory for Impressions in Older Adults
Cassidy, Brittany S.; Gutchess, Angela H.
2012-01-01
Previous research has demonstrated that older adults have difficulty retrieving contextual material over items alone. Recent research suggests this deficit can be reduced by adding emotional context, allowing for the possibility that memory for social impressions may show less age-related decline than memory for other types of contextual information. Two studies investigated how orienting to social or self-relevant aspects of information contributed to the learning and retrieval of impressions in young and older adults. Participants encoded impressions of others in conditions varying in the use of self-reference (Experiment 1) and interpersonal meaningfulness (Experiment 2), and completed memory tasks requiring the retrieval of specific traits. For both experiments, age groups remembered similar numbers of impressions. In Experiment 1, using more self-relevant encoding contexts increased memory for impressions over orienting to stimuli in a non-social way, regardless of age. In Experiment 2, older adults had enhanced memory for impressions presented in an interpersonally meaningful relative to a personally irrelevant way, whereas young adults were unaffected by this manipulation. The results provide evidence that increasing social relevance ameliorates age differences in memory for impressions, and enhances older adults’ ability to successfully retrieve contextual information. PMID:22364168
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Social relevance enhances memory for impressions in older adults.
Cassidy, Brittany S; Gutchess, Angela H
2012-01-01
Previous research has demonstrated that older adults have difficulty retrieving contextual material over items alone. Recent research suggests this deficit can be reduced by adding emotional context, allowing for the possibility that memory for social impressions may show less age-related decline than memory for other types of contextual information. Two studies investigated how orienting to social or self-relevant aspects of information contributed to the learning and retrieval of impressions in young and older adults. Participants encoded impressions of others in conditions varying in the use of self-reference (Experiment 1) and interpersonal meaningfulness (Experiment 2), and completed memory tasks requiring the retrieval of specific traits. For both experiments, age groups remembered similar numbers of impressions. In Experiment 1 using more self-relevant encoding contexts increased memory for impressions over orienting to stimuli in a non-social way, regardless of age. In Experiment 2 older adults had enhanced memory for impressions presented in an interpersonally meaningful relative to a personally irrelevant way, whereas young adults were unaffected by this manipulation. The results provide evidence that increasing social relevance ameliorates age differences in memory for impressions, and enhances older adults' ability to successfully retrieve contextual information.
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Rattray, Ivan; Pitiot, Alain; Lowe, James; Auer, Dorothee P; Lima, Sarah-Jane; Schubert, Mirjam I; Prior, Malcolm J W; Marsden, Charles A; Diaz, Fernando Pérez; Kendall, David A; Pardon, Marie-Christine
2010-01-01
We have previously shown that repeated exposure to mild novel cage stress prevents the onset of recent contextual fear memory deficits and attenuated amyloid deposition in the TASTPM mouse model of Alzheimer's disease. Here, we extended this investigation to remote contextual fear memory and extinction. TASTPM and wild-type mice acquired contextual fear at 4 months of age. Retention and extinction of contextual fear were assessed at 5.5 months prior to in vivo MRI assessment of regional T2 relaxation times and brain volumes followed by immunostaining to determine amyloid plaque load. Remote contextual fear memory was preserved in TASTPM mice regardless of the stress condition. Stress impaired extinction in wild-type mice but facilitated this process in TASTPM mice. Genotype-dependent effects of stress were observed on regional T2 times which were prolonged in the subiculum and thalamus of stressed TASTPM, possibly reflecting reduced amyloid pathology. Amyloid plaque load was particularly decreased in the retrosplenial cortex of stressed TASTPM mice, which also showed an overall reduction in the number of diffuse plaques. These findings support the hypothesis that repeated mild levels of stress induced by novel activities can delay the progression of pathological changes relevant to Alzheimer's disease.
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Object representations in visual memory: evidence from visual illusions.
Ben-Shalom, Asaf; Ganel, Tzvi
2012-07-26
Human visual memory is considered to contain different levels of object representations. Representations in visual working memory (VWM) are thought to contain relatively elaborated information about object structure. Conversely, representations in iconic memory are thought to be more perceptual in nature. In four experiments, we tested the effects of two different categories of visual illusions on representations in VWM and in iconic memory. Unlike VWM that was affected by both types of illusions, iconic memory was immune to the effects of within-object contextual illusions and was affected only by illusions driven by between-objects contextual properties. These results show that iconic and visual working memory contain dissociable representations of object shape. These findings suggest that the global properties of the visual scene are processed prior to the processing of specific elements.
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Nagayoshi, Taikai; Isoda, Kiichiro; Mamiya, Nori; Kida, Satoshi
2017-12-19
Memory consolidation, reconsolidation, and extinction have been shown to share similar molecular signatures, including new gene expression. Calpain is a Ca 2+ -dependent protease that exerts its effects through the proteolytic cleavage of target proteins. Neuron-specific conditional deletions of calpain 1 and 2 impair long-term potentiation in the hippocampus and spatial learning. Moreover, recent studies have suggested distinct roles of calpain 1 and 2 in synaptic plasticity. However, the role of hippocampal calpain in memory processes, especially memory consolidation, reconsolidation, and extinction, is still unclear. In the current study, we demonstrated the critical roles of hippocampal calpain in the consolidation, reconsolidation, and extinction of contextual fear memory in mice. We examined the effects of pharmacological inhibition of calpain in the hippocampus on these memory processes, using the N-Acetyl-Leu-Leu-norleucinal (ALLN; calpain 1 and 2 inhibitor). Microinfusion of ALLN into the dorsal hippocampus impaired long-term memory (24 h memory) without affecting short-term memory (2 h memory). Similarly, this pharmacological blockade of calpain in the dorsal hippocampus also disrupted reactivated memory but did not affect memory extinction. Importantly, the systemic administration of ALLN inhibited the induction of c-fos in the hippocampus, which is observed when memory is consolidated. Our observations showed that hippocampal calpain is required for the consolidation and reconsolidation of contextual fear memory. Further, the results suggested that calpain contributes to the regulation of new gene expression that is necessary for these memory processes as a regulator of Ca 2+ -signal transduction pathway.
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Schuette, Sven R M; Fernández-Fernández, Diego; Lamla, Thorsten; Rosenbrock, Holger; Hobson, Scott
2016-04-13
The persistently active protein kinase Mζ (PKMζ) has been found to be involved in the formation and maintenance of long-term memory. Most of the studies investigating PKMζ, however, have used either putatively unselective inhibitors or conventional knock-out animal models in which compensatory mechanisms may occur. Here, we overexpressed an active form of PKMζ in rat hippocampus, a structure highly involved in memory formation, and embedded in several neural networks. We investigated PKMζ's influence on synaptic plasticity using electrophysiological recordings of basal transmission, paired pulse facilitation, and LTP and combined this with behavioral cognitive experiments addressing formation and retention of both contextual memory during aversive conditioning and spatial memory during spontaneous exploration. We demonstrate that hippocampal slices overexpressing PKMζ show enhanced basal transmission, suggesting a potential role of PKMζ in postsynaptic AMPAR trafficking. Moreover, the PKMζ-overexpressing slices augmented LTP and this effect was not abolished by protein-synthesis blockers, indicating that PKMζ induces enhanced LTP formation in a protein-synthesis-independent manner. In addition, we found selectively enhanced long-term memory for contextual but not cued fear memory, underlining the theory of the hippocampus' involvement in the contextual aspect of aversive reinforced tasks. Memory for spatial orientation during spontaneous exploration remained unaltered, suggesting that PKMζ may not affect the neural circuits underlying spontaneous tasks that are different from aversive tasks. In this study, using an overexpression strategy as opposed to an inhibitor-based approach, we demonstrate an important modulatory role of PKMζ in synaptic plasticity and selective memory processing. Most of the literature investigating protein kinase Mζ (PKMζ) used inhibitors with selectivity that has been called into question or conventional knock-out animal models in which compensatory mechanisms may occur. To avoid these issues, some studies have been done using viral overexpression of PKMζ in different brain structures to show cognitive enhancement. However, electrophysiological experiments were exclusively done in knock-out models or inhibitory studies to show depletion of LTP. There was no study showing the effect of PKMζ overexpression in the hippocampus on behavior and LTP experiments. To our knowledge, this is the first study to combine these aspects with the result of enhanced memory for contextual fear memory and to show enhanced LTP in hippocampal slices overexpressing PKMζ. Copyright © 2016 Schuette et al.
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Tan, Ji-Wei; Duan, Ting-Ting; Zhou, Qi-Xin; Ding, Ze-Yang; Jing, Liang; Cao, Jun; Wang, Li-Ping; Mao, Rong-Rong; Xu, Lin
2015-07-01
Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood. © 2014 Society for the Study of Addiction.
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Pitts, Matthew W.; Todorovic, Cedomir; Blank, Thomas; Takahashi, Lorey K.
2009-01-01
The central nucleus of the amygdala (CeA) has been traditionally viewed in fear conditioning to serve as an output neural center that transfers conditioned information formed in the basolateral amygdala to brain structures that generate emotional responses. Recent studies suggest that the CeA may also be involved in fear memory consolidation. In addition, corticotropin-releasing factor systems were shown to facilitate memory consolidation in the amygdala, which contains a high density of CRF immunoreactive cell bodies and fibers in the lateral part of the CeA (CeAl). However, the involvement of CeA CRF in contextual fear conditioning remains poorly understood. Therefore, we first conducted a series of studies using fiber-sparing lesion and reversible inactivation methods to assess the general role of the CeA in contextual fear. We then used identical training and testing procedures to compare and evaluate the specific function of CeA CRF using CRF antisense oligonucleotides (CRF ASO). Rats microinjected with ibotenic acid, muscimol, or a CRF ASO into the CeA prior to contextual fear conditioning showed typical levels of freezing during acquisition training but exhibited significant reductions in contextual freezing in a retention test 48 h later. Furthermore, CeA inactivation induced by either muscimol or CRF ASO administration immediately prior to retention testing did not impair freezing, suggesting that the previously observed retention deficits were due to inhibition of consolidation rather than fear expression. Collectively, our results suggest CeA involvement in the consolidation of contextual fear memory and specifically implicate CeA CRF as an important mediator. PMID:19494159
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Unsworth, Nash; Spillers, Gregory J; Brewer, Gene A
2012-01-01
Remembering previous experiences from one's personal past is a principal component of psychological well-being, personality, sense of self, decision making, and planning for the future. In the current study the ability to search for autobiographical information in memory was examined by having college students recall their Facebook friends. Individual differences in working memory capacity manifested itself in the search of autobiographical memory by way of the total number of friends remembered, the number of clusters of friends, size of clusters, and the speed with which participants could output their friends' names. Although working memory capacity was related to the ability to search autobiographical memory, participants did not differ in the manner in which they approached the search and used contextual cues to help query their memories. These results corroborate recent theorising, which suggests that working memory is a necessary component of self-generating contextual cues to strategically search memory for autobiographical information.
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ERIC Educational Resources Information Center
Riggins, Tracy; Miller, Neely C.; Bauer, Patricia J.; Georgieff, Michael K.; Nelson, Charles A.
2009-01-01
The ability to recall contextual details associated with an event begins to develop in the first year of life, yet adult levels of recall are not reached until early adolescence. Dual-process models of memory suggest that the distinct retrieval process that supports the recall of such contextual information is recollection. In the present…
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Flexible Retrieval: When True Inferences Produce False Memories
Carpenter, Alexis C.; Schacter, Daniel L.
2016-01-01
Episodic memory involves flexible retrieval processes that allow us to link together distinct episodes, make novel inferences across overlapping events, and recombine elements of past experiences when imagining future events. However, the same flexible retrieval and recombination processes that underpin these adaptive functions may also leave memory prone to error or distortion, such as source misattributions in which details of one event are mistakenly attributed to another related event. To determine whether the same recombination-related retrieval mechanism supports both successful inference and source memory errors, we developed a modified version of an associative inference paradigm in which participants encoded everyday scenes comprised of people, objects, and other contextual details. These scenes contained overlapping elements (AB, BC) that could later be linked to support novel inferential retrieval regarding elements that had not appeared together previously (AC). Our critical experimental manipulation concerned whether contextual details were probed before or after the associative inference test, thereby allowing us to assess whether a) false memories increased for successful versus unsuccessful inferences, and b) any such effects were specific to after as compared to before participants received the inference test. In each of four experiments that used variants of this paradigm, participants were more susceptible to false memories for contextual details after successful than unsuccessful inferential retrieval, but only when contextual details were probed after the associative inference test. These results suggest that the retrieval-mediated recombination mechanism that underlies associative inference also contributes to source misattributions that result from combining elements of distinct episodes. PMID:27918169
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Properties of Contextual Memory Formed in the Absence of αCaMKII Autophosphorylation
2011-01-01
The alpha-isoform of calcium/calmodulin-dependent kinase II (αCaMKII) is a major synaptic kinase that undergoes autophosphorylation after NMDA receptor activation, switching the kinase into a calcium-independent activity state. This αCaMKII autophosphorylation is essential for NMDA receptor-dependent long-term potentiation (LTP), induced by a single tetanus, in hippocampal area CA1 and in neocortex. Furthermore, the αCaMKII autophosphorylation is essential for contextual long-term memory (LTM) formation after a single training trial but not after a massed training session. Here, we show that in the absence of αCaMKII autophosphorylation contextual fear conditioning is hippocampus dependent and that multi-tetanus-dependent late-LTP cannot be induced in hippocampal area CA1. Furthermore, we show that in the absence of αCaMKII autophosphorylation contextual LTM persists for 30 days, the latest time point tested. Additionally, contextual, but not cued, LTM formation in the absence of αCaMKII autophosphorylation appears to be impaired in 18 month-old mice. Taken together, our findings suggest that αCaMKII autophosphorylation-independent plasticity in the hippocampus is sufficient for contextual LTM formation and that αCaMKII autophosphorylation may be important for delaying age-related impairments in hippocampal memory formation. Furthermore, they propose that NMDA receptor-dependent LTP in hippocampal area CA1 is essential for contextual LTM formation after a single trial but not after massed training. Finally, our results challenge the proposal that NMDA receptor-dependent LTP in neocortex is required for remote contextual LTM. PMID:21276220
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Gafford, Georgette M; Parsons, Ryan G; Helmstetter, Fred J
2013-09-01
Prior work suggests that hippocampus-dependent memory undergoes a systems consolidation process such that recent memories are stored in the hippocampus, while older memories are independent of the hippocampus and instead dependent on cortical areas. One problem with interpreting these studies is that memory for the contextual stimuli weakens as time passes between the training event and testing and older memories are often less detailed, making it difficult to determine if memory storage in the hippocampus is related to the age or to the accuracy of the memory. Activity of the mammalian target of rapamycin (mTOR) signaling pathway is known to be important for controlling protein translation necessary for both memory consolidation after initial learning and for the reconsolidation of memory after retrieval. We tested whether p70s6 kinase (p70s6K), a key component of the mTOR signaling pathway, is activated following retrieval of context fear memory in the dorsal hippocampus (DH) and anterior cingulate cortex (ACC) at 1, 10, or 36 days after context fear conditioning. We also tested whether strengthening memory for the contextual stimuli changed p70s6K phosphorylation in these structures 36 days after training. We show that under standard training conditions retrieval of a recently formed memory is initially precise and involves the DH. Over time it loses detail, becomes independent of the DH and depends on the ACC. In a subsequent experiment, we preserved the accuracy of older memories through pre-exposure to the training context. We show that remote memory still involved the DH in animals given pre-exposure. These data support the notion that detailed memories depend on the DH regardless of their age. Copyright © 2013 Wiley Periodicals, Inc.
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Are C-reps contextual representations? A reply to Brewin and Burgess.
Pearson, David G
2014-03-01
Brewin and Burgess (2013) argue that our recent papers investigating the role of contextual representations in intrusive memories do not pose a challenge to dual-representation theory as originally claimed (Pearson, 2012; Pearson, Ross, & Webster, 2012). Here I point out that their alternative explanation for our results can be rejected using data already published in both papers. I also argue that their definition of what constitutes a contextual representation renders their revised dual-representation theory incompatible with experimental results that have previously been argued in the literature to support it. Valuable though their contribution is, it does not impact on our main conclusion that abstract contextual representations serve to increase intrusive memories for traumatic material. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Bidirectional switch of the valence associated with a hippocampal contextual memory engram.
Redondo, Roger L; Kim, Joshua; Arons, Autumn L; Ramirez, Steve; Liu, Xu; Tonegawa, Susumu
2014-09-18
The valence of memories is malleable because of their intrinsic reconstructive property. This property of memory has been used clinically to treat maladaptive behaviours. However, the neuronal mechanisms and brain circuits that enable the switching of the valence of memories remain largely unknown. Here we investigated these mechanisms by applying the recently developed memory engram cell- manipulation technique. We labelled with channelrhodopsin-2 (ChR2) a population of cells in either the dorsal dentate gyrus (DG) of the hippocampus or the basolateral complex of the amygdala (BLA) that were specifically activated during contextual fear or reward conditioning. Both groups of fear-conditioned mice displayed aversive light-dependent responses in an optogenetic place avoidance test, whereas both DG- and BLA-labelled mice that underwent reward conditioning exhibited an appetitive response in an optogenetic place preference test. Next, in an attempt to reverse the valence of memory within a subject, mice whose DG or BLA engram had initially been labelled by contextual fear or reward conditioning were subjected to a second conditioning of the opposite valence while their original DG or BLA engram was reactivated by blue light. Subsequent optogenetic place avoidance and preference tests revealed that although the DG-engram group displayed a response indicating a switch of the memory valence, the BLA-engram group did not. This switch was also evident at the cellular level by a change in functional connectivity between DG engram-bearing cells and BLA engram-bearing cells. Thus, we found that in the DG, the neurons carrying the memory engram of a given neutral context have plasticity such that the valence of a conditioned response evoked by their reactivation can be reversed by re-associating this contextual memory engram with a new unconditioned stimulus of an opposite valence. Our present work provides new insight into the functional neural circuits underlying the malleability of emotional memory.
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Bidirectional switch of the valence associated with a hippocampal contextual memory engram
Redondo, Roger L; Kim, Joshua; Arons, Autumn L; Ramirez, Steve; Liu, Xu; Tonegawa, Susumu
2014-01-01
The valence of memories is malleable because of their intrinsic reconstructive property1. This property of memory has been used clinically to treat maladaptive behaviours2. However, the neuronal mechanisms and brain circuits that enable the switching of the valence of memories remain largely unknown. Here, we investigated these mechanisms by applying the recently developed memory engram cell-labelling and -manipulation technique 3,4. We labelled, with Channelrhodopsin-2 (ChR2), a population of cells in either the dorsal dentate gyrus (DG) of the hippocampus or the basolateral complex of the amygdala (BLA) that were specifically activated during contextual fear or reward conditioning. Both groups of fear-conditioned mice displayed aversive light-dependent responses in an optogenetic place avoidance test, whereas both DG- and BLA-labelled mice that underwent reward conditioning exhibited an appetitive response in an optogenetic place preference test. Next, in an attempt to reverse the valence of memory within a subject, mice whose DG or BLA engram had initially been labelled by contextual fear or reward conditioning were subjected to a second conditioning of the opposite valence while their original DG or BLA engram was reactivated by blue light. Subsequent optogenetic place avoidance and preference tests revealed that while the DG-engram group displayed a response indicating a switch of the memory valence, the BLA-engram group did not. This switch was also evident at the cellular level by a change in functional connectivity between DG engram-bearing cells and BLA engram-bearing cells. Thus, we found that in the DG, the neurons carrying the memory engram of a given neutral context have plasticity such that the valence of a conditioned response evoked by their reactivation can be reversed by re-associating this contextual memory engram with a new US of an opposite valence. Our present work provides new insight into the functional neural circuit underlying the malleability of emotional memory. PMID:25162525
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Here Today, Gone Tomorrow – Adaptation to Change in Memory-Guided Visual Search
Zellin, Martina; Conci, Markus; von Mühlenen, Adrian; Müller, Hermann J.
2013-01-01
Visual search for a target object can be facilitated by the repeated presentation of an invariant configuration of nontargets (‘contextual cueing’). Here, we tested adaptation of learned contextual associations after a sudden, but permanent, relocation of the target. After an initial learning phase targets were relocated within their invariant contexts and repeatedly presented at new locations, before they returned to the initial locations. Contextual cueing for relocated targets was neither observed after numerous presentations nor after insertion of an overnight break. Further experiments investigated whether learning of additional, previously unseen context-target configurations is comparable to adaptation of existing contextual associations to change. In contrast to the lack of adaptation to changed target locations, contextual cueing developed for additional invariant configurations under identical training conditions. Moreover, across all experiments, presenting relocated targets or additional contexts did not interfere with contextual cueing of initially learned invariant configurations. Overall, the adaptation of contextual memory to changed target locations was severely constrained and unsuccessful in comparison to learning of an additional set of contexts, which suggests that contextual cueing facilitates search for only one repeated target location. PMID:23555038
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Over-Distribution in Source Memory
Brainerd, C. J.; Reyna, V. F.; Holliday, R. E.; Nakamura, K.
2012-01-01
Semantic false memories are confounded with a second type of error, over-distribution, in which items are attributed to contradictory episodic states. Over-distribution errors have proved to be more common than false memories when the two are disentangled. We investigated whether over-distribution is prevalent in another classic false memory paradigm: source monitoring. It is. Conventional false memory responses (source misattributions) were predominantly over-distribution errors, but unlike semantic false memory, over-distribution also accounted for more than half of true memory responses (correct source attributions). Experimental control of over-distribution was achieved via a series of manipulations that affected either recollection of contextual details or item memory (concreteness, frequency, list-order, number of presentation contexts, and individual differences in verbatim memory). A theoretical model was used to analyze the data (conjoint process dissociation) that predicts that predicts that (a) over-distribution is directly proportional to item memory but inversely proportional to recollection and (b) item memory is not a necessary precondition for recollection of contextual details. The results were consistent with both predictions. PMID:21942494
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Kessels, Roy P C; Meulenbroek, Olga; Fernández, Guillén; Olde Rikkert, Marcel G M
2010-09-01
Mild Cognitive Impairment (MCI) is characterized by episodic memory deficits, while aspects of working memory may also be implicated, but studies into this latter domain are scarce and results are inconclusive. Using a computerized search paradigm, this study compares 25 young adults, 25 typically aging older adults and 15 amnestic MCI patients as to their working-memory capacities for object-location information and potential differential effects of memory load and additional context cues. An age-related deficit in visuospatial working-memory maintenance was found that became more pronounced with increasing task demands. The MCI group additionally showed reduced maintenance of bound information, i.e., object-location associations, again especially at elevated memory load. No effects of contextual cueing were found. The current findings indicate that working memory should be considered when screening patients for suspected MCI and monitoring its progression.
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Emotion processing in the criminal psychopath: the role of attention in emotion-facilitated memory.
Glass, Samantha J; Newman, Joseph P
2009-02-01
The response modulation hypothesis specifies that low-anxious psychopathic individuals have difficulty processing information outside their primary attentional focus. To evaluate the applicability of this model to affective processing, the authors had 239 offenders, classified with the Psychopathy Checklist--Revised (R. D. Hare, 2003) and the Welsh Anxiety Scale (G. Welsh, 1956), perform 1 of 3 emotion memory tasks that examined the effects of emotion on memory for primary and contextual information. Regardless of anxiety level, psychopathic and control offenders demonstrated a significant and comparable memory bias for emotional over neutral words in the primary conditions. However, psychopathic individuals showed significantly less memory bias than did controls in the contextual conditions. Results indicate that the impact of emotion on memory is moderated by attentional factors.
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Krans, Julie; Langner, Oliver; Reinecke, Andrea; Pearson, David G
2013-12-01
The present study addressed the role of context information and dual-task interference during the encoding of negative pictures on intrusion development and voluntary recall. Healthy participants were shown negative pictures with or without context information. Pictures were either viewed alone or concurrently with a visuospatial or verbal task. Participants reported their intrusive images of the pictures in a diary. At follow-up, perceptual and contextual memory was tested. Participants in the context group reported more intrusive images and perceptual voluntary memory than participants in the no context group. No effects of the concurrent tasks were found on intrusive image frequency, but perceptual and contextual memory was affected according to the cognitive load of the task. The analogue method cannot be generalized to real-life trauma and the secondary tasks may differ in cognitive load. The findings challenge a dual memory model of PTSD but support an account in which retrieval strategy, rather than encoding processes, accounts for the experience of involuntary versus voluntary recall. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Hippocampal GABAB(1a) Receptors Constrain Generalized Contextual Fear
Lynch, Joseph F; Winiecki, Patrick; Gilman, T Lee; Adkins, Jordan M; Jasnow, Aaron M
2017-01-01
Many anxiety disorders are characterized by generalization of fear responses to neutral or ambiguous stimuli. Therefore, a comprehensive understanding of the mechanisms contributing to generalized fear is essential for formulating successful treatments for anxiety disorders. Previous research shows that GABA-mediated presynaptic inhibition has a critical role in cued fear generalization, as animals with genetically deleted presynaptic GABAB(1a) receptors cannot discriminate between CS+ and CS− tones. Work from our laboratory has further identified that GABAB(1a) receptors are necessary for maintaining contextual memory precision, thereby constraining generalized contextual fear. We previously found that GABAB(1a) KO mice show generalized fear to a neutral context 24 h after training, but not 2 h after training. A similar pattern was observed with object location and recognition, suggesting that this receptor subtype affects consolidation and/or retrieval of precise contextual and spatial memories. Here we sought to specifically examine the involvement of GABAB(1a) receptors in consolidation or retrieval of a precise fear memory. To do so, we infused a selective GABAB(1a) receptor antagonist, CGP 36216, intracerebroventricularly (ICV), or locally into the dorsal hippocampus, ventral hippocampus, or anterior cingulate cortex (ACC), during consolidation and retrieval of context fear training. Blockade of GABAB(1a) receptors through ICV, dorsal hippocampal, or ventral hippocampal infusions ‘after' training (consolidation) resulted in fear generalization to the neutral context when mice were tested 24, but not 6 h after training. Post-training infusions of CGP into the ACC, however, did not promote generalized fear. In addition, ICV, dorsal hippocampal, ventral hippocampal, or ACC infusions immediately ‘before' testing (retrieval) did not result in context fear generalization. These data suggest that GABA-mediated presynaptic inhibition is not critical for retrieval of precise contextual memory, but rather has an important role in the long-term consolidation of precise contextual memories and constrains generalized fear responses. PMID:27834391
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ERIC Educational Resources Information Center
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…
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ERIC Educational Resources Information Center
Biedenkapp, Joseph C.; Rudy, Jerry W.
2007-01-01
Contextual fear conditioning was maintained over a 15-day retention interval suggesting no forgetting of the conditioning experience. However, a more subtle generalization test revealed that, as the retention interval increased, rats showed enhanced generalized fear to an altered context. Preexposure to the training context prior to conditioning,…
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Staib, Jennifer M; Della Valle, Rebecca; Knox, Dayan K
2018-07-01
In classical fear conditioning, a neutral conditioned stimulus (CS) is paired with an aversive unconditioned stimulus (US), which leads to a fear memory. If the CS is repeatedly presented without the US after fear conditioning, the formation of an extinction memory occurs, which inhibits fear memory expression. A previous study has demonstrated that selective cholinergic lesions in the medial septum and vertical limb of the diagonal bands of Broca (MS/vDBB) prior to fear and extinction learning disrupt contextual fear memory discrimination and acquisition of extinction memory. MS/vDBB cholinergic neurons project to a number of substrates that are critical for fear and extinction memory. However, it is currently unknown which of these efferent projections are critical for contextual fear memory discrimination and extinction memory. To address this, we induced cholinergic lesions in efferent targets of MS/vDBB cholinergic neurons. These included the dorsal hippocampus (dHipp), ventral hippocampus (vHipp), medial prefrontal cortex (mPFC), and in the mPFC and dHipp combined. None of these lesion groups exhibited deficits in contextual fear memory discrimination or extinction memory. However, vHipp cholinergic lesions disrupted auditory fear memory. Because MS/vDBB cholinergic neurons are the sole source of acetylcholine in the vHipp, these results suggest that MS/vDBB cholinergic input to the vHipp is critical for auditory fear memory. Taken together with previous findings, the results of this study suggest that MS/vDBB cholinergic neurons are critical for fear and extinction memory, though further research is needed to elucidate the role of MS/vDBB cholinergic neurons in these types of emotional memory. Copyright © 2018 Elsevier Inc. All rights reserved.
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Manenti, Rosa; Sandrini, Marco; Brambilla, Michela; Cotelli, Maria
2016-09-15
Episodic memory displays the largest degree of age-related decline. A noninvasive brain stimulation technique that can be used to modulate memory in physiological aging is transcranial Direct Current Stimulation (tDCS). However, an aspect that has not been adequately investigated in previous studies is the optimal timing of stimulation to induce long-lasting positive effects on episodic memory function. Our previous studies showed episodic memory enhancement in older adults when anodal tDCS was applied over the left lateral prefrontal cortex during encoding or after memory consolidation with or without a contextual reminder. Here we directly compared the two studies to explore which of the tDCS protocols would induce longer-lasting positive effects on episodic memory function in older adults. In addition, we aimed to determine whether subjective memory complaints would be related to the changes in memory performance (forgetting) induced by tDCS, a relevant issue in aging research since individuals with subjective memory complaints seem to be at higher risk of later memory decline. The results showed that anodal tDCS applied after consolidation with a contextual reminder induced longer-lasting positive effects on episodic memory, conceivably through reconsolidation, than anodal tDCS during encoding. Furthermore, we reported, providing new data, a moderate negative correlation between subjective memory complaints and forgetting when anodal tDCS was applied after consolidation with a contextual reminder. This study sheds light on the best-suited timing of stimulation to induce long-lasting positive effects on memory function and might help the clinicians to select the most effective tDCS protocol to prevent memory decline. Copyright © 2016 Elsevier B.V. All rights reserved.
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Selective early-acquired fear memories undergo temporary suppression during adolescence
Pattwell, Siobhan S.; Bath, Kevin G.; Casey, B. J.; Ninan, Ipe; Lee, Francis S.
2011-01-01
Highly conserved neural circuitry between rodents and humans has allowed for in-depth characterization of behavioral and molecular processes associated with emotional learning and memory. Despite increased prevalence of affective disorders in adolescent humans, few studies have characterized how associative-emotional learning changes during the transition through adolescence or identified mechanisms underlying such changes. By examining fear conditioning in mice, as they transitioned into and out of adolescence, we found that a suppression of contextual fear occurs during adolescence. Although contextual fear memories were not expressed during early adolescence, they could be retrieved and expressed as the mice transitioned out of adolescence. This temporary suppression of contextual fear was associated with blunted synaptic activity in the basal amygdala and decreased PI3K and MAPK signaling in the hippocampus. These findings reveal a unique form of brain plasticity in fear learning during early adolescence and may prove informative for understanding endogenous mechanisms to suppress unwanted fear memories. PMID:21220344
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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 < 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. PMID:29238297
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Memory under pressure: secondary-task effects on contextual cueing of visual search.
Annac, Efsun; Manginelli, Angela A; Pollmann, Stefan; Shi, Zhuanghua; Müller, Hermann J; Geyer, Thomas
2013-11-04
Repeated display configurations improve visual search. Recently, the question has arisen whether this contextual cueing effect (Chun & Jiang, 1998) is itself mediated by attention, both in terms of selectivity and processing resources deployed. While it is accepted that selective attention modulates contextual cueing (Jiang & Leung, 2005), there is an ongoing debate whether the cueing effect is affected by a secondary working memory (WM) task, specifically at which stage WM influences the cueing effect: the acquisition of configural associations (e.g., Travis, Mattingley, & Dux, 2013) versus the expression of learned associations (e.g., Manginelli, Langer, Klose, & Pollmann, 2013). The present study re-investigated this issue. Observers performed a visual search in combination with a spatial WM task. The latter was applied on either early or late search trials--so as to examine whether WM load hampers the acquisition of or retrieval from contextual memory. Additionally, the WM and search tasks were performed either temporally in parallel or in succession--so as to permit the effects of spatial WM load to be dissociated from those of executive load. The secondary WM task was found to affect cueing in late, but not early, experimental trials--though only when the search and WM tasks were performed in parallel. This pattern suggests that contextual cueing involves a spatial WM resource, with spatial WM providing a workspace linking the current search array with configural long-term memory; as a result, occupying this workspace by a secondary WM task hampers the expression of learned configural associations.
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Telch, Michael J.; Bruchey, Aleksandra K.; Rosenfield, David; Cobb, Adam R.; Smits, Jasper; Pahl, Sandra; Gonzalez-Lima, F.
2015-01-01
Objective Preclinical studies have shown that low-dose USP methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. We report on the first controlled experiment to examine the memory-enhancing effects of post-training methylene blue administration on retention of fear extinction and contextual memory following fear extinction training. Method Adults (N = 42) displaying marked claustrophobic fear were randomized to double-blind administration of 260 mg of methylene blue versus placebo immediately following six five-minute extinction trials to an enclosed chamber. Retesting occurred one month later to assess fear renewal as indexed by peak fear during exposure to a non-trained enclosed chamber with the prediction that methylene blue's effects would vary as a function of fear reduction achieved during extinction training. Incidental contextual memory was assessed 1 and 30 days after training to assess the cognitive enhancing effects of methylene blue independent of its effects on fear attenuation. Results Consistent with predictions, participants displaying low end fear at post-training showed significantly less fear at follow-up if they received methylene blue post-training relative to placebo. In contrast, participants displaying moderate to high levels of post-training fear tended to fare worse at follow-up relative to placebo. Methylene blue's enhancement of contextual memory was unrelated to initial or post-training claustrophobic fear. Conclusions Methylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session, but may have a deleterious effect on extinction when administered after an unsuccessful exposure session. PMID:25018057
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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.
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Flexible retrieval: When true inferences produce false memories.
Carpenter, Alexis C; Schacter, Daniel L
2017-03-01
Episodic memory involves flexible retrieval processes that allow us to link together distinct episodes, make novel inferences across overlapping events, and recombine elements of past experiences when imagining future events. However, the same flexible retrieval and recombination processes that underpin these adaptive functions may also leave memory prone to error or distortion, such as source misattributions in which details of one event are mistakenly attributed to another related event. To determine whether the same recombination-related retrieval mechanism supports both successful inference and source memory errors, we developed a modified version of an associative inference paradigm in which participants encoded everyday scenes comprised of people, objects, and other contextual details. These scenes contained overlapping elements (AB, BC) that could later be linked to support novel inferential retrieval regarding elements that had not appeared together previously (AC). Our critical experimental manipulation concerned whether contextual details were probed before or after the associative inference test, thereby allowing us to assess whether (a) false memories increased for successful versus unsuccessful inferences, and (b) any such effects were specific to after compared with before participants received the inference test. In each of 4 experiments that used variants of this paradigm, participants were more susceptible to false memories for contextual details after successful than unsuccessful inferential retrieval, but only when contextual details were probed after the associative inference test. These results suggest that the retrieval-mediated recombination mechanism that underlies associative inference also contributes to source misattributions that result from combining elements of distinct episodes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
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Winters, Boyer D; Tucci, Mark C; Jacklin, Derek L; Reid, James M; Newsome, James
2011-11-30
Research has implicated the perirhinal cortex (PRh) in several aspects of object recognition memory. The specific role of the hippocampus (HPC) remains controversial, but its involvement in object recognition may pertain to processing contextual information in relation to objects rather than object representation per se. Here we investigated the roles of the PRh and HPC in object memory reconsolidation using the spontaneous object recognition task for rats. Intra-PRh infusions of the protein synthesis inhibitor anisomycin immediately following memory reactivation prevented object memory reconsolidation. Similar deficits were observed when a novel object or a salient contextual change was introduced during the reactivation phase. Intra-HPC infusions of anisomycin, however, blocked object memory reconsolidation only when a contextual change was introduced during reactivation. Moreover, disrupting functional interaction between the HPC and PRh by infusing anisomycin unilaterally into each structure in opposite hemispheres also impaired reconsolidation when reactivation was done in an altered context. These results show for the first time that the PRh is critical for reconsolidation of object memory traces and provide insight into the dynamic process of object memory storage; the selective requirement for hippocampal involvement following reactivation in an altered context suggests a substantial circuit level object trace reorganization whereby an initially PRh-dependent object memory becomes reliant on both the HPC and PRh and their interaction. Such trace reorganization may play a central role in reconsolidation-mediated memory updating and could represent an important aspect of lingering consolidation processes proposed to underlie long-term memory modulation and stabilization.
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Duclot, Florian; Perez-Taboada, Iara; Wright, Katherine N.; Kabbaj, Mohamed
2016-01-01
Only a portion of the population exposed to trauma will develop persistent emotional alterations characteristic of posttraumatic stress disorder (PTSD), which illustrates the necessity for identifying vulnerability factors and novel pharmacotherapeutic alternatives. Interestingly, clinical evidence suggests that novelty seeking is a good predictor for vulnerability to the development of excessive and persistent fear. Here, we first tested this hypothesis by analyzing contextual and cued fear responses of rats selected for their high (high responders, HR) or low (low responders, LR) exploration of a novel environment, indicator of novelty seeking. While HR and LR rats exhibited similar sensitivity to the shock and cued fear memory retention, fewer extinction sessions were required in HR than LR animals to reach extinction, indicating faster contextual and cued memory extinction. In a second part, we found an effective disruption of contextual fear reconsolidation by the N-methyl-D-aspartate receptor antagonist ketamine, associated with a down-regulation of early growth response 1 (Egr1) in the hippocampal CA1 area, and up-regulation of brain-derived neurotrophic factor (Bdnf) mRNA levels in the prelimbic and infralimbic cortices. Altogether, these data demonstrate a link between novelty seeking and conditioned fear extinction, and highlight a promising novel role of ketamine in affecting established fear memory. PMID:27343386
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Introduction to the Special Issue on Visual Working Memory
Wolfe, Jeremy M
2014-01-01
Objects are not represented individually in visual working memory (VWM), but in relation to the contextual information provided by other memorized objects. We studied whether the contextual information provided by the spatial configuration of all memorized objects is viewpoint-dependent. We ran two experiments asking participants to detect changes in locations between memory and probe for one object highlighted in the probe image. We manipulated the changes in viewpoint between memory and probe (Exp. 1: 0°, 30°, 60°; Exp. 2: 0°, 60°), as well as the spatial configuration visible in the probe image (Exp. 1: full configuration, partial configuration; Exp. 2: full configuration, no configuration). Location change detection was higher with the full spatial configuration than with the partial configuration or with no spatial configuration at viewpoint changes of 0°, thus replicating previous findings on the nonindependent representations of individual objects in VWM. Most importantly, the effect of spatial configurations decreased with increasing viewpoint changes, suggesting a viewpoint-dependent representation of contextual information in VWM. We discuss these findings within the context of this special issue, in particular whether research performed within the slots-versus-resources debate and research on the effects of contextual information might focus on two different storage systems within VWM. PMID:25341647
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Barak, Ohr; Vakil, Eli; Levy, Daniel A
2013-01-01
Contextual change or constancy between occasions of memory formation and retrieval are commonly assumed to affect retrieval success, yet such effects may be inconsistent, and the processes leading to the pattern of effects are still not well understood. We conducted a systematic investigation of environmental context effects on memory, using a range of materials (common objects, pictures of familiar and unfamiliar faces, words, and sentences), and four types of retrieval (free recall, cued recall, recognition, and order memory), all assessed within participants. Additionally, we examined the influence of mnemonic challenge on context effects by examining both healthy participants and a group of patients in rehabilitation following traumatic brain injury (TBI). We found no effects of contextual factors on tests of recognition for either group of participants, but effects did emerge for cued and free recall, with the most prominent effects being on memory for objects. Furthermore, while patients' memory abilities in general were impaired relative to the comparison group, they exhibited greater influences of contextual reinstatement on several recall tasks. These results support suggestions that environmental context effects on memory are dependent on retrieval mode and on the extent to which retrieval is challenging because of neurocognitive status. Additionally, findings of environmental context effects in memory-impaired TBI patients suggest that by harnessing such preserved indirect memory (e.g., using reminder technologies), it may be possible to ameliorate TBI patients' difficulties in explicit remembering.
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Selective effects of emotion on the phenomenal characteristics of autobiographical memories.
Schaefer, Alexandre; Philippot, Pierre
2005-02-01
The present study investigates the emotional determinants of the phenomenal characteristics of autobiographical memories. A total of 84 participants completed the Memory Characteristics Questionnaire (MCQ, Johnson, Foley, Suengas, & Raye, 1988) after retrieving and orally describing a negative, a positive, and a neutral autobiographical memory. In addition, self-report and physiological measures of emotional state at retrieval were recorded. Results suggest that recall of perceptual, sensory, and semantic elements is better for emotional memories than for neutral ones. This difference is not significant for contextual and temporal aspects, suggesting that emotional memories are more vivid but no more specific than are neutral ones. In addition, positive memories yielded higher MCQ ratings than did negative memories for sensory, temporal, and contextual aspects. Finally, correlations suggest a positive relation between emotional state at retrieval and level of phenomenal detail of retrieved memories. Results are interpreted in terms of multilevel models of emotion and of Conway and Pleydell-Pearce's (2000) model.
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Castelló, Stefanía; Molina, Juan Carlos; Arias, Carlos
2017-08-14
Conditioned tolerance can be conceptualized as a particular case of Pavlovian conditioning in which contextual cues play the role of the conditioned stimulus. Although the evidence is contradictory, it is frequently assumed that long-term contextual conditioning in pre-weanling rats is weak or even absent. This hypothesis comes from and is sustained mainly by behavioral studies that explored different contextual effects in 16-18day-old rats using a fear-conditioning paradigm, but their conclusions are stated in terms of an immature (hippocampal-dependent) declarative memory system. The main goal of the present manuscript was based on a recent antecedent from our laboratory, to analyze whether context-dependent tolerance induced by ethanol during the pre-weanling period persists over time. Results showed that the context was able to modulate ethanol-induced tolerance in 2- and 3-week-old rats. Interestingly, contextual conditioned tolerance was stronger (in terms of persistence) during the third than during the second postnatal week. When subjects were tested 8days after training, when the context presumably lost its influence over tolerance, the opposite effect emerged (sensitization). These results are important for the ethanol literature, adding new evidence of long-term retention of ethanol effects acquired during infancy, whilst also showing striking ontogenetic differences in the sensitivity to ethanol between the 2nd and 3rd postnatal weeks. Importantly, contextual information modulates the expression of these ethanol effects even eight days after training, a result that is particularly relevant to the discussion of the ontogeny of contextual memory. Copyright © 2017 Elsevier B.V. All rights reserved.
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Poplawski, Shane G; Schoch, Hannah; Wimmer, Mathieu; Hawk, Joshua D; Walsh, Jennifer L; Giese, Karl P; Abel, Ted
2014-12-01
Hippocampus-dependent learning is known to induce changes in gene expression, but information on gene expression differences between different learning paradigms that require the hippocampus is limited. The bulk of studies investigating RNA expression after learning use the contextual fear conditioning task, which couples a novel environment with a footshock. Although contextual fear conditioning has been useful in discovering gene targets, gene expression after spatial memory tasks has received less attention. In this study, we used the object-location memory task and studied gene expression at two time points after learning in a high-throughput manner using a microfluidic qPCR approach. We found that expression of the classic immediate-early genes changes after object-location training in a fashion similar to that observed after contextual fear conditioning. However, the temporal dynamics of gene expression are different between the two tasks, with object-location memory producing gene expression changes that last at least 2 hours. Our findings indicate that different training paradigms may give rise to distinct temporal dynamics of gene expression after learning. Copyright © 2014 Elsevier Inc. All rights reserved.
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Wimmer, Mathieu; Hawk, Joshua D.; Walsh, Jennifer L.; Giese, Karl P.; Abel, Ted
2014-01-01
Hippocampus-dependent learning is known to induce changes in gene expression, but information on gene expression differences between different learning paradigms that require the hippocampus is limited. The bulk of studies investigating RNA expression after learning use the contextual fear conditioning task, which couples a novel environment with a footshock. Although contextual fear conditioning has been useful in discovering gene targets, gene expression after spatial memory tasks has received less attention. In this study, we used the object-location memory task and studied gene expression at two time points after learning in a high-throughput manner using a microfluidic qPCR approach. We found that expression of the classic immediate-early genes changes after object-location training in a fashion similar to that observed after contextual fear conditioning. However, the temporal dynamics of gene expression are different between the two tasks, with object-location memory producing gene expression changes that last at least 2 hours. Our findings indicate that different training paradigms may give rise to distinct temporal dynamics of gene expression after learning. PMID:25242102
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Strain-dependent Differences in LTP and Hippocampus-dependent Memory in Inbred Mice
Nguyen, Peter V.; Abel, Ted; Kandel, Eric R.; Bourtchouladze, Roussoudan
2000-01-01
Many studies have used “reverse” genetics to produce “knock-out” and transgenic mice to explore the roles of various molecules in long-term potentiation (LTP) and spatial memory. The existence of a variety of inbred strains of mice provides an additional way of exploring the genetic bases of learning and memory. We examined behavioral memory and LTP expression in area CA1 of hippocampal slices prepared from four different inbred strains of mice: C57BL/6J, CBA/J, DBA/2J, and 129/SvEms-+Ter?/J. We found that LTP induced by four 100-Hz trains of stimulation was robust and long-lasting in C57BL/6J and DBA/2J mice but decayed in CBA/J and 129/SvEms-+Ter?/J mice. LTP induced by one 100-Hz train was significantly smaller after 1 hr in the 129/SvEms-+Ter?/J mice than in the other three strains. Theta-burst LTP was shorter lasting in CBA/J, DBA/2J, and 129/SvEms-+Ter?/J mice than in C57BL/6J mice. We also observed specific memory deficits, among particular mouse strains, in spatial and nonspatial tests of hippocampus-dependent memory. CBA/J mice showed defective learning in the Morris water maze, and both DBA/2J and CBA/J strains displayed deficient long-term memory in contextual and cued fear conditioning tests. Our findings provide strong support for a genetic basis for some forms of synaptic plasticity that are linked to behavioral long-term memory and suggest that genetic background can influence the electrophysiological and behavioral phenotypes observed in genetically modified mice generated for elucidating the molecular bases of learning, memory, and LTP. PMID:10837506
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Watabe, Ayako M; Nagase, Masashi; Hagiwara, Akari; Hida, Yamato; Tsuji, Megumi; Ochiai, Toshitaka; Kato, Fusao; Ohtsuka, Toshihisa
2016-01-01
Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, such as axon specifications and maturation in central and peripheral nervous systems. At mature pre-synaptic terminals, SAD-B is associated with synaptic vesicles and the active zone cytomatrix; however, how SAD-B regulates neurotransmission and synaptic plasticity in vivo remains unclear. Thus, we used SAD-B knockout (KO) mice to study the function of this pre-synaptic kinase in the brain. We found that the paired-pulse ratio was significantly enhanced at Shaffer collateral synapses in the hippocampal CA1 region in SAD-B KO mice compared with wild-type littermates. We also found that the frequency of the miniature excitatory post-synaptic current was decreased in SAD-B KO mice. Moreover, synaptic depression following prolonged low-frequency synaptic stimulation was significantly enhanced in SAD-B KO mice. These results suggest that SAD-B kinase regulates vesicular release probability at pre-synaptic terminals and is involved in vesicular trafficking and/or regulation of the readily releasable pool size. Finally, we found that hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice. These observations suggest that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, but their roles in mature brains were only partially known. Here, we demonstrated, at mature pre-synaptic terminals, that SAD-B regulates vesicular release probability and synaptic plasticity. Moreover, hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice, suggesting that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. © 2015 International Society for Neurochemistry.
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ERIC Educational Resources Information Center
Levy-Gigi, Einat; Vakil, Eli
2010-01-01
The influence of contextual similarity on children's recognition memory performance was examined using a retroactive interference paradigm. In the study, 9- and 12-year-olds were randomly assigned to one of two contextual conditions. In both conditions, target and interfering information were presented in distinctive contexts by using different…
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Effects of Normal Aging on Memory for Multiple Contextual Features
ERIC Educational Resources Information Center
Gagnon, Sylvain; Soulard, Kathleen; Brasgold, Melissa; Kreller, Joshua
2007-01-01
Twenty-four younger (18-35 years) and 24 older adult participants (65 or older) were exposed to three experimental conditions involving the memorization words and their associated contextual features, with contextual feature complexity increasing from Conditions 1 to 3. In Condition 1, words presented varied only on one binary feature (color,…
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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.
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28Silicon Irradiation Impairs Contextual Fear Memory in B6D2F1 Mice.
Raber, Jacob; Marzulla, Tessa; Stewart, Blair; Kronenberg, Amy; Turker, Mitchell S
2015-06-01
The space radiation environment consists of multiple species of charged particles, including (28)Si, (48)Ti and protons that may impact cognition, but their damaging effects have been poorly defined. In mouse studies, C57Bl6/J homozygous wild-type mice and genetic mutant mice on a C57Bl6/J background have typically been used for assessing effects of space radiation on cognition. In contrast, little is known about the radiation response of mice on a heterozygous background. Therefore, in the current study we tested the effects of (28)Si, (48)Ti and proton radiation on hippocampus-dependent contextual fear memory and hippocampus-independent cued fear memory in C57Bl6/J × DBA2/J F1 (B6D2F1) mice three months after irradiation. Contextual fear memory was impaired at a 1.6 Gy dose of (28)Si radiation, but not cued fear memory. (48)Ti or proton irradiation did not affect either type of memory. Based on earlier space radiation cognitive data in C57Bl6/J mice, these data highlight the importance of including different genetic backgrounds in studies aimed at assessing cognitive changes after exposure to space radiation.
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de la Fuente, Verónica; Freudenthal, Ramiro; Romano, Arturo
2011-04-13
In fear conditioning, aversive stimuli are readily associated with contextual features. A brief reexposure to the training context causes fear memory reconsolidation, whereas a prolonged reexposure induces memory extinction. The regulation of hippocampal gene expression plays a key role in contextual memory consolidation and reconsolidation. However, the mechanisms that determine whether memory will reconsolidate or extinguish are not known. Here, we demonstrate opposing roles for two evolutionarily related transcription factors in the mouse hippocampus. We found that nuclear factor-κB (NF-κB) is required for fear memory reconsolidation. Conversely, calcineurin phosphatase inhibited NF-κB and induced nuclear factor of activated T-cells (NFAT) nuclear translocation in the transition between reconsolidation and extinction. Accordingly, the hippocampal inhibition of both calcineurin and NFAT independently impaired memory extinction, whereas inhibition of NF-κB enhanced memory extinction. These findings represent the first insight into the molecular mechanisms that determine memory reprocessing after retrieval, supporting a transcriptional switch that directs memory toward reconsolidation or extinction. The precise molecular characterization of postretrieval processes has potential importance to the development of therapeutic strategies for fear memory disorders.
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Gadd45b knockout mice exhibit selective deficits in hippocampus-dependent long-term memory
Leach, Prescott T.; Poplawski, Shane G.; Kenney, Justin W.; Hoffman, Barbara; Liebermann, Dan A.; Abel, Ted; Gould, Thomas J.
2012-01-01
Growth arrest and DNA damage-inducible β (Gadd45b) has been shown to be involved in DNA demethylation and may be important for cognitive processes. Gadd45b is abnormally expressed in subjects with autism and psychosis, two disorders associated with cognitive deficits. Furthermore, several high-throughput screens have identified Gadd45b as a candidate plasticity-related gene. However, a direct demonstration of a link between Gadd45b and memory has not been established. The current studies first determined whether expression of the Gadd45 family of genes was affected by contextual fear conditioning. Gadd45b, and to a lesser extent Gadd45g, were up-regulated in the hippocampus following contextual fear conditioning, whereas Gadd45a was not. Next, Gadd45b knockout mice were tested for contextual and cued fear conditioning. Gadd45b knockout mice exhibited a significant deficit in long-term contextual fear conditioning; however, they displayed normal levels of short-term contextual fear conditioning. No differences between Gadd45b knockout and wild-type mice were observed in cued fear conditioning. Because cued fear conditioning is hippocampus independent, while contextual fear conditioning is hippocampus dependent, the current studies suggest that Gadd45b may be important for long-term hippocampus-dependent memory storage. Therefore, Gadd45b may be a novel therapeutic target for the cognitive deficits associated with many neurodevelopmental, neurological, and psychiatric disorders. PMID:22802593
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Both mineralocorticoid and glucocorticoid receptors regulate emotional memory in mice.
Zhou, Ming; Bakker, Eveline H M; Velzing, Els H; Berger, Stefan; Oitzl, Melly; Joëls, Marian; Krugers, Harm J
2010-11-01
Corticosteroid hormones are thought to promote optimal behavioral adaptation under fearful conditions, primarily via glucocorticoid receptors (GRs). Here, we examined - using pharmacological and genetic approaches in mice - if mineralocorticoid receptors (MRs) also play a role in fearful memory formation. As expected, administration of the GR-antagonist RU38486 prior to training in a fear conditioning paradigm impaired contextual memory when tested 24 (but not when tested 3) h after training. Tone-cue memory was enhanced by RU38486 when tested at 4 (but not 25) h after training. Interestingly, pre (but not post)-training administration of MR antagonist spironolactone impaired contextual memory, both at 3 and 24h after training. Similar effects were also found in forebrain-specific MR knockout mice. Spironolactone also impaired tone-cue memory, but only at 4h after training. These results reveal that - in addition to GRs - MRs also play a critical role in establishing fear memories, particularly in the early phase of memory formation. Copyright © 2010 Elsevier Inc. All rights reserved.
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Ishikawa, Rie; Fukushima, Hotaka; Frankland, Paul W; Kida, Satoshi
2016-01-01
Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re-exposures. Importantly, we find that long, but not short re-exposures activate gene expression in the hippocampus and induce hippocampus-dependent reconsolidation of remote contextual fear memory. Furthermore, remote memory retrieval becomes hippocampus-dependent after the long-time recall, suggesting that remote fear memory returns to a hippocampus dependent state after the long-time recall, thereby allowing enhanced forgetting by increased hippocampal neurogenesis. Forgetting of traumatic memory may contribute to the development of PTSD treatment. DOI: http://dx.doi.org/10.7554/eLife.17464.001 PMID:27669409
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ERIC Educational Resources Information Center
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.…
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[Role of context recall in destination memory decline in normal aging].
El Haj, Mohamad; Allain, Philippe
2014-12-01
Until recently, little was known about destination memory, or memory for the destination of outputted information. In the present work, this memory was evaluated in 32 older adults and 36 younger adults, who had to associate proverbs to pictures of famous people and decide, on a subsequent recognition task, whether they had previously told that proverb to that face or not. When deciding about the destination, participants had to provide contextual judgment, that is, whether each picture had been previously exposed in color or in black and white. Participants also performed a neuropsychological battery tapping episodic memory and executive functions. Findings showed poor destination recall in older participants. Destination recall in older adults was reliably predicted by with their context recall. Destination memory seems to be particularly affected by aging, a deterioration that can be related to deficits in processing contextual features during encoding.
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Temporal context memory in high-functioning autism.
Gras-Vincendon, Agnès; Mottron, Laurent; Salamé, Pierre; Bursztejn, Claude; Danion, Jean-Marie
2007-11-01
Episodic memory, i.e. memory for specific episodes situated in space and time, seems impaired in individuals with autism. According to weak central coherence theory, individuals with autism have general difficulty connecting contextual and item information which then impairs their capacity to memorize information in context. This study investigated temporal context memory for visual information in individuals with autism. Eighteen adolescents and adults with high-functioning autism (HFA) or Asperger syndrome (AS) and age- and IQ-matched typically developing participants were tested using a recency judgement task. The performance of the autistic group did not differ from that of the control group, nor did the performance between the AS and HFA groups. We conclude that autism in high-functioning individuals does not impair temporal context memory as assessed on this task. We suggest that individuals with autism are as efficient on this task as typically developing subjects because contextual memory performance here involves more automatic than organizational processing.
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Persson, Bjorn M; Ainge, James A; O'Connor, Akira R
2016-07-01
Current animal models of episodic memory are usually based on demonstrating integrated memory for what happened, where it happened, and when an event took place. These models aim to capture the testable features of the definition of human episodic memory which stresses the temporal component of the memory as a unique piece of source information that allows us to disambiguate one memory from another. Recently though, it has been suggested that a more accurate model of human episodic memory would include contextual rather than temporal source information, as humans' memory for time is relatively poor. Here, two experiments were carried out investigating human memory for temporal and contextual source information, along with the underlying dual process retrieval processes, using an immersive virtual environment paired with a 'Remember-Know' memory task. Experiment 1 (n=28) showed that contextual information could only be retrieved accurately using recollection, while temporal information could be retrieved using either recollection or familiarity. Experiment 2 (n=24), which used a more difficult task, resulting in reduced item recognition rates and therefore less potential for contamination by ceiling effects, replicated the pattern of results from Experiment 1. Dual process theory predicts that it should only be possible to retrieve source context from an event using recollection, and our results are consistent with this prediction. That temporal information can be retrieved using familiarity alone suggests that it may be incorrect to view temporal context as analogous to other typically used source contexts. This latter finding supports the alternative proposal that time since presentation may simply be reflected in the strength of memory trace at retrieval - a measure ideally suited to trace strength interrogation using familiarity, as is typically conceptualised within the dual process framework. Copyright © 2016 Elsevier Inc. All rights reserved.
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ERIC Educational Resources Information Center
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…
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Sleep Enhances Explicit Recollection in Recognition Memory
ERIC Educational Resources Information Center
Drosopoulos, Spyridon; Wagner, Ullrich; Born, Jan
2005-01-01
Recognition memory is considered to be supported by two different memory processes, i.e., the explicit recollection of information about a previous event and an implicit process of recognition based on a contextual sense of familiarity. Both types of memory supposedly rely on distinct memory systems. Sleep is known to enhance the consolidation of…
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Garfinkel, Sarah N; Abelson, James L; King, Anthony P; Sripada, Rebecca K; Wang, Xin; Gaines, Laura M; Liberzon, Israel
2014-10-01
Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression. Copyright © 2014 the authors 0270-6474/14/3413435-09$15.00/0.
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Lai, Shuhua; Wu, Gangwei; Jiang, Zhixian
2018-01-01
Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD). Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS) exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1) is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA) following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4) levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor) or LPS-RS (TLR4 antagonist) can prevent the development of SPS-induced fear extinction impairment. Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli. © 2018 The Author(s). Published by S. Karger AG, Basel.
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Post-Training Unilateral Amygdala Lesions Selectively Impair Contextual Fear Memories
ERIC Educational Resources Information Center
Flavell, Charlotte R.; Lee, Jonathan L. C.
2012-01-01
The basolateral amygdala (BLA) and the dorsal hippocampus (dHPC) are both structures with key roles in contextual fear conditioning. During fear conditioning, it is postulated that contextual representations of the environment are formed in the hippocampus, which are then associated with foot shock in the amygdala. However, it is not known to what…
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Stress Disrupts Context-Dependent Memory
ERIC Educational Resources Information Center
Schwabe, Lars; Bohringer, Andreas; Wolf, Oliver T.
2009-01-01
Memory is facilitated when the retrieval context resembles the learning context. The brain structures underlying contextual influences on memory are susceptible to stress. Whether stress interferes with context-dependent memory is still unknown. We exposed healthy adults to stress or a control procedure before they learned an object-location task…
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Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice.
Yang, Miyoung; Kim, Hwanseong; Kim, Juhwan; Kim, Sung-Ho; Kim, Jong-Choon; Bae, Chun-Sik; Kim, Joong-Sun; Shin, Taekyun; Moon, Changjong
2012-03-01
Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.
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Uncapher, Melina R.; Rugg, Michael D.
2009-01-01
Not all of what is experienced is remembered later. Behavioral evidence suggests that the manner in which an event is processed influences which aspects of the event will later be remembered. The present experiment investigated the neural correlates of ‘selective encoding’, or the mechanisms that support the encoding of some elements of an event in preference to others. Event-related functional magnetic resonance imaging (fMRI) data were acquired while volunteers selectively attended to one of two different contextual features of study items (color or location). A surprise memory test for the items and both contextual features was subsequently administered to determine the influence of selective attention on the neural correlates of contextual encoding. Activity in several cortical regions indexed later memory success selectively for color or location information, and this encoding-related activity was enhanced by selective attention to the relevant feature. Critically, a region in the hippocampus responded selectively to attended source information (whether color or location), demonstrating encoding-related activity for attended but not for nonattended source features. Together, the findings suggest that selective attention modulates the magnitude of activity in cortical regions engaged by different aspects of an event, and hippocampal encoding mechanisms seem to be sensitive to this modulation. Thus, the information that is encoded into a memory representation is biased by selective attention, and this bias is mediated by cortico-hippocampal interactions. PMID:19553466
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Uncapher, Melina R; Rugg, Michael D
2009-06-24
Not all of what is experienced is remembered later. Behavioral evidence suggests that the manner in which an event is processed influences which aspects of the event will later be remembered. The present experiment investigated the neural correlates of "selective encoding," or the mechanisms that support the encoding of some elements of an event in preference to others. Event-related MRI data were acquired while volunteers selectively attended to one of two different contextual features of study items (color or location). A surprise memory test for the items and both contextual features was subsequently administered to determine the influence of selective attention on the neural correlates of contextual encoding. Activity in several cortical regions indexed later memory success selectively for color or location information, and this encoding-related activity was enhanced by selective attention to the relevant feature. Critically, a region in the hippocampus responded selectively to attended source information (whether color or location), demonstrating encoding-related activity for attended but not for nonattended source features. Together, the findings suggest that selective attention modulates the magnitude of activity in cortical regions engaged by different aspects of an event, and hippocampal encoding mechanisms seem to be sensitive to this modulation. Thus, the information that is encoded into a memory representation is biased by selective attention, and this bias is mediated by cortical-hippocampal interactions.
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Factors affecting graded and ungraded memory loss following hippocampal lesions.
Winocur, Gordon; Moscovitch, Morris; Sekeres, Melanie J
2013-11-01
This review evaluates three current theories--Standard Consolidation (Squire & Wixted, 2011), Overshadowing (Sutherland, Sparks, & Lehmann, 2010), and Multiple Trace-Transformation (Winocur, Moscovitch, & Bontempi, 2010)--in terms of their ability to account for the role of the hippocampus in recent and remote memory in animals. Evidence, based on consistent findings from tests of spatial memory and memory for acquired food preferences, favours the transformation account, but this conclusion is undermined by inconsistent results from studies that measured contextual fear memory, probably the most commonly used test of hippocampal involvement in anterograde and retrograde memory. Resolution of this issue may depend on exercising greater control over critical factors (e.g., contextual environment, amount of pre-exposure to the conditioning chamber, the number and distribution of foot-shocks) that can affect the representation of the memory shortly after learning and over the long-term. Research strategies aimed at characterizing the neural basis of long-term consolidation/transformation, as well as other outstanding issues are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.
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JIP1-Mediated JNK Activation Negatively Regulates Synaptic Plasticity and Spatial Memory.
Morel, Caroline; Sherrin, Tessi; Kennedy, Norman J; Forest, Kelly H; Avcioglu Barutcu, Seda; Robles, Michael; Carpenter-Hyland, Ezekiel; Alfulaij, Naghum; Standen, Claire L; Nichols, Robert A; Benveniste, Morris; Davis, Roger J; Todorovic, Cedomir
2018-04-11
The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JNK-interacting protein 1 (JIP1) scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the Jip1 gene that selectively blocks JIP1-mediated JNK activation. These male mutant mice exhibited increased NMDAR currents, increased NMDAR-mediated gene expression, and a lower threshold for induction of hippocampal long-term potentiation. The JIP1 mutant mice also displayed improved hippocampus-dependent spatial memory and enhanced associative fear conditioning. These results were confirmed using a second JIP1 mutant mouse model that suppresses JNK activity. Together, these observations establish that JIP1-mediated JNK activation contributes to the regulation of hippocampus-dependent, NMDAR-mediated synaptic plasticity and learning. SIGNIFICANCE STATEMENT The results of this study demonstrate that c-Jun N-terminal kinase (JNK) activation induced by the JNK-interacting protein 1 (JIP1) scaffold protein negatively regulates the threshold for induction of long-term synaptic plasticity through the NMDA-type glutamate receptor. This change in plasticity threshold influences learning. Indeed, mice with defects in JIP1-mediated JNK activation display enhanced memory in hippocampus-dependent tasks, such as contextual fear conditioning and Morris water maze, indicating that JIP1-JNK constrains spatial memory. This study identifies JIP1-mediated JNK activation as a novel molecular pathway that negatively regulates NMDAR-dependent synaptic plasticity and memory. Copyright © 2018 the authors 0270-6474/18/383708-21$15.00/0.
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Zheng, Hui; Zhang, Yue; Li, Wen; Loh, Horace H; Law, Ping-Yee
2013-04-01
Addictive drugs, including opioids, modulate adult neurogenesis. In order to delineate the probable implications of neurogenesis on contextual memory associated with addiction, we investigated opioid agonist-selective regulation of neurogenic differentiation 1 (NeuroD) activities under the conditioned place preference (CPP) paradigm. Training mice with equivalent doses of morphine and fentanyl produced different CPP extinction rates without measurable differences in the CPP acquisition rate or magnitude. Fentanyl-induced CPP required much longer time for extinction than morphine-induced CPP. We observed a parallel decrease in NeuroD activities and neurogenesis after morphine-induced CPP, but not after fentanyl-induced CPP. Increasing NeuroD activities with NeuroD-lentivirus (nd-vir) injection at the dentate gyrus before CPP training reversed morphine-induced decreases in NeuroD activities and neurogenesis, and prolonged the time required for extinction of morphine-induced CPP. On the other hand, decreasing NeuroD activities via injection of miRNA-190-virus (190-vir) reversed the fentanyl effect on NeuroD and neurogenesis and shortened the time required for extinction of fentanyl-induced CPP. Another contextual memory task, the Morris Water Maze (MWM), was affected similarly by alteration of NeuroD activities. The reduction in NeuroD activities either by morphine treatment or 190-vir injection decreased MWM task retention, while the increase in NeuroD activities by nd-vir prolonged MWM task retention. Thus, by controlling NeuroD activities, opioid agonists differentially regulate adult neurogenesis and subsequent contextual memory retention. Such drug-related memory regulation could have implications in eventual context-associated relapse.
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Lateral Entorhinal Cortex is Critical for Novel Object-Context Recognition
Wilson, David IG; Langston, Rosamund F; Schlesiger, Magdalene I; Wagner, Monica; Watanabe, Sakurako; Ainge, James A
2013-01-01
Episodic memory incorporates information about specific events or occasions including spatial locations and the contextual features of the environment in which the event took place. It has been modeled in rats using spontaneous exploration of novel configurations of objects, their locations, and the contexts in which they are presented. While we have a detailed understanding of how spatial location is processed in the brain relatively little is known about where the nonspatial contextual components of episodic memory are processed. Initial experiments measured c-fos expression during an object-context recognition (OCR) task to examine which networks within the brain process contextual features of an event. Increased c-fos expression was found in the lateral entorhinal cortex (LEC; a major hippocampal afferent) during OCR relative to control conditions. In a subsequent experiment it was demonstrated that rats with lesions of LEC were unable to recognize object-context associations yet showed normal object recognition and normal context recognition. These data suggest that contextual features of the environment are integrated with object identity in LEC and demonstrate that recognition of such object-context associations requires the LEC. This is consistent with the suggestion that contextual features of an event are processed in LEC and that this information is combined with spatial information from medial entorhinal cortex to form episodic memory in the hippocampus. © 2013 Wiley Periodicals, Inc. PMID:23389958
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AMPK Signaling in the Dorsal Hippocampus Negatively Regulates Contextual Fear Memory Formation
Han, Ying; Luo, Yixiao; Sun, Jia; Ding, Zengbo; Liu, Jianfeng; Yan, Wei; Jian, Min; Xue, Yanxue; Shi, Jie; Wang, Ji-Shi; Lu, Lin
2016-01-01
Both the formation of long-term memory (LTM) and dendritic spine growth that serves as a physical basis for the long-term storage of information require de novo protein synthesis. Memory formation also critically depends on transcription. Adenosine monophosphate-activated protein kinase (AMPK) is a transcriptional regulator that has emerged as a major energy sensor that maintains cellular energy homeostasis. However, still unknown is its role in memory formation. In the present study, we found that AMPK is primarily expressed in neurons in the hippocampus, and then we demonstrated a time-dependent decrease in AMPK activity and increase in mammalian target of rapamycin complex 1 (mTORC1) activity after contextual fear conditioning in the CA1 but not CA3 area of the dorsal hippocampus. Using pharmacological methods and adenovirus gene transfer to bidirectionally regulate AMPK activity, we found that increasing AMPK activity in the CA1 impaired the formation of long-term fear memory, and decreasing AMPK activity enhanced fear memory formation. These findings were associated with changes in the phosphorylation of AMPK and p70s6 kinase (p70s6k) and expression of BDNF and membrane GluR1 and GluR2 in the CA1. Furthermore, the prior administration of an mTORC1 inhibitor blocked the enhancing effect of AMPK inhibition on fear memory formation, suggesting that this negative regulation of contextual fear memory by AMPK in the CA1 depends on the mTORC1 signaling pathway. Finally, we found that AMPK activity regulated hippocampal spine growth associated with memory formation. In summary, our results indicate that AMPK is a key negative regulator of plasticity and fear memory formation. PMID:26647974
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Waldum, Emily R; Sahakyan, Lili
2012-05-01
In three experiments, we evaluated remembering and intentional forgetting of attitude statements that were either congruent or incongruent with participants' own political attitudes. In Experiment 1, significant directed forgetting was obtained for incongruent statements, but not for congruent statements. In addition, in the remember group, recall was better for incongruent statements than congruent statements. To explain these findings, we propose a contextual competition at retrieval hypothesis, according to which incongruent statements become more strongly associated with their episodic context during encoding than do congruent statements. At the time of retrieval, incongruent statements compete with congruent statements due to the greater amount of contextual information stored in their memory trace. We tested this hypothesis in Experiment 2 by studying free recall of congruent and incongruent statements in a mixed-pure list design. In Experiment 3, memory for incongruent and congruent statements was tested under recognition test conditions that varied in terms of how much direct retrieval of contextual details they required. Overall, the results supported the contextual competition hypothesis, and they indicate the importance of context strength in both the remembering and intentional forgetting of attitude information.
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Waldum, Emily R; Sahakyan, Lili
2013-01-01
In three experiments, we evaluated remembering and intentional forgetting of attitude statements that were either congruent or incongruent with participants’ own political attitudes. In Experiment 1, significant directed forgetting was obtained for incongruent statements, but not for congruent statements. In addition, in the remember group, recall was better for incongruent statements than congruent statements. To explain these findings, we propose a contextual competition at retrieval hypothesis, according to which incongruent statements become more strongly associated with their episodic context during encoding than do congruent statements. At the time of retrieval, incongruent statements compete with congruent statements due to the greater amount of contextual information stored in their memory trace. We tested this hypothesis in Experiment 2 by studying free recall of congruent and incongruent statements in a mixed-pure list design. In Experiment 3, memory for incongruent and congruent statements was tested under recognition test conditions that varied in terms of how much direct retrieval of contextual details they required. Overall, the results supported the contextual competition hypothesis, and they indicate the importance of context strength in both the remembering and intentional forgetting of attitude information. PMID:23440945
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Gass, Peter; Fleischmann, Alexander; Hvalby, Oivind; Jensen, Vidar; Zacher, Christiane; Strekalova, Tatyana; Kvello, Ane; Wagner, Erwin F; Sprengel, Rolf
2004-11-04
The immediate early gene c-fos is part of the AP-1 transcription factor complex, which is involved in molecular mechanisms underlying learning and memory. Mice that lack c-Fos in the brain show impairments in spatial reference and contextual learning, and also exhibit a reduced long-term potentiation of synaptic transmission (LTP) at CA3-to-CA1 synapses. In the present study, we investigated mice in which c-fos was deleted and replaced by fra-1 (c-fos(fra-1) mice) to determine whether other members of the c-fos gene family can substitute for the functions of the c-fos gene. In c-fos(fra-1) mice, both CA3-to-CA1 LTP and contextual learning in a Pavlovian fear conditioning task were similar to wild-type littermates, indicating that Fra-1 expression restored the impairments caused by brain-specific c-Fos depletion. However, c-Fos-mediated learning deficits in a reference memory task of the Morris watermaze were also present in c-fos(fra-1) mice. These findings suggest that different c-Fos target genes are involved in LTP, contextual learning, and spatial reference memory formation.
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Sill, Orriana C; Smith, David M
2012-08-01
In recent years, many animal models of memory have focused on one or more of the various components of episodic memory. For example, the odor sequence memory task requires subjects to remember individual items and events (the odors) and the temporal aspects of the experience (the sequence of odor presentation). The well-known spatial context coding function of the hippocampus, as exemplified by place cell firing, may reflect the "where" component of episodic memory. In the present study, we added a contextual component to the odor sequence memory task by training rats to choose the earlier odor in one context and the later odor in another context and we compared the effects of temporary hippocampal lesions on performance of the original single context task and the new dual context task. Temporary lesions significantly impaired the single context task, although performance remained significantly above chance levels. In contrast, performance dropped all the way to chance when temporary lesions were used in the dual context task. These results demonstrate that rats can learn a dual context version of the odor sequence learning task that requires the use of contextual information along with the requirement to remember the "what" and "when" components of the odor sequence. Moreover, the addition of the contextual component made the task fully dependent on the hippocampus.
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The effect of contextual cues on the encoding of motor memories.
Howard, Ian S; Wolpert, Daniel M; Franklin, David W
2013-05-01
Several studies have shown that sensory contextual cues can reduce the interference observed during learning of opposing force fields. However, because each study examined a small set of cues, often in a unique paradigm, the relative efficacy of different sensory contextual cues is unclear. In the present study we quantify how seven contextual cues, some investigated previously and some novel, affect the formation and recall of motor memories. Subjects made movements in a velocity-dependent curl field, with direction varying randomly from trial to trial but always associated with a unique contextual cue. Linking field direction to the cursor or background color, or to peripheral visual motion cues, did not reduce interference. In contrast, the orientation of a visual object attached to the hand cursor significantly reduced interference, albeit by a small amount. When the fields were associated with movement in different locations in the workspace, a substantial reduction in interference was observed. We tested whether this reduction in interference was due to the different locations of the visual feedback (targets and cursor) or the movements (proprioceptive). When the fields were associated only with changes in visual display location (movements always made centrally) or only with changes in the movement location (visual feedback always displayed centrally), a substantial reduction in interference was observed. These results show that although some visual cues can lead to the formation and recall of distinct representations in motor memory, changes in spatial visual and proprioceptive states of the movement are far more effective than changes in simple visual contextual cues.
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Philippe, Frederick L; Bouizegarene, Nabil; Guilbault, Valérie; Rajotte, Guillaume; Houle, Iliane
2015-01-01
Narrative research claims that episodic/autobiographical memory characteristics and themes represent stable individual differences that relate to well-being. However, the effects of the order of administration of memory descriptions and well-being scales have never been investigated. Of importance, social cognitive research has shown that trivial contextual factors, such as completing a self-report measure, can influence the type of memories recollected afterwards and that memory recollection can transiently affect subsequent self-report ratings--both of which underscore that transient contextual effects, rather than stable individual differences in memory could be responsible for the correlation between memory characteristics and well-being. The present study examined if the order in which (positive or negative) memory and well-being scales are completed affects the characteristics and themes of the memory described, the scores of well-being reported and the relationship between the two. The results revealed some effects of order of administration when memories were described before completing well-being scales, but only on a situational measure of well-being, not on a trait measure. In sum, we recommend assessing memory-related material at the end of questionnaires to avoid potential mood-priming effects.
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Soya, Shingo; Shoji, Hirotaka; Hasegawa, Emi; Hondo, Mari; Miyakawa, Tsuyoshi; Yanagisawa, Masashi; Mieda, Michihiro; Sakurai, Takeshi
2013-09-04
The noradrenergic (NA) projections arising from the locus ceruleus (LC) to the amygdala and bed nucleus of the stria terminalis have been implicated in the formation of emotional memory. Since NA neurons in the LC (LC-NA neurons) abundantly express orexin receptor-1 (OX1R) and receive prominent innervation by orexin-producing neurons, we hypothesized that an OX1R-mediated pathway is involved in the physiological fear learning process via regulation of LC-NA neurons. To evaluate this hypothesis, we examined the phenotype of Ox1r(-/-) mice in the classic cued and contextual fear-conditioning test. We found that Ox1r(-/-) mice showed impaired freezing responses in both cued and contextual fear-conditioning paradigms. In contrast, Ox2r(-/-) mice showed normal freezing behavior in the cued fear-conditioning test, while they exhibited shorter freezing time in the contextual fear-conditioning test. Double immunolabeling of Fos and tyrosine hydroxylase showed that double-positive LC-NA neurons after test sessions of both cued and contextual stimuli were significantly fewer in Ox1r(-/-) mice. AAV-mediated expression of OX1R in LC-NA neurons in Ox1r(-/-) mice restored the freezing behavior to the auditory cue to a comparable level to that in wild-type mice in the test session. Decreased freezing time during the contextual fear test was not affected by restoring OX1R expression in LC-NA neurons. These observations support the hypothesis that the orexin system modulates the formation and expression of fear memory via OX1R in multiple pathways. Especially, OX1R in LC-NA neurons plays an important role in cue-dependent fear memory formation and/or retrieval.
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Memory for time and place contributes to enhanced confidence in memories for emotional events
Rimmele, Ulrike; Davachi, Lila; Phelps, Elizabeth A.
2012-01-01
Emotion strengthens the subjective sense of remembering. However, these confidently remembered emotional memories have not been found be more accurate for some types of contextual details. We investigated whether the subjective sense of recollecting negative stimuli is coupled with enhanced memory accuracy for three specific types of central contextual details using the remember/know paradigm and confidence ratings. Our results indicate that the subjective sense of remembering is indeed coupled with better recollection of spatial location and temporal context. In contrast, we found a double-dissociation between the subjective sense of remembering and memory accuracy for colored dots placed in the conceptual center of negative and neutral scenes. These findings show that the enhanced subjective recollective experience for negative stimuli reliably indicates objective recollection for spatial location and temporal context, but not for other types of details, whereas for neutral stimuli, the subjective sense of remembering is coupled with all the types of details assessed. Translating this finding to flashbulb memories, we found that, over time, more participants correctly remembered the location where they learned about the terrorist attacks on 9/11 than any other canonical feature. Likewise participants’ confidence was higher in their memory for location vs. other canonical features. These findings indicate that the strong recollective experience of a negative event corresponds to an accurate memory for some kinds of contextual details, but not other kinds. This discrepancy provides further evidence that the subjective sense of remembering negative events is driven by a different mechanism than the subjective sense of remembering neutral events. PMID:22642353
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Autophagy Enhances Memory Erasure through Synaptic Destabilization.
Shehata, Mohammad; Abdou, Kareem; Choko, Kiriko; Matsuo, Mina; Nishizono, Hirofumi; Inokuchi, Kaoru
2018-04-11
There is substantial interest in memory reconsolidation as a target for the treatment of anxiety disorders, such as post-traumatic stress disorder. However, its applicability is restricted by reconsolidation-resistant boundary conditions that constrain the initial memory destabilization. In this study, we investigated whether the induction of synaptic protein degradation through autophagy modulation, a major protein degradation pathway, can enhance memory destabilization upon retrieval and whether it can be used to overcome these conditions. Here, using male mice in an auditory fear reconsolidation model, we showed that autophagy contributes to memory destabilization and its induction can be used to enhance erasure of a reconsolidation-resistant auditory fear memory that depended on AMPAR endocytosis. Using male mice in a contextual fear reconsolidation model, autophagy induction in the amygdala or in the hippocampus enhanced fear or contextual memory destabilization, respectively. The latter correlated with AMPAR degradation in the spines of the contextual memory-ensemble cells. Using male rats in an in vivo LTP reconsolidation model, autophagy induction enhanced synaptic destabilization in an NMDAR-dependent manner. These data indicate that induction of synaptic protein degradation can enhance both synaptic and memory destabilization upon reactivation and that autophagy inducers have the potential to be used as a therapeutic tool in the treatment of anxiety disorders. SIGNIFICANCE STATEMENT It has been reported that inhibiting synaptic protein degradation prevents memory destabilization. However, whether the reverse relation is true and whether it can be used to enhance memory destabilization are still unknown. Here we addressed this question on the behavioral, molecular, and synaptic levels, and showed that induction of autophagy, a major protein degradation pathway, can enhance memory and synaptic destabilization upon reactivation. We also show that autophagy induction can be used to overcome a reconsolidation-resistant memory, suggesting autophagy inducers as a potential therapeutic tool in the treatment of anxiety disorders. Copyright © 2018 the authors 0270-6474/18/383809-14$15.00/0.
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Ball, B Hunter; DeWitt, Michael R; Knight, Justin B; Hicks, Jason L
2014-09-01
The current study sought to examine the relative contributions of encoding and retrieval processes in accessing contextual information in the absence of item memory using an extralist cuing procedure in which the retrieval cues used to query memory for contextual information were related to the target item but never actually studied. In Experiments 1 and 2, participants studied 1 category member (e.g., onion) from a variety of different categories and at test were presented with an unstudied category label (e.g., vegetable) to probe memory for item and source information. In Experiments 3 and 4, 1 member of unidirectional (e.g., credit or card) or bidirectional (e.g., salt or pepper) associates was studied, whereas the other unstudied member served as a test probe. When recall failed, source information was accessible only when items were processed deeply during encoding (Experiments 1 and 2) and when there was strong forward associative strength between the retrieval cue and target (Experiments 3 and 4). These findings suggest that a retrieval probe diagnostic of semantically related item information reinstantiates information bound in memory during encoding that results in reactivation of associated contextual information, contingent upon sufficient learning of the item itself and the association between the item and its context information.
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False Memories Seconds Later: The Rapid and Compelling Onset of Illusory Recognition
ERIC Educational Resources Information Center
Flegal, Kristin E.; Atkins, Alexandra S.; Reuter-Lorenz, Patricia A.
2010-01-01
Distortions of long-term memory (LTM) in the converging associates task are thought to arise from semantic associative processes and monitoring failures due to degraded verbatim and/or contextual memory. Sensory-based coding is traditionally considered more prevalent than meaning-based coding in short-term memory (STM), whereas the converse is…
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Intrusions in Episodic Memory: Reconsolidation or Interference?
ERIC Educational Resources Information Center
Klingmüller, Angela; Caplan, Jeremy B.; Sommer, Tobias
2017-01-01
It would be profoundly important if reconsolidation research in animals and other memory domains generalized to human episodic memory. A 3-d-list-discrimination procedure, based on free recall of objects, with a contextual reminder cue (the testing room), has been thought to demonstrate reconsolidation of human episodic memory (as noted in a…
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ERIC Educational Resources Information Center
Suzuki, Akinobu; Mukawa, Takuya; Tsukagoshi, Akinori; Frankland, Paul W.; Kida, Satoshi
2008-01-01
Previous studies have shown that inhibiting protein synthesis shortly after reactivation impairs the subsequent expression of a previously consolidated fear memory. This has suggested that reactivation returns a memory to a labile state and that protein synthesis is required for the subsequent restabilization of memory. While the molecular…
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Nakagawa, Toshiyuki; Itoh, Masanori; Ohta, Kazunori; Hayashi, Yuichi; Hayakawa, Miki; Yamada, Yasushi; Akanabe, Hiroshi; Chikaishi, Tokio; Nakagawa, Kiyomi; Itoh, Yoshinori; Muro, Takato; Yanagida, Daisuke; Nakabayashi, Ryo; Mori, Tetsuya; Saito, Kazuki; Ohzawa, Kaori; Suzuki, Chihiro; Li, Shimo; Ueda, Masashi; Wang, Miao-Xing; Nishida, Emika; Islam, Saiful; Tana; Kobori, Masuko; Inuzuka, Takashi
2016-06-15
Patients with Alzheimer's disease (AD) experience a wide array of cognitive deficits, which typically include the impairment of explicit memory. In previous studies, the authors reported that a flavonoid, quercetin, reduces the expression of ATF4 and delays memory deterioration in an early-stage AD mouse model. In the present study, the effects of long-term quercetin intake on memory recall were assessed using contextual fear conditioning in aged wild-type mice. In addition, the present study examined whether memory recall was affected by the intake of quercetin-rich onion (a new cultivar of hybrid onion 'Quergold') powder in early-stage AD patients. In-vivo analysis indicated that memory recall was enhanced in aged mice fed a quercetin-containing diet. Memory recall in early-stage AD patients, determined using the Revised Hasegawa Dementia Scale, was significantly improved by the intake of quercetin-rich onion (Quergold) powder for 4 weeks compared with the intake of control onion ('Mashiro' white onion) powder. These results indicate that quercetin might influence memory recall.
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Process dissociation between contextual retrieval and item recognition.
Weis, Susanne; Specht, Karsten; Klaver, Peter; Tendolkar, Indira; Willmes, Klaus; Ruhlmann, Jürgen; Elger, Christian E; Fernández, Guillén
2004-12-22
We employed a source memory task in an event related fMRI study to dissociate MTL processes associated with either contextual retrieval or item recognition. To introduce context during study, stimuli (photographs of buildings and natural landscapes) were transformed into one of four single-color-scales: red, blue, yellow, or green. In the subsequent old/new recognition memory test, all stimuli were presented as gray scale photographs, and old-responses were followed by a four-alternative source judgment referring to the color in which the stimulus was presented during study. Our results suggest a clear-cut process dissociation within the human MTL. While an activity increase accompanies successful retrieval of contextual information, an activity decrease provides a familiarity signal that is sufficient for successful item recognition.
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Memory consolidation and contextual interference effects with computer games.
Shewokis, Patricia A
2003-10-01
Some investigators of the contextual interference effect contend that there is a direct relation between the amount of practice and the contextual interference effect based on the prediction that the improvement in learning tasks in a random practice schedule, compared to a blocked practice schedule, increases in magnitude as the amount of practice during acquisition on the tasks increases. Research using computer games in contextual interference studies has yielded a large effect (f = .50) with a random practice schedule advantage during transfer. These investigations had a total of 36 and 72 acquisition trials, respectively. The present study tested this prediction by having 72 college students, who were randomly assigned to a blocked or random practice schedule, practice 102 trials of three computer-game tasks across three days. After a 24-hr. interval, 6 retention and 5 transfer trials were performed. Dependent variables were time to complete an event in seconds and number of errors. No significant differences were found for retention and transfer. These results are discussed in terms of how the amount of practice, task-related factors, and memory consolidation mediate the contextual interference effect.
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Contextual fear conditioning in zebrafish.
Kenney, Justin W; Scott, Ian C; Josselyn, Sheena A; Frankland, Paul W
2017-10-01
Zebrafish are a genetically tractable vertebrate that hold considerable promise for elucidating the molecular basis of behavior. Although numerous recent advances have been made in the ability to precisely manipulate the zebrafish genome, much less is known about many aspects of learning and memory in adult fish. Here, we describe the development of a contextual fear conditioning paradigm using an electric shock as the aversive stimulus. We find that contextual fear conditioning is modulated by shock intensity, prevented by an established amnestic agent (MK-801), lasts at least 14 d, and exhibits extinction. Furthermore, fish of various background strains (AB, Tu, and TL) are able to acquire fear conditioning, but differ in fear extinction rates. Taken together, we find that contextual fear conditioning in zebrafish shares many similarities with the widely used contextual fear conditioning paradigm in rodents. Combined with the amenability of genetic manipulation in zebrafish, we anticipate that our paradigm will prove to be a useful complementary system in which to examine the molecular basis of vertebrate learning and memory. © 2017 Kenney et al.; Published by Cold Spring Harbor Laboratory Press.
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Pierard, C; Dorey, R; Henkous, N; Mons, N; Béracochéa, D
2017-09-01
This study assessed the relative contributions of dorsal (dHPC) and ventral (vHPC) hippocampus regions in mediating the rapid effects of an acute stress on contextual memory retrieval. Indeed, we previously showed that an acute stress (3 electric footschocks; 0.9 mA each) delivered 15 min before the 24 h-test inversed the memory retrieval pattern in a contextual discrimination task. Specifically, mice learned in a four-hole board two successive discriminations (D1 and D2) varying by the color and texture of the floor. Twenty-four hours later, nonstressed animals remembered accurately D1 but not D2 whereas stressed mice showed an opposite memory retrieval pattern, D2 being more accurately remembered than D1. We showed here that, at the time of memory testing in that task, stressed animals exhibited no significant changes neither in pCREB activity nor in the time-course evolution of corticosterone into the vHPC; in contrast, a significant decrease in pCREB activity and a significant increase in corticosterone were observed in the dHPC as compared to nonstressed mice. Moreover, local infusion of the anesthetic lidocaine into the vHPC 15 min before the onset of the stressor did not modify the memory retrieval pattern in nonstress and stress conditions whereas lidocaine infusion into the dHPC induced in nonstressed mice an memory retrieval pattern similar to that observed in stressed animals. The overall set of data shows that memory retrieval in nonstress condition involved primarily the dHPC and that the inversion of memory retrieval pattern after stress is linked to a dHPC but not vHPC dysfunction. © 2017 Wiley Periodicals, Inc.
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Triazolam and zolpidem: effects on human memory and attentional processes.
Mintzer, M Z; Griffiths, R R
1999-05-01
The imidazopyridine hypnotic zolpidem may produce less memory and cognitive impairment than classic benzodiazepines, due to its relatively low binding affinity for the benzodiazepine receptor subtypes found in areas of the brain which are involved in learning and memory. The study was designed to compare the acute effects of single oral doses of zolpidem (5, 10, 20 mg/70 kg) and the benzodiazepine hypnotic triazolam (0.125, 0.25, and 0.5 mg/70 kg) on specific memory and attentional processes. Drug effects on memory for target (i.e., focal) information and contextual information (i.e., peripheral details surrounding a target stimulus presentation) were evaluated using a source monitoring paradigm, and drug effects on selective attention mechanisms were evaluated using a negative priming paradigm, in 18 healthy volunteers in a double-blind, placebo-controlled, crossover design. Triazolam and zolpidem produced strikingly similar dose-related effects on memory for target information. Both triazolam and zolpidem impaired subjects' ability to remember whether a word stimulus had been presented to them on the computer screen or whether they had been asked to generate the stimulus based on an antonym cue (memory for the origin of a stimulus, which is one type of contextual information). The results suggested that triazolam, but not zolpidem, impaired memory for the screen location of picture stimuli (spatial contextual information). Although both triazolam and zolpidem increased overall reaction time in the negative priming task, only triazolam increased the magnitude of negative priming relative to placebo. The observed differences between triazolam and zolpidem have implications for the cognitive and pharmacological mechanisms underlying drug-induced deficits in specific memory and attentional processes, as well for the cognitive and brain mechanisms underlying these processes.
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Sigwald, Eric L; Genoud, Manuel E; Giachero, Marcelo; de Olmos, Soledad; Molina, Víctor A; Lorenzo, Alfredo
2016-05-01
The retrosplenial cortex (RSC) is one of the largest cortical areas in rodents, and is subdivided in two main regions, A29 and A30, according to their cytoarchitectural organization and connectivities. However, very little is known about the functional activity of each RSC subdivision during the execution of complex cognitive tasks. Here, we used a well-established fear learning protocol that induced long-lasting contextual fear memory and showed that during evocation of the fear memory, the expression of early growth response gene 1 was up-regulated in A30, and in other brain areas implicated in fear and spatial memory, however, was down-regulated in A29, including layers IV and V. To search for the participation of A29 on fear memory, we triggered selective degeneration of neurons within cortical layers IV and V of A29 by using a non-invasive protocol that takes advantage of the vulnerability that these neurons have MK801-toxicity and the modulation of this neurodegeneration by testosterone. Application of 5 mg/kg MK801 in intact males induced negligible neuronal degeneration of A29 neurons and had no impact on fear memory retrieval. However, in orchiectomized rats, 5 mg/kg MK801 induced overt degeneration of layers IV-V neurons of A29, significantly impairing fear memory recall. Degeneration of A29 neurons did not affect exploratory or anxiety-related behavior nor altered unconditioned freezing. Importantly, protecting A29 neurons from MK801-toxicity by testosterone preserved fear memory recall in orchiectomized rats. Thus, neurons within cortical layers IV-V of A29 are critically required for efficient retrieval of contextual fear memory.
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Transfer of memory retrieval cues in rats.
Briggs, James F; Fitz, Kelly I; Riccio, David C
2007-06-01
Two experiments using rats were conducted to determine whether the retrieval of a memory could be brought under the control of new contextual cues that had not been present at the time of training. In Experiment 1, rats were trained in one context and then exposed to different contextual cues immediately, 60 min, or 120 min after training. When tested in the shifted context, rats that had been exposed shortly after training treated the shifted context as if it were the original context. The control that the previously neutral context had over retrieval disappeared with longer posttraining delays, suggesting the importance of an active memory representation during exposure. Experiment 2 replicated the basic finding and demonstrated that the transfer of retrieval cues was specific to the contextual cues present during exposure. These findings with rats are consistent with findings from infant research (see, e.g., Boller & Rovee-Collier, 1992) that have shown that a neutral context can come to serve as a retrieval cue for an episode experienced elsewhere.
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Jing, Xu; Sui, Wen-Hai; Wang, Shuai; Xu, Xu-Feng; Yuan, Rong-Rong; Chen, Xiao-Rong; Ma, Hui-Xian; Zhu, Ying-Xiao; Sun, Jin-Kai; Yi, Fan; Chen, Zhe-Yu; Wang, Yue
2017-04-05
Histone acetylation, an epigenetic modification, plays an important role in long-term memory formation. Recently, histone deacetylase (HDAC) inhibitors were demonstrated to promote memory formation, which raises the intriguing possibility that they may be used to rescue memory deficits. However, additional research is necessary to clarify the roles of individual HDACs in memory. In this study, we demonstrated that HDAC7, within the dorsal hippocampus of C57BL6J mice, had a late and persistent decrease after contextual fear conditioning (CFC) training (4-24 h), which was involved in long-term CFC memory formation. We also showed that HDAC7 decreased via ubiquitin-dependent degradation. CBX4 was one of the HDAC7 E3 ligases involved in this process. Nur77, as one of the target genes of HDAC7, increased 6-24 h after CFC training and, accordingly, modulated the formation of CFC memory. Finally, HDAC7 was involved in the formation of other hippocampal-dependent memories, including the Morris water maze and object location test. The current findings facilitate an understanding of the molecular and cellular mechanisms of HDAC7 in the regulation of hippocampal-dependent memory. SIGNIFICANCE STATEMENT The current findings demonstrated the effects of histone deacetylase 7 (HDAC7) on hippocampal-dependent memories. Moreover, we determined the mechanism of decreased HDAC7 in contextual fear conditioning (CFC) through ubiquitin-dependent protein degradation. We also verified that CBX4 was one of the HDAC7 E3 ligases. Finally, we demonstrated that Nur77, as one of the important targets for HDAC7, was involved in CFC memory formation. All of these proteins, including HDAC7, CBX4, and Nur77, could be potential therapeutic targets for preventing memory deficits in aging and neurological diseases. Copyright © 2017 the authors 0270-6474/17/373848-16$15.00/0.
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Xia, Frances; Richards, Blake A; Tran, Matthew M; Josselyn, Sheena A
2017-01-01
Following learning, increased coupling between spindle oscillations in the medial prefrontal cortex (mPFC) and ripple oscillations in the hippocampus is thought to underlie memory consolidation. However, whether learning-induced increases in ripple-spindle coupling are necessary for successful memory consolidation has not been tested directly. In order to decouple ripple-spindle oscillations, here we chemogenetically inhibited parvalbumin-positive (PV+) interneurons, since their activity is important for regulating the timing of spiking activity during oscillations. We found that contextual fear conditioning increased ripple-spindle coupling in mice. However, inhibition of PV+ cells in either CA1 or mPFC eliminated this learning-induced increase in ripple-spindle coupling without affecting ripple or spindle incidence. Consistent with the hypothesized importance of ripple-spindle coupling in memory consolidation, post-training inhibition of PV+ cells disrupted contextual fear memory consolidation. These results indicate that successful memory consolidation requires coherent hippocampal-neocortical communication mediated by PV+ cells. PMID:28960176
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Cortisol reduces recall of explicit contextual pain memory in healthy young men.
Schwegler, Kyrill; Ettlin, Dominik; Buser, Iris; Klaghofer, Richard; Goetzmann, Lutz; Buddeberg, Claus; Alon, Eli; Brügger, Mike; de Quervain, Dominique J-F
2010-09-01
Remembering painful incidents has important adaptive value but may also contribute to clinical symptoms of posttraumatic stress disorder and chronic pain states. Because glucocorticoids are known to impair memory retrieval processes, we investigated whether cortisol affects recall of previously experienced pain in healthy young men. In a double-blind, placebo-controlled crossover study, 20 male participants were presented pictures, half of them combined with a heat-pain stimulus. The next day, the same pictures were shown in the absence of pain. Cortisol (20 mg) administered 1h before retention testing reduced recall of explicit contextual pain memory, whereas it did not affect pain threshold or pain tolerance. Copyright 2010 Elsevier Ltd. All rights reserved.
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Segev, Amir; Akirav, Irit
2011-04-01
We examined whether the cannabinoid receptor agonist WIN55,212-2 (WIN; 5 µg/side) microinjected into the hippocampus or the amygdala would differentially affect memory processes in a neutral vs. an aversive task. In the aversive contextual fear task, WIN into the basolateral amygdala impaired fear acquisition/consolidation, but not retrieval. In the ventral subiculum (vSub), WIN impaired fear retrieval. In the neutral social discrimination task, WIN into the vSub impaired both acquisition/consolidation and retrieval, whereas in the medial amygdala WIN impaired acquisition. The results suggest that cannabinoid signaling differentially affects memory in a task-, region-, and memory stage-dependent manner.
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Preethi, Jayakumar; Singh, Hemant K; Venkataraman, Jois Shreyas; Rajan, Koilmani Emmanuvel
2014-05-01
Contextual fear conditioning is a paradigm for investigating cellular mechanisms involved in hippocampus-dependent memory. Earlier, we showed that standardised extract of Bacopa monniera (CDRI-08) improves hippocampus-dependent learning in postnatal rats by elevating the level of serotonin (5-hydroxytryptamine, 5-HT), activate 5-HT3A receptors, and cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein. In this study, we have further examined the molecular mechanism of CDRI-08 in hippocampus-dependent memory and compared to the histone deacetylase (HDACs) inhibitor sodium butyrate (NaB). To assess the hippocampus-dependent memory, wistar rat pups were subjected to contextual fear conditioning (CFC) following daily (postnatal days 15-29) administration of vehicle solution (0.5 % gum acacia + 0.9 % saline)/CDRI-08 (80 mg/kg, p.o.)/NaB (1.2 g/kg in PBS, i.p.). CDRI-08/NaB treated group showed enhanced freezing behavior compared to control group when re-exposed to the same context. Administration of CDRI-08/NaB resulted in activation of extracellular signal-regulated kinase ERK/CREB signaling cascade and up-regulation of p300, Ac-H3 and Ac-H4 levels, and down-regulation of HDACs (1, 2) and protein phosphatases (PP1α, PP2A) in hippocampus following CFC. This would subsequently result in an increased brain-derived neurotrophic factor (Bdnf) (exon IV) mRNA in hippocampus. Altogether, our results indicate that CDRI-08 enhances hippocampus-dependent contextual memory by differentially regulating histone acetylation and protein phosphatases in hippocampus.
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The Episodic Nature of Episodic-Like Memories
ERIC Educational Resources Information Center
Easton, Alexander; Webster, Lisa A. D.; Eacott, Madeline J.
2012-01-01
Studying episodic memory in nonhuman animals has proved difficult because definitions in humans require conscious recollection. Here, we assessed humans' experience of episodic-like recognition memory tasks that have been used with animals. It was found that tasks using contextual information to discriminate events could only be accurately…
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Temporal Context Memory in High-Functioning Autism
ERIC Educational Resources Information Center
Gras-Vincendon, Agnes; Mottron, Laurent; Salame, Pierre; Bursztejn, Claude; Danion, Jean-Marie
2007-01-01
Episodic memory, i.e. memory for specific episodes situated in space and time, seems impaired in individuals with autism. According to weak central coherence theory, individuals with autism have general difficulty connecting contextual and item information which then impairs their capacity to memorize information in context. This study…
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Variation in Working Memory Capacity and Temporal-Contextual Retrieval from Episodic Memory
ERIC Educational Resources Information Center
Spillers, Gregory J.; Unsworth, Nash
2011-01-01
Unsworth and Engle (2007) recently proposed a model of working memory capacity characterized by, among other things, the ability to conduct a strategic, cue-dependent search of long-term memory. Although this ability has been found to mediate individual variation in a number of higher order cognitive tasks, the component processes involved remain…
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ERIC Educational Resources Information Center
Yu, Yang-Jung; Huang, Chien-Hsuan; Chang, Chih-Hua; Gean, Po-Wu
2016-01-01
Destabilization refers to a memory that becomes unstable when reactivated and is susceptible to disruption by amnestic agents. Here we delineated the cellular mechanism underlying the destabilization of drug memory. Mice were conditioned with methamphetamine (MeAM) for 3 d, and drug memory was assessed with a conditioned place preference (CPP)…
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GABA-Mediated Presynaptic Inhibition Is Required for Precision of Long-Term Memory
ERIC Educational Resources Information Center
Cullen, Patrick K.; Dulka, Brooke N.; Ortiz, Samantha; Riccio, David C.; Jasnow, Aaron M.
2014-01-01
Though much attention has been given to the neural structures that underlie the long-term consolidation of contextual memories, little is known about the mechanisms responsible for the maintenance of memory precision. Here, we demonstrate a rapid time-dependent decline in memory precision in GABA [subscript B(1a)] receptor knockout mice. First, we…
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Sill, Orriana C.; Smith, David M.
2012-01-01
In recent years, many animal models of memory have focused on one or more of the various components of episodic memory. For example, the odor sequence memory task requires subjects to remember individual items and events (the odors) and the temporal aspects of the experience (the sequence of odor presentation). The well-known spatial context coding function of the hippocampus, as exemplified by place cell firing, may reflect the ‘where’ component of episodic memory. In the present study, we added a contextual component to the odor sequence memory task by training rats to choose the earlier odor in one context and the later odor in another context and we compared the effects of temporary hippocampal lesions on performance of the original single context task and the new dual context task. Temporary lesions significantly impaired the single context task, although performance remained significantly above chance levels. In contrast, performance dropped all the way to chance when temporary lesions were used in the dual context task. These results demonstrate that rats can learn a dual context version of the odor sequence learning task which requires the use of contextual information along with the requirement to remember the ‘what’ and ‘when’ components of the odor sequence. Moreover, the additional requirement of context-dependent expression of the ‘what-when’ memory made the task fully dependent on the hippocampus. Moreover, the addition of the contextual component made the task fully dependent on the hippocampus. PMID:22687149
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Chew, Benjamin; Ryu, Jae Ryun; Ng, Teclise; Ma, Dongliang; Dasgupta, Ananya; Neo, Sin Hui; Zhao, Jing; Zhong, Zhong; Bichler, Zoë; Sajikumar, Sreedharan; Goh, Eyleen L. K.
2015-01-01
Attempts have been made to use glycogen synthase kinase-3 beta (GSK3β) inhibitors for prophylactic treatment of neurocognitive conditions. However the use of lithium, a non-specific inhibitor of GSK3β results in mild cognitive impairment in humans. The effects of global GSK3β inhibition or knockout on learning and memory in healthy adult mice are also inconclusive. Our study aims to better understand the role of GSK3β in learning and memory through a more regionally, targeted approach, specifically performing lentiviral-mediated knockdown of GSK3β within the dentate gyrus (DG). DG-GSK3β-silenced mice showed impaired contextual fear memory retrieval. However, cue fear memory, spatial memory, locomotor activity and anxiety levels were similar to control. These GSK3β-silenced mice also showed increased induction and maintenance of DG long-term potentiation (DG-LTP) compared to control animals. Thus, this region-specific, targeted knockdown of GSK3β in the DG provides better understanding on the role of GSK3β in learning and memory. PMID:26157370
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16Oxygen irradiation enhances cued fear memory in B6D2F1 mice
NASA Astrophysics Data System (ADS)
Raber, Jacob; Marzulla, Tessa; Kronenberg, Amy; Turker, Mitchell S.
2015-11-01
The space radiation environment includes energetic charged particles that may impact cognitive performance. We assessed the effects of 16O ion irradiation on cognitive performance of C57BL/6J × DBA/2J F1 (B6D2F1) mice at OHSU (Portland, OR) one month following irradiation at Brookhaven National Laboratory (BNL, Upton, NY). Hippocampus-dependent contextual fear memory and hippocampus-independent cued fear memory of B6D2F1 mice were tested. 16O ion exposure enhanced cued fear memory. This effect showed a bell-shaped dose response curve. Cued fear memory was significantly stronger in mice irradiated with 16O ions at a dose of 0.4 or 0.8 Gy than in sham-irradiated mice or following irradiation at 1.6 Gy. In contrast to cued fear memory, contextual fear memory was not affected following 16O ion irradiation at the doses used in this study. These data indicate that the amygdala might be particularly susceptible to effects of 16O ion exposure.
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Context and Time Matter: Effects of Emotion and Motivation on Episodic Memory Overtime
Sun, Qing; Gu, Simeng
2018-01-01
Previous studies have shown that compared with neutral cues, stimuli with positive and negative/stressful contexts or reward and punishment cues are remembered better. However, it is unclear whether the enhanced effect differs in emotion or motivation dimensions and the passage of time. We addressed these issues by manipulating different contextual cues for neutral words at different time intervals. In experiment 1, subjects were asked to learn words with picture contexts in positive, negative/stressful, and neutral valences and were tested by old/new word recognition and contextual judgment 10 min, 1 day, and 1 week later. In experiment 2, the reward and punishment motivations were manipulated by monetary cues during learning. Word recognition and contextual judgment were assessed 10 min, 1 day, 1 week, and 1 month after the study. Compared with negative and punishment conditions, the words in positive and reward contexts were recognized better at shorter intervals, which was associated with recollection process. In contrast, the words in negative and punishment contexts were recognized better at longer intervals, which was mainly associated with familiarity process. These results clarified how different dimensions of emotional and motivational contexts influence memory at short and long intervals and highlighted the role of contextual features in memory formation and consolidation. PMID:29849564
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Context and Time Matter: Effects of Emotion and Motivation on Episodic Memory Overtime.
Sun, Qing; Gu, Simeng; Yang, Jiongjiong
2018-01-01
Previous studies have shown that compared with neutral cues, stimuli with positive and negative/stressful contexts or reward and punishment cues are remembered better. However, it is unclear whether the enhanced effect differs in emotion or motivation dimensions and the passage of time. We addressed these issues by manipulating different contextual cues for neutral words at different time intervals. In experiment 1, subjects were asked to learn words with picture contexts in positive, negative/stressful, and neutral valences and were tested by old/new word recognition and contextual judgment 10 min, 1 day, and 1 week later. In experiment 2, the reward and punishment motivations were manipulated by monetary cues during learning. Word recognition and contextual judgment were assessed 10 min, 1 day, 1 week, and 1 month after the study. Compared with negative and punishment conditions, the words in positive and reward contexts were recognized better at shorter intervals, which was associated with recollection process. In contrast, the words in negative and punishment contexts were recognized better at longer intervals, which was mainly associated with familiarity process. These results clarified how different dimensions of emotional and motivational contexts influence memory at short and long intervals and highlighted the role of contextual features in memory formation and consolidation.
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Poole, Rachel L.; Braak, David; Gould, Thomas J.
2015-01-01
Chronic caffeine exerts negligible effects on learning and memory in normal adults, but it is unknown whether this is also true for children and adolescents. The hippocampus, a brain region important for learning and memory, undergoes extensive structural and functional modifications during pre-adolescence and adolescence. As a result, chronic caffeine may have differential effects on hippocampus-dependent learning in pre-adolescents and adolescents compared with adults. Here, we characterized the effects of chronic caffeine and withdrawal from chronic caffeine on hippocampus-dependent (contextual) and hippocampus-independent (cued) fear conditioning in pre-adolescent, adolescent, and adult mice. The results indicate that chronic exposure to caffeine during pre-adolescence and adolescence enhances or impairs contextual conditioning depending on concentration, yet has no effect on cued conditioning. In contrast, withdrawal from chronic caffeine impairs contextual conditioning in pre-adolescent mice only. No changes in learning were seen for adult mice for either the chronic caffeine or withdrawal conditions. These findings support the hypothesis that chronic exposure to caffeine during pre-adolescence and adolescence can alter learning and memory and as changes were only seen in hippocampus-dependent learning, this suggests that the developing hippocampus may be sensitive to the effects of caffeine. PMID:25827925
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Fear Conditioning is Disrupted by Damage to the Postsubiculum
Robinson, Siobhan; Bucci, David J.
2011-01-01
The hippocampus plays a central role in spatial and contextual learning and memory, however relatively little is known about the specific contributions of parahippocampal structures that interface with the hippocampus. The postsubiculum (PoSub) is reciprocally connected with a number of hippocampal, parahippocampal and subcortical structures that are involved in spatial learning and memory. In addition, behavioral data suggest that PoSub is needed for optimal performance during tests of spatial memory. Together, these data suggest that PoSub plays a prominent role in spatial navigation. Currently it is unknown whether the PoSub is needed for other forms of learning and memory that also require the formation of associations among multiple environmental stimuli. To address this gap in the literature we investigated the role of PoSub in Pavlovian fear conditioning. In Experiment 1 male rats received either lesions of PoSub or Sham surgery prior to training in a classical fear conditioning procedure. On the training day a tone was paired with foot shock three times. Conditioned fear to the training context was evaluated 24 hr later by placing rats back into the conditioning chamber without presenting any tones or shocks. Auditory fear was assessed on the third day by presenting the auditory stimulus in a novel environment (no shock). PoSub-lesioned rats exhibited impaired acquisition of the conditioned fear response as well as impaired expression of contextual and auditory fear conditioning. In Experiment 2, PoSub lesions were made 1 day after training to specifically assess the role of PoSub in fear memory. No deficits in the expression of contextual fear were observed, but freezing to the tone was significantly reduced in PoSub-lesioned rats compared to shams. Together, these results indicate that PoSub is necessary for normal acquisition of conditioned fear, and that PoSub contributes to the expression of auditory but not contextual fear memory. PMID:22076971
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Itzhak, Yossef; Anderson, Karen L; Kelley, Jonathan B; Petkov, Martin
2012-05-01
Epigenetic regulation of chromatin structure is an essential molecular mechanism that contributes to the formation of synaptic plasticity and long-term memory (LTM). An important regulatory process of chromatin structure is acetylation and deacetylation of histone proteins. Inhibition of histone deacetylase (HDAC) increases acetylation of histone proteins and facilitate learning and memory. Nitric oxide (NO) signaling pathway has a role in synaptic plasticity, LTM and regulation of histone acetylation. We have previously shown that NO signaling pathway is required for contextual fear conditioning. The present study investigated the effects of systemic administration of the HDAC inhibitor sodium butyrate (NaB) on fear conditioning in neuronal nitric oxide synthase (nNOS) knockout (KO) and wild type (WT) mice. The effect of single administration of NaB on total H3 and H4 histone acetylation in hippocampus and amygdala was also investigated. A single administration of NaB prior to fear conditioning (a) rescued contextual fear conditioning of nNOS KO mice and (b) had long-term (weeks) facilitatory effect on the extinction of cued fear memory of WT mice. The facilitatory effect of NaB on extinction of cued fear memory of WT mice was confirmed in a study whereupon NaB was administered during extinction. Results suggest that (a) the rescue of contextual fear conditioning in nNOS KO mice is associated with NaB-induced increase in H3 histone acetylation and (b) the accelerated extinction of cued fear memory in WT mice is associated with NaB-induced increase in H4 histone acetylation. Hence, a single administration of HDAC inhibitor may rescue NO-dependent cognitive deficits and afford a long-term accelerating effect on extinction of fear memory of WT mice. Copyright © 2012 Elsevier Inc. All rights reserved.
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Low-dose systemic scopolamine disrupts context conditioning in rats.
Luyten, Laura; Nuyts, Shauni; Beckers, Tom
2017-06-01
Cholinergic neurotransmission plays a key role in learning and memory. Prior research with rats indicated that a low dose of pre-training scopolamine (0.1 mg/kg), a cholinergic receptor antagonist, did not affect cued fear conditioning, but did block renewal when injected before extinguishing a conditioned tone, opening up opportunities to pharmacologically improve exposure therapy for anxiety patients. Before translating these findings to the clinic, it is important to carefully examine how scopolamine affects contextual fear memories. Here, we investigated the effects of scopolamine on encoding of contextual anxiety and its generalization in male Wistar rats. We found a profound disruption of context conditioning, suggesting that, even at a low dose, systemic scopolamine may influence contextual encoding in the hippocampus, particularly when the context is the best predictor for the presence of shocks.
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Two roles of the context in Pavlovian fear conditioning.
Urcelay, Gonzalo P; Miller, Ralph R
2010-04-01
At both empirical and theoretical levels, multiple functional roles of contextual information upon memory performance have been proposed without a clear dissociation of these roles. Some theories have assumed that contexts are functionally similar to cues, whereas other views emphasize the retrieval facilitating properties of contextual information. In Experiment 1, we observed that one critical parameter, the spacing of trials, could determine whether the context would function as a conditioned stimulus or as a retrieval cue for memories trained in different phases. Experiments 2 and 3 doubly dissociated these functions by selectively disrupting one role but not the other, and vice versa. Overall, these observations identify one determinant of different functions of contextual information and pose a major challenge to theories of learning that assume exclusively one or the other function of the context. Moreover, these data emphasize the importance of parametric variations on behavioral control, which has critical implications for studies designed to understand the role of the hippocampus in processing of contextual attributes.
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On the Transition from Reconsolidation to Extinction of Contextual Fear Memories
ERIC Educational Resources Information Center
Cassini, Lindsey F.; Flavell, Charlotte R.; Amaral, Olavo B.; Lee, Jonathan L. C.
2017-01-01
Retrieval of an associative memory can lead to different phenomena. Brief reexposure sessions tend to trigger reconsolidation, whereas more extended ones trigger extinction. In appetitive and fear cued Pavlovian memories, an intermediate "null point" period has been observed where neither process seems to be engaged. Here we investigated…
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Contextual Cueing: Implicit Learning and Memory of Visual Context Guides Spatial Attention.
ERIC Educational Resources Information Center
Chun, Marvin M.; Jiang, Yuhong
1998-01-01
Six experiments involving a total of 112 college students demonstrate that a robust memory for visual context exists to guide spatial attention. Results show how implicit learning and memory of visual context can guide spatial attention toward task-relevant aspects of a scene. (SLD)
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Post-Retrieval Late Process Contributes to Persistence of Reactivated Fear Memory
ERIC Educational Resources Information Center
Nakayama, Daisuke; Yamasaki, Yoshiko; Matsuki, Norio; Nomura, Hiroshi
2013-01-01
Several studies have demonstrated the mechanisms involved in memory persistence after learning. However, little is known about memory persistence after retrieval. In this study, a protein synthesis inhibitor, anisomycin, was infused into the basolateral amygdala of mice 9.5 h after retrieval of contextual conditioned fear. Anisomycin attenuated…
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Benjamin, Aaron S.; Diaz, Michael; Matzen, Laura E.; Johnson, Benjamin
2011-01-01
Older adults exhibit a disproportionate deficit in their ability to recover contextual elements or source information about prior encounters with stimuli. A recent theoretical account, DRYAD (Benjamin, 2010), attributes this selective deficit to a global decrease in memory fidelity with age, moderated by weak representation of contextual information. The predictions of DRYAD are tested here in three experiments. We show that an age-related deficit obtains for whichever aspect of the stimulus subjects’ attention is directed away from during encoding (Experiment 1), suggesting a central role for attention in producing the age-related deficit in context. We also show that an analogous deficit can be elicited within young subjects with a manipulation of study time (Experiment 2), suggesting that any means of reducing memory fidelity yields an interaction of the same form as the age-related effect. Experiment 3 evaluates the critical prediction of DRYAD that endorsement probability in an exclusion task should vary nonmonotonically with memory strength. This prediction was confirmed by assessing the shape of the forgetting function in a continuous exclusion task. The results are consistent with the DRYAD account of aging and memory judgments and do not support the widely held view that aging entails the selective disruption of processes involved in encoding, storing, or retrieving contextual information. PMID:21875219
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Zhang, Chun-Lei; Houbaert, Xander; Lepleux, Marilyn; Deshors, Melissa; Normand, Elisabeth; Gambino, Frédéric; Herzog, Etienne; Humeau, Yann
2015-11-01
The process of learning mainly depends on the ability to store new information, while the ability to retrieve this information and express appropriate behaviors are also crucial for the adaptation of individuals to environmental cues. Thereby, all three components contribute to the cognitive fitness of an individual. While a lack of behavioral adaptation is a recurrent trait of intellectually disabled patients, discriminating between memory formation, memory retrieval or behavioral expression deficits is not easy to establish. Here, we report some deficits in contextual fear behavior in knockout mice for the intellectual disability gene Il1rapl1. Functional in vivo experiments revealed that the lack of conditioned response resulted from a local inhibitory to excitatory (I/E) imbalance in basolateral amygdala (BLA) consecutive to a loss of excitatory drive onto BLA principal cells by caudal hippocampus axonal projections. A normalization of the fear behavior was obtained in adult mutant mice following opsin-based in vivo synaptic priming of hippocampo-BLA synapses in adult il1rapl1 knockout mice, indicating that synaptic efficacy at hippocampo-BLA projections is crucial for contextual fear memory expression. Importantly, because this restoration was obtained after the learning phase, our results suggest that some of the genetically encoded cognitive deficits in humans may originate from a lack of restitution of genuinely formed memories rather than an exclusive inability to store new memories.
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Benjamin, Aaron S; Diaz, Michael; Matzen, Laura E; Johnson, Benjamin
2012-06-01
Older adults exhibit a disproportionate deficit in their ability to recover contextual elements or source information about prior encounters with stimuli. A recent theoretical account, DRYAD, attributes this selective deficit to a global decrease in memory fidelity with age, moderated by weak representation of contextual information. The predictions of DRYAD are tested here in three experiments. We show that an age-related deficit obtains for whichever aspect of the stimulus subjects' attention is directed away from during encoding (Experiment 1), suggesting a central role for attention in producing the age-related deficit in context. We also show that an analogous deficit can be elicited within young subjects with a manipulation of study time (Experiment 2), suggesting that any means of reducing memory fidelity yields an interaction of the same form as the age-related effect. Experiment 3 evaluates the critical prediction of DRYAD that endorsement probability in an exclusion task should vary nonmonotonically with memory strength. This prediction was confirmed by assessing the shape of the forgetting function in a continuous exclusion task. The results are consistent with the DRYAD account of aging and memory judgments and do not support the widely held view that aging entails the selective disruption of processes involved in encoding, storing, or retrieving contextual information. PsycINFO Database Record (c) 2012 APA, all rights reserved
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Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice
Hao, Shuang; Tang, Bin; Wu, Zhenyu; Ure, Kerstin; Sun, Yaling; Tao, Huifang; Gao, Yan; Patel, Akash J.; Curry, Daniel J.; Samaco, Rodney C.; Zoghbi, Huda Y.; Tang, Jianrong
2016-01-01
Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnestic rats have demonstrated that DBS targeted to the fimbria-fornix1-3, the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory3-5. Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder (IDD). IDDs are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We hypothesized that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett Syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP26, RTT appears by the second year of life, causing profound impairment in cognitive, motor, and social skills along with an array of neurological features7; RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity8-11. Here we show that forniceal DBS in RTT mice rescued contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restored in vivo hippocampal long-term potentiation (LTP) and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT. PMID:26469053
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ERIC Educational Resources Information Center
Daumas, Stephanie; Halley, Helene; Frances, Bernard; Lassalle, Jean-Michel
2005-01-01
Studies on human and animals shed light on the unique hippocampus contributions to relational memory. However, the particular role of each hippocampal subregion in memory processing is still not clear. Hippocampal computational models and theories have emphasized a unique function in memory for each hippocampal subregion, with the CA3 area acting…
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Memory Is Not Extinguished along with CS Presentation but within a Few Seconds after CS-Offset
ERIC Educational Resources Information Center
Perez-Cuesta, Luis Maria; Hepp, Yanil; Pedreira, Maria Eugenia; Maldonado, Hector
2007-01-01
Prior work with the crab's contextual memory model showed that CS-US conditioned animals undergoing an unreinforced CS presentation would either reconsolidate or extinguish the CS-US memory, depending on the length of the reexposure to the CS. Either memory process is only triggered once the CS is terminated. Based on these results, the following…
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Do animacy effects persist in memory for context?
Gelin, Margaux; Bonin, Patrick; Méot, Alain; Bugaiska, Aurélia
2018-04-01
The adaptive view of human memory assumes that animates (e.g, rabbit) are remembered better than inanimates (e.g. glass) because animates are ultimately more important for fitness than inanimates. Previous studies provided evidence for this view by showing that animates were recalled or recognized better than inanimates, but they did not assess memory for contextual details (e.g., where animates vs inanimates occurred). In this study, we tested recollection of spatial information (Study 1) and temporal information (Study 2) associated with animate versus inanimate words. The findings showed that the two types of contextual information were remembered better when they were related to animates than to inanimates. These findings provide further evidence for an ultimate explanation of animacy effects.
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Sindreu, Carlos Balet; Scheiner, Zachary S; Storm, Daniel R
2007-01-04
The cAMP and ERK/MAP kinase (MAPK) signal transduction pathways are critical for hippocampus-dependent memory, a process that depends on CREB-mediated transcription. However, the extent of crosstalk between these pathways and the downstream CREB kinase activated during memory formation has not been elucidated. Here we report that PKA, MAPK, and MSK1, a CREB kinase, are coactivated in a subset of hippocampal CA1 pyramidal neurons following contextual fear conditioning. Activation of PKA, MAPK, MSK1, and CREB is absolutely dependent on Ca(2+)-stimulated adenylyl cyclase activity. We conclude that adenylyl cyclase activity supports the activation of MAPK, and that MSK1 is the major CREB kinase activated during training for contextual memory.
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Ca2+-Stimulated Adenylyl Cyclases Regulate ERK-Dependent Activation of MSK1 During Fear Conditioning
Sindreu, Carlos Balet; Scheiner, Zachary S.; Storm, Daniel R.
2007-01-01
The cAMP and ERK/MAP kinase (MAPK) signal transduction pathways are critical for hippocampus-dependent memory, a process that depends on CREB-mediated transcription. However, the extent of crosstalk between these pathways and the downstream CREB kinase activated during memory formation have not been elucidated. Here we report that PKA, MAPK, and MSK1, a CREB kinase, are co-activated in a subset of hippocampal CA1 pyramidal neurons following contextual fear conditioning. Activation of PKA, MAPK, MSK1, and CREB is absolutely dependent on Ca2+-stimulated adenylyl cyclase activity. We conclude that adenylyl cyclase activity supports the activation of MAPK, and that MSK1 is the major CREB kinase activated during training for contextual memory. PMID:17196532
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Familiar real-world spatial cues provide memory benefits in older and younger adults.
Robin, Jessica; Moscovitch, Morris
2017-05-01
Episodic memory, future thinking, and memory for scenes have all been proposed to rely on the hippocampus, and evidence suggests that these all decline in healthy aging. Despite this age-related memory decline, studies examining the effects of context reinstatement on episodic memory have demonstrated that reinstating elements of the encoding context of an event leads to better memory retrieval in both younger and older adults. The current study was designed to test whether more familiar, real-world contexts, such as locations that participants visited often, would improve the detail richness and vividness of memory for scenes, autobiographical events, and imagination of future events in young and older adults. The predicted age-related decline in internal details across all 3 conditions was accompanied by persistent effects of contextual familiarity, in which a more familiar spatial context led to increased detail and vividness of remembered scenes, autobiographical events, and, to some extent, imagined future events. This study demonstrates that autobiographical memory, imagination of the future, and scene memory are similarly affected by aging, and all benefit from being associated with more familiar (real-world) contexts, illustrating the stability of contextual reinstatement effects on memory throughout the life span. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
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Post-Retrieval Extinction Attenuates Cocaine Memories
Sartor, Gregory C; Aston-Jones, Gary
2014-01-01
Recent studies have shown that post-retrieval extinction training attenuates fear and reward-related memories in both humans and rodents. This noninvasive, behavioral approach has the potential to be used in clinical settings to treat maladaptive memories that underlie several psychiatric disorders, including drug addiction. However, few studies to date have used a post-retrieval extinction approach to attenuate addiction-related memories. In the current study, we attempted to disrupt cocaine-related memories by using the post-retrieval extinction paradigm in male Sprague Dawley rats. Results revealed that starting extinction training 1 h after cocaine contextual memory was retrieved significantly attenuated cocaine-primed reinstatement of conditioned place preference (CPP) and relapse of cocaine CPP (drug-free and cocaine-primed) following 30 days of abstinence. However, animals that did not retrieve the contextual cocaine memory before extinction training, or animals that began extinction training 24 h after retrieval (outside of the reconsolidation window), demonstrated normal cocaine CPP. Conversely, animals that received additional CPP conditioning, rather than extinction training, 1 h after reactivation of cocaine memory showed enhanced cocaine CPP compared with animals that did not reactivate the cocaine memory before conditioning. These results reveal that a behavioral manipulation that takes advantage of reconsolidation and extinction of drug memories may be useful in decreasing preference for, and abuse of, cocaine. PMID:24257156
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Spatial context learning survives interference from working memory load
Vickery, Timothy J.; Sussman, Rachel S.; Jiang, Yuhong V.
2010-01-01
The human visual system is constantly confronted with an overwhelming amount of information, only a subset of which can be processed in complete detail. Attention and implicit learning are two important mechanisms that optimize vision. This study addresses the relationship between these two mechanisms. Specifically we ask: Is implicit learning of spatial context affected by the amount of working memory load devoted to an irrelevant task? We tested observers in visual search tasks where search displays occasionally repeated. Observers became faster searching repeated displays than unrepeated ones, showing contextual cueing. We found that the size of contextual cueing was unaffected by whether observers learned repeated displays under unitary attention or when their attention was divided using working memory manipulations. These results held when working memory was loaded by colors, dot patterns, individual dot locations, or multiple potential targets. We conclude that spatial context learning is robust to interference from manipulations that limit the availability of attention and working memory. PMID:20853996
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Brain oscillations track the formation of episodic memories in the real world.
Griffiths, Benjamin; Mazaheri, Ali; Debener, Stefan; Hanslmayr, Simon
2016-12-01
Despite the well-known influence of environmental context on episodic memory, little has been done to increase contextual richness within the lab. This leaves a blind spot lingering over the neuronal correlates of episodic memory formation in day-to-day life. To address this, we presented participants with a series of words to memorise along a pre-designated route across campus while a mobile EEG system acquired ongoing neural activity. Replicating lab-based subsequent memory effects (SMEs), we identified significant low to mid frequency power decreases (<30Hz), including beta power decreases over the left inferior frontal gyrus. When investigating the oscillatory correlates of temporal and spatial context binding, we found that items strongly bound to spatial context exhibited significantly greater theta power decreases than items strongly bound to temporal context. These findings expand upon lab-based studies by demonstrating the influence of real world contextual factors that underpin memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.
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Xiao, Xin; Zhao, Di; Zhang, Qin; Guo, Chun-yan
2012-03-01
The current study used the directed forgetting paradigm in implicit and explicit memory to investigate the concreteness effect. Event-related potentials (ERPs) were recorded to explore the neural basis of this phenomenon. The behavioral results showed a clear concreteness effect in both implicit and explicit memory tests; participants responded significantly faster to concrete words than to abstract words. The ERP results revealed a concreteness effect (N400) in both the encoding and retrieval phases. In addition, behavioral and ERP results showed an interaction between word concreteness and memory instruction (to-be-forgotten vs. to-be-remembered) in the late epoch of the explicit retrieval phase, revealing a significant concreteness effect only under the to-be-remembered instruction condition. This concreteness effect was realized as an increased P600-like component in response to concrete words relative to abstract words, likely reflecting retrieval of contextual details. The time course of the concreteness effect suggests advantages of concrete words over abstract words due to greater contextual information. Copyright © 2011 Elsevier Inc. All rights reserved.
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The Effect of Verbal Contextual Information in Processing Visual Art.
ERIC Educational Resources Information Center
Koroscik, Judith S.; And Others
1985-01-01
Verbal contextual information affected photography and nonphotography students' performance on semantic retention tests. For example, correct titles aided the formation and retention of accurate memories, while erroneous titles misled students into remembering meanings that had relatively little to do with what was actually pictured in the…
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ERIC Educational Resources Information Center
Poppenk, Jordan; Norman, Kenneth A.
2012-01-01
Recent cognitive research has revealed better source memory performance for familiar relative to novel stimuli. Here we consider two possible explanations for this finding. The source memory advantage for familiar stimuli could arise because stimulus novelty induces attention to stimulus features at the expense of contextual processing, resulting…
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Development of Flexible Visual Recognition Memory in Human Infants
ERIC Educational Resources Information Center
Robinson, Astri J.; Pascalis, Olivier
2004-01-01
Research using the visual paired comparison task has shown that visual recognition memory across changing contexts is dependent on the integrity of the hippocampal formation in human adults and in monkeys. The acquisition of contextual flexibility may contribute to the change in memory performance that occurs late in the first year of life. To…
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Predicting Which Childhood Memories Persist: Contributions of Memory Characteristics
ERIC Educational Resources Information Center
Peterson, Carole; Morris, Gwynn; Baker-Ward, Lynne; Flynn, Susan
2014-01-01
This investigation identified memory-level predictors of the survivability of 4- to 13-year-old children's earliest recollections over a 2-year period. Data previously reported by Peterson, Warren, and Short (2011) were coded for inclusion of emotion terms and thematic, chronological, and contextual narrative coherence. In addition, the…
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Context Memory Formation Requires Activity-Dependent Protein Degradation in the Hippocampus
ERIC Educational Resources Information Center
Cullen, Patrick K.; Ferrara, Nicole C.; Pullins, Shane E.; Helmstetter, Fred J.
2017-01-01
Numerous studies have indicated that the consolidation of contextual fear memories supported by an aversive outcome like footshock requires de novo protein synthesis as well as protein degradation mediated by the ubiquitin-proteasome system (UPS). Context memory formed in the absence of an aversive stimulus by simple exposure to a novel…
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Two Rooms, Two Representations? Episodic-Like Memory in Toddlers and Preschoolers
ERIC Educational Resources Information Center
Newcombe, Nora S.; Balcomb, Frances; Ferrara, Katrina; Hansen, Melissa; Koski, Jessica
2014-01-01
Episodic memory involves binding together what-where-when associations. In three experiments, we tested the development of memory for such contextual associations in a naturalistic setting. Children searched for toys in two rooms with two different experimenters; each room contained two identical sets of four containers, but arranged differently.…
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The spectro-contextual encoding and retrieval theory of episodic memory.
Watrous, Andrew J; Ekstrom, Arne D
2014-01-01
The spectral fingerprint hypothesis, which posits that different frequencies of oscillations underlie different cognitive operations, provides one account for how interactions between brain regions support perceptual and attentive processes (Siegel etal., 2012). Here, we explore and extend this idea to the domain of human episodic memory encoding and retrieval. Incorporating findings from the synaptic to cognitive levels of organization, we argue that spectrally precise cross-frequency coupling and phase-synchronization promote the formation of hippocampal-neocortical cell assemblies that form the basis for episodic memory. We suggest that both cell assembly firing patterns as well as the global pattern of brain oscillatory activity within hippocampal-neocortical networks represents the contents of a particular memory. Drawing upon the ideas of context reinstatement and multiple trace theory, we argue that memory retrieval is driven by internal and/or external factors which recreate these frequency-specific oscillatory patterns which occur during episodic encoding. These ideas are synthesized into a novel model of episodic memory (the spectro-contextual encoding and retrieval theory, or "SCERT") that provides several testable predictions for future research.
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Regulation of Memory Formation by the Transcription Factor XBP1.
Martínez, Gabriela; Vidal, René L; Mardones, Pablo; Serrano, Felipe G; Ardiles, Alvaro O; Wirth, Craig; Valdés, Pamela; Thielen, Peter; Schneider, Bernard L; Kerr, Bredford; Valdés, Jose L; Palacios, Adrian G; Inestrosa, Nibaldo C; Glimcher, Laurie H; Hetz, Claudio
2016-02-16
Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer's disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR), mediating adaptation to endoplasmic reticulum (ER) stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP), whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF), a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
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Gould, Thomas J; Wilkinson, Derek S; Yildirim, Emre; Poole, Rachel L F; Leach, Prescott T; Simmons, Steven J
2014-03-01
Acute nicotine enhances hippocampus-dependent learning through nicotine binding to β2-containing nicotinic acetylcholine receptors (nAChRs), but it is unclear if nicotine is targeting processes involved in short-term memory (STM) leading to a strong long-term memory (LTM) or directly targeting LTM. In addition, the molecular mechanisms involved in the effects of nicotine on learning are unknown. Previous research indicates that protein kinase A (PKA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein synthesis are crucial for LTM. Therefore, the present study examined the effects of nicotine on STM and LTM and the involvement of PKA, ERK1/2, and protein synthesis in the nicotine-induced enhancement of hippocampus-dependent contextual learning in C57BL/6J mice. The protein synthesis inhibitor anisomycin impaired contextual conditioning assessed at 4 h but not 2 h post-training, delineating time points for STM (2 h) and LTM (4 h and beyond). Nicotine enhanced contextual conditioning at 4, 8, and 24 h but not 2 h post-training, indicating nicotine specifically enhances LTM but not STM. Furthermore, nicotine did not rescue deficits in contextual conditioning produced by anisomycin, suggesting that the nicotine enhancement of contextual conditioning occurs through a protein synthesis-dependent mechanism. In addition, inhibition of dorsal hippocampal PKA activity blocked the effect of acute nicotine on learning, and nicotine shifted the timing of learning-related PKA and ERK1/2 activity in the dorsal and ventral hippocampus. Thus, the present results suggest that nicotine specifically enhances LTM through altering the timing of PKA and ERK1/2 signaling in the hippocampus, and suggests that the timing of PKA and ERK1/2 activity could contribute to the strength of memories. Copyright © 2014 Elsevier Inc. All rights reserved.
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Carnicella, Sebastien; Pain, Laure; Oberling, Philippe
2005-04-01
The cholinergic system has been shown to modulate contextual fear conditioning. However, with the exception of trace conditioning studies, most of the available data have focussed on independent context, i.e., context that do not compete with the conditioned stimulus to control for the conditioned response (interactive context). In the present series of experiments, the effects of the muscarinic antagonist, atropine, were assessed when contextual fear memory interacts with cued fear memory to regulate conditioned response, using a Pavlovian degraded contingency preparation in rats. This preparation not only afforded an insight into simple Pavlovian associations but also enabled us to test for the processes of competition that made use of these associations to make an appropriate response to a stimulus [degraded contingency effect (DCE)]. In experiment 1, three doses of atropine [2.5, 5.0, and 10.0 mg/kg, intraperitoneally (i.p.)] were evaluated on male Sprague-Dawley rats. In experiment 2, physostigmine (0.037-0.3 mg/kg, i.p.) was injected after the administration of 5 mg/kg of atropine. Experiment 1A and its partial replication (experiment 1B) showed that at asymptotic level of training, atropine did not alter contextual and cued fear memories when the subjects were directly tested for them, whereas it suppressed the DCE for a 5 mg/kg dose. Indeed, atropine-induced suppression of the DCE was found to be an inverted U-shaped dose-response curve. Experiment 2 showed that physostigmine caused a dose-dependent reversal of the atropine-induced alleviation of the DCE, without altering the expression of simple cued and contextual fear memories. These results evidence at asymptotic level of training a cholinergic modulation of the processing of interactive context, but not of independent ones. They are discussed in the framework of the mechanisms that are involved in both types of contextual processing.
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Gould, Thomas J.; Wilkinson, Derek S.; Yildirim, Emre; Poole, Rachel L. F.; Leach, Prescott T.; Simmons, Steven J.
2014-01-01
Acute nicotine enhances hippocampus-dependent learning through nicotine binding to β2-containing nicotinic acetylcholine receptors (nAChRs), but it is unclear if nicotine is targeting processes involved in short-term memory (STM) leading to a strong long-term memory (LTM) or directly targeting LTM. In addition, the molecular mechanisms involved in the effects of nicotine on learning are unknown. Previous research indicates that protein kinase A (PKA), extracellular regulated signaling kinase 1/2 (ERK1/2), and protein synthesis are crucial for LTM. Therefore, the present study examined the effects of nicotine on STM and LTM and the involvement of PKA, ERK1/2, and protein synthesis in the nicotine-induced enhancement of hippocampus-dependent contextual learning in C57BL/6J mice. The protein synthesis inhibitor anisomycin impaired contextual conditioning assessed at 4 hours but not 2 hours post-training, delineating time points for STM (2 hours) and LTM (4 hours and beyond). Nicotine enhanced contextual conditioning at 4, 8, and 24 hours but not 2 hours post-training, indicating nicotine specifically enhances LTM but not STM. Furthermore, nicotine did not rescue deficits in contextual conditioning produced by anisomycin, suggesting that the nicotine enhancement of contextual conditioning occurs through a protein synthesis-dependent mechanism. In addition, inhibition of dorsal hippocampal PKA activity blocked the effect of acute nicotine on learning and nicotine shifted the timing of learning-related PKA and ERK1/2 activity in the dorsal and ventral hippocampus. Thus, the present results suggest that nicotine specifically enhances LTM through altering the timing of PKA and ERK1/2 signaling in the hippocampus, and suggests that the timing of PKA and ERK1/2 activity could contribute to the strength of memories. PMID:24457151
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Malikowska-Racia, Natalia; Podkowa, Adrian; Sałat, Kinga
2018-04-21
Nowadays cognitive impairments are a growing unresolved medical issue which may accompany many diseases and therapies, furthermore, numerous researchers investigate various neurobiological aspects of human memory to find possible ways to improve it. Until any other method is discovered, in vivo studies remain the only available tool for memory evaluation. At first, researchers need to choose a model of amnesia which may strongly influence observed results. Thereby a deeper insight into a model itself may increase the quality and reliability of results. The most common method to impair memory in rodents is the pretreatment with drugs that disrupt learning and memory. Taking this into consideration, we compared the activity of agents commonly used for this purpose. We investigated effects of phencyclidine (PCP), a non-competitive NMDA receptor antagonist, and scopolamine (SCOP), an antagonist of muscarinic receptors, on short-term spatial memory and classical fear conditioning in mice. PCP (3 mg/kg) and SCOP (1 mg/kg) were administrated intraperitoneally 30 min before behavioral paradigms. To assess the influence of PCP and SCOP on short-term spatial memory, the Barnes maze test in C57BL/J6 mice was used. Effects on classical conditioning were evaluated using contextual fear conditioning test. Additionally, spontaneous locomotor activity of mice was measured. These two tests were performed in CD-1 mice. Our study reports that both tested agents disturbed short-term spatial memory in the Barnes maze test, however, SCOP revealed a higher activity. Surprisingly, learning in contextual fear conditioning test was impaired only by SCOP. Graphical Abstract ᅟ.
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Low-dose systemic scopolamine disrupts context conditioning in rats
Luyten, Laura; Nuyts, Shauni; Beckers, Tom
2017-01-01
Cholinergic neurotransmission plays a key role in learning and memory. Prior research with rats indicated that a low dose of pre-training scopolamine (0.1 mg/kg), a cholinergic receptor antagonist, did not affect cued fear conditioning, but did block renewal when injected before extinguishing a conditioned tone, opening up opportunities to pharmacologically improve exposure therapy for anxiety patients. Before translating these findings to the clinic, it is important to carefully examine how scopolamine affects contextual fear memories. Here, we investigated the effects of scopolamine on encoding of contextual anxiety and its generalization in male Wistar rats. We found a profound disruption of context conditioning, suggesting that, even at a low dose, systemic scopolamine may influence contextual encoding in the hippocampus, particularly when the context is the best predictor for the presence of shocks. PMID:28417664
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The KAPTUR environment: An operations concept
NASA Technical Reports Server (NTRS)
1989-01-01
This report presents a high-level specification and operations concept for KAPTUR, a development environment based on knowledge acquisition for preservation of tradeoffs and underlying rationales. KAPTUR is intended to do what its name implies: to capture knowledge that is required or generated during the development process, but that is often lost because it is contextual, i.e., it does not appear directly in the end-products of development. Such knowledge includes issues that were raised during development, alternatives that were considered, and the reasons for choosing one alternative over others. Contextual information is usually only maintained as a memory in a developer's mind. As time passes, the memories become more vague and individuals become unavailable, and eventually the knowledge is lost. KAPTUR seeks to mitigate this process of attrition by recording and organizing contextual knowledge as it is generated.
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Paradoxical sleep as a tool for understanding the hippocampal mechanisms of contextual memory.
Sil'kis, I G
2010-01-01
Existing data on the involvement of the hippocampus in contextual memory and the fact that contextual memory is impaired in dreams occurring during paradoxical sleep allowed us to suggest that one of the causes of this impairment consists of changes in the efficiency of synaptic transmission in the hippocampus due to increases (as compared with waking) in the concentrations of acetylcholine, dopamine, and cortisol, as well as the absence of serotonin and noradrenaline. Our previous analysis showed that in paradoxical sleep, long-term depression can be induced all components of the polysynaptic pathway through the hippocampal formation, while potentiation can occur at the inputs from the entorhinal cortex to hippocampal fields CA1 and CA3 and in the associative connections in field CA3. It is hypothesized that the correct functioning of episodic memory requires efficient transmission of signals in each component of the polysynaptic pathway through the hippocampus, allowing a neuronal representation of the context to be created within it. In the state of waking, reproduction of the context of an episode simultaneously activates the neuronal representation of the context remembered in the hippocampus and neuronal representations of the details of the episode remembered in those areas of the cortex in which they were processed. It follows from the proposed mechanism that any neurotransmitter or neuropeptide able to promote longterm potentiation in all components of the polysynaptic pathway through the hippocampus can improve episodic memory. As the consequences of the mechanism are consistent with experimental data, it can be used to seek agents improving episodic memory.
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James, Taylor; Strunk, Jonathan; Arndt, Jason; Duarte, Audrey
2016-06-01
Previous event-related potential (ERP) and neuroimaging evidence suggests that directing attention toward single item-context associations compared to intra-item features at encoding improves context memory performance and reduces demands on strategic retrieval operations in young and older adults. In everyday situations, however, there are multiple event features competing for our attention. It is not currently known how selectively attending to one contextual feature while attempting to ignore another influences context memory performance and the processes that support successful retrieval in the young and old. We investigated this issue in the current ERP study. Young and older participants studied pictures of objects in the presence of two contextual features: a color and a scene, and their attention was directed to the object's relationship with one of those contexts. Participants made context memory decisions for both attended and unattended contexts and rated their confidence in those decisions. Behavioral results showed that while both groups were generally successful in applying selective attention during context encoding, older adults were less confident in their context memory decisions for attended features and showed greater dependence in context memory accuracy for attended and unattended contextual features (i.e., hyper-binding). ERP results were largely consistent between age groups but older adults showed a more pronounced late posterior negativity (LPN) implicated in episodic reconstruction processes. We conclude that age-related suppression deficits during encoding result in reduced selectivity in context memory, thereby increasing subsequent demands on episodic reconstruction processes when sought after details are not readily retrieved. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Sleep-dependent facilitation of episodic memory details.
van der Helm, Els; Gujar, Ninad; Nishida, Masaki; Walker, Matthew P
2011-01-01
While a role for sleep in declarative memory processing is established, the qualitative nature of this consolidation benefit, and the physiological mechanisms mediating it, remain debated. Here, we investigate the impact of sleep physiology on characteristics of episodic memory using an item- (memory elements) and context- (contextual details associated with those elements) learning paradigm; the latter being especially dependent on the hippocampus. Following back-to-back encoding of two word lists, each associated with a different context, participants were assigned to either a Nap-group, who obtained a 120-min nap, or a No Nap-group. Six hours post-encoding, participants performed a recognition test involving item-memory and context-memory judgments. In contrast to item-memory, which demonstrated no between-group differences, a significant benefit in context-memory developed in the Nap-group, the extent of which correlated both with the amount of stage-2 NREM sleep and frontal fast sleep-spindles. Furthermore, a difference was observed on the basis of word-list order, with the sleep benefit and associated physiological correlations being selective for the second word-list, learned last (most proximal to sleep). These findings suggest that sleep may preferentially benefit contextual (hippocampal-dependent) aspects of memory, supported by sleep-spindle oscillations, and that the temporal order of initial learning differentially determines subsequent offline consolidation.
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A comparison of self-generated versus taught internal strategies for working memory.
Dirette, Diane Powers
2015-01-01
Internal strategies are effective for improving working memory. These internal working memory strategies can be taught or self-generated. This study compares working memory performance using taught versus self-generated internal working memory strategies and explores the quantity, type and carry-over of the use of these strategies. An experimental cohort design with randomly assigned groups compared the performances among 120 participants on 5 memory tests given prior, immediately following and at 1 month post intervention. There were no significant differences in the number or type of internal memory strategies used by the groups with chunking, repetition and association used most commonly. The group that self-generated strategies performed significantly better on a contextual memory test and the group that was taught strategies performed better on a face/name recall test for which a specific strategy was taught. The group that was taught strategies performed significantly worse on contextual memory tests from pre-test to follow-up. Participants who generated their own strategies or used a specific strategy for a specific task did as well as participants who were taught myriad internal WM strategies. Teaching too many strategies may overwhelm participants or may distract them from using the context that is available in such tasks.
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NMDA Signaling in CA1 Mediates Selectively the Spatial Component of Episodic Memory
ERIC Educational Resources Information Center
Place, Ryan; Lykken, Christy; Beer, Zachery; Suh, Junghyup; McHugh, Thomas J.; Tonegawa, Susumu; Eichenbaum, Howard; Sauvage, Magdalena M.
2012-01-01
Recent studies focusing on the memory for temporal order have reported that CA1 plays a critical role in the memory for the sequences of events, in addition to its well-described role in spatial navigation. In contrast, CA3 was found to principally contribute to the memory for the association of items with spatial or contextual information in…
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ERIC Educational Resources Information Center
Remaud, Jessica; Ceccom, Johnatan; Carponcy, Julien; Dugué, Laura; Menchon, Gregory; Pech, Stéphane; Halley, Helene; Francés, Bernard; Dahan, Lionel
2014-01-01
Protein synthesis is involved in the consolidation of short-term memory into long-term memory. Previous electrophysiological data concerning LTP in CA3 suggest that protein synthesis in that region might also be necessary for short-term memory. We tested this hypothesis by locally injecting the protein synthesis inhibitor anisomycin in hippocampal…
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ERIC Educational Resources Information Center
Semino, Sara; Ring, Melanie; Bowler, Dermot M.; Gaigg, Sebastian B.
2018-01-01
Autism Spectrum Disorder (ASD) is generally associated with difficulties in contextual source memory but not single item memory. There are surprising inconsistencies in the literature, however, that the current study seeks to address by examining item and source memory in age and ability matched groups of 22 ASD and 21 comparison adults. Results…
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Choi, Moonseok; Ahn, Sangzin; Yang, Eun-Jeong; Kim, Hyunju; Chong, Young Hae; Kim, Hye-Sun
2016-07-26
Astrocytes have been reported to exist in two states, the resting and the reactive states. Morphological changes in the reactive state of astrocytes include an increase in thickness and number of processes, and an increase in the size of the cell body. Molecular changes also occur, such as an increase in the expression of glial fibrillary acidic protein (GFAP). However, the morphological and molecular changes during the process of learning and memory have not been elucidated. In the current study, we subjected Fvb/n mice to contextual fear conditioning, and checked for morphological and molecular changes in astrocytes. 1 h after fear conditioning, type II and type III astrocytes exhibited a unique status with an increased number of processes and decreased GFAP expression which differed from the typical resting or reactive state. In addition, the protein level of excitatory excitatory amino acid transporter 2 (EAAT2) was increased 1 h to 24 h after contextual fear conditioning while EAAT1 did not show any alterations. Connexin 43 (Cx43) protein was found to be increased at 24 h after fear conditioning. These data suggest that hippocampus-based contextual memory process induces changes in the status of astrocytes towards a novel status different from typical resting or reactive states. These morphological and molecular changes may be in line with functional changes.
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Gender dependent contribution of muscarinic receptors in memory retrieval under sub-chronic stress.
Rashid, Habiba; Ahmed, Touqeer
2018-05-15
Stress induces retrograde amnesia in humans and rodents. Muscarinic antagonism under normal physiological conditions causes gender dependent impairment in episodic memory retrieval. We aimed to explore the gender dependent role of muscarinic receptors in memory retrieval under sub-chronic stress condition. Male and female mice were trained for Morris water maze test and contextual fear conditioning, followed by 3 h restraint stress per day for five days. Stress was either given alone or in combination with a daily subcutaneous injection of scopolamine (1 mg/kg) or donepezil (1 mg/kg). Control mice were given saline without any stress. Sub-chronic stress (induced for five days) impaired spatial memory retrieval in males (P < 0.005) but not in females (P > 0.05). Stress induced spatial memory recall deficit in male mice was independent of muscarinic receptor activity (P > 0.05). However, stress induced contextual fear memory recall impairment was reversed by donepezil treatment in male (P < 0.005) and female (P < 0.0001) mice. These findings suggest that differential role of muscarinic activity in retrieving different types of memories under stress depends on gender of subjects. Copyright © 2018 Elsevier B.V. All rights reserved.
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Culture impacts the magnitude of the emotion-induced memory trade-off effect.
Gutchess, Angela; Garner, Lauryn; Ligouri, Laura; Konuk, Ayse Isilay; Boduroglu, Aysecan
2017-10-04
The present study assessed the extent to which culture impacts the emotion-induced memory trade-off effect. This trade-off effect occurs because emotional items are better remembered than neutral ones, but this advantage comes at the expense of memory for backgrounds such that neutral backgrounds are remembered worse when they occurred with an emotional item than with a neutral one. Cultures differ in their prioritisation of focal object versus contextual background information, with Westerners focusing more on objects and Easterners focusing more on backgrounds. Americans, a Western culture, and Turks, an Eastern-influenced culture, incidentally encoded positive, negative, and neutral items placed against neutral backgrounds, and then completed a surprise memory test with the items and backgrounds tested separately. Results revealed a reduced trade-off for Turks compared to Americans. Although both groups exhibited an emotional enhancement in item memory, Turks did not show a decrement in memory for backgrounds that had been paired with emotional items. These findings complement prior ones showing reductions in trade-off effects as a result of task instructions. Here, we suggest that a contextual-focus at the level of culture can mitigate trade-off effects in emotional memory.
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Li, Jay-Shake; Hsiao, Kun-Yuan; Chen, Wei-Min
2011-03-17
Previous animal studies have defined the ability to remember the details of what, where, and when of an event as an episodic-like memory to be used to model episodic memory in humans. Numerous findings indicate that the hippocampal-frontal cortical circuitry plays a major part in its neural mechanism. Researchers have intensively studied roles of diverse hippocampus sub-regions using animal models. By contrast, the impact of prefrontal cortex lesions on episodic-like memory in animals is still unknown. Here we show that Wistar rats with bilateral medial prefrontal cortex lesions failed to use the temporal-contextual information to retrieve memory of a fear-conditioning event, indicating impairments in their episodic-like memory. Subsequent experiments excluded alternative interpretations that the manipulation impaired the fear-conditioning per se, or interfered with the sensory preconditioning process. We concluded that damages in this area might impair temporal information processing, or interfere with integrating temporal and contextual elements of fear-conditioning events to form a conjunctive entity. These findings can help understand how the medial prefrontal cortex contributes to episodic-like memory. Copyright © 2010 Elsevier B.V. All rights reserved.
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A Revised Model of Short-Term Memory and Long-Term Learning of Verbal Sequences
ERIC Educational Resources Information Center
Burgess, Neil; Hitch, Graham J.
2006-01-01
The interaction between short- and long-term memory is studied within a model in which phonemic and (temporal) contextual information have separate influences on immediate verbal serial recall via connections with short- and long-term plasticity [Burgess, N., & Hitch, G.J. (1999). Memory for serial order: a network model of the phonological loop…
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ERIC Educational Resources Information Center
Wells, Audrey M.; Lasseter, Heather C.; Xie, Xiaohu; Cowhey, Kate E.; Reittinger, Andrew M.; Fuchs, Rita A.
2011-01-01
Contextual stimulus control over instrumental drug-seeking behavior relies on the reconsolidation of context-response-drug associative memories into long-term memory storage following retrieval-induced destabilization. According to previous studies, the basolateral amygdala (BLA) and dorsal hippocampus (DH) regulate cocaine-related memory…
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ERIC Educational Resources Information Center
Fustiñana, María Sol; de la Fuente, Verónica; Federman, Noel; Freudenthal, Ramiro; Romano, Arturo
2014-01-01
The ubiquitin-proteasome system (UPS) of protein degradation has been evaluated in different forms of neural plasticity and memory. The role of UPS in such processes is controversial. Several results support the idea that the activation of this system in memory consolidation is necessary to overcome negative constrains for plasticity. In this…
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Do Adults with Autism Spectrum Disorders Compensate in Naturalistic Prospective Memory Tasks?
ERIC Educational Resources Information Center
Altgassen, Mareike; Koban, Nancy; Kliegel, Matthias
2012-01-01
The present study is the first to directly compare event- and time-based prospective memory in Autism Spectrum Disorders (ASD) using a contextual task mirroring real life demands of prospective memory. Twenty-five individuals with ASD and 25 age- and ability-matched controls completed the Dresden Breakfast task which required participants to…
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ERIC Educational Resources Information Center
Geyer, Thomas; Shi, Zhuanghua; Muller, Hermann J.
2010-01-01
Three experiments examined memory-based guidance of visual search using a modified version of the contextual-cueing paradigm (Jiang & Chun, 2001). The target, if present, was a conjunction of color and orientation, with target (and distractor) features randomly varying across trials (multiconjunction search). Under these conditions, reaction times…
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Prospective memory in context: Moving through a familiar space.
Smith, Rebekah E; Hunt, R Reed; Murray, Amy E
2017-02-01
Successful completion of delayed intentions is a common but important aspect of daily behavior. Such behavior requires not only memory for the intended action but also recognition of the opportunity to perform that action, known collectively as prospective memory. The fact that prospective memory tasks occur in the midst of other activities is captured in laboratory tasks by embedding the prospective memory task in an ongoing activity. In many cases the requirement to perform the prospective memory task results in a reduction in ongoing performance relative to when the ongoing task is performed alone. This is referred to as the cost to the ongoing task and reflects the allocation of attentional resources to the prospective memory task. The current study examined the pattern of cost across the ongoing task when the ongoing task provided contextual information that in turn allowed participants to anticipate when target events would occur within the ongoing task. The availability of contextual information reduced ongoing task response times overall, with an increase in response times closer to the target locations (Experiments 1-3). The fourth study, drawing on the Event Segmentation Theory, provided support for the proposal made by the Preparatory Attentional and Memory Processes theory of prospective memory that decisions about the allocation of attention to the prospective memory task are more likely to be made at points of transition. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
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Early remodeling of the neocortex upon episodic memory encoding
Bero, Adam W.; Meng, Jia; Cho, Sukhee; Shen, Abra H.; Canter, Rebecca G.; Ericsson, Maria; Tsai, Li-Huei
2014-01-01
Understanding the mechanisms by which long-term memories are formed and stored in the brain represents a central aim of neuroscience. Prevailing theory suggests that long-term memory encoding involves early plasticity within hippocampal circuits, whereas reorganization of the neocortex is thought to occur weeks to months later to subserve remote memory storage. Here we report that long-term memory encoding can elicit early transcriptional, structural, and functional remodeling of the neocortex. Parallel studies using genome-wide RNA sequencing, ultrastructural imaging, and whole-cell recording in wild-type mice suggest that contextual fear conditioning initiates a transcriptional program in the medial prefrontal cortex (mPFC) that is accompanied by rapid expansion of the synaptic active zone and postsynaptic density, enhanced dendritic spine plasticity, and increased synaptic efficacy. To address the real-time contribution of the mPFC to long-term memory encoding, we performed temporally precise optogenetic inhibition of excitatory mPFC neurons during contextual fear conditioning. Using this approach, we found that real-time inhibition of the mPFC inhibited activation of the entorhinal–hippocampal circuit and impaired the formation of long-term associative memory. These findings suggest that encoding of long-term episodic memory is associated with early remodeling of neocortical circuits, identify the prefrontal cortex as a critical regulator of encoding-induced hippocampal activation and long-term memory formation, and have important implications for understanding memory processing in healthy and diseased brain states. PMID:25071187
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Integration of contextual cues into memory depends on "prefrontal" N-methyl-D-aspartate receptors.
Starosta, Sarah; Bartetzko, Isabelle; Stüttgen, Maik C; Güntürkün, Onur
2017-10-01
Every learning event is embedded in a context, but not always does the context become an integral part of the memory; however, for extinction learning it usually does, resulting in context-specific conditioned responding. The neuronal mechanisms underlying contextual control have been mainly investigated for Pavlovian fear extinction with a focus on hippocampal structures. However, the initial acquisition of novel responses can be subject to contextual control as well, although the neuronal mechanisms are mostly unknown. Here, we tested the hypothesis that contextual control of acquisition depends on glutamatergic transmission underlying executive functions in forebrain areas, e.g. by shifting attention to critical cues. Thus, we antagonized N-methyl-D-aspartate (NMDA) receptors with 2-amino-5-phosphonovaleric acid (AP5) in the pigeon nidopallium caudolaterale, the functional analogue of mammalian prefrontal cortex, during the concomitant acquisition and extinction of conditioned responding to two different stimuli. This paradigm has previously been shown to lead to contextual control over extinguished as well as non-extinguished responding. NMDA receptor blockade resulted in an impairment of extinction learning, but left the acquisition of responses to a novel stimulus unaffected. Critically, when responses were tested in a different context in the retrieval phase, we observed that NMDA receptor blockade led to the abolishment of contextual control over acquisition performance. This result is predicted by a model describing response inclination as the product of associative strength and contextual gain. In this model, learning under AP5 leads to a change in the contextual gain on the learned association, possibly via the modulation of attentional mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.
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SNAP-25 in hippocampal CA3 region is required for long-term memory formation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hou Qiuling; Gao Xiang; Lu Qi
SNAP-25 is a synaptosomal protein of 25 kDa, a key component of synaptic vesicle-docking/fusion machinery, and plays a critical role in exocytosis and neurotransmitter release. We previously reported that SNAP-25 in the hippocampal CA1 region is involved in consolidation of contextual fear memory and water-maze spatial memory (Hou et al. European J Neuroscience, 20: 1593-1603, 2004). SNAP-25 is expressed not only in the CA1 region, but also in the CA3 region, and the SNAP-25 mRNA level in the CA3 region is higher than in the CA1 region. Here, we provide evidence that SNAP-25 in the CA3 region is also involvedmore » in learning/memory. Intra-CA3 infusion of SNAP-25 antisense oligonucleotide impaired both long-term contextual fear memory and water-maze spatial memory, with short-term memory intact. Furthermore, the SNAP-25 antisense oligonucleotide suppressed the long-term potentiation (LTP) of field excitatory post-synaptic potential (fEPSP) in the mossy-fiber pathway (DG-CA3 pathway), with no effect on paired-pulse facilitation of the fEPSP. These results are consistent with the notion that SNAP-25 in the hippocampal CA3 region is required for long-term memory formation.« less
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Impaired Dendritic Development and Memory in Sorbs2 Knock-Out Mice
Zhang, Qiangge; Gao, Xian; Li, Chenchen; Feliciano, Catia; Wang, Dongqing; Zhou, Dingxi; Mei, Yuan; Monteiro, Patricia; Anand, Michelle; Itohara, Shigeyoshi; Dong, Xiaowei; Fu, Zhanyan
2016-01-01
Intellectual disability is a common neurodevelopmental disorder characterized by impaired intellectual and adaptive functioning. Both environmental insults and genetic defects contribute to the etiology of intellectual disability. Copy number variations of SORBS2 have been linked to intellectual disability. However, the neurobiological function of SORBS2 in the brain is unknown. The SORBS2 gene encodes ArgBP2 (Arg/c-Abl kinase binding protein 2) protein in non-neuronal tissues and is alternatively spliced in the brain to encode nArgBP2 protein. We found nArgBP2 colocalized with F-actin at dendritic spines and growth cones in cultured hippocampal neurons. In the mouse brain, nArgBP2 was highly expressed in the cortex, amygdala, and hippocampus, and enriched in the outer one-third of the molecular layer in dentate gyrus. Genetic deletion of Sorbs2 in mice led to reduced dendritic complexity and decreased frequency of AMPAR-miniature spontaneous EPSCs in dentate gyrus granule cells. Behavioral characterization revealed that Sorbs2 deletion led to a reduced acoustic startle response, and defective long-term object recognition memory and contextual fear memory. Together, our findings demonstrate, for the first time, an important role for nArgBP2 in neuronal dendritic development and excitatory synaptic transmission, which may thus inform exploration of neurobiological basis of SORBS2 deficiency in intellectual disability. SIGNIFICANCE STATEMENT Copy number variations of the SORBS2 gene are linked to intellectual disability, but the neurobiological mechanisms are unknown. We found that nArgBP2, the only neuronal isoform encoded by SORBS2, colocalizes with F-actin at neuronal dendritic growth cones and spines. nArgBP2 is highly expressed in the cortex, amygdala, and dentate gyrus in the mouse brain. Genetic deletion of Sorbs2 in mice leads to impaired dendritic complexity and reduced excitatory synaptic transmission in dentate gyrus granule cells, accompanied by behavioral deficits in acoustic startle response and long-term memory. This is the first study of Sorbs2 function in the brain, and our findings may facilitate the study of neurobiological mechanisms underlying SORBS2 deficiency in the development of intellectual disability. PMID:26888934
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Awad, Walaa; Ferreira, Guillaume; Maroun, Mouna
2015-01-01
Medial prefrontal circuits have been reported to undergo a major reorganization over time and gradually take a more important role for remote emotional memories such as contextual fear memory or food aversion memory. The medial prefrontal cortex, and specifically its ventral subregion, the infralimbic cortex (IL), was also reported to be critical for recent memory extinction of contextual fear conditioning and conditioned odor aversion. However, its exact role in the extinction of remotely acquired information is still not clear. Using postretrieval blockade of protein synthesis or inactivation of the IL, we showed that the IL is similarly required for extinction consolidation of recent and remote fear memory. However, in odor aversion memory, the IL was only involved in extinction consolidation of recent, but not remote, memory. In contrast, only remote retrieval of aversion memory induced c-Fos activation in the IL and preretrieval inactivation of the IL with lidocaine impaired subsequent extinction of remote but not recent memory, indicating IL is necessary for extinction learning of remote aversion memory. In contrast to the effects in odor aversion, our data show that the involvement of the IL in the consolidation of fear extinction does not depend on the memory age. More importantly, our data indicate that the IL is implicated in the extinction of fear and nonfear-based associations and suggest dissociation in the engagement of the IL in the learning and consolidation of food aversion extinction over time. PMID:25872918
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Bourtchouladze, Rusiko; Lidge, Regina; Catapano, Ray; Stanley, Jennifer; Gossweiler, Scott; Romashko, Darlene; Scott, Rod; Tully, Tim
2003-01-01
Mice carrying a truncated form of cAMP-responsive element binding protein (CREB)-binding protein (CBP) show several developmental abnormalities similar to patients with Rubinstein-Taybi syndrome (RTS). RTS patients suffer from mental retardation, whereas long-term memory formation is defective in mutant CBP mice. A critical role for cAMP signaling during CREB-dependent long-term memory formation appears to be evolutionarily conserved. From this observation, we reasoned that drugs that modulate CREB function by enhancing cAMP signaling might yield an effective treatment for the memory defect(s) of CBP+/− mice. To this end, we designed a cell-based drug screen and discovered inhibitors of phosphodiesterase 4 (PDE4) to be particularly effective enhancers of CREB function. We extend previous behavioral observations by showing that CBP+/− mutants have impaired long-term memory but normal learning and short-term memory in an object recognition task. We demonstrate that the prototypical PDE4 inhibitor, rolipram, and a novel one (HT0712) abolish the long-term memory defect of CBP+/− mice. Importantly, the genetic lesion in CBP acts specifically to shift the dose sensitivity for HT0712 to enhance memory formation, which conveys molecular specificity on the drug's mechanism of action. Our results suggest that PDE4 inhibitors may be used to treat the cognitive dysfunction of RTS patients. PMID:12930888
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Bugg, Julie M; Ball, B Hunter
2017-07-01
Participants use simple contextual cues to reduce deployment of costly monitoring processes in contexts in which prospective memory (PM) targets are not expected. This study investigated whether this strategic monitoring pattern is observed in response to complex and probabilistic contextual cues. Participants performed a lexical decision task in which words or nonwords were presented in upper or lower locations on screen. The specific condition was informed that PM targets ("tor" syllable) would occur only in words in the upper location, whereas the nonspecific condition was informed that targets could occur in any location or word type. Context was blocked such that word type and location changed every 8 trials. In Experiment 1, the specific condition used the complex contextual cue to reduce monitoring in unexpected contexts relative to the nonspecific condition. This pattern largely was not evidenced when the complex contextual cue was probabilistic (Experiment 2). Experiment 3 confirmed that strategic monitoring is observed for a complex cue that is deterministic, but not one that is probabilistic. Additionally, Experiments 1 and 3 demonstrated a disadvantage associated with strategic monitoring-namely, that the specific condition was less likely to respond to a PM target in an unexpected context. Experiment 3 provided evidence that this disadvantage is attributable to impaired noticing of the target. The novel findings suggest use of a complex contextual cue per se is not a boundary condition for the strategic, context-specific allocation of monitoring processes to support prospective remembering; however, strategic monitoring is constrained by the predictive utility of the complex contextual cue.
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Baartman, Tamzyn L; Swanepoel, Tanya; Barrientos, Ruth M; Laburn, Helen P; Mitchell, Duncan; Harden, Lois M
2017-05-01
The influence of brain interleukin-1 (IL-1ß) on memory processes includes both detrimental and beneficial effects. To further explore the dynamics of brain IL-1ß in mediating learning and memory during acute sickness, we injected species-homologous rat IL-1ß (100ng/5μl) or vehicle (0.1% bovine serum albumin, 5μl) directly into the cisterna magna (i.c.m.) of male Sprague-Dawley rats. We measured, in parallel, body temperature, food intake, body mass, cage activity, as well as learning and memory using contextual fear conditioning. To investigate the effects of IL-1ß on learning and memory processes we used: (1) a retrograde experiment that involved injecting rats i.c.m. with IL-1ß immediately after training in the novel context, and (2) an anterograde experiment that involved injecting rats i.c.m. with IL-1ß two hours before training in the novel context. In addition, hypothalamic and hippocampal concentrations of IL-1β were measured at several time points following injection. Administration of IL-1ß induced fever, lethargy and anorexia for∼two-to-three days and increased the concentration of IL-1ß in the hippocampus and hypothalamus for at least eight hours. Training in the context immediately before IL-1ß administration (retrograde experiment), did not impair contextual and auditory fear memory. However, when training in the context occurred concurrently with elevated hippocampal IL-1ß levels, two hours after IL-1ß administration (anterograde experiment), contextual, but not auditory, fear memory was impaired. Our results show that there are instances where memory consolidation can occur concurrently with elevated levels of IL-1ß in the hippocampus, fever, anorexia and lethargy during acute short-term sickness. Copyright © 2017 Elsevier B.V. All rights reserved.
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Finite element analysis of Al 2024/Cu-Al-Ni shape memory alloy composites with defects/cracks
NASA Astrophysics Data System (ADS)
Kotresh, M.; Benal, M. M., Dr; Siddalinga Swamy, N. H., Dr
2018-02-01
In this work, a numerical approach to predict the stress field behaviour of defect/crack in shape memory alloy (SMA) particles reinforced composite known as the adaptive composite is presented. Simulation is based on the finite element method. The critical stress field approach was used to determine the stresses around defect/crack. Thereby stress amplification issue is being resolved. In this paper, the effect volume % of shape memory alloy and shape memory effect of reinforcement for as-cast and SME trained composites are examined and discussed. Shape memory effect known as training is achieved by pre-straining of reinforcement particles by equivalent changes in their expansion coefficients.
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Role of dorsal hippocampus κ opioid receptors in contextual aversive memory consolidation in rats.
Vanz, Felipe; Bicca, Maíra Assunção; Linartevichi, Vagner Fagnani; Giachero, Marcelo; Bertoglio, Leandro José; Monteiro de Lima, Thereza C
2018-06-01
The main κ opioid receptors (κORs) subtypes already described (κ 1 ORs and κ 2 ORs) are expressed in brain regions involved in aversive memory consolidation, including the dorsal hippocampus (DH). However, the role of DH κORs in consolidation of aversive memories with varied intensity and specificity is still uncertain. The present study aimed to investigate this question using pharmacological agents in rats subjected to a weak, moderate or strong contextual aversive conditioning (CAC) protocol. Antagonizing DH κORs with nor-binaltorphimine (nor-BNI), immediately after, but not 6 h later, a moderate CAC leads to intensified freezing behavior in the re-exposure to the paired context. Thus, indicating that DH κORs have an inhibitory role in the consolidation of an aversive memory. Increased DH κORs expression 1 h and 3 h after the moderate CAC was also observed. This up-regulation was absent in animals only exposed to the shock or to the context, indicating that this phenomenon requires a shock-context pairing to occur. Intra-DH nor-BNI infusion induced no changes following a weak CAC, but it was able to potentiate the expression of freezing behavior in novel and unpaired context after a strong CAC, indicating that DH κORs also modulate the consolidation of a more intense and generalized memory. Moreover, infusing the κ 2 ORs agonist GR 89696, but not the κ 1 ORs agonist U-69593, into the DH reduced the conditioned freezing expression. Nor-BNI pretreatment in a sub-effective dose prevented the κ 2 ORs agonist effects. Altogether, the present findings provide convergent evidence that κORs activation negatively modulates contextual aversive memory consolidation in rat dorsal hippocampus. Copyright © 2018. Published by Elsevier Ltd.
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Slouzkey, Ilana; Maroun, Mouna
2016-12-01
The basolateral amygdala (BLA), medial prefrontal cortex (mPFC) circuit, plays a crucial role in acquisition and extinction of fear memory. Extinction of aversive memories is mediated, at least in part, by the phosphoinositide-3 kinase (PI3K)/Akt pathway in adult rats. There is recent interest in the neural mechanisms that mediate fear and extinction in juvenile animals and whether these mechanisms are distinctive from those in adult animals. In the present study, we examined (1) changes in phosphorylation of Akt in the BLA and mPFC after fear conditioning and extinction in juvenile and adult rats and (2) the effect of BLA and mPFC localized inhibition of the PI3K following acquisition and extinction of contextual fear memory. Our results show that Akt phosphorylation is increased following acquisition of contextual fear learning in the BLA but not in the mPFC in adult and juvenile rats. Extinction learning was not associated with changes in Akt phosphorylation. Although there were no differences in the pattern of phosphorylation of Akt either in adult or juvenile rats, microinjection of the PI3K inhibitor, LY294002, into the BLA or mPFC elicited differential effects on fear memory acquisition and extinction, depending on the site and timing of the microinjection, as well as on the age of the animal. These results suggest that PI3K/Akt has a differential role in formation, retrieval, and extinction of contextual fear memory in juvenile and adult animals, and point to developmental differences between adult and juvenile rats in mechanisms of extinction. © 2016 Slouzkey and Maroun; Published by Cold Spring Harbor Laboratory Press.
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Zhang, Yue; Kibaly, Cherkaouia; Xu, Chi; Loh, Horace H; Law, Ping-Yee
2017-11-01
The treatment of opioid addiction is challenging because addicts are highly prone to relapse when the memory of the former drug experience is triggered by emotional or environmental cues. An emerging and promising concept in addiction biology is that by manipulating adult hippocampal neurogenesis, a phenomenon involved in learning and memory, drug reward-like behaviors and relapse can be attenuated. We tested a new synthetic compound, KHS101, in an animal model of drug-associated contextual memory. KHS101 has been reported to increase the expression of neurogenic differentiation 1 (NeuroD1), a transcription factor involved in adult neurogenesis, and to specifically induce neuronal differentiation both in vitro and in vivo. Our results indicated that the subcutaneous injection of 3 mg/kg KHS101 for 7 days before conditioned place preference (CPP) training prolonged CPP extinction, while the same treatment after training accelerated extinction. This effect paralleled that observed following temporally controlled, tetracycline-induced NeuroD1 overexpression. Furthermore, the effect of KHS101 may occur via its induction of NeuroD1 expression as demonstrated by the abolition of the KHS101-mediated modulation of morphine-induced CPP extinction after the stereotaxic injection of lentiviral NeuroD1 small interfering RNA into the dentate gyrus (DG) of the hippocampus. These results suggest that the KHS101-mediated modulation of neurogenesis at a critical stage of the conditioning or the extinction of an opioid-associated experience may disrupt the memory trace of the existing opioid-associated experience to facilitate the extinction of drug-associated contextual memory. This implies that KHS101 has therapeutic potential for the treatment of opioid addiction. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Lin, Tzu-Wei; Chen, Shean-Jen; Huang, Tung-Yi; Chang, Chia-Yuan; Chuang, Jih-Ing; Wu, Fong-Sen; Kuo, Yu-Min; Jen, Chauying J
2012-01-01
Different exercise paradigms show differential effects on various forms of memory. We hypothesize that the differential effects of exercises on memory performance are caused by different neuroplasticity changes in relevant brain regions in response to different exercise trainings. We examined the effects of treadmill running (TR) and wheel running (WR) on the Pavlovian fear conditioning task that assesses learning and memory performance associated with the amygdala (cued conditioning) and both the amygdala and hippocampus (contextual conditioning). The skeletal muscle citrate synthase activity, an indicator of aerobic capacity, was elevated in rats received 4 w of TR, but not WR. While both TR and WR elevated the contextual conditional response, only TR facilitated the cued conditional response. Using a single-neuron labeling technique, we found that while both TR and MR enlarged the dendritic field and increased the spine density in hippocampal CA3 neurons, only TR showed these effects in basolateral amygdalar neurons. Moreover, both types of exercise upregulated synaptic proteins (i.e., TrkB and SNAP-25) in the hippocampus; however only TR showed similar effects in the amygdala. Injection of K252a, a TrkB kinase inhibitor, in the dorsal hippocampus or basolateral amygdala abolished the exercise-facilitated contextual or cued fear learning and memory performance, respectively, regardless of the types of exercise. In summary, our results supported that different types of exercise affect the performance of learning and memory via BDNF-TrkB signaling and neuroplasticity in specific brain regions. The brain region-specific neuronal adaptations are possibly induced by various levels of intensity/stress elicited by different types of exercise. Copyright © 2011 Elsevier Inc. All rights reserved.
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Mather, Mara; Knight, Marisa
2008-12-01
A key function of memory is to use past experience to predict when something important might happen next. Indeed, cues that previously predicted arousing events (emotional harbingers) garner more attention than other cues. However, the current series of five experiments demonstrates that people have poorer memory for the context of emotional harbinger cues than of neutral harbinger cues. Participants first learned that some harbinger cues (neutral tones or faces) predicted emotionally arousing pictures and others predicted neutral pictures. Then they studied associations between the harbinger cues and new contextual details. They were worse at remembering associations with emotional harbingers than with neutral harbingers. Memory was impaired not only for the association between emotional harbingers and nearby digits, but also for contextual details that overlapped with or were intrinsic to the emotional harbingers. However, new cues that were inherently emotionally arousing did not yield the same memory impairments as the emotional harbingers. Thus, emotional harbinger cues seem to suffer more from proactive interference than do neutral harbinger cues, impairing formation of new associations with cues that previously predicted something arousing. 2008 APA, all rights reserved
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Mather, Mara; Knight, Marisa
2009-01-01
A key function of memory is to use past experience to predict when something important might happen next. Indeed, cues that previously predicted arousing events (emotional harbingers) garner more attention than other cues. However, the current series of five experiments demonstrates that people have poorer memory for the context of emotional harbinger cues than of neutral harbinger cues. Participants first learned that some harbinger cues (neutral tones or faces) predicted emotionally arousing pictures and others predicted neutral pictures. Then they studied associations between the harbinger cues and new contextual details. They were worse at remembering associations with emotional harbingers than with neutral harbingers. Memory was impaired not only for the association between emotional harbingers and nearby digits but also for contextual details that overlapped with or were intrinsic to the emotional harbingers. However, new cues that were inherently emotionally arousing did not yield the same memory impairments as the emotional harbingers. Thus, emotional harbinger cues seem to suffer more from proactive interference than do neutral harbinger cues, impairing formation of new associations with cues that previously predicted something arousing. PMID:19102596
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Acute stress blocks the caffeine-induced enhancement of contextual memory retrieval in mice.
Pierard, Chistophe; Krazem, Ali; Henkous, Nadia; Decorte, Laurence; Béracochéa, Daniel
2015-08-15
This study investigated in mice the dose-effect of caffeine on memory retrieval in non-stress and stress conditions. C57 Bl/6 Jico mice learned two consecutive discriminations (D1 and D2) in a four-hole board which involved either distinct contextual (CSD) or similar contextual (SSD) cues. All mice received an i.p. injection of vehicle or caffeine (8, 16 or 32mg/kg) 30min before the test session. Results showed that in non-stress conditions, the 16mg/kg caffeine dose induced a significant enhancement of D1 performance in CSD but not in SSD. Hence, we studied the effect of an acute stress (electric footshocks) administered 15min before the test session on D1 performance in caffeine-treated mice. Results showed that stress significantly decreased D1 performance in vehicle-treated controls and the memory-enhancing effect induced by the 16mg/kg caffeine dose in non-stress condition is no longer observed. Interestingly, whereas caffeine-treated mice exhibited weaker concentrations of plasma corticosterone as compared to vehicles in non-stress condition, stress significantly increased plasma corticosterone concentrations in caffeine-treated mice which reached similar level to that of controls. Overall, the acute stress blocked both the endocrinological and memory retrieval enhancing effects of caffeine. Copyright © 2015 Elsevier B.V. All rights reserved.
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Li, Yong; Kim, Jimok
2016-01-01
Neurocognitive effects of cannabinoids have been extensively studied with a focus on CB1 cannabinoid receptors because CB1 receptors have been considered the major cannabinoid receptor in the nervous system. However, recent discoveries of CB2 cannabinoid receptors in the brain demand accurate determination of whether and how CB2 receptors are involved in the cognitive effects of cannabinoids. CB2 cannabinoid receptors are primarily involved in immune functions, but also implicated in psychiatric disorders such as schizophrenia and depression. Here, we examined the effects of CB2 receptor knockout in mice on memory to determine the roles of CB2 receptors in modulating cognitive function. Behavioral assays revealed that hippocampus-dependent, long-term contextual fear memory was impaired whereas hippocampus-independent, cued fear memory was normal in CB2 receptor knockout mice. These mice also displayed enhanced spatial working memory when tested in a Y-maze. Motor activity and anxiety of CB2 receptor knockout mice were intact when assessed in an open field arena and an elevated zero maze. In contrast to the knockout of CB2 receptors, acute blockade of CB2 receptors by AM603 in C57BL/6J mice had no effect on memory, motor activity, or anxiety. Our results suggest that CB2 cannabinoid receptors play diverse roles in regulating memory depending on memory types and/or brain areas. PMID:26819779
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ERIC Educational Resources Information Center
Hanczakowski, Maciej; Mazzoni, Giuliana
2013-01-01
Retrieval-induced forgetting (RIF) is the finding of impaired memory performance for information stored in long-term memory due to retrieval of a related set of information. This phenomenon is often assigned to operations of a specialized mechanism recruited to resolve interference during retrieval by deactivating competing memory representations.…
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Research on Contextual Memorizing of Meaning in Foreign Language Vocabulary
ERIC Educational Resources Information Center
Xu, Linjing; Xiong, Qingxia; Qin, Yufang
2018-01-01
The purpose of this study was to examine the role of contexts in the memory of meaning in foreign vocabularies. The study was based on the cognitive processing hierarchy theory of Craik and Lockhart (1972), the memory trace theory of McClelland and Rumelhart (1986) and the memory trace theory of cognitive psychology. The subjects were non-English…
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ERIC Educational Resources Information Center
Ceccom, Johnatan; Bouhsira, Emilie; Halley, Helene; Daumas, Stephanie; Lassalle, Jean Michel
2013-01-01
One peculiarity of the hippocampal CA3 mossy fiber terminals is the co-release of zinc and glutamate upon synaptic transmission. How these two players act on hippocampal-dependent memories is still unclear. To decipher their respective involvement in memory consolidation, a pharmacological approach was chosen. Using two hippocampal-dependent…
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ERIC Educational Resources Information Center
Costanzi, Marco; Cannas, Sara; Saraulli, Daniele; Rossi-Arnaud, Clelia; Cestari, Vincenzo
2011-01-01
Long-lasting memories of adverse experiences are essential for individuals' survival but are also involved, in the form of recurrent recollections of the traumatic experience, in the aetiology of anxiety diseases (e.g., post-traumatic stress disorder [PTSD]). Extinction-based erasure of fear memories has long been pursued as a behavioral way to…
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Casagrande, Mirelle A; Haubrich, Josué; Pedraza, Lizeth K; Popik, Bruno; Quillfeldt, Jorge A; de Oliveira Alvares, Lucas
2018-04-01
Memories are not instantly created in the brain, requiring a gradual stabilization process called consolidation to be stored and persist in a long-lasting manner. However, little is known whether this time-dependent process is dynamic or static, and the factors that might modulate it. Here, we hypothesized that the time-course of consolidation could be affected by specific learning parameters, changing the time window where memory is susceptible to retroactive interference. In the rodent contextual fear conditioning paradigm, we compared weak and strong training protocols and found that in the latter memory is susceptible to post-training hippocampal inactivation for a shorter period of time. The accelerated consolidation process triggered by the strong training was mediated by glucocorticoids, since this effect was blocked by pre-training administration of metyrapone. In addition, we found that pre-exposure to the training context also accelerates fear memory consolidation. Hence, our results demonstrate that the time window in which memory is susceptible to post-training interferences varies depending on fear conditioning intensity and contextual familiarity. We propose that the time-course of memory consolidation is dynamic, being directly affected by attributes of the learning experiences. Copyright © 2018 Elsevier Inc. All rights reserved.
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Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition
Miller, Adam M. P.; Vedder, Lindsey C.; Law, L. Matthew; Smith, David M.
2014-01-01
Spatial navigation requires memory representations of landmarks and other navigation cues. The retrosplenial cortex (RSC) is anatomically positioned between limbic areas important for memory formation, such as the hippocampus (HPC) and the anterior thalamus, and cortical regions along the dorsal stream known to contribute importantly to long-term spatial representation, such as the posterior parietal cortex. Damage to the RSC severely impairs allocentric representations of the environment, including the ability to derive navigational information from landmarks. The specific deficits seen in tests of human and rodent navigation suggest that the RSC supports allocentric representation by processing the stable features of the environment and the spatial relationships among them. In addition to spatial cognition, the RSC plays a key role in contextual and episodic memory. The RSC also contributes importantly to the acquisition and consolidation of long-term spatial and contextual memory through its interactions with the HPC. Within this framework, the RSC plays a dual role as part of the feedforward network providing sensory and mnemonic input to the HPC and as a target of the hippocampal-dependent systems consolidation of long-term memory. PMID:25140141
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Hippocampal Administration of Levothyroxine Impairs Contextual Fear Memory Consolidation in Rats.
Yu, Dafu; Zhou, Heng; Zou, Lin; Jiang, Yong; Wu, Xiaoqun; Jiang, Lizhu; Zhou, Qixin; Yang, Yuexiong; Xu, Lin; Mao, Rongrong
2017-01-01
Thyroid hormone (TH) receptors are highly distributed in the hippocampus, which plays a vital role in memory processes. However, how THs are involved in the different stages of memory process is little known. Herein, we used hippocampus dependent contextual fear conditioning to address the effects of hippocampal THs on the different stages of fear memory. First, we found that a single systemic levothyroxine (LT 4 ) administration increased the level of free triiodothyronine (FT 3 ) and free tetraiodothyroxine (FT 4 ) not only in serum but also in hippocampus. In addition, a single systemic LT 4 administration immediately after fear conditioning significantly impaired fear memory. These results indicated the important role of hippocampal THs in fear memory process. To further confirm the effects of hippocampal THs on the different stages of fear memory, LT 4 (0.4 μg/μl, 1 μl/side) was injected bilaterally into hippocampus. Rats given LT 4 into hippocampus before training or tests had no effect on the acquisition or retrieval of fear memory, however rats given LT 4 into hippocampus either immediately or 2 h after training showed being significantly impaired fear memory, which demonstrated LT 4 administration into hippocampus impairs the consolidation but has no effect on the acquisition and retrieval of fear memory. Furthermore, hippocampal injection of LT 4 did not affect rats' locomotor activity, thigmotaxis and THs level in prefrontal cortex (PFC) and serum. These findings may have important implications for understanding mechanisms underlying contribution of THs to memory disorders.
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Hippocampal Administration of Levothyroxine Impairs Contextual Fear Memory Consolidation in Rats
Yu, Dafu; Zhou, Heng; Zou, Lin; Jiang, Yong; Wu, Xiaoqun; Jiang, Lizhu; Zhou, Qixin; Yang, Yuexiong; Xu, Lin; Mao, Rongrong
2017-01-01
Thyroid hormone (TH) receptors are highly distributed in the hippocampus, which plays a vital role in memory processes. However, how THs are involved in the different stages of memory process is little known. Herein, we used hippocampus dependent contextual fear conditioning to address the effects of hippocampal THs on the different stages of fear memory. First, we found that a single systemic levothyroxine (LT4) administration increased the level of free triiodothyronine (FT3) and free tetraiodothyroxine (FT4) not only in serum but also in hippocampus. In addition, a single systemic LT4 administration immediately after fear conditioning significantly impaired fear memory. These results indicated the important role of hippocampal THs in fear memory process. To further confirm the effects of hippocampal THs on the different stages of fear memory, LT4 (0.4 μg/μl, 1 μl/side) was injected bilaterally into hippocampus. Rats given LT4 into hippocampus before training or tests had no effect on the acquisition or retrieval of fear memory, however rats given LT4 into hippocampus either immediately or 2 h after training showed being significantly impaired fear memory, which demonstrated LT4 administration into hippocampus impairs the consolidation but has no effect on the acquisition and retrieval of fear memory. Furthermore, hippocampal injection of LT4 did not affect rats’ locomotor activity, thigmotaxis and THs level in prefrontal cortex (PFC) and serum. These findings may have important implications for understanding mechanisms underlying contribution of THs to memory disorders. PMID:28824379
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Dal Bosco, Lidiane; Weber, Gisele E B; Parfitt, Gustavo M; Paese, Karina; Gonçalves, Carla O F; Serodre, Tiago M; Furtado, Clascídia A; Santos, Adelina P; Monserrat, José M; Barros, Daniela M
2015-01-01
Carbon nanotubes (CNT) are promising materials for biomedical applications, especially in the field of neuroscience; therefore, it is essential to evaluate the neurotoxicity of these nanomaterials. The present work assessed the effects of single-walled CNT functionalized with polyethylene glycol (SWCNT-PEG) on the consolidation and retrieval of contextual fear memory in rats and on oxidative stress parameters in the hippocampus. SWCNT-PEG were dispersed in water at concentrations of 0.5, 1.0, and 2.1 mg/mL and infused into the rat hippocampus. The infusion was completed immediately after training and 30 min before testing of a contextual fear conditioning task, resulting in exposure times of 24 h and 30 min, respectively. The results showed that a short exposure to SWCNT-PEG impaired fear memory retrieval and caused lipid peroxidation in the hippocampus. This response was transient and overcome by the mobilization of antioxidant defenses at 24 h. These effects occurred at low and intermediate but not high concentration of SWCNT-PEG, suggesting that the observed biological response may be related to the concentration-dependent increase in particle size in SWCNT-PEG dispersions.
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Dal Bosco, Lidiane; Weber, Gisele E. B.; Parfitt, Gustavo M.; Paese, Karina; Gonçalves, Carla O. F.; Serodre, Tiago M.; Furtado, Clascídia A.; Santos, Adelina P.; Monserrat, José M.; Barros, Daniela M.
2015-01-01
Carbon nanotubes (CNT) are promising materials for biomedical applications, especially in the field of neuroscience; therefore, it is essential to evaluate the neurotoxicity of these nanomaterials. The present work assessed the effects of single-walled CNT functionalized with polyethylene glycol (SWCNT-PEG) on the consolidation and retrieval of contextual fear memory in rats and on oxidative stress parameters in the hippocampus. SWCNT-PEG were dispersed in water at concentrations of 0.5, 1.0, and 2.1 mg/mL and infused into the rat hippocampus. The infusion was completed immediately after training and 30 min before testing of a contextual fear conditioning task, resulting in exposure times of 24 h and 30 min, respectively. The results showed that a short exposure to SWCNT-PEG impaired fear memory retrieval and caused lipid peroxidation in the hippocampus. This response was transient and overcome by the mobilization of antioxidant defenses at 24 h. These effects occurred at low and intermediate but not high concentration of SWCNT-PEG, suggesting that the observed biological response may be related to the concentration-dependent increase in particle size in SWCNT-PEG dispersions. PMID:25738149
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Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory.
Sindreu, Carlos; Palmiter, Richard D; Storm, Daniel R
2011-02-22
The physiological role of vesicular zinc at central glutamatergic synapses remains poorly understood. Here we show that mice lacking the synapse-specific vesicular zinc transporter ZnT3 (ZnT3KO mice) have reduced activation of the Erk1/2 MAPK in hippocampal mossy fiber terminals, disinhibition of zinc-sensitive MAPK tyrosine phosphatase activity, and impaired MAPK signaling during hippocampus-dependent learning. Activity-dependent exocytosis is required for the effect of zinc on presynaptic MAPK and phosphatase activity. ZnT3KO mice have complete deficits in contextual discrimination and spatial working memory. Local blockade of zinc or MAPK in the mossy fiber pathway of wild-type mice impairs contextual discrimination. We conclude that ZnT3 is important for zinc homeostasis modulating presynaptic MAPK signaling and is required for hippocampus-dependent memory.
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Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory
Sindreu, Carlos; Palmiter, Richard D.; Storm, Daniel R.
2011-01-01
The physiological role of vesicular zinc at central glutamatergic synapses remains poorly understood. Here we show that mice lacking the synapse-specific vesicular zinc transporter ZnT3 (ZnT3KO mice) have reduced activation of the Erk1/2 MAPK in hippocampal mossy fiber terminals, disinhibition of zinc-sensitive MAPK tyrosine phosphatase activity, and impaired MAPK signaling during hippocampus-dependent learning. Activity-dependent exocytosis is required for the effect of zinc on presynaptic MAPK and phosphatase activity. ZnT3KO mice have complete deficits in contextual discrimination and spatial working memory. Local blockade of zinc or MAPK in the mossy fiber pathway of wild-type mice impairs contextual discrimination. We conclude that ZnT3 is important for zinc homeostasis modulating presynaptic MAPK signaling and is required for hippocampus-dependent memory. PMID:21245308
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Adaptability to Changes in Temporal Structure Is Fornix-Dependent
ERIC Educational Resources Information Center
Kwok, Sze Chai; Mitchell, Anna S.; Buckley, Mark J.
2015-01-01
Recognition memory deficits, even after short delays, are sometimes observed following hippocampal damage. One hypothesis links the hippocampus with processes in updating contextual memory representation. Here, we used fornix transection, which partially disconnects the hippocampal system, and compares the performance of fornix-transected monkeys…
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Adaptability to Changes Intemporal Structure Is Fornix-Dependent
ERIC Educational Resources Information Center
Kwok, Sze Chai; Mitchell, Anna S.; Buckley, Mark J.
2015-01-01
Recognition memory deficits, even after short delays, are sometimes observed following hippocampal damage. One hypothesis links the hippocampus with processes in updating contextual memory representation. Here, we used fornix transection, which partially disconnects the hippocampal system, and compares the performance of fornix-transected monkeys…
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Zamri, Azra Elia; Stroeder, Jasper; Rao-Ruiz, Priyanka; Lodder, Johannes C; van der Loo, Rolinka J
2017-01-01
Glutamatergic synapses rely on AMPA receptors (AMPARs) for fast synaptic transmission and plasticity. AMPAR auxiliary proteins regulate receptor trafficking, and modulate receptor mobility and its biophysical properties. The AMPAR auxiliary protein Shisa7 (CKAMP59) has been shown to interact with AMPARs in artificial expression systems, but it is unknown whether Shisa7 has a functional role in glutamatergic synapses. We show that Shisa7 physically interacts with synaptic AMPARs in mouse hippocampus. Shisa7 gene deletion resulted in faster AMPAR currents in CA1 synapses, without affecting its synaptic expression. Shisa7 KO mice showed reduced initiation and maintenance of long-term potentiation of glutamatergic synapses. In line with this, Shisa7 KO mice showed a specific deficit in contextual fear memory, both short-term and long-term after conditioning, whereas auditory fear memory and anxiety-related behavior were normal. Thus, Shisa7 is a bona-fide AMPAR modulatory protein affecting channel kinetics of AMPARs, necessary for synaptic hippocampal plasticity, and memory recall. PMID:29199957
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Neural correlates of the encoding of multimodal contextual features
Gottlieb, Lauren J.; Wong, Jenny; de Chastelaine, Marianne; Rugg, Michael D.
2012-01-01
Functional magnetic resonance imaging (fMRI) was employed to identify neural regions engaged during the encoding of contextual features belonging to different modalities. Subjects studied objects that were presented to the left or right of fixation. Each object was paired with its name, spoken in either a male or a female voice. The test requirement was to discriminate studied from unstudied pictures and, for each picture judged old, to retrieve its study location and the gender of the voice that spoke its name. Study trials associated with accurate rather than inaccurate location memory demonstrated enhanced activity in the fusiform and parahippocampal cortex and the hippocampus and reduced activity (a negative subsequent memory effect) in the medial occipital cortex. Successful encoding of voice information was associated with enhanced study activity in the right middle superior temporal sulcus and activity reduction in the right superior frontal cortex. These findings support the proposal that encoding of a contextual feature is associated with enhanced activity in regions engaged during its online processing. In addition, they indicate that negative subsequent memory effects can also demonstrate feature-selectivity. Relative to other classes of study trials, trials for which both contextual features were later retrieved demonstrated enhanced activity in the lateral occipital complex and reduced activity in the temporo-parietal junction. These findings suggest that multifeatural encoding was facilitated when the study item was processed efficiently and study processing was not interrupted by redirection of attention toward extraneous events. PMID:23166292
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Competitive Trace Theory: A Role for the Hippocampus in Contextual Interference during Retrieval.
Yassa, Michael A; Reagh, Zachariah M
2013-01-01
Much controversy exists regarding the role of the hippocampus in retrieval. The two dominant and competing accounts have been the Standard Model of Systems Consolidation (SMSC) and Multiple Trace Theory (MTT), which specifically make opposing predictions as to the necessity of the hippocampus for retrieval of remote memories. Under SMSC, memories eventually become independent of the hippocampus as they become more reliant on cortical connectivity, and thus the hippocampus is not required for retrieval of remote memories, only recent ones. MTT on the other hand claims that the hippocampus is always required no matter the age of the memory. We argue that this dissociation may be too simplistic, and a continuum model may be better suited to address the role of the hippocampus in retrieval of remote memories. Such a model is presented here with the main function of the hippocampus during retrieval being "recontextualization," or the reconstruction of memory using overlapping traces. As memories get older, they are decontextualized due to competition among partially overlapping traces and become more semantic and reliant on neocortical storage. In this framework dubbed the Competitive Trace Theory (CTT), consolidation events that lead to the strengthening of memories enhance conceptual knowledge (semantic memory) at the expense of contextual details (episodic memory). As a result, remote memories are more likely to have a stronger semantic representation. At the same time, remote memories are also more likely to include illusory details. The CTT is a novel candidate model that may provide some resolution to the memory consolidation debate.
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Competitive Trace Theory: A Role for the Hippocampus in Contextual Interference during Retrieval
Yassa, Michael A.; Reagh, Zachariah M.
2013-01-01
Much controversy exists regarding the role of the hippocampus in retrieval. The two dominant and competing accounts have been the Standard Model of Systems Consolidation (SMSC) and Multiple Trace Theory (MTT), which specifically make opposing predictions as to the necessity of the hippocampus for retrieval of remote memories. Under SMSC, memories eventually become independent of the hippocampus as they become more reliant on cortical connectivity, and thus the hippocampus is not required for retrieval of remote memories, only recent ones. MTT on the other hand claims that the hippocampus is always required no matter the age of the memory. We argue that this dissociation may be too simplistic, and a continuum model may be better suited to address the role of the hippocampus in retrieval of remote memories. Such a model is presented here with the main function of the hippocampus during retrieval being “recontextualization,” or the reconstruction of memory using overlapping traces. As memories get older, they are decontextualized due to competition among partially overlapping traces and become more semantic and reliant on neocortical storage. In this framework dubbed the Competitive Trace Theory (CTT), consolidation events that lead to the strengthening of memories enhance conceptual knowledge (semantic memory) at the expense of contextual details (episodic memory). As a result, remote memories are more likely to have a stronger semantic representation. At the same time, remote memories are also more likely to include illusory details. The CTT is a novel candidate model that may provide some resolution to the memory consolidation debate. PMID:23964216
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Item and source memory for emotional associates is mediated by different retrieval processes.
Ventura-Bort, Carlos; Dolcos, Florin; Wendt, Julia; Wirkner, Janine; Hamm, Alfons O; Weymar, Mathias
2017-12-12
Recent event-related potential (ERP) data showed that neutral objects encoded in emotional background pictures were better remembered than objects encoded in neutral contexts, when recognition memory was tested one week later. In the present study, we investigated whether this long-term memory advantage for items is also associated with correct memory for contextual source details. Furthermore, we were interested in the possibly dissociable contribution of familiarity and recollection processes (using a Remember/Know procedure). The results revealed that item memory performance was mainly driven by the subjective experience of familiarity, irrespective of whether the objects were previously encoded in emotional or neutral contexts. Correct source memory for the associated background picture, however, was driven by recollection and enhanced when the content was emotional. In ERPs, correctly recognized old objects evoked frontal ERP Old/New effects (300-500ms), irrespective of context category. As in our previous study (Ventura-Bort et al., 2016b), retrieval for objects from emotional contexts was associated with larger parietal Old/New differences (600-800ms), indicating stronger involvement of recollection. Thus, the results suggest a stronger contribution of recollection-based retrieval to item and contextual background source memory for neutral information associated with an emotional event. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Circadian timed episodic-like memory - a bee knows what to do when, and also where.
Pahl, Mario; Zhu, Hong; Pix, Waltraud; Tautz, Juergen; Zhang, Shaowu
2007-10-01
This study investigates how the colour, shape and location of patterns could be memorized within a time frame. Bees were trained to visit two Y-mazes, one of which presented yellow vertical (rewarded) versus horizontal (non-rewarded) gratings at one site in the morning, while another presented blue horizontal (rewarded) versus vertical (non-rewarded) gratings at another site in the afternoon. The bees could perform well in the learning tests and various transfer tests, in which (i) all contextual cues from the learning test were present; (ii) the colour cues of the visual patterns were removed, but the location cue, the orientation of the visual patterns and the temporal cue still existed; (iii) the location cue was removed, but other contextual cues, i.e. the colour and orientation of the visual patterns and the temporal cue still existed; (iv) the location cue and the orientation cue of the visual patterns were removed, but the colour cue and temporal cue still existed; (v) the location cue, and the colour cue of the visual patterns were removed, but the orientation cue and the temporal cue still existed. The results reveal that the honeybee can recall the memory of the correct visual patterns by using spatial and/or temporal information. The relative importance of different contextual cues is compared and discussed. The bees' ability to integrate elements of circadian time, place and visual stimuli is akin to episodic-like memory; we have therefore named this kind of memory circadian timed episodic-like memory.
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Pitel, Anne Lise; Beaunieux, Hélène; Witkowski, Thomas; Vabret, François; de la Sayette, Vincent; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis
2008-07-01
The exact nature of episodic and working memory impairments in alcoholic Korsakoff patients (KS) remains unclear, as does the specificity of these neuropsychological deficits compared with those of non-Korsakoff alcoholics (AL). The goals of the present study were therefore to (1) specify the nature of episodic and working memory impairments in KS, (2) determine the specificity of the KS neuropsychological profile compared with the AL profile, and (3) observe the distribution of individual performances within the 2 patient groups. We investigated episodic memory (encoding and retrieval abilities, contextual memory and state of consciousness associated with memories), the slave systems of working memory (phonological loop, visuospatial sketchpad and episodic buffer) and executive functions (inhibition, flexibility, updating and integration abilities) in 14 strictly selected KS, 40 AL and 55 control subjects (CS). Compared with CS, KS displayed impairments of episodic memory encoding and retrieval, contextual memory, recollection, the slave systems of working memory and executive functions. Although episodic memory was more severely impaired in KS than in AL, the single specificity of the KS profile was a disproportionately large encoding deficit. Apart from organizational and updating abilities, the slave systems of working memory and inhibition, flexibility and integration abilities were impaired to the same extent in both alcoholic groups. However, some KS were unable to complete the most difficult executive tasks. There was only a partial overlap of individual performances by KS and AL for episodic memory and a total mixture of the 2 groups for working memory. Korsakoff's syndrome encompasses impairments of the different episodic and working memory components. AL and KS displayed similar profiles of episodic and working memory deficits, in accordance with neuroimaging investigations showing similar patterns of brain damage in both alcoholic groups.
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Mental Schemas Hamper Memory Storage of Goal-Irrelevant Information
Sweegers, C. C. G.; Coleman, G. A.; van Poppel, E. A. M.; Cox, R.; Talamini, L. M.
2015-01-01
Mental schemas exert top-down control on information processing, for instance by facilitating the storage of schema-related information. However, given capacity-limits and competition in neural network processing, schemas may additionally exert their effects by suppressing information with low momentary relevance. In particular, when existing schemas suffice to guide goal-directed behavior, this may actually reduce encoding of the redundant sensory input, in favor of gaining efficiency in task performance. The present experiment set out to test this schema-induced shallow encoding hypothesis. Our approach involved a memory task in which faces had to be coupled to homes. For half of the faces the responses could be guided by a pre-learned schema, for the other half of the faces such a schema was not available. Memory storage was compared between schema-congruent and schema-incongruent items. To characterize putative schema effects, memory was assessed both with regard to visual details and contextual aspects of each item. The depth of encoding was also assessed through an objective neural measure: the parietal old/new ERP effect. This ERP effect, observed between 500–800 ms post-stimulus onset, is thought to reflect the extent of recollection: the retrieval of a vivid memory, including various contextual details from the learning episode. We found that schema-congruency induced substantial impairments in item memory and even larger ones in context memory. Furthermore, the parietal old/new ERP effect indicated higher recollection for the schema-incongruent than the schema-congruent memories. The combined findings indicate that, when goals can be achieved using existing schemas, this can hinder the in-depth processing of novel input, impairing the formation of perceptually detailed and contextually rich memory traces. Taking into account both current and previous findings, we suggest that schemas can both positively and negatively bias the processing of sensory input. An important determinant in this matter is likely related to momentary goals, such that mental schemas facilitate memory processing of goal-relevant input, but suppress processing of goal-irrelevant information. Highlights – Schema-congruent information suffers from shallow encoding. – Schema congruency induces poor item and context memory. – The parietal old/new effect is less pronounced for schema-congruent items. – Schemas exert different influences on memory formation depending on current goals. PMID:26635582
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Uzer, Tugba
2016-02-01
Previous research has shown that memories cued by concrete concepts, such as objects, are retrieved faster than those cued by more abstract concepts, such as emotions. This effect has been explained by the fact that more memories are directly retrieved from object versus emotion cues. In the present study, we tested whether RT differences between memories cued by emotion versus object terms occur not only because object cues elicit direct retrieval of more memories (Uzer, Lee, & Brown, 2012), but also because of differences in memory generation in response to emotions versus objects. One hundred university students retrieved memories in response to basic-level (e.g. orange), superordinate-level (e.g. plant), and emotion (e.g. surprised) cues. Retrieval speed was measured and participants reported whether memories were directly retrieved or generated on each trial. Results showed that memories were retrieved faster in response to basic-level versus superordinate-level and emotion cues because a) basic-level cues elicited more directly retrieved memories, and b) generating memories was more difficult when cues were abstract versus concrete. These results suggest that generative retrieval is a cue generation process in which additional cues that provide contextual information including the target event are produced. Memories are retrieved more slowly in response to emotion cues in part because emotion labels are less effective cues of appropriate contextual information. This particular finding is inconsistent with the idea that emotion is a primary organizational unit for autobiographical memories. In contrast, the difficulty of emotional memory generation implies that emotions represent low-level event information in the organization of autobiographical memory. Copyright © 2016 Elsevier B.V. All rights reserved.
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Bueno, Ana Paula A; de Paiva, Joselisa Péres Queiroz; Corrêa, Moisés Dos Santos; Tiba, Paula Ayako; Fornari, Raquel Vecchio
2017-03-15
It is well established that corticosterone (CORT) enhances memory consolidation of emotionally arousing experiences. Despite emotional memories being usually referred to as well remembered for long periods, there are no studies that have investigated the effects of CORT in modulating the duration and specificity of memory. In the present study, we trained Wistar rats in a single-trial contextual fear conditioning protocol and injected CORT (0.3, 1.0 or 3.0mg/kg), immediately after training, to investigate its effects on memory consolidation. Rats were tested 2 and 29days after the training session or only 29days after training to assess recent or remote memory. Our results show that animals tested for recent memory discriminated the training context from a novel one, while those tested only for remote memory generalized the fear response to both contexts. Animals tested for remote memory after being tested for recent memory were able to discriminate both contexts. These results support the literature regarding memory specificity and duration. However, CORT treatment, even at the dose of 1.0mg/kg that effectively enhanced the plasmatic hormone levels, did not affect the strength or the specificity of memory in either recent or remote memory tests. We hypothesize that the lack of effect of CORT treatment could be due to the low arousing training experience of the single-trial protocol which, despite being sufficient to induce significant recent and remote memory consolidation, may not be sufficient to allow the memory-enhancing effect of CORT. Copyright © 2017 Elsevier Inc. All rights reserved.
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Mental Images and the Modification of Learning Defects.
ERIC Educational Resources Information Center
Patten, Bernard M.
Because human memory and thought involve extremely complex processes, it is possible to employ unusual modalities and specific visual strategies for remembering and problem-solving to assist patients with memory defects. This three-part paper discusses some of the research in the field of human memory and describes practical applications of these…
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ERIC Educational Resources Information Center
Manelis, Anna; Reder, Lynne M.
2012-01-01
Using a combination of eye tracking and fMRI in a contextual cueing task, we explored the mechanisms underlying the facilitation of visual search for repeated spatial configurations. When configurations of distractors were repeated, greater activation in the right hippocampus corresponded to greater reductions in the number of saccades to locate…
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ERIC Educational Resources Information Center
Segev, Amir; Akirav, Irit
2011-01-01
We examined whether the cannabinoid receptor agonist WIN55,212-2 (WIN; 5 [mu]g/side) microinjected into the hippocampus or the amygdala would differentially affect memory processes in a neutral vs. an aversive task. In the aversive contextual fear task, WIN into the basolateral amygdala impaired fear acquisition/consolidation, but not retrieval.…
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ERIC Educational Resources Information Center
Reagh, Zachariah M.; Yassa, Michael A.
2014-01-01
Most theories of memory assume that representations are strengthened with repetition. We recently proposed Competitive Trace Theory, building on the hippocampus' powerful capacity to orthogonalize inputs into distinct outputs. We hypothesized that repetition elicits a similar but nonidentical memory trace, and that contextual details of…
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Recovering Faces from Memory: The Distracting Influence of External Facial Features
ERIC Educational Resources Information Center
Frowd, Charlie D.; Skelton, Faye; Atherton, Chris; Pitchford, Melanie; Hepton, Gemma; Holden, Laura; McIntyre, Alex H.; Hancock, Peter J. B.
2012-01-01
Recognition memory for unfamiliar faces is facilitated when contextual cues (e.g., head pose, background environment, hair and clothing) are consistent between study and test. By contrast, inconsistencies in external features, especially hair, promote errors in unfamiliar face-matching tasks. For the construction of facial composites, as carried…
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A Contextual View of Adult Learning and Memory.
ERIC Educational Resources Information Center
Glynn, Shawn M.
Explanations of age-related differences in adult memory usually assume two forms: processing deficits and structural deficits. Processing deficit explanations attribute recall differences to a failure of older adults to effectively use the processes of attention, organization, mediation (the use of such devices as visual images and verbal images…
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Research on Adult Learning and Memory: Retrospect and Prospect.
ERIC Educational Resources Information Center
Hultsch, David F.; Pentz, C. A.
1980-01-01
Descriptions of cognitive development are determined by the metamodel on which theories and data are based. The associative and information processing approaches have generated much of the research on adult learning and memory. A contextual approach, emphasizing perceiving, comprehending, and remembering, is emerging in the present historical…
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A Comparison of Behavioral and Pharmacological Interventions to Attenuate Reactivated Fear Memories
ERIC Educational Resources Information Center
Monti, Roque I. Ferrer; Alfei, Joaquin M.; Mugnaini, Matias; Bueno, Adrian M.; Beckers, Tom; Urcelay, Gonzalo P.; Molina, Victor A.
2017-01-01
Two experiments using rats in a contextual fear memory preparation compared two approaches to reduce conditioned fear: (1) pharmacological reconsolidation blockade and (2) reactivation-plus-extinction training. In Experiment 1, we explored different combinations of reactivation-plus-extinction parameters to reduce conditioned fear and attenuate…
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Contextualizing Instruction for English Language Learners with Learning Disabilities
ERIC Educational Resources Information Center
Miller, Rhonda D.
2016-01-01
English language learners (ELLs) with learning disabilities (LD) can find navigating the content areas quite difficult due to challenges involving limitations in English language proficiency, gaps in English academic vocabulary, difficulties with working memory and long-term memory, and limited background knowledge on content area topics. However,…
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Engaging "Gangland" Visual Culture: Memorializing Beltzhoover's Victims of Violence, 1993-1997
ERIC Educational Resources Information Center
Bey, Sharif
2012-01-01
This autoethnographic study contextualizes gangland visual culture (graffiti, tattoos, public/private shrines) in order to illustrate how young African American males memorialized victims of violence between the years 1993-1997 in Beltzhoover, an inner city African American community on Pittsburgh's Southside. The author, a former resident of the…
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Levy-Gigi, Einat; Vakil, Eli
2012-01-01
The influence of contextual factors on encoding and retrieval in recognition memory was investigated using a retroactive interference paradigm. Participants were randomly assigned to four context conditions constructed by manipulating types of presentation modality (pictures vs words) for study, interference, and test stages, respectively (ABA, ABB, AAA, & AAB). In Experiment 1 we presented unrelated items in the study and interference stages, while in Experiment 2 each stage contained items from the same semantic category. The results demonstrate a dual role for context in memory processes-at encoding as well as at retrieval. In Experiment 1 there is a hierarchical order between the four context conditions, depending on both target-test and target-interference contextual similarity. Adding a categorical context in Experiment 2 helped to specify each list and therefore better distinguish between target and interferer information, and in some conditions compensated for their perceptual similarity.
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Revillo, D A; Cotella, E; Paglini, M G; Arias, C
2015-09-01
Over the last 30years a considerable number of reports have explored learning about context during infancy in both humans and rats. This research was stimulated by two different theoretical frameworks. The first, known as the neuromaturational model, postulates that learning and behavior are context-independent during early ontogeny, a hypothesis based on the idea that contextual learning is dependent on the hippocampal function, and that this brain structure does not reach full maturity until late in infancy. The second theoretical framework views infants not as immature organisms, but rather as perfectly matured ones, given that their behavioral and cognitive capacities allow them to adapt appropriately to the demands of their specific environment in accordance with their maturational level. This model predicts significant ontogenetic variations in learning and memory due to developmental differences in what is perceived and attended to during learning episodes, which can result in ontogenetic differences in contextual learning depending on the specific demands of the task. The present manuscript reviews those studies that have examined potential developmental differences in contextual learning and context effects in rats. The reviewed results show that, during infancy, context can exert a similar influence over learning and memory as that described for the adult rat. Moreover, in some cases, contextual learning and context effects were greater in infants than in adults. In contrast, under other experimental conditions, no evidence of contextual learning or context effects was observed. We analyzed the procedural factors of these studies with the aim of detecting those that favor or impede contextual learning during infancy, and we discussed whether existing empirical evidence supports the claim that the functionality of the hippocampus is a limiting factor for this type of learning during infancy. Finally, conclusions from human research into contextual learning capacities during infancy were also examined. In view of the wealth of evidence showing contextual learning and context effects during infancy, we suggest that future research aimed at exploring the involvement of the hippocampus in this type of learning should be conducted using parameters which allow the expression of contextual learning during each ontogenetic period. Copyright © 2015 Elsevier Inc. All rights reserved.
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Neuronal Allocation to a Hippocampal Engram
Park, Sungmo; Kramer, Emily E; Mercaldo, Valentina; Rashid, Asim J; Insel, Nathan; Frankland, Paul W; Josselyn, Sheena A
2016-01-01
The dentate gyrus (DG) is important for encoding contextual memories, but little is known about how a population of DG neurons comes to encode and support a particular memory. One possibility is that recruitment into an engram depends on a neuron's excitability. Here, we manipulated excitability by overexpressing CREB in a random population of DG neurons and examined whether this biased their recruitment to an engram supporting a contextual fear memory. To directly assess whether neurons overexpressing CREB at the time of training became critical components of the engram, we examined memory expression while the activity of these neurons was silenced. Chemogenetically (hM4Di, an inhibitory DREADD receptor) or optogenetically (iC++, a light-activated chloride channel) silencing the small number of CREB-overexpressing DG neurons attenuated memory expression, whereas silencing a similar number of random neurons not overexpressing CREB at the time of training did not. As post-encoding reactivation of the activity patterns present during initial experience is thought to be important in memory consolidation, we investigated whether post-training silencing of neurons allocated to an engram disrupted subsequent memory expression. We found that silencing neurons 5 min (but not 24 h) following training disrupted memory expression. Together these results indicate that the rules of neuronal allocation to an engram originally described in the lateral amygdala are followed in different brain regions including DG, and moreover, that disrupting the post-training activity pattern of these neurons prevents memory consolidation. PMID:27187069
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Neuronal Allocation to a Hippocampal Engram.
Park, Sungmo; Kramer, Emily E; Mercaldo, Valentina; Rashid, Asim J; Insel, Nathan; Frankland, Paul W; Josselyn, Sheena A
2016-12-01
The dentate gyrus (DG) is important for encoding contextual memories, but little is known about how a population of DG neurons comes to encode and support a particular memory. One possibility is that recruitment into an engram depends on a neuron's excitability. Here, we manipulated excitability by overexpressing CREB in a random population of DG neurons and examined whether this biased their recruitment to an engram supporting a contextual fear memory. To directly assess whether neurons overexpressing CREB at the time of training became critical components of the engram, we examined memory expression while the activity of these neurons was silenced. Chemogenetically (hM4Di, an inhibitory DREADD receptor) or optogenetically (iC++, a light-activated chloride channel) silencing the small number of CREB-overexpressing DG neurons attenuated memory expression, whereas silencing a similar number of random neurons not overexpressing CREB at the time of training did not. As post-encoding reactivation of the activity patterns present during initial experience is thought to be important in memory consolidation, we investigated whether post-training silencing of neurons allocated to an engram disrupted subsequent memory expression. We found that silencing neurons 5 min (but not 24 h) following training disrupted memory expression. Together these results indicate that the rules of neuronal allocation to an engram originally described in the lateral amygdala are followed in different brain regions including DG, and moreover, that disrupting the post-training activity pattern of these neurons prevents memory consolidation.
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Lee, Hae-June; Kim, Joong-Sun; Song, Myoung-Sub; Seo, Heung-Sik; Yang, Miyoung; Kim, Jong Choon; Jo, Sung-Kee; Shin, Taekyun; Moon, Changjong; Kim, Sung-Ho
2010-03-01
This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.
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Anticipation in Real-World Scenes: The Role of Visual Context and Visual Memory.
Coco, Moreno I; Keller, Frank; Malcolm, George L
2016-11-01
The human sentence processor is able to make rapid predictions about upcoming linguistic input. For example, upon hearing the verb eat, anticipatory eye-movements are launched toward edible objects in a visual scene (Altmann & Kamide, 1999). However, the cognitive mechanisms that underlie anticipation remain to be elucidated in ecologically valid contexts. Previous research has, in fact, mainly used clip-art scenes and object arrays, raising the possibility that anticipatory eye-movements are limited to displays containing a small number of objects in a visually impoverished context. In Experiment 1, we confirm that anticipation effects occur in real-world scenes and investigate the mechanisms that underlie such anticipation. In particular, we demonstrate that real-world scenes provide contextual information that anticipation can draw on: When the target object is not present in the scene, participants infer and fixate regions that are contextually appropriate (e.g., a table upon hearing eat). Experiment 2 investigates whether such contextual inference requires the co-presence of the scene, or whether memory representations can be utilized instead. The same real-world scenes as in Experiment 1 are presented to participants, but the scene disappears before the sentence is heard. We find that anticipation occurs even when the screen is blank, including when contextual inference is required. We conclude that anticipatory language processing is able to draw upon global scene representations (such as scene type) to make contextual inferences. These findings are compatible with theories assuming contextual guidance, but posit a challenge for theories assuming object-based visual indices. Copyright © 2015 Cognitive Science Society, Inc.
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de Lima, Miguel Antonio Xavier; Baldo, Marcus Vinicius C; Canteras, Newton Sabino
2017-01-01
Previous studies from our group have shown that cytotoxic lesions in the ventral portion of the anteromedial thalamic nucleus (AMv), one of the main targets of the hypothalamic predator-responsive circuit, strongly impairs contextual fear responses to an environment previously associated with a predator. The AMv is in a position to convey information to cortico-hippocampal-amygdalar circuits involved in the processing of fear memory. However, it remains to be determined whether the nucleus is involved in the acquisition or subsequent expression of contextual fear. In the present investigation, we addressed this question by inactivating the rat AMv with muscimol either prior to cat exposure or prior to exposure to the cat-related context. Accordingly, AMv pharmacological inactivation prior to cat exposure did not interfere with innate fear responses, but it drastically reduced contextual conditioning to the predator-associated environment. On the other hand, AMv inactivation prior to exposure to the environment associated with the predator threat did not affect contextual fear responses. The behavioral results were further supported by the demonstration that AMv inactivation prior to cat exposure also blocked the activation of sites critically involved in the expression of anti-predatory contextual defensive responses (i.e., the dorsal premammillary nucleus and the dorsolateral periaqueductal gray) in animals exposed to the predator-associated context. The AMv projections were also examined, and the results of this investigation outline important paths that can influence hippocampal circuitry and raise new ideas for anterior thalamic-hippocampal paths involved in emotional learning.
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Ortiz, Vanesa; Giachero, Marcelo; Espejo, Pablo Javier; Molina, Víctor Alejandro
2015-01-01
Background: Withdrawal from chronic ethanol facilitates the formation of contextual fear memory and delays the onset to extinction, with its retrieval promoting an increase in ethanol consumption. Consequently, manipulations aimed to reduce these aversive memories, may be beneficial in the treatment of alcohol discontinuation symptoms. Related to this, pharmacological memory reconsolidation blockade has received greater attention due to its therapeutic potential. Methods: Here, we examined the effect of post-reactivation amnestic treatments such as Midazolam (MDZ, 3 mg/kg i.p) and Propranolol (PROP, 5 mg/kg i.p) on contextual fear memory reconsolidation in ethanol- withdrawn (ETOH) rats. Next, we examined whether the activation of N-methyl-D-aspartate (NMDA) receptors induced by d-cycloserine (DCS, 5 mg/kg i.p., a NMDA partial agonist) before memory reactivation can facilitate the disruptive effect of PROP and MDZ on fear memory in ETOH rats. Results: We observed a resistance to the disruptive effect of both MDZ and PROP following memory reactivation. Although intra-basolateral amygdala (BLA; 1.25 ug/side) and systemic PROP administration attenuated fear memory in DCS pre-treated ETOH rats, DCS/MDZ treatment did not affect memory in these animals. Finally, a decrease of both total and surface protein expression of the α1 GABAA receptor (GABAA-R) subunit in BLA was found in the ETOH rats. Conclusions: Ethanol withdrawal facilitated the formation of fear memory resistant to labilization post-reactivation. DCS administration promoted the disruptive effect of PROP on memory reconsolidation in ETOH rats. The resistance to MDZ’s disruptive effect on fear memory reconsolidation may be, at least in part, associated with changes in the GABAA-R composition induced by chronic ethanol administration/withdrawal. PMID:25617327
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Memory reconsolidation and psychotherapeutic process.
Liberzon, Israel; Javanbakht, Arash
2015-01-01
Lane et al. propose a heuristic model in which distinct, and seemingly irreconcilable, therapies can coexist. Authors postulate that memory reconsolidation is a key common neurobiological process mediating the therapeutic effects. This conceptualization raises a set of important questions regarding neuroscience and translational aspects of fear memory reconsolidation. We discuss the implications of the target article's memory reconsolidation model in the development of more effective interventions, and in the identification of less effective, or potentially harmful approaches, as well as concepts of contextualization, optimal arousal, and combined therapy.
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Effects of Pharmacologic and Genetic Inhibition of Alk on Cognitive Impairments in NF1 Mutant Mice
2016-08-01
impairments. 15. SUBJECT TERMS cognitive performance, pharmacological inhibition, spatial memory , hippocampus 16. SECURITY CLASSIFICATION OF: 17...mouse model; hippocampus ; pharmacological inhibition; spatial memory 2 ACCOMPLISHMENTS: ▪ Major goals of the project Specific Aim (months 1-24...speeds seen in the water maze (Fig. 2). Contextual fear learning and memory Next the mice were tested for acquisition and extinction of hippocampus
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ERIC Educational Resources Information Center
Srikoon, Sanit; Bunterm, Tassanee; Nethanomsak, Teerachai; Ngang, Tang Keow
2017-01-01
Purpose: The attention, working memory, and mood of learners are the most important abilities in the learning process. This study was concerned with the comparison of contextualized attention, working memory, and mood through a neurocognitive-based model (5P) and a conventional model (5E). It sought to examine the significant change in attention,…
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Brockmole, James R; Le-Hoa Võ, Melissa
2010-10-01
When encountering familiar scenes, observers can use item-specific memory to facilitate the guidance of attention to objects appearing in known locations or configurations. Here, we investigated how memory for relational contingencies that emerge across different scenes can be exploited to guide attention. Participants searched for letter targets embedded in pictures of bedrooms. In a between-subjects manipulation, targets were either always on a bed pillow or randomly positioned. When targets were systematically located within scenes, search for targets became more efficient. Importantly, this learning transferred to bedrooms without pillows, ruling out learning that is based on perceptual contingencies. Learning also transferred to living room scenes, but it did not transfer to kitchen scenes, even though both scene types contained pillows. These results suggest that statistical regularities abstracted across a range of stimuli are governed by semantic expectations regarding the presence of target-predicting local landmarks. Moreover, explicit awareness of these contingencies led to a central tendency bias in recall memory for precise target positions that is similar to the spatial category effects observed in landmark memory. These results broaden the scope of conditions under which contextual cuing operates and demonstrate how semantic memory plays a causal and independent role in the learning of associations between objects in real-world scenes.
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Lateral entorhinal cortex is necessary for associative but not nonassociative recognition memory
Wilson, David IG; Watanabe, Sakurako; Milner, Helen; Ainge, James A
2013-01-01
The lateral entorhinal cortex (LEC) provides one of the two major input pathways to the hippocampus and has been suggested to process the nonspatial contextual details of episodic memory. Combined with spatial information from the medial entorhinal cortex it is hypothesised that this contextual information is used to form an integrated spatially selective, context-specific response in the hippocampus that underlies episodic memory. Recently, we reported that the LEC is required for recognition of objects that have been experienced in a specific context (Wilson et al. (2013) Hippocampus 23:352-366). Here, we sought to extend this work to assess the role of the LEC in recognition of all associative combinations of objects, places and contexts within an episode. Unlike controls, rats with excitotoxic lesions of the LEC showed no evidence of recognizing familiar combinations of object in place, place in context, or object in place and context. However, LEC lesioned rats showed normal recognition of objects and places independently from each other (nonassociative recognition). Together with our previous findings, these data suggest that the LEC is critical for associative recognition memory and may bind together information relating to objects, places, and contexts needed for episodic memory formation. PMID:23836525
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Zamorano, Cristina; Fernández-Albert, Jordi; Storm, Daniel R; Carné, Xavier; Sindreu, Carlos
2018-02-01
The hippocampus enables a range of behaviors through its intrinsic circuits and concerted actions with other brain regions. One such important function is the retrieval of episodic memories. How hippocampal cells support retrieval of contextual fear memory remains largely unclear. Here we monitored phospho-activation of extracellular-regulated kinase (Erk1/2) across neuronal populations of the hippocampus to find that CA1 pyramidal neurons, but not cells in CA3 or dentate gyrus, specifically respond to retrieval of an aversive context. In contrast, retrieval of a neutral context that fails to elicit a threat response did not activate Erk1/2. Moreover, retrieval preferentially re-activated Erk1/2 in the same set of CA1 neurons previously activated during conditioning in a context-specific manner. By confining drug inhibition within dorsal CA1, we established the crucial role for Erk1/2 activity in retrieval of long-term memory, as well as in amygdala activation associated with fear expression. These data provide functional evidence that Erk1/2 signaling in CA1 encodes a specific neural representation of contextual memory with emotional value. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
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The effect of ketamine on the consolidation and extinction of contextual fear memory
Thomas, Kerrie L; Hall, Jeremy
2018-01-01
Ketamine, principally an antagonist of N-methyl-ᴅ-aspartate receptors, induces schizophrenia-like symptoms in adult humans, warranting its use in the investigation of psychosis-related phenotypes in animal models. Genomic studies further implicate N-methyl-ᴅ-aspartate receptor-mediated processes in schizophrenia pathology, together with more broadly-defined synaptic plasticity and associative learning processes. Strong pathophysiological links have been demonstrated between fear learning and psychiatric disorders such as schizophrenia. To further investigate the impact of ketamine on associative fear learning, we studied the effects of pre- and post-training ketamine on the consolidation and extinction of contextual fear memory in rats. Administration of 25 mg/kg ketamine prior to fear conditioning did not affect consolidation when potentially confounding effects of state dependency were controlled for. Pre-training ketamine (25 mg/kg) impaired the extinction of the conditioned fear response, which was mirrored with the use of a lower dose (8 mg/kg). Post-training ketamine (25 mg/kg) had no effect on the consolidation or extinction of conditioned fear. These observations implicate processes relating to the extinction of contextual fear memory in the manifestation of ketamine-induced phenotypes, and are consistent with existing hypotheses surrounding abnormal associative learning in schizophrenia. PMID:29338491
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Alvarez-Ricartes, Nathalie; Oliveros-Matus, Patricia; Mendoza, Cristhian; Perez-Urrutia, Nelson; Echeverria, Florencia; Iarkov, Alexandre; Barreto, George E; Echeverria, Valentina
2018-02-27
Failure in fear extinction is one of the more troublesome characteristics of posttraumatic stress disorder (PTSD). Cotinine facilitates fear memory extinction and reduces depressive-like behavior when administered 24 h after fear conditioning in mice. In this study, it was investigated the behavioral and molecular effects of cotinine, and other antidepressant preparations infused intranasally. Intranasal (IN) cotinine, IN krill oil, IN cotinine plus krill oil, and oral sertraline were evaluated on depressive-like behavior and fear retention and extinction after fear conditioning in C57BL/6 mice. Since calcineurin A has been involved in facilitating fear extinction in rodents, we also investigated changes of calcineurin in the hippocampus, a region key on contextual fear extinction. Short-term treatment with cotinine formulations was superior to krill oil and oral sertraline in reducing depressive-like behavior and fear consolidation and enhancing contextual fear memory extinction in mice. IN krill oil slowed the extinction of fear. IN cotinine preparations increased the levels of calcineurin A in the hippocampus of conditioned mice. In the light of the results, the future investigation of the use of IN cotinine preparations for the extinction of contextual fear memory and treatment of treatment-resistant depression (TRD) in PTSD is discussed.
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The role of calsenilin/DREAM/KChIP3 in contextual fear conditioning.
Alexander, Jon C; McDermott, Carmel M; Tunur, Tumay; Rands, Vicky; Stelly, Claire; Karhson, Debra; Bowlby, Mark R; An, W Frank; Sweatt, J David; Schrader, Laura A
2009-03-01
Potassium channel interacting proteins (KChIPs) are members of a family of calcium binding proteins that interact with Kv4 potassium (K(+)) channel primary subunits and also act as transcription factors. The Kv4 subunit is a primary K(+) channel pore-forming subunit, which contributes to the somatic and dendritic A-type currents throughout the nervous system. These A-type currents play a key role in the regulation of neuronal excitability and dendritic processing of incoming synaptic information. KChIP3 is also known as calsenilin and as the transcription factor, downstream regulatory element antagonist modulator (DREAM), which regulates a number of genes including prodynorphin. KChIP3 and Kv4 primary channel subunits are highly expressed in hippocampus, an area of the brain important for learning and memory. Through its various functions, KChIP3 may play a role in the regulation of synaptic plasticity and learning and memory. We evaluated the role of KChIP3 in a hippocampus-dependent memory task, contextual fear conditioning. Male KChIP3 knockout (KO) mice showed significantly enhanced memory 24 hours after training as measured by percent freezing. In addition, we found that membrane association and interaction with Kv4.2 of KChIP3 protein was significantly decreased and nuclear KChIP3 expression was increased six hours after the fear conditioning training paradigm with no significant change in KChIP3 mRNA. In addition, prodynorphin mRNA expression was significantly decreased six hours after fear conditioning training in wild-type (WT) but not in KO animals. These data suggest a role for regulation of gene expression by KChIP3/DREAM/calsenilin in consolidation of contextual fear conditioning memories.
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Hayes, Scott M; Nadel, Lynn; Ryan, Lee
2007-01-01
Previous research has investigated intentional retrieval of contextual information and contextual influences on object identification and word recognition, yet few studies have investigated context effects in episodic memory for objects. To address this issue, unique objects embedded in a visually rich scene or on a white background were presented to participants. At test, objects were presented either in the original scene or on a white background. A series of behavioral studies with young adults demonstrated a context shift decrement (CSD)-decreased recognition performance when context is changed between encoding and retrieval. The CSD was not attenuated by encoding or retrieval manipulations, suggesting that binding of object and context may be automatic. A final experiment explored the neural correlates of the CSD, using functional Magnetic Resonance Imaging. Parahippocampal cortex (PHC) activation (right greater than left) during incidental encoding was associated with subsequent memory of objects in the context shift condition. Greater activity in right PHC was also observed during successful recognition of objects previously presented in a scene. Finally, a subset of regions activated during scene encoding, such as bilateral PHC, was reactivated when the object was presented on a white background at retrieval. Although participants were not required to intentionally retrieve contextual information, the results suggest that PHC may reinstate visual context to mediate successful episodic memory retrieval. The CSD is attributed to automatic and obligatory binding of object and context. The results suggest that PHC is important not only for processing of scene information, but also plays a role in successful episodic memory encoding and retrieval. These findings are consistent with the view that spatial information is stored in the hippocampal complex, one of the central tenets of Multiple Trace Theory. (c) 2007 Wiley-Liss, Inc.
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Sintoni, Silvia; Kurtys, Ewelina; Scandaglia, Marilyn; Contestabile, Antonio; Monti, Barbara
2013-05-01
Valproic acid (VPA), a long-standing anti-epileptic and anti-manic drug, exerts multiple actions in the nervous system through various molecular mechanisms. Neuroprotective properties have been attributed to VPA in different models of neurodegeneration, but contrasting results on its improvement of learning and memory have been reported in non-pathologic conditions. In the present study, we have tested on a hippocampal-dependent learning test, the contextual fear conditioning, the effect of chronic VPA administration through alimentary supplementation that allows relatively steady concentrations to be reached by a drug otherwise very rapidly eliminated in rodents. Contextual fear memory was significantly impaired in rats chronically treated with VPA for 4 weeks. To understand the cellular and molecular correlates of this amnesic effect with particular regard to hippocampus, we addressed three putatively memory-related targets of VPA action in this brain area, obtaining the following main results: i) chronic VPA promoted an increase of post-translational modifications of histone H3 (acetylation and phosphorylation) known to favor gene transcription; ii) adult neurogenesis in the dentate gyrus, which has been controversially reported to be affected by VPA, was unchanged; and iii) GSK-3β, a kinase playing a key role in hippocampal plasticity, as well as in learning and memory, was dysregulated by VPA treatment. These results point at GSK-3β dysregulation in the hippocampus as an important parameter in the amnesic effect of VPA. The VPA amnesic effect in the animal model here reported is also supported by some observations in patients and, therefore, it should be taken into account and monitored in VPA-based therapies. Copyright © 2013 Elsevier Inc. All rights reserved.
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Aging affects the interaction between attentional control and source memory: an fMRI study.
Dulas, Michael R; Duarte, Audrey
2014-12-01
Age-related source memory impairments may be due, at least in part, to deficits in executive processes mediated by the PFC at both study and test. Behavioral work suggests that providing environmental support at encoding, such as directing attention toward item-source associations, may improve source memory and reduce age-related deficits in the recruitment of these executive processes. The present fMRI study investigated the effects of directed attention and aging on source memory encoding and retrieval. At study, participants were shown pictures of objects. They were either asked to attend to the objects and their color (source) or to their size. At test, participants determined if objects were seen before, and if so, whether they were the same color as previously. Behavioral results showed that direction of attention improved source memory for both groups; however, age-related deficits persisted. fMRI results revealed that, across groups, direction of attention facilitated medial temporal lobe-mediated contextual binding processes during study and attenuated right PFC postretrieval monitoring effects at test. However, persistent age-related source memory deficits may be related to increased recruitment of medial anterior PFC during encoding, indicative of self-referential processing, as well as underrecruitment of lateral anterior PFC-mediated relational processes. Taken together, this study suggests that, even when supported, older adults may fail to selectively encode goal-relevant contextual details supporting source memory performance.
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How sodium arsenite improve amyloid β-induced memory deficit?
Nassireslami, Ehsan; Nikbin, Parmida; Amini, Elham; Payandemehr, Borna; Shaerzadeh, Fatemeh; Khodagholi, Fariba; Yazdi, Behnoosh Bonakdar; Kebriaeezadeh, Abbas; Taghizadeh, Ghorban; Sharifzadeh, Mohammad
2016-09-01
Evidence has shown that arsenic exposure, besides its toxic effects results in impairment of learning and memory, but its molecular mechanisms are not fully understood. In the present study, we examined sodium arsenite (1, 5, 10, 100nM) effects on contextual and tone memory of male rats in Pavlovian fear conditioning paradigm alone and in co-administration with β-amyloid. We detected changes in the level of caspase-3, nuclear factor kappa-B (NF-κB), cAMP response element-binding (CREB), heme oxygenase-1 and NF-E2-related factor-2 (Nrf2) by Western blot. Sodium arsenite in high doses induced significant memory impairment 9 and 16days after infusion. By contrast, low doses of sodium arsenite attenuate memory deficit in Aβ injected rats after 16days. Our data revealed that treatment with high concentration of sodium arsenite increased caspase-3 cleavage and NF-κB level, 9days after injection. Whereas, low doses of sodium arsenite cause Nrf2 and HO-1 activation and increased CREB phosphorylation in the hippocampus. These findings suggest the concentration dependent effects of sodium arsenite on contextual and tone memory. Moreover, it seems that the neuroprotective effects of ultra-low concentrations of sodium arsenite on Aβ-induced memory impairment is mediated via an increase Nrf2, HO-1 and CREB phosphorylation levels and decrease caspase-3 and NF-κB amount. Copyright © 2016. Published by Elsevier Inc.
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Morice, Elise; Farley, Séverine; Poirier, Roseline; Dallerac, Glenn; Chagneau, Carine; Pannetier, Solange; Hanauer, André; Davis, Sabrina; Vaillend, Cyrille; Laroche, Serge
2013-10-01
The Coffin-Lowry syndrome (CLS) is a syndromic form of intellectual disability caused by loss-of-function of the RSK2 serine/threonine kinase encoded by the rsk2 gene. Rsk2 knockout mice, a murine model of CLS, exhibit spatial learning and memory impairments, yet the underlying neural mechanisms are unknown. In the current study, we examined the performance of Rsk2 knockout mice in cued, trace and contextual fear memory paradigms and identified selective deficits in the consolidation and reconsolidation of hippocampal-dependent fear memories as task difficulty and hippocampal demand increase. Electrophysiological, biochemical and electron microscopy analyses were carried out in the dentate gyrus of the hippocampus to explore potential alterations in neuronal functions and structure. In vivo and in vitro electrophysiology revealed impaired synaptic transmission, decreased network excitability and reduced AMPA and NMDA conductance in Rsk2 knockout mice. In the absence of RSK2, standard measures of short-term and long-term potentiation (LTP) were normal, however LTP-induced CREB phosphorylation and expression of the transcription factors EGR1/ZIF268 were reduced and that of the scaffolding protein SHANK3 was blocked, indicating impaired activity-dependent gene regulation. At the structural level, the density of perforated and non-perforated synapses and of multiple spine boutons was not altered, however, a clear enlargement of spine neck width and post-synaptic densities indicates altered synapse ultrastructure. These findings show that RSK2 loss-of-function is associated in the dentate gyrus with multi-level alterations that encompass modifications of glutamate receptor channel properties, synaptic transmission, plasticity-associated gene expression and spine morphology, providing novel insights into the mechanisms contributing to cognitive impairments in CLS. Copyright © 2013 Elsevier Inc. All rights reserved.
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Zou, D; Chen, L; Deng, D; Jiang, D; Dong, F; McSweeney, C; Zhou, Y; Liu, L; Chen, G; Wu, Y; Mao, Y
2016-01-01
Parvalbumin (PV)-positive interneurons in the hippocampus play a critical role in animal memory, such as spatial working memory. However, how PV-positive interneurons in the subregions of the hippocampus affect animal behaviors remains poorly defined. Here, we achieved specific and reversible activation of PV-positive interneurons using designer receptors exclusively activated by designer drugs (DREADD) technology. Inducible DREADD expression was demonstrated in vitro in cultured neurons, in which co-transfection of the hM3D-Gq-mCherry vector with a Cre plasmid resulted in a cellular response to hM3Dq ligand clozapine-N-oxide (CNO) stimulation. In addition, the dentate gyrus (DG) of PV-Cre mice received bilateral injection of control lentivirus or lentivirus expressing double floxed hM3D-Gq-mCherry. Selective activation of PV-positive interneurons in the DG did not affect locomotor activity or depression-related behavior in mice. Interestingly, stimulation of PV-positive interneurons induced an anxiolytic effect. Activation of PVpositive interneurons appears to impair social interaction to novelty, but has no effect on social motivation. However, this defect is likely due to the anxiolytic effect as the exploratory behavior of mice expressing hM3DGq is significantly increased. Mice expressing hM3D-Gq did not affect novel object recognition. Activation of PV-positive interneurons in the DG maintains intact cued and contextual fear memory but facilitates fear extinction. Collectively, our results demonstrated that proper control of PV interneurons activity in the DG is critical for regulation of the anxiety, social interaction and fear extinction. These results improve our fundamental understanding of the physiological role of PV-positive interneurons in the hippocampus.
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An Eye-Movement Study of Relational Memory in Adults with Autism Spectrum Disorder
ERIC Educational Resources Information Center
Ring, Melanie; Bowler, Dermot M.; Gaigg, Sebastian B.
2017-01-01
Persons with Autism Spectrum Disorder (ASD) demonstrate good memory for single items but difficulties remembering contextual information related to these items. Recently, we found compromised explicit but intact implicit retrieval of object-location information in ASD (Ring et al. "Autism Res" 8(5):609-619, 2015). Eye-movement data…
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Extinction Partially Reverts Structural Changes Associated with Remote Fear Memory
ERIC Educational Resources Information Center
Vetere, Gisella; Restivo, Leonardo; Novembre, Giovanni; Aceti, Massimiliano; Lumaca, Massimo; Ammassari-Teule, Martine
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…
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ERIC Educational Resources Information Center
McCabe, David P.; Roediger, Henry L., III; McDaniel, Mark A.; Balota, David A.
2009-01-01
In 1985 Tulving introduced the remember-know procedure, whereby subjects are asked to distinguish between memories that involve retrieval of contextual details (remembering) and memories that do not (knowing). Several studies have been reported showing age-related declines in remember hits, which has typically been interpreted as supporting…
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ERIC Educational Resources Information Center
Miranda, Maria Isabel; Quirarte, Gina L.; Rodriguez-Garcia, Gabriela; McGaugh, James L.; Roozendaal, Benno
2008-01-01
It is well established that glucocorticoid hormones strengthen the consolidation of hippocampus-dependent spatial and contextual memory. The present experiments investigated glucocorticoid effects on the long-term formation of conditioned taste aversion (CTA), an associative learning task that does not depend critically on hippocampal function.…
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Repeatedly Reactivated Memories Become More Resistant to Hippocampal Damage
ERIC Educational Resources Information Center
Lehmann, Hugo; McNamara, Kathryn C.
2011-01-01
We examined whether repeated reactivations of a context memory would prevent the typical amnesic effects of post-training damage to the hippocampus (HPC). Rats were given a single contextual fear-conditioning session followed by 10 reactivations, involving a brief return to the conditioning context (no shock). Subsequently, the rats received sham…
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ERIC Educational Resources Information Center
van den Broek, Gesa S. E.; Takashima, Atsuko; Segers, Eliane; Verhoeven, Ludo
2018-01-01
Learning new vocabulary from context typically requires multiple encounters during which word meaning can be retrieved from memory or inferred from context. We compared the effect of memory retrieval and context inferences on short- and long-term retention in three experiments. Participants studied novel words and then practiced the words either…
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ERIC Educational Resources Information Center
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…
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An Observation on the Spontaneous Noticing of Prospective Memory Event-Based Cues
ERIC Educational Resources Information Center
Knight, Justin B.; Meeks, J. Thadeus; Marsh, Richard L.; Cook, Gabriel I.; Brewer, Gene A.; Hicks, Jason L.
2011-01-01
In event-based prospective memory, current theories make differing predictions as to whether intention-related material can be spontaneously noticed (i.e., noticed without relying on preparatory attentional processes). In 2 experiments, participants formed an intention that was contextually associated to the final phase of the experiment, and…
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Loaiza, Vanessa M; McCabe, David P
2012-02-01
Three experiments are reported that addressed the nature of processing in working memory by investigating patterns of delayed cued recall and free recall of items initially studied during complex and simple span tasks. In Experiment 1, items initially studied during a complex span task (i.e., operation span) were more likely to be recalled after a delay in response to temporal-contextual cues, relative to items from subspan and supraspan list lengths in a simple span task (i.e., word span). In Experiment 2, items initially studied during operation span were more likely to be recalled from neighboring serial positions during delayed free recall than were items studied during word span trials. Experiment 3 demonstrated that the number of attentional refreshing opportunities strongly predicts episodic memory performance, regardless of whether the information is presented in a spaced or massed format in a modified operation span task. The results indicate that the content-context bindings created during complex span trials reflect attentional refreshing opportunities that are used to maintain items in working memory.
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Function in context: why American and Trinidadian young and older adults remember the personal past.
Alea, Nicole; Bluck, Susan; Ali, Sideeka
2015-01-01
Multiple and interacting contextual (culture, life phase) and person-specific predictors (i.e., personality, tendency to think-talk about the past) of the functions of autobiographical memory were examined using the Thinking about Life Experiences Scale. American (N = 174) and Trinidadian (N = 182) young and older adults self-reported how frequently they remembered the personal past to serve self, social and directive functions, how often they thought and talked about their past overall, and completed a measure of trait personality. Independent contextual and person-specific predictors were found for using memory to serve a social-bonding function: Americans, young adults, those higher in extraversion, lower in conscientiousness and individuals who frequently think and talk about the past more often use autobiographical memory for social bonding. Across cultures, younger adults report more frequently using memory to serve all three functions, whereas Trinidadians who think more often about the past compared with those who reflect less often are more likely to use it for self and directive functions. Findings are discussed in terms of the individual's embeddedness in cultural and life phase contexts when remembering.
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Angiotensin-(1-7)/Mas axis modulates fear memory and extinction in mice.
Lazaroni, Thiago Luiz do Nascimento; Bastos, Cristiane Perácio; Moraes, Márcio Flávio Dutra; Santos, Robson Souza; Pereira, Grace Schenatto
2016-01-01
Inappropriate defense-alerting reaction to fear is a common feature of neuropsychiatric diseases. Therefore, impairments in brain circuits, as well as in molecular pathways underlying the neurovegetative adjustments to fear may play an essential role on developing neuropsychiatric disorders. Here we tested the hypothesis that interfering with angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis homeostasis, which appears to be essential to arterial pressure control, would affect fear memory and extinction. Mas knockout (MasKO) mice, in FVB/N background, showed normal cued fear memory and extinction, but increased freezing in response to context. Next, as FVB/N has poor performance in contextual fear memory, we tested MasKO in mixed 129xC57BL/6 background. MasKO mice behaved similarly to wild-type (WT), but memory extinction was slower in contextual fear conditioning to a weak protocol (1CS/US). In addition, delayed extinction in MasKO mice was even more pronounced after a stronger protocol (3CS/US). We showed previously that Angiotensin II receptor AT1 antagonist, losantan, rescued object recognition memory deficit in MasKO mice. Here, losartan was also effective. Memory extinction was accelerated in MasKO mice after treatment with losartan. In conclusion, we showed for the first time that Ang-(1-7)/Mas axis may modulate fear memory extinction. Furthermore, we suggest MasKO mice as an animal model to study post-traumatic stress disorder (PTSD). Copyright © 2015 Elsevier Inc. All rights reserved.
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Ab initio theory of the N2V defect in diamond for quantum memory implementation
NASA Astrophysics Data System (ADS)
Udvarhelyi, Péter; Thiering, Gergő; Londero, Elisa; Gali, Adam
2017-10-01
The N2V defect in diamond is characterized by means of ab initio methods relying on density functional theory calculated parameters of a Hubbard model Hamiltonian. It is shown that this approach appropriately describes the energy levels of correlated excited states induced by this defect. By determining its critical magneto-optical parameters, we propose to realize a long-living quantum memory by N2V defect, i.e., H 3 color center in diamond.
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Role of cholinergic receptors in memory retrieval depends on gender and age of memory.
Rashid, Habiba; Mahboob, Aamra; Ahmed, Touqeer
2017-07-28
The phenomenon of utilizing information acquired in the past to make decision and performance in present depends on memory retrieval, which is affected in retrograde amnesia. Role of cholinergic receptors in memory retrieval is not much explored. In this study we evaluated the gender specific role of cholinergic receptors, i.e. muscarinic and nicotinic receptors, in memory retrieval in young Balb/c mice. Acute (only one injection, 30min before test) and sub-chronic (five days) muscarinic blockade (using scopolamine=1mg/kg) before test impaired retrieval of contextual fear memory in male (31.45±5.39% and 33.36±3.78% respectively) and female mice (22.88±5.73%; P<0.05), except sub-chronically treated female group (33.31±4.90%; P>0.05). Only sub-chronic nicotinic receptor antagonism (using methyllycaconitine MLA=87.5μg/kg and dihydro β erythroidine DHβE=1mg/kg) in female showed significantly higher freezing response than control during contextual fear memory retrieval (60.85±7.71% and 40.91±7.53% respectively; P<0.001). Acute and sub-chronic muscarinic antagonism (but not nicotinic antagonism) impaired spatial memory retrieval in male (P<0.05) but not in female mice (P>0.05). There was no effect of acute and sub-chronic cholinergic receptor antagonism on discriminating novel object from the familiar one in male and female mice, however, nicotinic receptor blockade affected the working memory of all male and female mice on test day compared to the training sessions. Our results suggested that cholinergic receptors involvement in retrieving spatial and fear memories depends on the age of the memory and gender. Copyright © 2017 Elsevier B.V. All rights reserved.
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Social and novel contexts modify hippocampal CA2 representations of space
Alexander, Georgia M.; Farris, Shannon; Pirone, Jason R.; Zheng, Chenguang; Colgin, Laura L.; Dudek, Serena M.
2016-01-01
The hippocampus supports a cognitive map of space and is critical for encoding declarative memory (who, what, when and where). Recent studies have implicated hippocampal subfield CA2 in social and contextual memory but how it does so remains unknown. Here we find that in adult male rats, presentation of a social stimulus (novel or familiar rat) or a novel object induces global remapping of place fields in CA2 with no effect on neuronal firing rate or immediate early gene expression. This remapping did not occur in CA1, suggesting this effect is specific for CA2. Thus, modification of existing spatial representations might be a potential mechanism by which CA2 encodes social and novel contextual information. PMID:26806606
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Brosowsky, Nicholaus P; Crump, Matthew J C
2016-08-01
Recent work suggests that environmental cues associated with previous attentional control settings can rapidly and involuntarily adjust attentional priorities. The current study tests predictions from adaptive-learning and memory-based theories of contextual control about the role of intentions for setting attentional priorities. To extend the empirical boundaries of contextual control phenomena, and to determine whether theoretical principles of contextual control are generalizable we used a novel bi-dimensional stimulus sampling task. Subjects viewed briefly presented arrays of letters and colors presented above or below fixation, and identified specific stimuli according to a dimensional (letter or color) and positional cue. Location was predictive of the cued dimension, but not the position or identity. In contrast to previous findings, contextual control failed to develop through automatic, adaptive-learning processes. Instead, previous experience with intentionally changing attentional sampling priorities between different contexts was required for contextual control to develop. Copyright © 2016 Elsevier Inc. All rights reserved.
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Post-retrieval late process contributes to persistence of reactivated fear memory.
Nakayama, Daisuke; Yamasaki, Yoshiko; Matsuki, Norio; Nomura, Hiroshi
2013-05-16
Several studies have demonstrated the mechanisms involved in memory persistence after learning. However, little is known about memory persistence after retrieval. In this study, a protein synthesis inhibitor, anisomycin, was infused into the basolateral amygdala of mice 9.5 h after retrieval of contextual conditioned fear. Anisomycin attenuated fear memory after 7 d, but not after 2 d. In contrast, infusion of anisomycin 5- or 24-h post-retrieval was ineffective. These findings indicate that anisomycin attenuates the persistence of reactivated fear memory in a time-dependent manner. We propose that late protein synthesis is required for memory persistence after retrieval.
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Effects of the beta-blocker propranolol on cued and contextual fear conditioning in humans.
Grillon, Christian; Cordova, Jeremy; Morgan, Charles Andrew; Charney, Dennis S; Davis, Michael
2004-09-01
Beta-adrenergic receptors are involved in the consolidation of emotional memories. Yet, a number of studies using Pavlovian cued fear conditioning have been unable to demonstrate an effect of beta-adrenergic blockade on acquisition or retention of fear conditioning. Evidence for the involvement of beta-adrenergic receptors in emotional memories comes mostly from studies using fear inhibitory avoidance in rodents. It is possible that fear inhibitory avoidance is more akin to contextual conditioning than to cued fear conditioning, suggesting that context conditioning may be disrupted by beta-adrenergic blockade. This study investigated the effects of the beta-adrenergic blocker propranolol on cued and contextual fear conditioning in humans. Subjects were given either placebo (n=15) or 40 mg propranolol (n=15) prior to differential cued conditioning. A week later, they were tested for retention of context and cued fear conditioning using physiological (startle reflex and electrodermal activity) and subjective measures of emotional arousal. The results were consistent with the hypothesis. The skin conductance level (SCL) and the subjective measure of arousal suggested reduced emotional arousal upon returning to the conditioning context in the propranolol group, compared to the placebo group. The acquisition and retention of cued fear conditioning were not affected by propranolol. These results suggest that beta-adrenergic receptors are involved in contextual fear conditioning.
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Contextual cueing impairment in patients with age-related macular degeneration.
Geringswald, Franziska; Herbik, Anne; Hoffmann, Michael B; Pollmann, Stefan
2013-09-12
Visual attention can be guided by past experience of regularities in our visual environment. In the contextual cueing paradigm, incidental learning of repeated distractor configurations speeds up search times compared to random search arrays. Concomitantly, fewer fixations and more direct scan paths indicate more efficient visual exploration in repeated search arrays. In previous work, we found that simulating a central scotoma in healthy observers eliminated this search facilitation. Here, we investigated contextual cueing in patients with age-related macular degeneration (AMD) who suffer from impaired foveal vision. AMD patients performed visual search using only their more severely impaired eye (n = 13) as well as under binocular viewing (n = 16). Normal-sighted controls developed a significant contextual cueing effect. In comparison, patients showed only a small nonsignificant advantage for repeated displays when searching with their worse eye. When searching binocularly, they profited from contextual cues, but still less than controls. Number of fixations and scan pattern ratios showed a comparable pattern as search times. Moreover, contextual cueing was significantly correlated with acuity in monocular search. Thus, foveal vision loss may lead to impaired guidance of attention by contextual memory cues.
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Geyer, Thomas; Shi, Zhuanghua; Müller, Hermann J
2010-06-01
Three experiments examined memory-based guidance of visual search using a modified version of the contextual-cueing paradigm (Jiang & Chun, 2001). The target, if present, was a conjunction of color and orientation, with target (and distractor) features randomly varying across trials (multiconjunction search). Under these conditions, reaction times (RTs) were faster when all items in the display appeared at predictive ("old") relative to nonpredictive ("new") locations. However, this RT benefit was smaller compared to when only one set of items, namely that sharing the target's color (but not that in the alternative color) appeared in predictive arrangement. In all conditions, contextual cueing was reliable on both target-present and -absent trials and enhanced if a predictive display was preceded by a predictive (though differently arranged) display, rather than a nonpredictive display. These results suggest that (1) contextual cueing is confined to color subsets of items, that (2) retrieving contextual associations for one color subset of items can be impeded by associations formed within the alternative subset ("contextual interference"), and (3) that contextual cueing is modulated by intertrial priming.
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The effects of acute nicotine on contextual safety discrimination.
Kutlu, Munir G; Oliver, Chicora; Gould, Thomas J
2014-11-01
Anxiety disorders, such as post-traumatic stress disorder (PTSD), may be related to an inability to distinguish safe versus threatening environments and to extinguish fear memories. Given the high rate of cigarette smoking in patients with PTSD, as well as the recent finding that an acute dose of nicotine impairs extinction of contextual fear memory, we conducted a series of experiments to investigate the effect of acute nicotine in an animal model of contextual safety discrimination. Following saline or nicotine (at 0.0275, 0.045, 0.09 and 0.18 mg/kg) administration, C57BL/6J mice were trained in a contextual discrimination paradigm, in which the subjects received presentations of conditioned stimuli (CS) that co-terminated with a foot-shock in one context (context A (CXA)) and only CS presentations without foot-shock in a different context (context B (CXB)). Therefore, CXA was designated as the 'dangerous context', whereas CXB was designated as the 'safe context'. Our results suggested that saline-treated animals showed a strong discrimination between dangerous and safe contexts, while acute nicotine dose-dependently impaired contextual safety discrimination (Experiment 1). Furthermore, our results demonstrate that nicotine-induced impairment of contextual safety discrimination learning was not a result of increased generalized freezing (Experiment 2) or contingent on the common CS presentations in both contexts (Experiment 3). Finally, our results show that increasing the temporal gap between CXA and CXB during training abolished the impairing effects of nicotine (Experiment 4). The findings of this study may help link nicotine exposure to the safety learning deficits seen in anxiety disorder and PTSD patients. © The Author(s) 2014.
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Béracochéa, Daniel; Liscia, Pierrette; Tronche, Christophe; Chauveau, Frédéric; Jouanin, Jean-Claude; Piérard, Christophe
2008-01-01
This study investigated the dose-effect relationship of modafinil administration on contextual memory processes, in parallel with the measurements of plasma corticosterone levels in acutely stressed mice. Memory was first evaluated in normal (nonstressed) mice either in contextual (CSD) or spatial (SSD) tasks. Thus, C57 Bl/6 Jico mice learned two consecutive discriminations (D1 and D2) in a four-hole board. The discriminations occurred on either distinct (CSD) or identical (SSD) floors (internal contextual cues). All mice received a vehicle intraperitoneal injection before learning and were injected 24 h later (20 min before the test session) either with vehicle or modafinil. Results showed that modafinil-treated mice behaved similarly as vehicles in the spatial SSD task, whereas in contrast, memory of the first-learned discrimination (D1) in the CSD task was enhanced by a 32- but not a 16-mg/kg modafinil dose. Hence, we studied the effect of a pretest acute stress (electric footshocks) specifically on D1 performance in modafinil-treated subjects. Immediately after behavioral testing, blood was sampled to measure plasma corticosterone levels. Results showed that: (1) stress significantly improved performance in vehicles, (2) stress decreased the efficiency threshold of modafinil, as performance was enhanced at the low dose (16 mg/kg), whereas this enhancement was obtained for the high dose (32 mg/kg) under nonstress conditions, (3) the performance was impaired at the high (32 mg/kg) dose, and (4) modafinil significantly reduced the magnitude of the stress-induced corticosterone secretion, mainly at the dose of 32 mg/kg.
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Vignisse, Julie; Steinbusch, Harry W M; Grigoriev, Vladimir; Bolkunov, Alexei; Proshin, Alexey; Bettendorff, Lucien; Bachurin, Sergey; Strekalova, Tatyana
2014-02-01
Bifunctional drug therapy targeting distinct receptor signalling systems can generate increased efficacy at lower concentrations compared to monofunctional therapy. Non-competitive blockade of the NMDA receptors or the potentiation of AMPA receptors is well documented to result in memory enhancement. Here, we compared the efficacy of the low-affinity NMDA receptor blocker memantine or the positive modulator of AMPA receptor QXX (in C57BL/6J at 1 or 5mg/kg, ip) with new derivatives of isothiourea (0.5-1 mg/kg, ip) that have bifunctional efficacy. Low-affinity NMDA blockade by these derivatives was achieved by introducing greater flexibility into the molecule, and AMPA receptor stimulation was produced by a sulfamide-containing derivative of isothiourea. Contextual learning was examined in a step-down avoidance task and extinction of contextual memory was studied in a fear-conditioning paradigm. Memantine enhanced contextual learning while QXX facilitated memory extinction; both drugs were effective at 5 mg/kg. The new derivative IPAC-5 elevated memory scores in both tasks at the dose 0.5 mg/kg and exhibited the lowest IC₅₀ values of NMDA receptor blockade and highest potency of AMPA receptor stimulation. Thus, among the new drugs tested, IPAC-5 replicated the properties of memantine and QXX in one administration with increased potency. Our data suggest that a concomitant manipulation of NMDA- and AMPA-receptors results in pro-cognitive effects and supports the concept bifunctional drug therapy as a promising strategy to replace monofunctional therapies with greater efficacy and improved compliance. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.
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Long-term stabilization of place cell remapping produced by a fearful experience
Wang, Melissa E.; Wann, Ellen G.; Yuan, Robin K.; Ramos Álvarez, Manuel M.; Stead, Squire M.; Muzzio, Isabel A.
2012-01-01
Fear is an emotional response to danger that is highly conserved throughout evolution because it is critical for survival. Accordingly, episodic memory for fearful locations is widely studied using contextual fear conditioning, a hippocampus-dependent task (Kim and Fanselow, 1992; Phillips and LeDoux, 1992). The hippocampus has been implicated in episodic emotional memory and is thought to integrate emotional stimuli within a spatial framework. Physiological evidence supporting the role of the hippocampus in contextual fear indicates that pyramidal cells in this region, which fire in specific locations as an animal moves through an environment, shift their preferred firing locations shortly after the presentation of an aversive stimulus (Moita et al., 2004). However, the long-term physiological mechanisms through which emotional memories are encoded by the hippocampus are unknown. Here we show that during and directly after a fearful experience, new hippocampal representations are established and persist in the long term. We recorded from the same place cells in mouse hippocampal area CA1 over several days during predator odor contextual fear conditioning and found that a subset of cells changed their preferred firing locations in response to the fearful stimulus. Furthermore, the newly formed representations of the fearful context stabilized in the long term. Our results demonstrate that place cells respond to the presence of an aversive stimulus, modify their firing patterns during emotional learning, and stabilize a long-term spatial representation in response to a fearful encounter. The persistent nature of these representations may contribute to the enduring quality of emotional memories. PMID:23136419
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Impaired Dendritic Development and Memory in Sorbs2 Knock-Out Mice.
Zhang, Qiangge; Gao, Xian; Li, Chenchen; Feliciano, Catia; Wang, Dongqing; Zhou, Dingxi; Mei, Yuan; Monteiro, Patricia; Anand, Michelle; Itohara, Shigeyoshi; Dong, Xiaowei; Fu, Zhanyan; Feng, Guoping
2016-02-17
Intellectual disability is a common neurodevelopmental disorder characterized by impaired intellectual and adaptive functioning. Both environmental insults and genetic defects contribute to the etiology of intellectual disability. Copy number variations of SORBS2 have been linked to intellectual disability. However, the neurobiological function of SORBS2 in the brain is unknown. The SORBS2 gene encodes ArgBP2 (Arg/c-Abl kinase binding protein 2) protein in non-neuronal tissues and is alternatively spliced in the brain to encode nArgBP2 protein. We found nArgBP2 colocalized with F-actin at dendritic spines and growth cones in cultured hippocampal neurons. In the mouse brain, nArgBP2 was highly expressed in the cortex, amygdala, and hippocampus, and enriched in the outer one-third of the molecular layer in dentate gyrus. Genetic deletion of Sorbs2 in mice led to reduced dendritic complexity and decreased frequency of AMPAR-miniature spontaneous EPSCs in dentate gyrus granule cells. Behavioral characterization revealed that Sorbs2 deletion led to a reduced acoustic startle response, and defective long-term object recognition memory and contextual fear memory. Together, our findings demonstrate, for the first time, an important role for nArgBP2 in neuronal dendritic development and excitatory synaptic transmission, which may thus inform exploration of neurobiological basis of SORBS2 deficiency in intellectual disability. Copy number variations of the SORBS2 gene are linked to intellectual disability, but the neurobiological mechanisms are unknown. We found that nArgBP2, the only neuronal isoform encoded by SORBS2, colocalizes with F-actin at neuronal dendritic growth cones and spines. nArgBP2 is highly expressed in the cortex, amygdala, and dentate gyrus in the mouse brain. Genetic deletion of Sorbs2 in mice leads to impaired dendritic complexity and reduced excitatory synaptic transmission in dentate gyrus granule cells, accompanied by behavioral deficits in acoustic startle response and long-term memory. This is the first study of Sorbs2 function in the brain, and our findings may facilitate the study of neurobiological mechanisms underlying SORBS2 deficiency in the development of intellectual disability. Copyright © 2016 the authors 0270-6474/16/362248-14$15.00/0.
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Contextual Distinctiveness Produces Long-Lasting Priming of Pop-Out
ERIC Educational Resources Information Center
Thomson, David R.; Milliken, Bruce
2013-01-01
Maljkovic and Nakayama have demonstrated memory influences in singleton search from one trial to the next, an effect they termed "priming of pop-out" (PoP). This effect was described as resulting from the persistence of an implicit memory trace, the influence of which could be observed for around 5-8 subsequent trials. Thomson and…
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ERIC Educational Resources Information Center
Diana, Rachel A.; Yonelinas, Andrew P.; Ranganath, Charan
2008-01-01
Performance on tests of source memory is typically based on recollection of contextual information associated with an item. However, recent neuroimaging results have suggested that the perirhinal cortex, a region thought to support familiarity-based item recognition, may support source attributions if source information is encoded as a feature of…
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The Rate of Source Memory Decline across the Adult Life Span
ERIC Educational Resources Information Center
Cansino, Selene; Estrada-Manilla, Cinthya; Hernandez-Ramos, Evelia; Martinez-Galindo, Joyce Graciela; Torres-Trejo, Frine; Gomez-Fernandez, Tania; Ayala-Hernandez, Mariana; Osorio, David; Cedillo-Tinoco, Melisa; Garces-Flores, Lissete; Gomez-Melgarejo, Sandra; Beltran-Palacios, Karla; Guadalupe Garcia-Lazaro, Haydee; Garcia-Gutierrez, Fabiola; Cadena-Arenas, Yadira; Fernandez-Apan, Luisa; Bartschi, Andrea; Resendiz-Vera, Julieta; Rodriguez-Ortiz, Maria Dolores
2013-01-01
Previous studies have suggested that the ability to remember contextual information related to specific episodic experiences declines with advancing age; however, the exact moment in the adult life span when this deficit begins is still controversial. Source memory for spatial information was tested in a life span sample of 1,500 adults between…
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ERIC Educational Resources Information Center
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…
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Activity in Prelimbic Cortex Subserves Fear Memory Reconsolidation over Time
ERIC Educational Resources Information Center
Stern, Cristina A. J.; Gazarini, Lucas; Vanvossen, Ana C.; Hames, Mayara S.; Bertoglio, Leandro J.
2014-01-01
The prelimbic cortex has been implicated in the consolidation of previously learned fear. Herein, we report that temporarily inactivating this medial prefrontal cortex subregion with the GABA [subscript A] agonist muscimol (4.0 nmol in 0.2 µL per hemisphere) was able to equally disrupt 1-, 7-, and 21-d-old contextual fear memories after their…
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ERIC Educational Resources Information Center
Xiao, Xin; Zhao, Di; Zhang, Qin; Guo, Chun-yan
2012-01-01
The current study used the directed forgetting paradigm in implicit and explicit memory to investigate the concreteness effect. Event-related potentials (ERPs) were recorded to explore the neural basis of this phenomenon. The behavioral results showed a clear concreteness effect in both implicit and explicit memory tests; participants responded…
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ERIC Educational Resources Information Center
Brightwell, Jennifer J.; Countryman, Renee A.; Neve, Rachael L.; Colombo, Paul J.; Smith, Clayton A.
2005-01-01
Phosphorylation of the transcription factor CREB on Ser133 is implicated in the establishment of long-term memory for hippocampus-dependent tasks, including spatial learning and contextual fear conditioning. We reported previously that training on a hippocampus-dependent social transmission of food preference (STFP) task increases CREB…
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Conditioning- and Time-Dependent Increases in Context Fear and Generalization
ERIC Educational Resources Information Center
Poulos, Andrew M.; Mehta, Nehali; Lu, Bryan; Amir, Dorsa; Livingston, Briana; Santarelli, Anthony; Zhuravka, Irina; Fanselow, Michael S.
2016-01-01
A prominent feature of fear memories and anxiety disorders is that they endure across extended periods of time. Here, we examine how the severity of the initial fear experience influences incubation, generalization, and sensitization of contextual fear memories across time. Adult rats were presented with either five, two, one, or zero shocks (1.2…
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Ontogeny of Contextual Fear Memory Formation, Specificity, and Persistence in Mice
ERIC Educational Resources Information Center
Akers, Katherine G.; Arruda-Carvalho, Maithe; Josselyn, Sheena A.; Frankland, Paul W.
2012-01-01
Pinpointing the precise age when young animals begin to form memories of aversive events is valuable for understanding the onset of anxiety and mood disorders and for detecting early cognitive impairment in models of childhood-onset disorders. Although these disorders are most commonly modeled in mice, we know little regarding the development of…
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ERIC Educational Resources Information Center
Kaczorowski, Catherine C.; Disterhoft, John F.
2009-01-01
Normal aging disrupts hippocampal neuroplasticity and learning and memory. Aging deficits were exposed in a subset (30%) of middle-aged mice that performed below criterion on a hippocampal-dependent contextual fear conditioning task. Basal neuronal excitability was comparable in middle-aged and young mice, but learning-related modulation of the…
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Retrosplenial Cortex Is Required for the Retrieval of Remote Memory for Auditory Cues
ERIC Educational Resources Information Center
Todd, Travis P.; Mehlman, Max L.; Keene, Christopher S.; DeAngeli, Nicole E.; Bucci, David J.
2016-01-01
The retrosplenial cortex (RSC) has a well-established role in contextual and spatial learning and memory, consistent with its known connectivity with visuo-spatial association areas. In contrast, RSC appears to have little involvement with delay fear conditioning to an auditory cue. However, all previous studies have examined the contribution of…
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Reconsolidation of a Context Long-Term Memory in the Terrestrial Snail Requires Protein Synthesis
ERIC Educational Resources Information Center
Gainutdinova, Tatiana H.; Tagirova, Rosa R.; Ismailova, Asja I.; Muranova, Lyudmila N.; Samarova, Elena I.; Gainutdinov, Khalil L.; Balaban, Pavel M.
2005-01-01
We investigated the influence of the protein synthesis blocker anisomycin on contextual memory in the terrestrial snail "Helix." Prior to the training session, the behavioral responses in two contexts were similar. Two days after a session of electric shocks (5 d) in one context only, the context conditioning was observed as the significant…
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ERIC Educational Resources Information Center
Benjamin, Aaron S.
2010-01-01
It is widely assumed that older adults suffer a deficit in the psychological processes that underlie remembering of contextual or source information. This conclusion is based in large part on empirical interactions, including disordinal ones, that reveal differential effects of manipulations of memory strength on recognition in young and old…
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ERIC Educational Resources Information Center
Winocur, Gordon; Frankland, Paul W.; Sekeres, Melanie; Fogel, Stuart; Moscovitch, Morris
2009-01-01
After acquisition, memories associated with contextual fear conditioning pass through a labile phase, in which they are vulnerable to hippocampal lesions, to a more stable state, via consolidation, in which they engage extrahippocampal structures and are resistant to such disruption. The process is accompanied by changes in the form of the memory…
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Shaw, Jillian L.; Zhang, Shixing
2015-01-01
Aging individuals with Down syndrome (DS) have an increased risk of developing Alzheimer's disease (AD), a neurodegenerative disorder characterized by impaired memory. Memory problems in both DS and AD individuals usually develop slowly and progressively get worse with age, but the cause of this age-dependent memory impairment is not well understood. This study examines the functional interactions between Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. Using Drosophila as a model, we find that overexpression of nebula (fly homolog of DSCR1) initially protects against APP-induced memory defects by correcting calcineurin and cAMP signaling pathways but accelerates the rate of memory loss and exacerbates mitochondrial dysfunction in older animals. We report that transient upregulation of Nebula/DSCR1 or acute pharmacological inhibition of calcineurin in aged flies protected against APP-induced memory loss. Our data suggest that calcineurin dyshomeostasis underlies age-dependent memory impairments and further imply that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory impairments in AD in DS. SIGNIFICANCE STATEMENT Most Down syndrome (DS) individuals eventually develop Alzheimer's disease (AD)-like dementia, but mechanisms underlying this age-dependent memory impairment remain poorly understood. This study examines Nebula/Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. We uncover a previously unidentified role for Nebula/DSCR1 in modulating APP-induced memory defects during aging. We show that upregulation of Nebula/DSCR1, an inhibitor of calcineurin, rescues APP-induced memory defects in young flies but enhances memory loss of older flies. Excitingly, transient Nebula/DSCR1 overexpression or calcineurin inhibition in aged flies ameliorates APP-mediated memory problems. These results suggest that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory loss in DS and AD and points to correcting calcineurin signaling as a means to improve memory during aging. PMID:26269644
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Shaw, Jillian L; Zhang, Shixing; Chang, Karen T
2015-08-12
Aging individuals with Down syndrome (DS) have an increased risk of developing Alzheimer's disease (AD), a neurodegenerative disorder characterized by impaired memory. Memory problems in both DS and AD individuals usually develop slowly and progressively get worse with age, but the cause of this age-dependent memory impairment is not well understood. This study examines the functional interactions between Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. Using Drosophila as a model, we find that overexpression of nebula (fly homolog of DSCR1) initially protects against APP-induced memory defects by correcting calcineurin and cAMP signaling pathways but accelerates the rate of memory loss and exacerbates mitochondrial dysfunction in older animals. We report that transient upregulation of Nebula/DSCR1 or acute pharmacological inhibition of calcineurin in aged flies protected against APP-induced memory loss. Our data suggest that calcineurin dyshomeostasis underlies age-dependent memory impairments and further imply that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory impairments in AD in DS. Most Down syndrome (DS) individuals eventually develop Alzheimer's disease (AD)-like dementia, but mechanisms underlying this age-dependent memory impairment remain poorly understood. This study examines Nebula/Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. We uncover a previously unidentified role for Nebula/DSCR1 in modulating APP-induced memory defects during aging. We show that upregulation of Nebula/DSCR1, an inhibitor of calcineurin, rescues APP-induced memory defects in young flies but enhances memory loss of older flies. Excitingly, transient Nebula/DSCR1 overexpression or calcineurin inhibition in aged flies ameliorates APP-mediated memory problems. These results suggest that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory loss in DS and AD and points to correcting calcineurin signaling as a means to improve memory during aging. Copyright © 2015 the authors 0270-6474/15/3511374-10$15.00/0.
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Bindi, Ricardo Passoni; Baldo, Marcus Vinicius C; Canteras, Newton Sabino
2018-04-16
The basolateral amygdala complex, which includes the lateral, basolateral and basomedial nuclei, has been implicated in innate and contextual fear responses to predator threats. In the basolateral complex, the lateral and posterior basomedial nuclei are able to process predator odor information, and they project to the predator-responsive hypothalamic circuit; lesions in these amygdalar sites reduce innate responses and practically abolish contextual fear responses to predatory threats. In contrast to the lateral and posterior basomedial nuclei, the basolateral nucleus does not receive direct information from predator olfactory cues and has no direct link to the predator-responsive hypothalamic circuit. No attempt has previously been made to determine the specific role of the basolateral nucleus in fear responses to predatory threats, and we currently addressed this question by making bilateral N-methyl-D-aspartate lesions in the anterior basolateral nucleus of the amygdala (BLAa), which is often regarded as being contiguous with the lateral amygdalar nucleus, and tested both innate and contextual fear in response to cat exposure. Accordingly, BLAa lesions decreased both innate and contextual fear responses to predator exposure. Considering the targets of the BLAa, the nucleus accumbens appears to be a potential candidate to influence innate defensive responses to predator threats. The present findings also suggest that the BLAa has a role in fear memory of predator threat. The BLAa is likely involved in memory consolidation, which could potentially engage BLAa projection targets, opening interesting possibilities in the investigation of how these targets could be involved in the consolidation of predator-related fear memory. Copyright © 2018 Elsevier B.V. All rights reserved.
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Wu, Zhong-Min; Yang, Li-Hua; Cui, Rong; Ni, Gui-Lian; Wu, Feng-Tian; Liang, Yong
2017-05-01
One of the hypotheses about the pathogenesis of posttraumatic stress disorder (PTSD) is the dysfunction of serotonin (5-HT) neurotransmission. While certain 5-HT receptor subtypes are likely critical for the symptoms of PTSD, few studies have examined the role of 5-HT 3 receptor in the development of PTSD, even though 5-HT 3 receptor is critical for contextual fear extinction and anxiety-like behavior. Therefore, we hypothesized that stimulation of 5-HT 3 receptor in the dorsal hippocampus (DH) could prevent hippocampal autophagy and the development of PTSD-like behavior in animals. To this end, we infused SR57227, selective 5-HT 3 agonist, into the DH after a single prolonged stress (SPS) treatment in rats. Three weeks later, we evaluated the effects of this pharmacological treatment on anxiety-related behaviors and extinction of contextual fear memory. We also accessed hippocampal autophagy and the expression of 5-HT 3A subunit, Beclin-1, LC3-I, and LC3-II in the DH. We found that SPS treatment did not alter anxiety-related behaviors but prolonged the extinction of contextual fear memory, and such a behavioral phenomenon was correlated with increased hippocampal autophagy, decreased 5-HT 3A expression, and increased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. Furthermore, intraDH infusions of SR57227 dose-dependently promoted the extinction of contextual fear memory, prevented hippocampal autophagy, and decreased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. These results indicated that 5-HT 3 receptor in the hippocampus may play a critical role in the pathogenesis of hippocampal autophagy, and is likely involved in the pathophysiology of PTSD.
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Early life stress impairs contextual threat expression in female, but not male, mice.
Manzano-Nieves, Gabriela; Gaillard, Mizan; Gallo, Meghan; Bath, Kevin G
2018-05-21
Early life stress (ELS) is associated with altered processing of threat signals, and increased lifetime risk of anxiety and affective pathology, disorders that disproportionately affect females. We tested the impact of a limited bedding paradigm of ELS (from P4-11) on contextual threat learning, context memory, footshock sensitivity, and anxietylike behavior, in adult male and female mice. To examine contextual threat learning, mice conditioned by context/footshock association were tested 24 hr later for the context memory. To determine the effect of ELS on footshock sensitivity, a separate cohort of mice were exposed to footshocks of increasing intensity (0.06 to 0.40 mA) and behavioral responses (jump and audible vocalization) were assessed by observers blind to treatment condition, sex, and cycle stage. ELS impaired context memory in female, but not male, mice. ELS increased footshock-induced threshold to vocalize, but not to jump, in both sexes. In female mice, this effect was most apparent during estrus. Decreased body weight, indicative of higher stress incurred by an individual mouse, correlated with increased threshold to jump in both sexes reared in ELS, and to audibly vocalize in ELS females. As ELS effects on shock sensitivity were present in both sexes, the contextual recall deficit in females was not likely driven by changes in the salience of aversive footshocks. No effects on anxietylike behavior, as measured in the elevated plus maze (EPM), were observed. More work is needed to better understand the impact of ELS on both somatic and gonadal development, and their potential contribution to threat learning. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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Do-Monte, Fabrício H M; Allensworth, Melody; Carobrez, Antônio P
2010-07-29
Long-lasting memories of aversive or stressful events have been associated with the noradrenergic system activation. Alpha-1-adrenergic antagonist prazosin has successfully been used in the last years to treat anxiety disorders related to aversive memories recurrence in humans. Contextual conditioned fear extinction paradigm in rats has been used to better understand the mechanisms involved in the attenuation of defensive behaviour after a traumatic situation. Here we investigated the effects of systemic administration of prazosin in the fear extinction processes. Rats were previously paired in a contextual fear conditioning box (1 footshock, 1 mA, 2s duration), further returning to the same box during three consecutive days receiving an intraperitoneal injection of vehicle or prazosin 30 min before (acquisition of extinction; 0.1 or 0.5mg/kg) or immediately after (consolidation of extinction, 0.5 or 1.5mg/kg) each extinction session (10 min). On the last day, all animals were re-exposed undrugged to the apparatus. Since the medial prefrontal cortex (mPFC) has been described as a key structure in the modulation of conditioned fear extinction, the effects of intra-mPFC microinjection (0.2 microl per side) of vehicle (PBS) or prazosin (0.75 or 2.5 nmol) in the acquisition of fear extinction (10 min before extinction session 1) were further evaluated. Subjects were drug-free re-exposed to the same box in the next day (extinction session 2). The percentage of freezing time was used as the memory retention parameter. The results showed that either systemic or intra-mPFC-alpha-1-adrenergic blockade increased the freezing time in the last extinction sessions, suggesting impairment of the extinction of contextual conditioned fear in rats. Copyright 2010 Elsevier B.V. All rights reserved.
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Cambon, K; Venero, C; Berezin, V; Bock, E; Sandi, C
2003-01-01
The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory formation. We have recently developed a synthetic peptide, termed C3d, which, through the binding to the first, N-terminal immunoglobulin-like (Ig) module in the extracellular portion of NCAM, has been shown to promote neurite outgrowth and synapse formation in vitro, and to interfere with passive avoidance memory in rats in vivo. In this study, we investigated whether the i.c.v. administration of C3d, either 5.5 h after or 2 days before training, could be effective to modulate the strength at which emotional memory for aversive situations is established into a long-term memory. The effects of the peptide were evaluated in adult male Wistar rats trained in the contextual fear conditioning task. The results indicated that C3d significantly reduced the subsequent long-term retention of the conditioned fear response when administered 5.5 h post-training, as indicated by retention tests performed 2-3 and 7 days post-training. However, this treatment failed to influence conditioning for this task when injected 2 days pre-training. Additional experiments showed that C3d did not influence the emotional or locomotor behaviour of the animals, when tested in the open field task. Furthermore, hippocampal levels of microtubule-associated protein 2 (MAP2), Synaptophysin and NCAM were found unchanged when evaluated by enzyme-linked immunosorbent assay in crude synaptosomal preparations 2 days after peptide i.c.v. injection. Therefore, post-training injection of this synthetic peptide was efficient to attenuate the strength at which memory for contextual fear conditioning was enduringly stored, whilst it did not affect the acquisition of new memories. In addition to further support the view that NCAM is critically involved in memory consolidation, the current findings suggest that the NCAM IgI module is a potential target for the development of therapeutic drugs capable to reduce the cognitive impact induced by exposure to intensive stress experiences.
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Bouchet, Courtney A; Lloyd, Brian A; Loetz, Esteban C; Farmer, Caroline E; Ostrovskyy, Mykola; Haddad, Natalie; Foright, Rebecca M; Greenwood, Benjamin N
2017-08-01
Fear extinction-based exposure therapy is the most common behavioral therapy for anxiety and trauma-related disorders, but fear extinction memories are labile and fear tends to return even after successful extinction. The relapse of fear contributes to the poor long-term efficacy of exposure therapy. A single session of voluntary exercise can enhance the acquisition and consolidation of fear extinction in male rats, but the effects of exercise on relapse of fear after extinction are not well understood. Here, we characterized the effects of 2 h of voluntary exercise during the consolidation phase of contextual or auditory fear extinction learning on long-term fear extinction memory and renewal in adult, male and female, Long-Evans rats. Results indicate that exercise enhances consolidation of fear extinction memory and reduces fear relapse after extinction in a sex-dependent manner. These data suggest that brief bouts of exercise could be used as an augmentation strategy for exposure therapy, even in previously sedentary subjects. Fear memories of discrete cues, rather than of contextual ones, may be most susceptible to exercise-augmented extinction, especially in males. Additionally, exercise seems to have the biggest impact on fear relapse phenomena, even if fear extinction memories themselves are only minimally enhanced. © 2017 Bouchet et al.; Published by Cold Spring Harbor Laboratory Press.
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Costanzi, Marco; Cannas, Sara; Saraulli, Daniele; Rossi-Arnaud, Clelia; Cestari, Vincenzo
2011-01-01
Long-lasting memories of adverse experiences are essential for individuals' survival but are also involved, in the form of recurrent recollections of the traumatic experience, in the aetiology of anxiety diseases (e.g., post-traumatic stress disorder [PTSD]). Extinction-based erasure of fear memories has long been pursued as a behavioral way to treat anxiety disorders; yet, such a procedure turns out to be transient, context-dependent, and ineffective unless it is applied immediately after trauma. Recent evidence indicates that, in both rats and humans, extinction training can prevent the return of fear if administered within the reconsolidation window, when memories become temporarily labile and susceptible of being updated. Here, we show that the reconsolidation-extinction procedure fails to prevent the spontaneous recovery of a remote contextual fear memory in a mouse model of PTSD, as well as the long-lasting behavioral abnormalities induced by traumatic experience on anxiety and in both social and cognitive domains (i.e., social withdrawal and spatial learning deficits). Such a failure appears to be related to the ineffectiveness of the reconsolidation-extinction procedure in targeting the pathogenic process of fear sensitization, a nonassociative component of traumatic memory that causes animals to react aberrantly to harmless stimuli. This indicates fear sensitization as a major target for treatments aimed at mitigating anxiety and the behavioral outcomes of traumatic experiences.
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Sleep-Effects on Implicit and Explicit Memory in Repeated Visual Search
Assumpcao, Leonardo; Gais, Steffen
2013-01-01
In repeated visual search tasks, facilitation of reaction times (RTs) due to repetition of the spatial arrangement of items occurs independently of RT facilitation due to improvements in general task performance. Whereas the latter represents typical procedural learning, the former is a kind of implicit memory that depends on the medial temporal lobe (MTL) memory system and is impaired in patients with amnesia. A third type of memory that develops during visual search is the observers’ explicit knowledge of repeated displays. Here, we used a visual search task to investigate whether procedural memory, implicit contextual cueing, and explicit knowledge of repeated configurations, which all arise independently from the same set of stimuli, are influenced by sleep. Observers participated in two experimental sessions, separated by either a nap or a controlled rest period. In each of the two sessions, they performed a visual search task in combination with an explicit recognition task. We found that (1) across sessions, MTL-independent procedural learning was more pronounced for the nap than rest group. This confirms earlier findings, albeit from different motor and perceptual tasks, showing that procedural memory can benefit from sleep. (2) Likewise, the sleep group compared with the rest group showed enhanced context-dependent configural learning in the second session. This is a novel finding, indicating that the MTL-dependent, implicit memory underlying contextual cueing is also sleep-dependent. (3) By contrast, sleep and wake groups displayed equivalent improvements in explicit recognition memory in the second session. Overall, the current study shows that sleep affects MTL-dependent as well as MTL-independent memory, but it affects different, albeit simultaneously acquired, forms of MTL-dependent memory differentially. PMID:23936363
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Saab, Bechara J; Maclean, Ashley J B; Kanisek, Marijana; Zurek, Agnieszka A; Martin, Loren J; Roder, John C; Orser, Beverley A
2010-11-01
Memory blockade is an essential component of the anesthetic state. However, postanesthesia memory deficits represent an undesirable and poorly understood adverse effect. Inhibitory α5 subunit-containing γ-aminobutyric acid subtype A receptors (α5GABAA) are known to play a critical role in memory processes and are highly sensitive to positive modulation by anesthetics. We postulated that inhibiting the activity of α5GABAA receptors during isoflurane anesthesia would prevent memory deficits in the early postanesthesia period. Mice were pretreated with L-655,708, an α5GABAA receptor-selective inverse agonist, or vehicle. They were then exposed to isoflurane for 1 h (1.3%, or 1 minimum alveolar concentration, or air-oxygen control). Then, either 1 or 24 h later, mice were conditioned in fear-associated contextual and cued learning paradigms. In addition, the effect of L-655,708 on the immobilizing dose of isoflurane was studied. Motor coordination, sedation, anxiety, and the concentration of isoflurane in the brain at 5 min, 1 h, and 24 h after isoflurane were also examined. Motor and sensory function recovered within minutes after termination of isoflurane administration. In contrast, a robust deficit in contextual fear memory persisted for at least 24 h. The α5GABAA receptor inverse agonist, L-655,708, completely prevented memory deficits without changing the immobilizing dose of isoflurane. Trace concentrations of isoflurane were measured in the brain 24 h after treatment. Memory deficits occurred long after the sedative, analgesic, and anxiolytic effects of isoflurane subsided. L-655,708 prevented memory deficit, suggesting that an isoflurane interaction at α5GABAA receptors contributes to memory impairment during the early postanesthesia period.
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Strekalova, Tatyana; Sun, Mu; Sibbe, Mirjam; Evers, Matthias; Dityatev, Alexander; Gass, Peter; Schachner, Melitta
2002-09-01
The extracellular matrix molecule tenascin-C (TN-C) has been shown to be involved in hippocampal synaptic plasticity in vitro. Here, we describe a deficit in hippocampus-dependent contextual memory in TN-C-deficient mice using the step-down avoidance paradigm. We further show that a fragment of TN-C containing the fibronectin type-III repeats 6-8 (FN6-8), but not a fragment containing repeats 3-5, bound to pyramidal and granule cell somata in the hippocampal formation of C57BL/6J mice and repelled axons of pyramidal neurons when presented as a border in vitro. Injection of the FN6-8 fragment into the hippocampus inhibited retention of memory in the step-down paradigm and reduced levels of long-term potentiation in the CA1 region of the hippocampus. In summary, our data show that TN-C is involved in hippocampus-dependent contextual memory and synaptic plasticity and identify the FN6-8 domain as one of molecular determinants mediating these functions.
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Adaptive Value Normalization in the Prefrontal Cortex Is Reduced by Memory Load.
Holper, L; Van Brussel, L D; Schmidt, L; Schulthess, S; Burke, C J; Louie, K; Seifritz, E; Tobler, P N
2017-01-01
Adaptation facilitates neural representation of a wide range of diverse inputs, including reward values. Adaptive value coding typically relies on contextual information either obtained from the environment or retrieved from and maintained in memory. However, it is unknown whether having to retrieve and maintain context information modulates the brain's capacity for value adaptation. To address this issue, we measured hemodynamic responses of the prefrontal cortex (PFC) in two studies on risky decision-making. In each trial, healthy human subjects chose between a risky and a safe alternative; half of the participants had to remember the risky alternatives, whereas for the other half they were presented visually. The value of safe alternatives varied across trials. PFC responses adapted to contextual risk information, with steeper coding of safe alternative value in lower-risk contexts. Importantly, this adaptation depended on working memory load, such that response functions relating PFC activity to safe values were steeper with presented versus remembered risk. An independent second study replicated the findings of the first study and showed that similar slope reductions also arose when memory maintenance demands were increased with a secondary working memory task. Formal model comparison showed that a divisive normalization model fitted effects of both risk context and working memory demands on PFC activity better than alternative models of value adaptation, and revealed that reduced suppression of background activity was the critical parameter impairing normalization with increased memory maintenance demand. Our findings suggest that mnemonic processes can constrain normalization of neural value representations.
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Knowledge supports memory retrieval through familiarity, not recollection.
Wang, Wei-Chun; Brashier, Nadia M; Wing, Erik A; Marsh, Elizabeth J; Cabeza, Roberto
2018-05-01
Semantic memory, or general knowledge of the world, guides learning and supports the formation and retrieval of new episodic memories. Behavioral evidence suggests that this knowledge effect is supported by recollection-a more controlled form of memory retrieval generally accompanied by contextual details-to a greater degree than familiarity-a more automatic form of memory retrieval generally absent of contextual details. In the current study, we used functional magnetic resonance imaging (fMRI) to investigate the role that regions associated with recollection and familiarity play in retrieving recent instances of known (e.g., The Summer Olympic Games are held four years apart) and unknown (e.g., A flaky deposit found in port bottles is beeswing) statements. Our results revealed a surprising pattern: Episodic retrieval of known statements recruited regions associated with familiarity, but not recollection. Instead, retrieval of unknown statements recruited regions associated with recollection. These data, in combination with quicker reaction times for the retrieval of known than unknown statements, suggest that known statements can be successfully retrieved on the basis of familiarity, whereas unknown statements were retrieved on the basis of recollection. Our results provide insight into how knowledge influences episodic retrieval and demonstrate the role of neuroimaging in providing insights into cognitive processes in the absence of explicit behavioral responses. Copyright © 2018 Elsevier Ltd. All rights reserved.
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ERIC Educational Resources Information Center
Gilmartin, Marieke R.; Kwapis, Janine L.; Helmstetter, Fred J.
2013-01-01
Activation of "N"-methyl-D-aspartate receptors (NMDAR) in the prelimbic medial prefrontal cortex (PL mPFC) is necessary for the acquisition of both trace and contextual fear memories, but it is not known how specific NR2 subunits support each association. The NR2B subunit confers unique properties to the NMDAR and may differentially…
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Steele, John W; Brautigam, Hannah; Short, Jennifer A; Sowa, Allison; Shi, Mengxi; Yadav, Aniruddha; Weaver, Christina M; Westaway, David; Fraser, Paul E; St George-Hyslop, Peter H; Gandy, Sam; Hof, Patrick R; Dickstein, Dara L
2014-07-01
Alzheimer's disease (AD) is a complex and slowly progressing dementing disorder that results in neuronal and synaptic loss, deposition in brain of aberrantly folded proteins, and impairment of spatial and episodic memory. Most studies of mouse models of AD have employed analyses of cognitive status and assessment of amyloid burden, gliosis, and molecular pathology during disease progression. Here we sought to understand the behavioral, cellular, ultrastructural, and molecular changes that occur at a pathological stage equivalent to the early stages of human AD. We studied the TgCRND8 mouse, a model of aggressive AD amyloidosis, at an early stage of plaque pathology (3 months of age) in comparison to their wildtype littermates and assessed changes in cognition, neuron and spine structure, and expression of synaptic glutamate receptor proteins. We found that, at this age, TgCRND8 mice display substantial plaque deposition in the neocortex and hippocampus and impairment on cued and contextual memory tasks. Of particular interest, we also observed a significant decrease in the number of neurons in the hippocampus. Furthermore, analysis of CA1 neurons revealed significant changes in apical and basal dendritic spine types, as well as altered expression of GluN1 and GluA2 receptors. This change in molecular architecture within the hippocampus may reflect a rising representation of inherently less stable thin spine populations, which can cause cognitive decline. These changes, taken together with toxic insults from amyloid-β protein, may underlie the observed neuronal loss. Copyright © 2014 Wiley Periodicals, Inc.
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Narrating Surroundings and Suppression: The Role of School in Soviet Childhood Memories
ERIC Educational Resources Information Center
Nugin, Raili; Jõesalu, Kirsti
2016-01-01
The article explores how people born in Estonia in the 1970s contextualize their memories about their Soviet childhood in the context of school. Focusing on small group of people who grew up in the Soviet Estonia, we argue that in biographical narratives, school is treated as the representative of the Soviet regime. Nostalgic reminiscences from…
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ERIC Educational Resources Information Center
Ferrer Monti, Roque I.; Giachero, Marcelo; Alfei, Joaquín M.; Bueno, Adrián M.; Cuadra, Gabriel; Molina, Victor A.
2016-01-01
It is known that a consolidated memory can return to a labile state and become transiently malleable following reactivation. This instability is followed by a restabilization phase termed reconsolidation. In this work, we explored whether an unrelated appetitive experience (voluntary consumption of diluted sucrose) can affect a contextual fear…
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Rumor Mongering and Remembering: How Rumors Originating in Children's Inferences Can Affect Memory
ERIC Educational Resources Information Center
Principe, Gabrielle F.; Guiliano, Stephanie; Root, Courtney
2008-01-01
This study examined how rumors originating in 3- to 6-year-olds' causal inferences can affect their own and their peers' memories for a personally experienced event. This was accomplished by exposing some members of classrooms to contextual clues that were designed to induce inferences about the causes of two unresolved components of the event.…
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ERIC Educational Resources Information Center
Gruenenfelder, Thomas M.; Recchia, Gabriel; Rubin, Tim; Jones, Michael N.
2016-01-01
We compared the ability of three different contextual models of lexical semantic memory (BEAGLE, Latent Semantic Analysis, and the Topic model) and of a simple associative model (POC) to predict the properties of semantic networks derived from word association norms. None of the semantic models were able to accurately predict all of the network…
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Function in context: Why American and Trinidadian young and older adults remember the personal past
Bluck, Susan; Ali, Sideeka
2014-01-01
Multiple and interacting contextual (culture, life phase) and person-specific predictors (i.e., personality, tendency to think-talk about the past) of the functions of autobiographical memory were examined using the Thinking about Life Experiences scale. American (N = 174) and Trinidadian (N = 182) young and older adults self-reported how frequently they remembered the personal past to serve self, social, and directive functions, how often they thought and talked about their past overall, and completed a measure of trait personality. Independent contextual and person-specific predictors were found for using memory to serve a social-bonding function: Americans, young adults, those higher in extraversion, lower in conscientiousness, and individuals who frequently think and talk about the past more often use autobiographical memory for social-bonding. Across cultures, younger adults report more frequently using memory to serve all three functions, whereas Trinidadians who think more often about the past compared with those who reflect less often, are more likely to use it for self and directive functions. Findings are discussed in terms of the individual’s embeddedness in cultural and life phase contexts when remembering. PMID:24992649
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2008-05-01
patterns. Our strategy to nucleate Ag nanoparticles has been to use a templating protein (e.g., streptavidin) that has been chemically pre- charged with...assembly is used to direct the formation of switching devices and wires to create logic circuitry, memory, and I/O interfaces . We can control the reaction...determines the formation of structures (through complementarity ). Sequence design is important because it determines many aspects of the target DNA
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Neural correlates of contextual cueing are modulated by explicit learning.
Westerberg, Carmen E; Miller, Brennan B; Reber, Paul J; Cohen, Neal J; Paller, Ken A
2011-10-01
Contextual cueing refers to the facilitated ability to locate a particular visual element in a scene due to prior exposure to the same scene. This facilitation is thought to reflect implicit learning, as it typically occurs without the observer's knowledge that scenes repeat. Unlike most other implicit learning effects, contextual cueing can be impaired following damage to the medial temporal lobe. Here we investigated neural correlates of contextual cueing and explicit scene memory in two participant groups. Only one group was explicitly instructed about scene repetition. Participants viewed a sequence of complex scenes that depicted a landscape with five abstract geometric objects. Superimposed on each object was a letter T or L rotated left or right by 90°. Participants responded according to the target letter (T) orientation. Responses were highly accurate for all scenes. Response speeds were faster for repeated versus novel scenes. The magnitude of this contextual cueing did not differ between the two groups. Also, in both groups repeated scenes yielded reduced hemodynamic activation compared with novel scenes in several regions involved in visual perception and attention, and reductions in some of these areas were correlated with response-time facilitation. In the group given instructions about scene repetition, recognition memory for scenes was superior and was accompanied by medial temporal and more anterior activation. Thus, strategic factors can promote explicit memorization of visual scene information, which appears to engage additional neural processing beyond what is required for implicit learning of object configurations and target locations in a scene. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Neural correlates of contextual cueing are modulated by explicit learning
Westerberg, Carmen E.; Miller, Brennan B.; Reber, Paul J.; Cohen, Neal J.; Paller, Ken A.
2011-01-01
Contextual cueing refers to the facilitated ability to locate a particular visual element in a scene due to prior exposure to the same scene. This facilitation is thought to reflect implicit learning, as it typically occurs without the observer’s knowledge that scenes repeat. Unlike most other implicit learning effects, contextual cueing can be impaired following damage to the medial temporal lobe. Here we investigated neural correlates of contextual cueing and explicit scene memory in two participant groups. Only one group was explicitly instructed about scene repetition. Participants viewed a sequence of complex scenes that depicted a landscape with five abstract geometric objects. Superimposed on each object was a letter T or L rotated left or right by 90°. Participants responded according to the target letter (T) orientation. Responses were highly accurate for all scenes. Response speeds were faster for repeated versus novel scenes. The magnitude of this contextual cueing did not differ between the two groups. Also, in both groups repeated scenes yielded reduced hemodynamic activation compared with novel scenes in several regions involved in visual perception and attention, and reductions in some of these areas were correlated with response-time facilitation. In the group given instructions about scene repetition, recognition memory for scenes was superior and was accompanied by medial temporal and more anterior activation. Thus, strategic factors can promote explicit memorization of visual scene information, which appears to engage additional neural processing beyond what is required for implicit learning of object configurations and target locations in a scene. PMID:21889947
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Shi, Xiangdang; Miller, Jonathan S; Harper, Lauren J; Poole, Rachel L; Gould, Thomas J; Unterwald, Ellen M
2014-08-01
Memories return to a labile state following their retrieval and must undergo a process of reconsolidation to be maintained. Thus, disruption of cocaine reward memories by interference with reconsolidation may be therapeutically beneficial in the treatment of cocaine addiction. The objectives were to elucidate the signaling pathway involved in reconsolidation of cocaine reward memory and to test whether targeting this pathway could disrupt cocaine-associated contextual memory. Using a mouse model of conditioned place preference, regulation of the activity of glycogen synthase kinase-3 (GSK3), mammalian target of Rapamycin complex 1 (mTORC1), P70S6K, β-catenin, and the upstream signaling molecule Akt, was studied in cortico-limbic-striatal circuitry after re-exposure to an environment previously paired with cocaine. Levels of phosporylated Akt-Thr308, GSK3α-Ser21, GSK3β-Ser9, mTORC1, and P70S6K were reduced in the nucleus accumbens and hippocampus 10 min after the reactivation of cocaine cue memories. Levels of pAkt and pGSK3 were also reduced in the prefrontal cortex. Since reduced phosphorylation of GSK3 indicates heightened enzyme activity, the effect of a selective GSK3 inhibitor, SB216763, on reconsolidation was tested. Administration of SB216763 immediately after exposure to an environment previously paired with cocaine abrogated a previously established place preference, suggesting that GSK3 inhibition interfered with reconsolidation of cocaine-associated reward memories. These findings suggest that the Akt/GSK3/mTORC1 signaling pathway in the nucleus accumbens, hippocampus, and/or prefrontal cortex is critically involved in the reconsolidation of cocaine contextual reward memory. Inhibition of GSK3 activity during memory retrieval can erase an established cocaine place preference.
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Behavioural memory reconsolidation of food and fear memories
Flavell, Charlotte R.; Barber, David J.; Lee, Jonathan L. C.
2012-01-01
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 analog of memory reconsolidation, we show that prevention of contextual fear memory reactivation by the LVGCC blocker nimodipine interferes with the amnestic outcome. Therefore, the reconsolidation process can be manipulated behaviourally to disrupt both aversive and appetitive memories. PMID:22009036
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Loss of memory B cells impairs maintenance of long-term serologic memory during HIV-1 infection.
Titanji, Kehmia; De Milito, Angelo; Cagigi, Alberto; Thorstensson, Rigmor; Grützmeier, Sven; Atlas, Ann; Hejdeman, Bo; Kroon, Frank P; Lopalco, Lucia; Nilsson, Anna; Chiodi, Francesca
2006-09-01
Circulating memory B cells are severely reduced in the peripheral blood of HIV-1-infected patients. We investigated whether dysfunctional serologic memory to non-HIV antigens is related to disease progression by evaluating the frequency of memory B cells, plasma IgG, plasma levels of antibodies to measles, and Streptococcus pneumoniae, and enumerating measles-specific antibody-secreting cells in patients with primary, chronic, and long-term nonprogressive HIV-1 infection. We also evaluated the in vitro production of IgM and IgG antibodies against measles and S pneumoniae antigens following polyclonal activation of peripheral blood mononuclear cells (PBMCs) from patients. The percentage of memory B cells correlated with CD4+ T-cell counts in patients, thus representing a marker of disease progression. While patients with primary and chronic infection had severe defects in serologic memory, long-term nonprogressors had memory B-cell frequency and levels of antigen-specific antibodies comparable with controls. We also evaluated the effect of antiretroviral therapy on these serologic memory defects and found that antiretroviral therapy did not restore serologic memory in primary or in chronic infection. We suggest that HIV infection impairs maintenance of long-term serologic immunity to HIV-1-unrelated antigens and this defect is initiated early in infection. This may have important consequences for the response of HIV-infected patients to immunizations.
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NFκB–Pim-1–Eomesodermin axis is critical for maintaining CD8 T-cell memory quality
Knudson, Karin M.; Saxena, Vikas; Altman, Amnon; Daniels, Mark A.; Teixeiro, Emma
2017-01-01
T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory. Strikingly, we found that antigen receptor [T-cell receptor (TCR)] signaling regulates this process through expression of the NFκB-dependent kinase proviral integration site for Moloney murine leukemia virus-1 (PIM-1), which in turn regulates NFκB and Eomes. T cells defective in TCR-dependent NFκB signaling were impaired in late expression of Pim-1, Eomes, and CD8 memory. These defects were rescued when TCR-dependent NFκB signaling was restored. We also found that NFκB–Pim-1 signals were required at memory to maintain memory CD8 T-cell longevity, effector function, and Eomes expression. Hence, an NFκB–Pim-1–Eomes axis regulates Eomes levels to maintain memory fitness. PMID:28193872
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Engrams and Circuits Crucial for Systems Consolidation of a Memory
Kitamura, Takashi; Ogawa, Sachie K.; Roy, Dheeraj S.; Okuyama, Teruhiro; Morrissey, Mark D.; Smith, Lillian M.; Redondo, Roger L.; Tonegawa, Susumu
2017-01-01
Episodic memories initially require rapid synaptic plasticity within the hippocampus for their formation and are gradually consolidated in neocortical networks for permanent storage. However, the engrams and circuits that support neocortical memory consolidation remain unknown. We found that neocortical prefrontal memory engram cells, critical for remote contextual fear memory, were rapidly generated during initial learning via inputs from both hippocampal-entorhinal cortex and basolateral amygdala. After their generation, the prefrontal engram cells, with support from hippocampal memory engram cells, became functionally mature with time. Whereas hippocampal engram cells gradually became silent with time, engram cells in the basolateral amygdala, which were necessary for fear memory, are maintained. Our data provide new insights into the functional reorganization of engrams and circuits underlying systems consolidation of memory. PMID:28386011
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Long-term adaptation to change in implicit contextual learning.
Zellin, Martina; von Mühlenen, Adrian; Müller, Hermann J; Conci, Markus
2014-08-01
The visual world consists of spatial regularities that are acquired through experience in order to guide attentional orienting. For instance, in visual search, detection of a target is faster when a layout of nontarget items is encountered repeatedly, suggesting that learned contextual associations can guide attention (contextual cuing). However, scene layouts sometimes change, requiring observers to adapt previous memory representations. Here, we investigated the long-term dynamics of contextual adaptation after a permanent change of the target location. We observed fast and reliable learning of initial context-target associations after just three repetitions. However, adaptation of acquired contextual representations to relocated targets was slow and effortful, requiring 3 days of training with overall 80 repetitions. A final test 1 week later revealed equivalent effects of contextual cuing for both target locations, and these were comparable to the effects observed on day 1. That is, observers learned both initial target locations and relocated targets, given extensive training combined with extended periods of consolidation. Thus, while implicit contextual learning efficiently extracts statistical regularities of our environment at first, it is rather insensitive to change in the longer term, especially when subtle changes in context-target associations need to be acquired.
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Stereotype Threat Alters the Subjective Experience of Memory.
Mazerolle, Marie; Régner, Isabelle; Rigalleau, François; Huguet, Pascal
2015-01-01
There is now evidence that negative age-related stereotypes about memory reduce older adults' memory performance, and inflate age differences in this domain. Here, we examine whether stereotype threat may also influence the basic feeling that one is more or less able to remember. Using the Remember/Know paradigm, we demonstrated that stereotype threat conducted older adults to a greater feeling of familiarity with events, while failing to retrieve any contextual detail. This finding indicates that stereotype threat alters older adults' subjective experience of memory, and strengthens our understanding of the mechanisms underlying stereotype threat effects.
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Baumann, Oliver; Mattingley, Jason B
2016-02-24
The human parahippocampal cortex has been ascribed central roles in both visuospatial and mnemonic processes. More specifically, evidence suggests that the parahippocampal cortex subserves both the perceptual analysis of scene layouts as well as the retrieval of associative contextual memories. It remains unclear, however, whether these two functional roles can be dissociated within the parahippocampal cortex anatomically. Here, we provide evidence for a dissociation between neural activation patterns associated with visuospatial analysis of scenes and contextual mnemonic processing along the parahippocampal longitudinal axis. We used fMRI to measure parahippocampal responses while participants engaged in a task that required them to judge the contextual relatedness of scene and object pairs, which were presented either as words or pictures. Results from combined factorial and conjunction analyses indicated that the posterior section of parahippocampal cortex is driven predominantly by judgments associated with pictorial scene analysis, whereas its anterior section is more active during contextual judgments regardless of stimulus category (scenes vs objects) or modality (word vs picture). Activation maxima associated with visuospatial and mnemonic processes were spatially segregated, providing support for the existence of functionally distinct subregions along the parahippocampal longitudinal axis and suggesting that, in humans, the parahippocampal cortex serves as a functional interface between perception and memory systems. Copyright © 2016 the authors 0270-6474/16/362536-07$15.00/0.
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Contextual diversity facilitates learning new words in the classroom.
Rosa, Eva; Tapia, José Luis; Perea, Manuel
2017-01-01
In the field of word recognition and reading, it is commonly assumed that frequently repeated words create more accessible memory traces than infrequently repeated words, thus capturing the word-frequency effect. Nevertheless, recent research has shown that a seemingly related factor, contextual diversity (defined as the number of different contexts [e.g., films] in which a word appears), is a better predictor than word-frequency in word recognition and sentence reading experiments. Recent research has shown that contextual diversity plays an important role when learning new words in a laboratory setting with adult readers. In the current experiment, we directly manipulated contextual diversity in a very ecological scenario: at school, when Grade 3 children were learning words in the classroom. The new words appeared in different contexts/topics (high-contextual diversity) or only in one of them (low-contextual diversity). Results showed that words encountered in different contexts were learned and remembered more effectively than those presented in redundant contexts. We discuss the practical (educational [e.g., curriculum design]) and theoretical (models of word recognition) implications of these findings.
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Contextual diversity facilitates learning new words in the classroom
Tapia, José Luis; Perea, Manuel
2017-01-01
In the field of word recognition and reading, it is commonly assumed that frequently repeated words create more accessible memory traces than infrequently repeated words, thus capturing the word-frequency effect. Nevertheless, recent research has shown that a seemingly related factor, contextual diversity (defined as the number of different contexts [e.g., films] in which a word appears), is a better predictor than word-frequency in word recognition and sentence reading experiments. Recent research has shown that contextual diversity plays an important role when learning new words in a laboratory setting with adult readers. In the current experiment, we directly manipulated contextual diversity in a very ecological scenario: at school, when Grade 3 children were learning words in the classroom. The new words appeared in different contexts/topics (high-contextual diversity) or only in one of them (low-contextual diversity). Results showed that words encountered in different contexts were learned and remembered more effectively than those presented in redundant contexts. We discuss the practical (educational [e.g., curriculum design]) and theoretical (models of word recognition) implications of these findings. PMID:28586354
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Severe and protracted sleep disruptions in mouse model of post-traumatic stress disorder.
Sharma, Rishi; Sahota, Pradeep; Thakkar, Mahesh M
2018-03-01
Increasing evidences suggest that the predator threat model is a valid animal model of post-traumatic stress disorder (PTSD). However, sleep has never been examined in this model. Since sleep disturbances, including insomnia and excessive daytime sleepiness, are severe and protracted symptoms of PTSD, we hypothesized that mice exposed to predator odor trauma (POT) will display contextual fear conditioning along with severe and protracted sleep disruptions. Adult male C57BL/6J mice, instrumented with wire electrodes (to record hippocampal local field potentials [LFP] and nuchal muscle [electromyogram, EMG] activity), were exposed to contextual conditioning using soiled cat litter as unconditional stimulus (US). On day 1, fear memory acquisition (FMA) training was performed by exposing mice to contextual cage (conditional stimulus; CS) for 30 min followed by exposure to CS + US for 90 min. On day 5, fear memory recall (FMR) testing was performed by exposing mice to CS (without US) for 120 min. LFP and EMG were recorded continuously for 5 days. Mice exposed to POT displayed as follows: (1) hyperarousal coupled with electrophysiological indicators of memory acquisition and retrieval (increased hippocampal θ and γ power) during FMA and FMR; (2) increased nonrapid eye movement (NREM) δ and rapid eye movement θ power during sleep post FMA, indicating memory consolidation; (3) protracted sleep disturbances as evident by increased wakefulness, reduced NREM sleep and NREM δ power, increased NREM β power during light (sleep) period, and increased sleep during dark (active) period. Based on these results, we suggest that mice exposed to POT display severe and protracted sleep disturbances mimicking sleep disturbance observed in human PTSD.
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A dissociation between renewal and contextual fear conditioning in juvenile rats.
Park, Chun Hui J; Ganella, Despina E; Kim, Jee Hyun
2017-05-01
We investigated whether juvenile rats do not express renewal following extinction of conditioned fear due to their inability to form a long-term contextual fear memory. In experiment 1, postnatal day (P) 18 and 25 rats received 3 white-noise and footshock pairings, followed by 60 white-noise alone presentations the next day. When tested in a different context to extinction, P25 rats displayed renewal whereas P18 rats did not. Experiments 2A and 2B surprisingly showed that P18 and P25 rats do not show differences in contextual and cued fear, regardless of the conditioning-test intervals and the number of white-noise-footshock pairings received. Finally, we observed age differences in contextual fear when P25 rats were weaned at P21 in experiment 3. These results indicate that the developmental dissociation observed in renewal of extinguished fear is not related to the widely believed late emergence of contextual fear learning. © 2017 Wiley Periodicals, Inc.
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Long-term knowledge acquisition using contextual information in a memory-inspired robot architecture
NASA Astrophysics Data System (ADS)
Pratama, Ferdian; Mastrogiovanni, Fulvio; Lee, Soon Geul; Chong, Nak Young
2017-03-01
In this paper, we present a novel cognitive framework allowing a robot to form memories of relevant traits of its perceptions and to recall them when necessary. The framework is based on two main principles: on the one hand, we propose an architecture inspired by current knowledge in human memory organisation; on the other hand, we integrate such an architecture with the notion of context, which is used to modulate the knowledge acquisition process when consolidating memories and forming new ones, as well as with the notion of familiarity, which is employed to retrieve proper memories given relevant cues. Although much research has been carried out, which exploits Machine Learning approaches to provide robots with internal models of their environment (including objects and occurring events therein), we argue that such approaches may not be the right direction to follow if a long-term, continuous knowledge acquisition is to be achieved. As a case study scenario, we focus on both robot-environment and human-robot interaction processes. In case of robot-environment interaction, a robot performs pick and place movements using the objects in the workspace, at the same time observing their displacement on a table in front of it, and progressively forms memories defined as relevant cues (e.g. colour, shape or relative position) in a context-aware fashion. As far as human-robot interaction is concerned, the robot can recall specific snapshots representing past events using both sensory information and contextual cues upon request by humans.
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Effects of corticosterone on contextual fear consolidation in intact and ovariectomized female rats.
Kashefi, Adel; Rashidy-Pour, Ali
2014-10-01
Previous studies have shown that post-training administration of glucocorticoids enhances memory consolidation in male rats, but theirs effects on female rats are not known. Thus, this study was conducted to examine the effects of corticosterone (CORT) on contextual fear memory consolidation in intact and ovariectomized (OVX) female rats. In Experiment 1, post-training administration of CORT (0.3, 3, and 10 mg/kg) to OVX female rats impaired memory consolidation at a 0.3 mg dose of CORT. In Experiment 2, post-training injection of CORT (0.3 mg/kg) to female rats in proestrus stage (when the levels of estrogens are highest) enhances and in the estrus stage (when the levels of estrogens are lowest) impaired memory retention. In Experiment 3, OVX female rats injected with CORT (0.3 mg/kg) and one of the three doses of 17β-estradiol (1, 10 or 100 μg/kg) following training. 48-h memory retention test indicated that CORT enhanced memory retention in OVX female rats that received concurrent injection of 10 or 100 μg doses of 17β-estradiol. These findings indicate that cognitive effects of CORT in female rats can be modulated with the plasma levels of estrogens: when the levels of estrogens are low, corticosterone has a negative effect, while when the levels of estrogens are high; the corticosterone has a positive enhancing effect. Copyright © 2014 Elsevier Inc. All rights reserved.
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Adaptive Value Normalization in the Prefrontal Cortex Is Reduced by Memory Load
Burke, C. J.; Seifritz, E.; Tobler, P. N.
2017-01-01
Abstract Adaptation facilitates neural representation of a wide range of diverse inputs, including reward values. Adaptive value coding typically relies on contextual information either obtained from the environment or retrieved from and maintained in memory. However, it is unknown whether having to retrieve and maintain context information modulates the brain’s capacity for value adaptation. To address this issue, we measured hemodynamic responses of the prefrontal cortex (PFC) in two studies on risky decision-making. In each trial, healthy human subjects chose between a risky and a safe alternative; half of the participants had to remember the risky alternatives, whereas for the other half they were presented visually. The value of safe alternatives varied across trials. PFC responses adapted to contextual risk information, with steeper coding of safe alternative value in lower-risk contexts. Importantly, this adaptation depended on working memory load, such that response functions relating PFC activity to safe values were steeper with presented versus remembered risk. An independent second study replicated the findings of the first study and showed that similar slope reductions also arose when memory maintenance demands were increased with a secondary working memory task. Formal model comparison showed that a divisive normalization model fitted effects of both risk context and working memory demands on PFC activity better than alternative models of value adaptation, and revealed that reduced suppression of background activity was the critical parameter impairing normalization with increased memory maintenance demand. Our findings suggest that mnemonic processes can constrain normalization of neural value representations. PMID:28462394
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Performance of defect-tolerant set-associative cache memories
NASA Technical Reports Server (NTRS)
Frenzel, J. F.
1991-01-01
The increased use of on-chip cache memories has led researchers to investigate their performance in the presence of manufacturing defects. Several techniques for yield improvement are discussed and results are presented which indicate that set-associativity may be used to provide defect tolerance as well as improve the cache performance. Tradeoffs between several cache organizations and replacement strategies are investigated and it is shown that token-based replacement may be a suitable alternative to the widely-used LRU strategy.
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ERIC Educational Resources Information Center
Pletcher, Mathew T.; Wiltshire, Tim; Tarantino, Lisa M.; Mayford, Mark; Reijmers, Leon G.; Coats, Jennifer K.
2006-01-01
Targeted mutagenesis in mice has shown that genes from a wide variety of gene families are involved in memory formation. The efficient identification of genes involved in learning and memory could be achieved by random mutagenesis combined with high-throughput phenotyping. Here, we provide the first report of a mutagenesis screen that has…
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ERIC Educational Resources Information Center
Pevzner, Aleksandr; Guzowski, John F.
2015-01-01
No studies to date have examined whether immediate-early gene (IEG) activation is driven by context memory recall. To address this question, we utilized the context preexposure facilitation effect (CPFE) paradigm. In CPFE, animals acquire contextual fear conditioning through hippocampus-dependent rapid retrieval of a previously formed contextual…
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ERIC Educational Resources Information Center
Sachser, Ricardo Marcelo; Crestani, Ana Paula; Quillfeldt, Jorge Alberto; e Souza, Tadeu Mello; de Oliveira Alvares, Lucas
2015-01-01
Despite the fact that the cannabinoid receptor type 1 (CB1R) plays a pivotal role in emotional memory processing in different regions of the brain, its function in the retrosplenial cortex (RSC) remains unknown. Here, using contextual fear conditioning in rats, we showed that a post-training intra-RSC infusion of the CB1R antagonist AM251…
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ERIC Educational Resources Information Center
Gilmartin, Marieke R.; Helmstetter, Fred J.
2010-01-01
The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a…
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In Search for Boundary Conditions of Reconsolidation: A Failure of Fear Memory Interference
Schroyens, Natalie; Beckers, Tom; Kindt, Merel
2017-01-01
The presentation of a fear memory cue can result in mere memory retrieval, destabilization of the reactivated memory trace, or the formation of an extinction memory. The interaction between the degree of novelty during reactivation and previous learning conditions is thought to determine the outcome of a reactivation session. This study aimed to evaluate whether contextual novelty can prevent cue-induced destabilization and disruption of a fear memory acquired by non-asymptotic learning. To this end, fear memory was reactivated in a novel context or in the original context of learning, and fear memory reactivation was followed by the administration of propranolol, an amnestic drug. Remarkably, fear memory was not impaired by post-reactivation propranolol administration or extinction training under the usual conditions used in our lab, irrespective of the reactivation context. These unexpected findings are discussed in the light of our current experimental parameters and alleged boundary conditions on memory destabilization. PMID:28469565
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Mikulincer, M; Gillath, O; Halevy, V; Avihou, N; Avidan, S; Eshkoli, N
2001-12-01
Five studies examined the effects of chronic and contextual activation of attachment security on reactions to others' needs. The sense of attachment security was contextually primed by asking participants to recollect personal memories, read a story, or look at a picture of supportive others or by subliminally exposing them to proximity-related words. This condition was compared against the priming of neutral themes, positive affect, or attachment-insecurity schemas. Then reports of empathy and personal distress or the accessibility of empathy and personal-distress memories were assessed. Attachment-security priming strengthened empathic reactions and inhibited personal distress. Self-reports of attachment anxiety and avoidance were inversely related to empathy, and attachment anxiety was positively related to personal distress. The discussion emphasizes the relevance of attachment theory for explaining reactions to others' needs.
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Rapid eye movement sleep does not seem to unbind memories from their emotional context.
Deliens, Gaétane; Neu, Daniel; Peigneux, Philippe
2013-12-01
Sleep unbinds memories from their emotional learning context, protecting them from emotional interference due to a change of mood between learning and recall. According to the 'sleep to forget and sleep to remember' model, emotional unbinding takes place during rapid eye movement sleep. To test this hypothesis, we investigated emotional contextual interference effects after early versus late post-learning sleep periods, in which slow wave and rapid eye movement sleep, respectively, predominate. Participants learned a list of neutral word pairs after induction of a happy or a sad mood, then slept immediately afterwards for 3 h of early or late sleep under polysomnographic recording, in a within-subject counterbalanced design. They slept for 3 h before learning in the late sleep condition. Polysomnographic data confirmed more rapid eye movement sleep in the late than in the early sleep condition. After awakening, half the list was recalled after induction of a similar mood than during the encoding session (non-interference condition), and the other half of the list was recalled after induction of a different mood (interference condition). The results disclosed an emotional interference effect on recall both in the early and late sleep conditions, which does not corroborate the hypothesis of a rapid eye movement sleep-related protection of recent memories from emotional contextual interference. Alternatively, the contextual demodulation process initiated during the first post-learning night might need several consecutive nights of sleep to be achieved. © 2013 European Sleep Research Society.
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Contextual cueing of tactile search is coded in an anatomical reference frame.
Assumpção, Leonardo; Shi, Zhuanghua; Zang, Xuelian; Müller, Hermann J; Geyer, Thomas
2018-04-01
This work investigates the reference frame(s) underlying tactile context memory, a form of statistical learning in a tactile (finger) search task. In this task, if a searched-for target object is repeatedly encountered within a stable spatial arrangement of task-irrelevant distractors, detecting the target becomes more efficient over time (relative to nonrepeated arrangements), as learned target-distractor spatial associations come to guide tactile search, thus cueing attention to the target location. Since tactile search displays can be represented in several reference frames, including multiple external and an anatomical frame, in Experiment 1 we asked whether repeated search displays are represented in tactile memory with reference to an environment-centered or anatomical reference frame. In Experiment 2, we went on examining a hand-centered versus anatomical reference frame of tactile context memory. Observers performed a tactile search task, divided into a learning and test session. At the transition between the two sessions, we introduced postural manipulations of the hands (crossed ↔ uncrossed in Expt. 1; palm-up ↔ palm-down in Expt. 2) to determine the reference frame of tactile contextual cueing. In both experiments, target-distractor associations acquired during learning transferred to the test session when the placement of the target and distractors was held constant in anatomical, but not external, coordinates. In the latter, RTs were even slower for repeated displays. We conclude that tactile contextual learning is coded in an anatomical reference frame. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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Liu, Jun; Wei, Wei; Kuang, Hui; Zhao, Fang; Tsien, Joe Z
2013-01-01
Heart physiology is a highly useful indicator for measuring not only physical states, but also emotional changes in animals. Yet changes of heart rate variability during fear conditioning have not been systematically studied in mice. Here, we investigated changes in heart rate and heart rate variability in both short-term and long-term contextual and cued fear conditioning. We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I) and a more variable phase (stage-II). We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories. Moreover, it could also detect fear extinction effect during the repeated tone recall. These results suggest that heart rate variability is a valuable physiological indicator for sensitively measuring the consolidation and expression of fear memories in mice.
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Sakata, Kazuko; Martinowich, Keri; Woo, Newton H.; Schloesser, Robert J.; Jimenez, Dennisse V.; Ji, Yuanyuan; Shen, Liya; Lu, Bai
2013-01-01
Activity-dependent gene transcription, including that of the brain-derived neurotrophic factor (Bdnf) gene, has been implicated in various cognitive functions. We previously demonstrated that mutant mice with selective disruption of activity-dependent BDNF expression (BDNF-KIV mice) exhibit deficits in GABA-mediated inhibition in the prefrontal cortex (PFC). Here, we show that disruption of activity-dependent BDNF expression impairs BDNF-dependent late-phase long-term potentiation (L-LTP) in CA1, a site of hippocampal output to the PFC. Interestingly, early-phase LTP and conventional L-LTP induced by strong tetanic stimulation were completely normal in BDNF-KIV mice. In parallel, attenuation of activity-dependent BDNF expression significantly impairs spatial memory reversal and contextual memory extinction, two executive functions that require intact hippocampal–PFC circuitry. In contrast, spatial and contextual memory per se were not affected. Thus, activity-dependent BDNF expression in the hippocampus and PFC may contribute to cognitive and behavioral flexibility. These results suggest distinct roles for different forms of L-LTP and provide a link between activity-dependent BDNF expression and behavioral perseverance, a hallmark of several psychiatric disorders. PMID:23980178
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Huang, Tzyy-Nan; Hsueh, Yi-Ping
2017-01-01
Human genetic studies have indicated that mutations in calcium/calmodulin-dependent serine protein kinase ( CASK ) result in X-linked mental retardation and autism-spectrum disorders. We aimed to establish a mouse model to study how Cask regulates mental ability. Because Cask encodes a multidomain scaffold protein, a possible strategy to dissect how CASK regulates mental ability and cognition is to disrupt specific protein-protein interactions of CASK in vivo and then investigate the impact of individual specific protein interactions. Previous in vitro analyses indicated that a rat CASK T724A mutation reduces the interaction between CASK and T-brain-1 (TBR1) in transfected COS cells. Because TBR1 is critical for glutamate receptor, ionotropic, N -methyl-D-aspartate receptor subunit 2B ( Grin2b ) expression and is a causative gene for autism and intellectual disability, we then generated CASK T740A (corresponding to rat CASK T724A) mutant mice using a gene-targeting approach. Immunoblotting, coimmunoprecipitation, histological methods and behavioural assays (including home cage, open field, auditory and contextual fear conditioning and conditioned taste aversion) were applied to investigate expression of CASK and its related proteins, the protein-protein interactions of CASK, and anatomic and behavioural features of CASK T740A mice. The CASK T740A mutation attenuated the interaction between CASK and TBR1 in the brain. However, CASK T740A mice were generally healthy, without obvious defects in brain morphology. The most dramatic defect among the mutant mice was in extinction of associative memory, though acquisition was normal. The functions of other CASK protein interactions cannot be addressed using CASK T740A mice. Disruption of the CASK and TBR1 interaction impairs extinction, suggesting the involvement of CASK in cognitive flexibility.
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Context-based automated defect classification system using multiple morphological masks
Gleason, Shaun S.; Hunt, Martin A.; Sari-Sarraf, Hamed
2002-01-01
Automatic detection of defects during the fabrication of semiconductor wafers is largely automated, but the classification of those defects is still performed manually by technicians. This invention includes novel digital image analysis techniques that generate unique feature vector descriptions of semiconductor defects as well as classifiers that use these descriptions to automatically categorize the defects into one of a set of pre-defined classes. Feature extraction techniques based on multiple-focus images, multiple-defect mask images, and segmented semiconductor wafer images are used to create unique feature-based descriptions of the semiconductor defects. These feature-based defect descriptions are subsequently classified by a defect classifier into categories that depend on defect characteristics and defect contextual information, that is, the semiconductor process layer(s) with which the defect comes in contact. At the heart of the system is a knowledge database that stores and distributes historical semiconductor wafer and defect data to guide the feature extraction and classification processes. In summary, this invention takes as its input a set of images containing semiconductor defect information, and generates as its output a classification for the defect that describes not only the defect itself, but also the location of that defect with respect to the semiconductor process layers.
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Lambert, Hilary K; Sheridan, Margaret A; Sambrook, Kelly A; Rosen, Maya L; Askren, Mary K; McLaughlin, Katie A
2017-02-15
Context can drastically influence responses to environmental stimuli. For example, a gunshot should provoke a different response at a public park than a shooting range. Little is known about how contextual processing and neural correlates change across human development or about individual differences related to early environmental experiences. Children ( N = 60; 8-19 years, 24 exposed to interpersonal violence) completed a context encoding task during fMRI scanning using a delayed match-to-sample design with neutral, happy, and angry facial cues embedded in realistic background scenes. Outside the scanner, participants completed a memory test for context-face pairings. Context memory and neural correlates of context encoding did not vary with age. Larger hippocampal volume was associated with better context memory. Posterior hippocampus was recruited during context encoding, and greater activation in this region predicted better memory for contexts paired with angry faces. Children exposed to violence had poor memory of contexts paired with angry faces, reduced hippocampal volume, and atypical neural recruitment on encoding trials with angry faces, including reduced hippocampal activation and greater functional connectivity between hippocampus and ventrolateral prefrontal cortex (vlPFC). Greater hippocampus-vlPFC connectivity was associated with worse memory for contexts paired with angry faces. Posterior hippocampus appears to support context encoding, a process that does not exhibit age-related variation from middle childhood to late adolescence. Exposure to dangerous environments in childhood is associated with poor context encoding in the presence of threat, likely due to greater vlPFC-dependent attentional narrowing on threat cues at the expense of hippocampus-dependent processing of the broader context. SIGNIFICANCE STATEMENT The ability to use context to guide reactions to environmental stimuli promotes flexible behavior. Remarkably little research has examined how contextual processing changes across development or about influences of the early environment. We provide evidence for posterior hippocampus involvement in context encoding in youth and lack of age-related variation from middle childhood to late adolescence. Children exposed to interpersonal violence exhibited poor memory of contexts paired with angry faces and atypical neural recruitment during context encoding in the presence of threatening facial cues. Heightened attention to threat following violence exposure may come at the expense of encoding contextual information, which may ultimately contribute to pathological fear expressed in safe contexts. Copyright © 2017 the authors 0270-6474/17/371925-10$15.00/0.
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Defect reduction for semiconductor memory applications using jet and flash imprint lithography
NASA Astrophysics Data System (ADS)
Ye, Zhengmao; Luo, Kang; Lu, Xiaoming; Fletcher, Brian; Liu, Weijun; Xu, Frank; LaBrake, Dwayne; Resnick, Douglas J.; Sreenivasan, S. V.
2012-07-01
Acceptance of imprint lithography for manufacturing will require demonstration that it can attain defect levels commensurate with the defect specifications of high-end memory devices. Defects occurring during imprinting can generally be broken into two categories; random defects and repeating defects. Examples of random defects include fluid phase imprint defects, such as bubbles, and solid phase imprint defects, such as line collapse. Examples of repeater defects include mask fabrication defects and particle induced defects. Previous studies indicated that soft particles cause nonrepeating defects. Hard particles, on the other hand, can cause either permanent resist plugging or mask damage. In a previous study, two specific defect types were examined; random nonfill defects occurring during the resist filling process and repeater defects caused by interactions with particles on the substrate. We attempted to identify the different types of imprint defect types using a mask with line/space patterns at dimensions as small as 26 nm. An Imprio 500 twenty-wafer per hour development tool was used to study the various defect types. The imprint defect density was reduced nearly four orders of magnitude, down to ˜4/cm2 in a period of two years following the availability of low defect imprint masks at 26-nm half-pitch. This reduction was achieved by identifying the root cause of various defects and then taking the appropriate corrective action.
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Identification and optogenetic manipulation of memory engrams in the hippocampus
Ramirez, Steve; Tonegawa, Susumu; Liu, Xu
2014-01-01
With the accumulation of our knowledge about how memories are formed, consolidated, retrieved, and updated, neuroscience is now reaching a point where discrete memories can be identified and manipulated at rapid timescales. Here, we start with historical studies that lead to the modern memory engram theory. Then, we will review recent advances in memory engram research that combine transgenic and optogenetic approaches to reveal the underlying neuronal substrates sufficient for activating mnemonic processes. We will focus on three concepts: (1) isolating memory engrams at the level of single cells to tag them for subsequent manipulation; (2) testing the sufficiency of these engrams for memory recall by artificially activating them; and (3) presenting new stimuli during the artificial activation of these engrams to induce an association between the two to form a false memory. We propose that hippocampal cells that show activity-dependent changes during learning construct a cellular basis for contextual memory engrams. PMID:24478647
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Iborra, Salvador; Ramos, Manuel; Arana, David M.; Lázaro, Silvia; Aguilar, Francisco; Santos, Eugenio; López, Daniel
2013-01-01
Signals from the TCR that specifically contribute to effector versus memory CD8+ T cell differentiation are poorly understood. Using mice and adoptively transferred T lymphocytes lacking the small GTPase N-ras, we found that N-ras–deficient CD8+ T cells differentiate efficiently into antiviral primary effectors but have a severe defect in generating protective memory cells. This defect was rescued, although only partly, by rapamycin-mediated inhibition of mammalian target of rapamycin (mTOR) in vivo. The memory defect correlated with a marked impairment in vitro and in vivo of the antigen-mediated early induction of T-box transcription factor Eomesodermin (Eomes), whereas T-bet was unaffected. Besides N-ras, early Eomes induction in vitro required phosphoinositide 3-kinase (PI3K)–AKT but not extracellular signal-regulated kinase (ERK) activation, and it was largely insensitive to rapamycin. Consistent with N-ras coupling Eomes to T cell memory, retrovirally enforced expression of Eomes in N-ras–deficient CD8+ T cells effectively rescued their memory differentiation. Thus, our study identifies a critical role for N-ras as a TCR-proximal regulator of Eomes for early determination of the CD8+ T cell memory fate. PMID:23776078
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Fabrication of a Bioactive, PCL-based "Self-fitting" Shape Memory Polymer Scaffold.
Nail, Lindsay N; Zhang, Dawei; Reinhard, Jessica L; Grunlan, Melissa A
2015-10-23
Tissue engineering has been explored as an alternative strategy for the treatment of critical-sized cranio-maxillofacial (CMF) bone defects. Essential to the success of this approach is a scaffold that is able to conformally fit within an irregular defect while also having the requisite biodegradability, pore interconnectivity and bioactivity. By nature of their shape recovery and fixity properties, shape memory polymer (SMP) scaffolds could achieve defect "self-fitting." In this way, following exposure to warm saline (~60 ºC), the SMP scaffold would become malleable, permitting it to be hand-pressed into an irregular defect. Subsequent cooling (~37 ºC) would return the scaffold to its relatively rigid state within the defect. To meet these requirements, this protocol describes the preparation of SMP scaffolds prepared via the photochemical cure of biodegradable polycaprolactone diacrylate (PCL-DA) using a solvent-casting particulate-leaching (SCPL) method. A fused salt template is utilized to achieve pore interconnectivity. To realize bioactivity, a polydopamine coating is applied to the surface of the scaffold pore walls. Characterization of self-fitting and shape memory behaviors, pore interconnectivity and in vitro bioactivity are also described.
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Hebscher, Melissa; Gilboa, Asaf
2016-09-01
The ventromedial prefrontal cortex (vmPFC) has been implicated in a wide array of functions across multiple domains. In this review, we focus on the vmPFC's involvement in mediating strategic aspects of memory retrieval, memory-related schema functions, and decision-making. We suggest that vmPFC generates a confidence signal that informs decisions and memory-guided behaviour. Confidence is central to these seemingly diverse functions: (1) Strategic retrieval: lesions to the vmPFC impair an early, automatic, and intuitive monitoring process ("feeling of rightness"; FOR) often associated with confabulation (spontaneous reporting of erroneous memories). Critically, confabulators typically demonstrate high levels of confidence in their false memories, suggesting that faulty monitoring following vmPFC damage may lead to indiscriminate confidence signals. (2) Memory schemas: the vmPFC is critically involved in instantiating and maintaining contextually relevant schemas, broadly defined as higher level knowledge structures that encapsulate lower level representational elements. The correspondence between memory retrieval cues and these activated schemas leads to FOR monitoring. Stronger, more elaborate schemas produce stronger FOR and influence confidence in the veracity of memory candidates. (3) Finally, we review evidence on the vmPFC's role in decision-making, extending this role to decision-making during memory retrieval. During non-mnemonic and mnemonic decision-making the vmPFC automatically encodes confidence. Confidence signal in the vmPFC is revealed as a non-linear relationship between a first-order monitoring assessment and second-order action or choice. Attempting to integrate the multiple functions of the vmPFC, we propose a posterior-anterior organizational principle for this region. More posterior vmPFC regions are involved in earlier, automatic, subjective, and contextually sensitive functions, while more anterior regions are involved in controlled actions based on these earlier functions. Confidence signals reflect the non-linear relationship between first-order, posterior-mediated and second-order, anterior-mediated processes and are represented along the entire axis. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Implicit Learning of Complex Visual Contexts Under Non-Optimal Conditions
2007-07-27
Perception & Performance, 31(6), 1439-1448. 3. Jiang Y, Song J-H, Rigas A (2005). High-capacity spatial contextual memory. Psychonomic Bulletin & Review , 12...Makovski T., & Jiang YV (in press). Distributing versus focusing attention in visual short-term memory. Psychonomic Bulletin & Review . 8. Rausei V...Implicit learning of ignored visual context. Psychonomic Bulletin & Review , 12(1), 100-106. Jiang, Y. H., & Song, J. H. (2005). Spatial context
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How Administration of the Beta-Blocker Propranolol Before Extinction can Prevent the Return of Fear
Kroes, Marijn C W; Tona, Klodiana-Daphne; den Ouden, Hanneke E M; Vogel, Susanne; van Wingen, Guido A; Fernández, Guillén
2016-01-01
Combining beta-blockers with exposure therapy has been advocated to reduce fear, yet experimental studies combining beta-blockers with memory reactivation have had contradictory results. We explored how beta-blockade might affect the course of safety learning and the subsequent return of fear in a double-blind placebo-controlled functional magnetic resonance imaging study in humans (N=46). A single dose of propranolol before extinction learning caused a loss of conditioned fear responses, and prevented the subsequent return of fear and decreased explicit memory for the fearful events in the absence of drug. Fear-related neural responses were persistently attenuated in the dorsal medial prefrontal cortex (dmPFC), increased in the hippocampus 24 h later, and correlated with individual behavioral indices of fear. Prediction error-related responses in the ventral striatum persisted during beta-blockade. We suggest that this pattern of results is most consistent with a model where beta-blockade can prevent the return of fear by (i) reducing retrieval of fear memory, via the dmPFC and (ii) increasing contextual safety learning, via the hippocampus. Our findings suggest that retrieval of fear memory and contextual safety learning form potential mnemonic target mechanisms to optimize exposure-based therapy with beta-blockers. PMID:26462618
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2010-01-01
The downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, binds specifically to DNA and several nucleoproteins regulating gene expression and with proteins outside the nucleus to regulate membrane excitability or calcium homeostasis. DREAM is highly expressed in the central nervous system including the hippocampus and cortex; however, the roles of DREAM in hippocampal synaptic transmission and plasticity have not been investigated. Taking advantage of transgenic mice overexpressing a Ca2+-insensitive DREAM mutant (TgDREAM), we used integrative methods including electrophysiology, biochemistry, immunostaining, and behavior tests to study the function of DREAM in synaptic transmission, long-term plasticity and fear memory in hippocampal CA1 region. We found that NMDA receptor but not AMPA receptor-mediated current was decreased in TgDREAM mice. Moreover, synaptic plasticity, such as long-term depression (LTD) but not long-term potentiation (LTP), was impaired in TgDREAM mice. Biochemical experiments found that DREAM interacts with PSD-95 and may inhibit NMDA receptor function through this interaction. Contextual fear memory was significantly impaired in TgDREAM mice. By contrast, sensory responses to noxious stimuli were not affected. Our results demonstrate that DREAM plays a novel role in postsynaptic modulation of the NMDA receptor, and contributes to synaptic plasticity and behavioral memory. PMID:20205763
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Clark, Caron A C; Fernandez, Fabian; Sakhon, Stella; Spanò, Goffredina; Edgin, Jamie O
2017-06-01
Recent studies have highlighted the dentate gyrus as a region of increased vulnerability in mouse models of Down syndrome (DS). It is unclear to what extent these findings are reflected in the memory profile of people with the condition. We developed a series of novel tasks to probe distinct medial temporal functions in children and young adults with DS, including object, spatial, and temporal order memory. Relative to mental age-matched controls (n = 45), individuals with DS (n = 28) were unimpaired on subtests involving short-term object or configural recall that was divorced from spatial or temporal contexts. By contrast, the DS group had difficulty recalling spatial locations when contextual information was salient and recalling the order in which objects were serially presented. Results are consistent with dysfunction of spatial and temporal contextual pattern separation abilities in individuals with DS, mediated by the hippocampus, including the dentate gyrus. Amidst increasing calls to bridge human and animal work, the memory profile demonstrated here in humans with DS is strikingly similar to that of the Ts65Dn mouse model of DS. The study highlights the trisynaptic circuit as a potentially fruitful intervention target to mitigate cognitive impairments associated with DS. © 2017 Wiley Periodicals, Inc.
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Quaedflieg, Conny W E M; Schwabe, Lars
2018-03-01
Stressful events have a major impact on memory. They modulate memory formation in a time-dependent manner, closely linked to the temporal profile of action of major stress mediators, in particular catecholamines and glucocorticoids. Shortly after stressor onset, rapidly acting catecholamines and fast, non-genomic glucocorticoid actions direct cognitive resources to the processing and consolidation of the ongoing threat. In parallel, control of memory is biased towards rather rigid systems, promoting habitual forms of memory allowing efficient processing under stress, at the expense of "cognitive" systems supporting memory flexibility and specificity. In this review, we discuss the implications of this shift in the balance of multiple memory systems for the dynamics of the memory trace. Specifically, stress appears to hinder the incorporation of contextual details into the memory trace, to impede the integration of new information into existing knowledge structures, to impair the flexible generalisation across past experiences, and to hamper the modification of memories in light of new information. Delayed, genomic glucocorticoid actions might reverse the control of memory, thus restoring homeostasis and "cognitive" control of memory again.
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Kenney, Justin W.; Raybuck, Jonathan D.; Gould, Thomas J.
2012-01-01
Nicotine administration alters various forms of hippocampus-dependent learning and memory. Increasing work has found that the dorsal and ventral hippocampus differentially contribute to multiple behaviors. Thus, the present study examined whether the effects of nicotine in the dorsal and ventral hippocampus have distinct influences on contextual fear learning in male C57BL/6J mice. Direct infusion of nicotine into the dorsal hippocampus resulted in an enhancement of contextual fear learning, whereas nicotine infused into the ventral hippocampus resulted in deficits. Nicotine infusions into the ventral hippocampus did not alter hippocampus-independent cued fear conditioning or time spent in the open arm of the elevated plus maze, a measure of anxiety, suggesting the effects are due to alterations in contextual learning and not other general processes. Finally, results from using direct infusions of MLA, a low-affinity α7 nicotinic acetylcholine receptor (nAChR) antagonist, in conjunction with systemic nicotine, provide evidence that α7-nAChRs in the ventral hippocampus mediate the detrimental effect of ventral hippocampal nicotine on contextual fear learning. These results suggest that with systemic nicotine administration, competition exists between the dorsal and ventral hippocampus for behavioral control over contextual learning. PMID:22271264
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The role of the parahippocampal cortex in cognition
Aminoff, Elissa M.; Kveraga, Kestutis; Bar, Moshe
2013-01-01
The parahippocampal cortex (PHC) has been associated with many cognitive processes, including visuospatial processing and episodic memory. To characterize the role of PHC in cognition a framework is required that unifies these disparate processes. An overarching account was proposed, whereby the PHC is part of a network of brain regions that processes contextual associations. Contextual associations are the principal element underlying many higher-level cognitive processes, and thus are suitable for unifying the PHC literature. Recent findings are reviewed that provide support for the contextual associations account of PHC function. In addition to reconciling a vast breadth of literature, the synthesis presented expands the implications of the proposed account and gives rise to new and general questions about context and cognition. PMID:23850264
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The role of nitrogen doping in ALD Ta2O5 and its influence on multilevel cell switching in RRAM
NASA Astrophysics Data System (ADS)
Sedghi, N.; Li, H.; Brunell, I. F.; Dawson, K.; Potter, R. J.; Guo, Y.; Gibbon, J. T.; Dhanak, V. R.; Zhang, W. D.; Zhang, J. F.; Robertson, J.; Hall, S.; Chalker, P. R.
2017-03-01
The role of nitrogen doping on the stability and memory window of resistive state switching in N-doped Ta2O5 deposited by atomic layer deposition is elucidated. Nitrogen incorporation increases the stability of resistive memory states which is attributed to neutralization of electronic defect levels associated with oxygen vacancies. The density functional simulations with the screened exchange hybrid functional approximation show that the incorporation of nitrogen dopant atoms in the oxide network removes the O vacancy midgap defect states, thus nullifying excess defects and eliminating alternative conductive paths. By effectively reducing the density of vacancy-induced defect states through N doping, 3-bit multilevel cell switching is demonstrated, consisting of eight distinctive resistive memory states achieved by either controlling the set current compliance or the maximum voltage during reset. Nitrogen doping has a threefold effect: widening the switching memory window to accommodate the more intermediate states, improving the stability of states, and providing a gradual reset for multi-level cell switching during reset. The N-doped Ta2O5 devices have relatively small set and reset voltages (< 1 V) with reduced variability due to doping.
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Rescue of long-term memory after reconsolidation blockade
Trent, Simon; Barnes, Philip; Hall, Jeremy; Thomas, Kerrie L.
2015-01-01
Memory reconsolidation is considered to be the process whereby stored memories become labile on recall, allowing updating. Blocking the restabilization of a memory during reconsolidation is held to result in a permanent amnesia. The targeted knockdown of either Zif268 or Arc levels in the brain, and inhibition of protein synthesis, after a brief recall results in a non-recoverable retrograde amnesia, known as reconsolidation blockade. These experimental manipulations are seen as key proof for the existence of reconsolidation. However, here we demonstrate that despite disrupting the molecular correlates of reconsolidation in the hippocampus, rodents are still able to recover contextual memories. Our results challenge the view that reconsolidation is a separate memory process and instead suggest that the molecular events activated initially at recall act to constrain premature extinction. PMID:26238574
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Source memory enhancement for emotional words.
Doerksen, S; Shimamura, A P
2001-03-01
The influence of emotional stimuli on source memory was investigated by using emotionally valenced words. The words were colored blue or yellow (Experiment 1) or surrounded by a blue or yellow frame (Experiment 2). Participants were asked to associate the words with the colors. In both experiments, emotionally valenced words elicited enhanced free recall compared with nonvalenced words; however, recognition memory was not affected. Source memory for the associated color was also enhanced for emotional words, suggesting that even memory for contextual information is benefited by emotional stimuli. This effect was not due to the ease of semantic clustering of emotional words because semantically related words were not associated with enhanced source memory, despite enhanced recall (Experiment 3). It is suggested that enhancement resulted from facilitated arousal or attention, which may act to increase organization processes important for source memory.
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Extinction of Contextual Fear with Timed Exposure to Enriched Environment: A Differential Effect
Hegde, Preethi; O'Mara, Shane; Laxmi, Thenkanidiyoor Rao
2017-01-01
Background Extinction of fear memory depends on the environmental and emotional cues. Furthermore, consolidation of extinction is also dependent on the environmental exposure. But, the relationship of the time of the exposure to a variety of environmental cues is not well known. The important region involved in facilitation of extinction of fear memory is through diversion of the flow of information leaving the lateral nucleus of amygdala. Purpose The study aimed to address a question to explain how these brain regions react to environmental stimulation during the retention and extinction of fear memory. Methods An enriched environment (EE) is assumed to mediate extinction of fear memory, we examined the apparent discrepancy between the effects of defensive response, the freezing behavior induced by Pavlovian classical fear conditioning by subjecting them to variance in the timing to EE. The different timing of EE exposure was 10 days of EE either before fear conditioning and/or after extinction training to the rats. The local field potentials was recorded from CA1 hippocampus, lateral nucleus of amygdala and infralimbic region of medial prefrontal cortex (mPFC) during the fear learning and extinction from the control rats and rats exposed to EE before and after fear conditioning. Results Exposure to EE before the fear conditioning and after extinction training was more effective in the extinction fear memory. In addition, we also found switching from exploratory locomotion to freezing during retention of contextual fear memory which was associated with decreased theta power and reduced synchronized theta oscillations in CA1-hippocampus, lateral nucleus of amygdala, and infralimbic region of mPFC. Conclusion Thus, we propose that the timing of exposure to EE play a key role in the extinction of fear memory. PMID:28588364
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CRTC1 Function During Memory Encoding Is Disrupted in Neurodegeneration.
Parra-Damas, Arnaldo; Chen, Meng; Enriquez-Barreto, Lilian; Ortega, Laura; Acosta, Sara; Perna, Judith Camats; Fullana, M Neus; Aguilera, José; Rodríguez-Alvarez, José; Saura, Carlos A
2017-01-15
Associative memory impairment is an early clinical feature of dementia patients, but the molecular and cellular mechanisms underlying these deficits are largely unknown. In this study, we investigated the functional regulation of the cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) by associative learning in physiological and neurodegenerative conditions. We evaluated the activation of CRTC1 in the hippocampus of control mice and mice lacking the Alzheimer's disease-linked presenilin genes (presenilin conditional double knockout [PS cDKO]) after one-trial contextual fear conditioning by using biochemical, immunohistochemical, and gene expression analyses. PS cDKO mice display classical features of neurodegeneration occurring in Alzheimer's disease including age-dependent cortical atrophy, neuron loss, dendritic degeneration, and memory deficits. Context-associative learning, but not single context or unconditioned stimuli, induces rapid dephosphorylation (Ser151) and translocation of CRTC1 from the cytosol/dendrites to the nucleus of hippocampal neurons in the mouse brain. Accordingly, context-associative learning induces differential CRTC1-dependent transcription of c-fos and the nuclear receptor subfamily 4 (Nr4a) genes Nr4a1-3 in the hippocampus through a mechanism that involves CRTC1 recruitment to CRE promoters. Deregulation of CRTC1 dephosphorylation, nuclear translocation, and transcriptional function are associated with long-term contextual memory deficits in PS cDKO mice. Importantly, CRTC1 gene therapy in the hippocampus ameliorates context memory and transcriptional deficits and dendritic degeneration despite ongoing cortical degeneration in this neurodegeneration mouse model. These findings reveal a critical role of CRTC1 in the hippocampus during associative memory, and provide evidence that CRTC1 deregulation underlies memory deficits during neurodegeneration. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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Troyner, Fernanda; Bicca, Maira A; Bertoglio, Leandro J
2018-05-10
The thalamic nucleus reuniens (NR) has been shown to support bidirectional medial prefrontal cortex-hippocampus communication and synchronization relevant for cognitive processing. Using non-selective or prolonged inactivation of the NR, previous studies reported its activity positively modulates aversive memory consolidation. Here we examined the NR's role in consolidating contextual fear memories with varied strength, at both recent and more remote time points, using muscimol-induced temporary inactivation in rats. Results indicate the NR negatively modulates fear memory intensity, specificity and long-term maintenance. The more intense, generalized and enduring fear memory induced by NR inactivation during consolidation was also less prone to behavioral suppression by extinction or reconsolidation disruption induced by clonidine, an alpha-2 adrenergic receptor agonist. Lastly, we used immunohistochemistry for Arc protein, which is involved in synaptic modifications underlying aversive memory consolidation, to investigate whether treatment condition and/or conditioning status could change its levels in the NR, the hippocampus (dorsal and ventral CA1 subregions) and the medial prefrontal cortex (anterior cingulate, prelimbic and infralimbic subregions). Results indicate a significant imbalance in the number of Arc-expressing neurons in the brain areas investigated in muscimol fear conditioned animals when compared with controls. Collectively, present results provide convergent evidence for the NR's role as a hub regulating quantitative and qualitative aspects of a contextual fear memory during its consolidation that seem to influence the subsequent susceptibility to experimental interventions aiming at attenuating its expression. They also indicate the selectivity and duration of a given inactivation approach may influence its outcomes. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.
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Conscious experience and episodic memory: hippocampus at the crossroads.
Behrendt, Ralf-Peter
2013-01-01
If an instance of conscious experience of the seemingly objective world around us could be regarded as a newly formed event memory, much as an instance of mental imagery has the content of a retrieved event memory, and if, therefore, the stream of conscious experience could be seen as evidence for ongoing formation of event memories that are linked into episodic memory sequences, then unitary conscious experience could be defined as a symbolic representation of the pattern of hippocampal neuronal firing that encodes an event memory - a theoretical stance that may shed light into the mind-body and binding problems in consciousness research. Exceedingly detailed symbols that describe patterns of activity rapidly self-organizing, at each cycle of the θ rhythm, in the hippocampus are instances of unitary conscious experience that jointly constitute the stream of consciousness. Integrating object information (derived from the ventral visual stream and orbitofrontal cortex) with contextual emotional information (from the anterior insula) and spatial environmental information (from the dorsal visual stream), the hippocampus rapidly forms event codes that have the informational content of objects embedded in an emotional and spatiotemporally extending context. Event codes, formed in the CA3-dentate network for the purpose of their memorization, are not only contextualized but also allocentric representations, similarly to conscious experiences of events and objects situated in a seemingly objective and observer-independent framework of phenomenal space and time. Conscious perception, creating the spatially and temporally extending world that we perceive around us, is likely to be evolutionarily related to more fleeting and seemingly internal forms of conscious experience, such as autobiographical memory recall, mental imagery, including goal anticipation, and to other forms of externalized conscious experience, namely dreaming and hallucinations; and evidence pointing to an important contribution of the hippocampus to these conscious phenomena will be reviewed.
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Engrams and circuits crucial for systems consolidation of a memory.
Kitamura, Takashi; Ogawa, Sachie K; Roy, Dheeraj S; Okuyama, Teruhiro; Morrissey, Mark D; Smith, Lillian M; Redondo, Roger L; Tonegawa, Susumu
2017-04-07
Episodic memories initially require rapid synaptic plasticity within the hippocampus for their formation and are gradually consolidated in neocortical networks for permanent storage. However, the engrams and circuits that support neocortical memory consolidation have thus far been unknown. We found that neocortical prefrontal memory engram cells, which are critical for remote contextual fear memory, were rapidly generated during initial learning through inputs from both the hippocampal-entorhinal cortex network and the basolateral amygdala. After their generation, the prefrontal engram cells, with support from hippocampal memory engram cells, became functionally mature with time. Whereas hippocampal engram cells gradually became silent with time, engram cells in the basolateral amygdala, which were necessary for fear memory, were maintained. Our data provide new insights into the functional reorganization of engrams and circuits underlying systems consolidation of memory. Copyright © 2017, American Association for the Advancement of Science.
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Portugal, George S.; Wilkinson, Derek S.; Kenney, Justin W.; Sullivan, Colleen
2013-01-01
The effects of nicotine on cognitive processes such as learning and memory may play an important role in the addictive liability of tobacco. However, it remains unknown whether genetic variability modulates the effects of nicotine on learning and memory. The present study characterized the effects of acute, chronic, and withdrawal from chronic nicotine administration on fear conditioning, somatic signs, and the elevated plus maze in 8 strains of inbred mice. Strain-dependent effects of acute nicotine and nicotine withdrawal on contextual fear conditioning, somatic signs, and the elevated plus maze were observed, but no association between the effects of acute nicotine and nicotine withdrawal on contextual fear conditioning were observed, suggesting that different genetic substrates may mediate these effects. The identification of genetic factors that may alter the effects of nicotine on cognition may lead to more efficacious treatments for nicotine addiction. PMID:21822688
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Light exposure before learning improves memory consolidation at night
Shan, Li-Li; Guo, Hao; Song, Ning-Ning; Jia, Zheng-Ping; Hu, Xin-Tian; Huang, Jing-Fei; Ding, Yu-Qiang; Richter-Levine, Gal; Zhou, Qi-Xin; Xu, Lin
2015-01-01
Light is recently recognized as a modulator able to activate the hippocampus and modulate memory processing, but little is known about the molecular mechanisms. Here, we report that in mice, a short pulse of white light before learning dramatically improves consolidation of contextual fear memory during the night. The light exposure increases hippocampal active p21-activated kinase 1 (PAK1) and CA1 long-term potentiation (LTP). These light effects are abolished in PAK1 knockout and dominant-negative transgenic mice, but preserved by expression of constitutively active PAK1 in the hippocampus. Our results indicate that light can act as a switch of PAK1 activity that modulate CA1 LTP and thereby memory consolidation without affecting learning and short-term memory. PMID:26493375
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NASA Astrophysics Data System (ADS)
Xu, Kunshan; Qiu, Xingqi; Tian, Xiaoshuai
2018-01-01
The metal magnetic memory testing (MMMT) technique has been extensively applied in various fields because of its unique advantages of easy operation, low cost and high efficiency. However, very limited theoretical research has been conducted on application of MMMT to buried defects. To promote study in this area, the equivalent magnetic charge method is employed to establish a self-magnetic flux leakage (SMFL) model of a buried defect. Theoretical results based on the established model successfully capture basic characteristics of the SMFL signals of buried defects, as confirmed via experiment. In particular, the newly developed model can calculate the buried depth of a defect based on the SMFL signals obtained via testing. The results show that the new model can successfully assess the characteristics of buried defects, which is valuable in the application of MMMT in non-destructive testing.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Clima, Sergiu, E-mail: clima@imec.be; Chen, Yang Yin; Goux, Ludovic
Resistive Random Access Memories are among the most promising candidates for the next generation of non-volatile memory. Transition metal oxides such as HfOx and TaOx attracted a lot of attention due to their CMOS compatibility. Furthermore, these materials do not require the inclusion of extrinsic conducting defects since their operation is based on intrinsic ones (oxygen vacancies). Using Density Functional Theory, we evaluated the thermodynamics of the defects formation and the kinetics of diffusion of the conducting species active in transition metal oxide RRAM materials. The gained insights based on the thermodynamics in the Top Electrode, Insulating Matrix and Bottommore » Electrode and at the interfaces are used to design a proper defect reservoir, which is needed for a low-energy reliable switching device. The defect reservoir has also a direct impact on the retention of the Low Resistance State due to the resulting thermodynamic driving forces. The kinetics of the diffusing conducting defects in the Insulating Matrix determine the switching dynamics and resistance retention. The interface at the Bottom Electrode has a significant impact on the low-current operation and long endurance of the memory cell. Our first-principles findings are confirmed by experimental measurements on fabricated RRAM devices.« less
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Sun, Xiu-Min; Tu, Wen-Qiang; Shi, Yan-Wei; Xue, Li; Zhao, Hu
2014-07-01
Early life stress is one of the major susceptible factors for stress-related pathologies like posttraumatic stress disorder (PTSD). Recent studies in rats suggest that rather than being overall unfavorable, early life stress may prepare the organism to perform optimally to stressful environments later in life. In this study, severely adverse early life stress was conducted by six consecutive hours of maternal separation (MS), from PND1 to PND21, and contextual fear conditioning model was used on PND90 to mimic the second stress in adulthood and the re-experiencing symptom of PTSD. It was observed that in this investigation pups experienced MS showed decreased sensibility to contextual fear conditioning in adulthood, and there sex plays an important role. For example, female rats suffered MS had much lower freezing than males and controls. Meanwhile, Morris water maze test indicated that MS did not impair rat's performance of spatial learning and memory. Furthermore, suppression subtractive hybridization (SSH) was used to screen the related genes of fear memory, by examining the changes of mRNA expression in CA1 area between female MS and control rats after contextual fear conditioning. Finally, nine up-regulated and one down-regulated genes, including β2-MG, MAF, Nd1-L, TorsinA and MACF1 gene were found in this study. It is assumed that the TorsinA, MACF1 and Nd1-L gene may contribute to the decreased sensitivity of PTSD induced by MS. Copyright © 2014 Elsevier B.V. All rights reserved.
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The Impact of Affective Context on Autobiographical Recollection in Depression.
Hitchcock, Caitlin; Golden, Ann-Marie J; Werner-Seidler, Aliza; Kuyken, Willem; Dalgleish, Tim
2018-05-01
Across two studies we investigated the influence of contextual cues on autobiographical memory recall. In Study 1, participants ( N = 37) with major depressive disorder, in episode or in varying degrees of remission, were administered a Negative Autobiographical Memory Task (NAMT) that required them to retrieve negatively valenced memories in response to positive cue words (a positive context). We reasoned that increased depression symptom severity would be associated with a reduced ability to override priming from this disadvantageous context. Consequently, we hypothesized that increased depressive severity would counterintuitively be associated with reduced negativity ratings for retrieved personal memories to positive cues on the NAMT. This hypothesis was supported. Study 2, using a community sample ( N = 63), demonstrated that a similar reduction in memory negativity was observed in individuals with lower working memory capacity-an index of executive control. Implications for autobiographical memory and executive training paradigms for depression are discussed.
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Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding.
Du, Huiyun; Deng, Wei; Aimone, James B; Ge, Minyan; Parylak, Sarah; Walch, Keenan; Zhang, Wei; Cook, Jonathan; Song, Huina; Wang, Liping; Gage, Fred H; Mu, Yangling
2016-09-13
Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2-expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioral experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Overall, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience.
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Effects of semantic relatedness on recall of stimuli preceding emotional oddballs.
Smith, Ryan M; Beversdorf, David Q
2008-07-01
Semantic and episodic memory networks function as highly interconnected systems, both relying on the hippocampal/medial temporal lobe complex (HC/MTL). Episodic memory encoding triggers the retrieval of semantic information, serving to incorporate contextual relationships between the newly acquired memory and existing semantic representations. While emotional material augments episodic memory encoding at the time of stimulus presentation, interactions between emotion and semantic memory that contribute to subsequent episodic recall are not well understood. Using a modified oddball task, we examined the modulatory effects of negative emotion on semantic interactions with episodic memory by measuring the free-recall of serially presented neutral or negative words varying in semantic relatedness. We found increased free-recall for words related to and preceding emotionally negative oddballs, suggesting that negative emotion can indirectly facilitate episodic free-recall by enhancing semantic contributions during encoding. Our findings demonstrate the ability of emotion and semantic memory to interact to mutually enhance free-recall.
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Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding
Du, Huiyun; Deng, Wei; Aimone, James B.; Ge, Minyan; Parylak, Sarah; Walch, Keenan; Zhang, Wei; Cook, Jonathan; Song, Huina; Wang, Liping; Gage, Fred H.; Mu, Yangling
2016-01-01
Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2–expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioral experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Overall, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience. PMID:27573822
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Stimulus homogeneity enhances implicit learning: evidence from contextual cueing.
Feldmann-Wüstefeld, Tobias; Schubö, Anna
2014-04-01
Visual search for a target object is faster if the target is embedded in a repeatedly presented invariant configuration of distractors ('contextual cueing'). It has also been shown that the homogeneity of a context affects the efficiency of visual search: targets receive prioritized processing when presented in a homogeneous context compared to a heterogeneous context, presumably due to grouping processes at early stages of visual processing. The present study investigated in three Experiments whether context homogeneity also affects contextual cueing. In Experiment 1, context homogeneity varied on three levels of the task-relevant dimension (orientation) and contextual cueing was most pronounced for context configurations with high orientation homogeneity. When context homogeneity varied on three levels of the task-irrelevant dimension (color) and orientation homogeneity was fixed, no modulation of contextual cueing was observed: high orientation homogeneity led to large contextual cueing effects (Experiment 2) and low orientation homogeneity led to low contextual cueing effects (Experiment 3), irrespective of color homogeneity. Enhanced contextual cueing for homogeneous context configurations suggest that grouping processes do not only affect visual search but also implicit learning. We conclude that memory representation of context configurations are more easily acquired when context configurations can be processed as larger, grouped perceptual units. However, this form of implicit perceptual learning is only improved by stimulus homogeneity when stimulus homogeneity facilitates grouping processes on a dimension that is currently relevant in the task. Copyright © 2014 Elsevier B.V. All rights reserved.