Hippocampal Overexpression of Mutant CREB Blocks Long-Term, but Not Short-Term Memory for a Socially Transmitted Food Preference

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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…

Neural activity in the hippocampus predicts individual visual short-term memory capacity.

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von Allmen, David Yoh; Wurmitzer, Karoline; Martin, Ernst; Klaver, Peter

2013-07-01

Although the hippocampus had been traditionally thought to be exclusively involved in long-term memory, recent studies raised controversial explanations why hippocampal activity emerged during short-term memory tasks. For example, it has been argued that long-term memory processes might contribute to performance within a short-term memory paradigm when memory capacity has been exceeded. It is still unclear, though, whether neural activity in the hippocampus predicts visual short-term memory (VSTM) performance. To investigate this question, we measured BOLD activity in 21 healthy adults (age range 19-27 yr, nine males) while they performed a match-to-sample task requiring processing of object-location associations (delay period  =  900 ms; set size conditions 1, 2, 4, and 6). Based on individual memory capacity (estimated by Cowan's K-formula), two performance groups were formed (high and low performers). Within whole brain analyses, we found a robust main effect of "set size" in the posterior parietal cortex (PPC). In line with a "set size × group" interaction in the hippocampus, a subsequent Finite Impulse Response (FIR) analysis revealed divergent hippocampal activation patterns between performance groups: Low performers (mean capacity  =  3.63) elicited increased neural activity at set size two, followed by a drop in activity at set sizes four and six, whereas high performers (mean capacity  =  5.19) showed an incremental activity increase with larger set size (maximal activation at set size six). Our data demonstrated that performance-related neural activity in the hippocampus emerged below capacity limit. In conclusion, we suggest that hippocampal activity reflected successful processing of object-location associations in VSTM. Neural activity in the PPC might have been involved in attentional updating. Copyright © 2013 Wiley Periodicals, Inc.

Working Memory, Long-Term Memory, and Medial Temporal Lobe Function

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Jeneson, Annette; Squire, Larry R.

2012-01-01

Early studies of memory-impaired patients with medial temporal lobe (MTL) damage led to the view that the hippocampus and related MTL structures are involved in the formation of long-term memory and that immediate memory and working memory are independent of these structures. This traditional idea has recently been revisited. Impaired performance…

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

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

2016-01-01

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

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

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

2016-02-01

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

Erythropoietin enhances hippocampal long-term potentiation and memory

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El-Kordi Ahmed

2008-09-01

Full Text Available Abstract Background Erythropoietin (EPO improves cognition of human subjects in the clinical setting by as yet unknown mechanisms. We developed a mouse model of robust cognitive improvement by EPO to obtain the first clues of how EPO influences cognition, and how it may act on hippocampal neurons to modulate plasticity. Results We show here that a 3-week treatment of young mice with EPO enhances long-term potentiation (LTP, a cellular correlate of learning processes in the CA1 region of the hippocampus. This treatment concomitantly alters short-term synaptic plasticity and synaptic transmission, shifting the balance of excitatory and inhibitory activity. These effects are accompanied by an improvement of hippocampus dependent memory, persisting for 3 weeks after termination of EPO injections, and are independent of changes in hematocrit. Networks of EPO-treated primary hippocampal neurons develop lower overall spiking activity but enhanced bursting in discrete neuronal assemblies. At the level of developing single neurons, EPO treatment reduces the typical increase in excitatory synaptic transmission without changing the number of synaptic boutons, consistent with prolonged functional silencing of synapses. Conclusion We conclude that EPO improves hippocampus dependent memory by modulating plasticity, synaptic connectivity and activity of memory-related neuronal networks. These mechanisms of action of EPO have to be further exploited for treating neuropsychiatric diseases.

NF-κB p50 subunit knockout impairs late LTP and alters long term memory in the mouse hippocampus

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Oikawa Kensuke

2012-07-01

Full Text Available Abstract Background Nuclear factor kappa B (NF-κB is a transcription factor typically expressed with two specific subunits (p50, p65. Investigators have reported that NF-κB is activated during the induction of in vitro long term potentiation (LTP, a paradigm of synaptic plasticity and correlate of memory, suggesting that NF-κB may be necessary for some aspects of memory encoding. Furthermore, NF-κB has been implicated as a potential requirement in behavioral tests of memory. Unfortunately, very little work has been done to explore the effects of deleting specific NF-κB subunits on memory. Studies have shown that NF-κB p50 subunit deletion (p50−/− leads to memory deficits, however some recent studies suggest the contrary where p50−/− mice show enhanced memory in the Morris water maze (MWM. To more critically explore the role of the NF-κB p50 subunit in synaptic plasticity and memory, we assessed long term spatial memory in vivo using the MWM, and synaptic plasticity in vitro utilizing high frequency stimuli capable of eliciting LTP in slices from the hippocampus of NF-κB p50−/− versus their controls (p50+/+. Results We found that the lack of the NF-κB p50 subunit led to significant decreases in late LTP and in selective but significant alterations in MWM tests (i.e., some improvements during acquisition, but deficits during retention. Conclusions These results support the hypothesis that the NF-κ p50 subunit is required in long term spatial memory in the hippocampus.

Persistent increased PKMζ in long-term and remote spatial memory.

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Hsieh, Changchi; Tsokas, Panayiotis; Serrano, Peter; Hernández, A Iván; Tian, Dezhi; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2017-02-01

PKMζ is an autonomously active PKC isoform that is thought to maintain both LTP and long-term memory. Whereas persistent increases in PKMζ protein sustain the kinase's action in LTP, the molecular mechanism for the persistent action of PKMζ during long-term memory has not been characterized. PKMζ inhibitors disrupt spatial memory when introduced into the dorsal hippocampus from 1day to 1month after training. Therefore, if the mechanisms of PKMζ's persistent action in LTP maintenance and long-term memory were similar, persistent increases in PKMζ would last for the duration of the memory, far longer than most other learning-induced gene products. Here we find that spatial conditioning by aversive active place avoidance or appetitive radial arm maze induces PKMζ increases in dorsal hippocampus that persist from 1day to 1month, coinciding with the strength and duration of memory retention. Suppressing the increase by intrahippocampal injections of PKMζ-antisense oligodeoxynucleotides prevents the formation of long-term memory. Thus, similar to LTP maintenance, the persistent increase in the amount of autonomously active PKMζ sustains the kinase's action during long-term and remote spatial memory maintenance. Copyright © 2016. Published by Elsevier Inc.

Blocking Synaptic Removal of GluA2-Containing AMPA Receptors Prevents the Natural Forgetting of Long-Term Memories.

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Migues, Paola Virginia; Liu, Lidong; Archbold, Georgina E B; Einarsson, Einar Ö; Wong, Jacinda; Bonasia, Kyra; Ko, Seung Hyun; Wang, Yu Tian; Hardt, Oliver

2016-03-23

The neurobiological processes underpinning the natural forgetting of long-term memories are poorly understood. Based on the critical role of GluA2-containing AMPA receptors (GluA2/AMPARs) in long-term memory persistence, we tested in rats whether their synaptic removal underpins time-dependent memory loss. We found that blocking GluA2/AMPAR removal with the interference peptides GluA23Y or G2CT in the dorsal hippocampus during a memory retention interval prevented the normal forgetting of established, long-term object location memories, but did not affect their acquisition. The same intervention also preserved associative memories of food-reward conditioned place preference that would otherwise be lost over time. We then explored whether this forgetting process could play a part in behavioral phenomena involving time-dependent memory change. We found that infusing GluA23Y into the dorsal hippocampus during a 2 week retention interval blocked generalization of contextual fear expression, whereas infusing it into the infralimbic cortex after extinction of auditory fear prevented spontaneous recovery of the conditioned response. Exploring possible physiological mechanisms that could be involved in this form of memory decay, we found that bath application of GluA23Y prevented depotentiation, but not induction of long-term potentiation, in a hippocampal slice preparation. Together, these findings suggest that a decay-like forgetting process that involves the synaptic removal of GluA2/AMPARs erases consolidated long-term memories in the hippocampus and other brain structures over time. This well regulated forgetting process may critically contribute to establishing adaptive behavior, whereas its dysregulation could promote the decline of memory and cognition in neuropathological disorders. The neurobiological mechanisms involved in the natural forgetting of long-term memory and its possible functions are not fully understood. Based on our previous work describing the

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

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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

Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

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Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

2011-01-01

To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

c-Fos expression predicts long-term social memory retrieval in mice.

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Lüscher Dias, Thomaz; Fernandes Golino, Hudson; Moura de Oliveira, Vinícius Elias; Dutra Moraes, Márcio Flávio; Schenatto Pereira, Grace

2016-10-15

The way the rodent brain generally processes socially relevant information is rather well understood. How social information is stored into long-term social memory, however, is still under debate. Here, brain c-Fos expression was measured after adult mice were exposed to familiar or novel juveniles and expression was compared in several memory and socially relevant brain areas. Machine Learning algorithm Random Forest was then used to predict the social interaction category of adult mice based on c-Fos expression in these areas. Interaction with a familiar co-specific altered brain activation in the olfactory bulb, amygdala, hippocampus, lateral septum and medial prefrontal cortex. Remarkably, Random Forest was able to predict interaction with a familiar juvenile with 100% accuracy. Activity in the olfactory bulb, amygdala, hippocampus and the medial prefrontal cortex were crucial to this prediction. From our results, we suggest long-term social memory depends on initial social olfactory processing in the medial amygdala and its output connections synergistically with non-social contextual integration by the hippocampus and medial prefrontal cortex top-down modulation of primary olfactory structures. Copyright © 2016 Elsevier B.V. All rights reserved.

Item-location binding in working memory: is it hippocampus-dependent?

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Allen, Richard J; Vargha-Khadem, Faraneh; Baddeley, Alan D

2014-07-01

A general consensus is emerging that the hippocampus has an important and active role in the creation of new long-term memory representations of associations or bindings between elements. However, it is less clear whether this contribution can be extended to the creation of temporary bound representations in working memory, involving the retention of small numbers of items over short delays. We examined this by administering a series of recognition and recall tests of working memory for colour-location binding and object-location binding to a patient with highly selective hippocampal damage (Jon), and groups of control participants. Jon achieved high levels of accuracy in all working memory tests of recognition and recall binding across retention intervals of up to 10s. In contrast, Jon performed at chance on an unexpected delayed test of the same object-location binding information. These findings indicate a clear dissociation between working memory and long-term memory, with no evidence for a critical hippocampal contribution to item-location binding in working memory. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition

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Adam M P Miller

2014-08-01

Full Text Available Spatial navigation requires 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 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 hippocampus. Within this framework, the RSC plays a dual role as part of the feedforward network providing sensory and mnemonic input to the hippocampus and as a target of the hippocampal-dependent systems consolidation of long-term memory.

HDAC Inhibition Modulates Hippocampus-Dependent Long-Term Memory for Object Location in a CBP-Dependent Manner

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Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

2011-01-01

Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation…

Focal adhesion kinase regulates neuronal growth, synaptic plasticity and hippocampus-dependent spatial learning and memory.

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Monje, Francisco J; Kim, Eun-Jung; Pollak, Daniela D; Cabatic, Maureen; Li, Lin; Baston, Arthur; Lubec, Gert

2012-01-01

The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly expressed in the mammalian brain and highly enriched in neuronal growth cones. Inhibitory and facilitatory activities of FAK on neuronal growth have been reported and its role in neuritic outgrowth remains controversial. Unlike other tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth and plasticity, the relevance of FAK for learning and memory in vivo has not been clearly defined yet. A comprehensive study aimed at determining the role of FAK in neuronal growth, neurotransmitter release and synaptic plasticity in hippocampal neurons and in hippocampus-dependent learning and memory was therefore undertaken using the mouse model. Gain- and loss-of-function experiments indicated that FAK is a critical regulator of hippocampal cell morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK inhibition affected both miniature excitatory postsynaptic potentials and activity-dependent hippocampal long-term potentiation prompting us to explore the possible role of FAK in spatial learning and memory in vivo. Our data indicate that FAK has a growth-promoting effect, is importantly involved in the regulation of the synaptic function and mediates in vivo hippocampus-dependent spatial learning and memory. Copyright © 2011 S. Karger AG, Basel.

PKA-CREB-BDNF signaling pathway mediates propofol-induced long-term learning and memory impairment in hippocampus of rats.

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Zhong, Yu; Chen, Jing; Li, Li; Qin, Yi; Wei, Yi; Pan, Shining; Jiang, Yage; Chen, Jialin; Xie, Yubo

2018-04-20

Studies have found that propofol can induce widespread neuroapoptosis in developing brains, which leads to cause long-term learning and memory abnormalities. However, the specific cellular and molecular mechanisms underlying propofol-induced neuroapoptosis remain elusive. The aim of the present study was to explore the role of PKA-CREB-BDNF signaling pathway in propofol-induced long-term learning and memory impairment during brain development. Seven-day-old rats were randomly assigned to control, intralipid and three treatment groups (n = 5). Rats in control group received no treatment. Intralipid (10%, 10 mL/kg) for vehicle control and different dosage of propofol for three treatment groups (50, 100 and 200 mg/kg) were administered intraperitoneally. FJB staining, immunohistochemistry analysis for neuronal nuclei antigen and transmission electron microscopy were used to detect neuronal apoptosis and structure changes. MWM test examines the long-term spatial learning and memory impairment. The expression of PKA, pCREB and BDNF was quantified using western blots. Propofol induced significant increase of FJB-positive cells and decrease of PKA, pCREB and BDNF protein levels in the immature brain of P7 rats. Using the MWM test, propofol-treated rats demonstrated long-term spatial learning and memory impairment. Moreover, hippocampal NeuN-positive cell loss, long-lasting ultrastructural abnormalities of the neurons and synapses, and long-term down-regulation of PKA, pCREB and BDNF protein expression in adult hippocampus were also found. Our results indicated that neonatal propofol exposure can significantly result in long-term learning and memory impairment in adulthood. The possible mechanism involved in the propofol-induced neuroapoptosis was related to down-regulation of PKA-CREB-BDNF signaling pathway. Copyright © 2018. Published by Elsevier B.V.

Hypertension impairs hippocampus-related adult neurogenesis, CA1 neuron dendritic arborization and long-term memory.

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Shih, Y-H; Tsai, S-F; Huang, S-H; Chiang, Y-T; Hughes, M W; Wu, S-Y; Lee, C-W; Yang, T-T; Kuo, Y-M

2016-05-13

Hypertension is associated with neurodegenerative diseases and cognitive impairment. Several studies using spontaneous hypertensive rats to study the effect of hypertension on memory performance and adult hippocampal neurogenesis have reached inconsistent conclusions. The contradictory findings may be related to the genetic variability of spontaneous hypertensive rats due to the conventional breeding practices. The objective of this study is to examine the effect of hypertension on hippocampal structure and function in isogenic mice. Hypertension was induced by the '2 kidneys, 1 clip' method (2K1C) which constricted one of the two renal arteries. The blood pressures of 2K1C mice were higher than the sham group on post-operation day 7 and remained high up to day 28. Mice with 2K1C-induced hypertension had impaired long-term, but not short-term, memory. Dendritic complexity of CA1 neurons and hippocampal neurogenesis were reduced by 2K1C-induced hypertension on post-operation day 28. Furthermore, 2K1C decreased the levels of hippocampal brain-derived neurotrophic factor, while blood vessel density and activation status of astrocytes and microglia were not affected. In conclusion, hypertension impairs hippocampus-associated long-term memory, dendritic arborization and neurogenesis, which may be caused by down-regulation of brain-derived neurotrophic factor signaling pathways. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

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Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2016-05-17

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

Distinct neural correlates of associative working memory and long-term memory encoding in the medial temporal lobe

NARCIS (Netherlands)

Bergmann, H.C.; Rijpkema, M.J.P.; Fernandez, G.S.E.; Kessels, R.P.C.

2012-01-01

Increasing evidence suggests a role for the hippocampus not only in long-term memory (LTM) but also in relational working memory (WM) processes, challenging the view of the hippocampus as being solely involved in episodic LTM. However, hippocampal involvement reported in some neuroimaging studies

Genetic deletion of melanin-concentrating hormone neurons impairs hippocampal short-term synaptic plasticity and hippocampal-dependent forms of short-term memory.

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Le Barillier, Léa; Léger, Lucienne; Luppi, Pierre-Hervé; Fort, Patrice; Malleret, Gaël; Salin, Paul-Antoine

2015-11-01

The cognitive role of melanin-concentrating hormone (MCH) neurons, a neuronal population located in the mammalian postero-lateral hypothalamus sending projections to all cortical areas, remains poorly understood. Mainly activated during paradoxical sleep (PS), MCH neurons have been implicated in sleep regulation. The genetic deletion of the only known MCH receptor in rodent leads to an impairment of hippocampal dependent forms of memory and to an alteration of hippocampal long-term synaptic plasticity. By using MCH/ataxin3 mice, a genetic model characterized by a selective deletion of MCH neurons in the adult, we investigated the role of MCH neurons in hippocampal synaptic plasticity and hippocampal-dependent forms of memory. MCH/ataxin3 mice exhibited a deficit in the early part of both long-term potentiation and depression in the CA1 area of the hippocampus. Post-tetanic potentiation (PTP) was diminished while synaptic depression induced by repetitive stimulation was enhanced suggesting an alteration of pre-synaptic forms of short-term plasticity in these mice. Behaviorally, MCH/ataxin3 mice spent more time and showed a higher level of hesitation as compared to their controls in performing a short-term memory T-maze task, displayed retardation in acquiring a reference memory task in a Morris water maze, and showed a habituation deficit in an open field task. Deletion of MCH neurons could thus alter spatial short-term memory by impairing short-term plasticity in the hippocampus. Altogether, these findings could provide a cellular mechanism by which PS may facilitate memory encoding. Via MCH neuron activation, PS could prepare the day's learning by increasing and modulating short-term synaptic plasticity in the hippocampus. © 2015 Wiley Periodicals, Inc.

Behavioral tagging is a general mechanism of long-term memory formation.

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Ballarini, Fabricio; Moncada, Diego; Martinez, Maria Cecilia; Alen, Nadia; Viola, Haydée

2009-08-25

In daily life, memories are intertwined events. Little is known about the mechanisms involved in their interactions. Using two hippocampus-dependent (spatial object recognition and contextual fear conditioning) and one hippocampus-independent (conditioned taste aversion) learning tasks, we show that in rats subjected to weak training protocols that induce solely short term memory (STM), long term memory (LTM) is promoted and formed only if training sessions took place in contingence with a novel, but not familiar, experience occurring during a critical time window around training. This process requires newly synthesized proteins induced by novelty and reveals a general mechanism of LTM formation that begins with the setting of a "learning tag" established by a weak training. These findings represent the first comprehensive set of evidences indicating the existence of a behavioral tagging process that in analogy to the synaptic tagging and capture process, need the creation of a transient, protein synthesis-independent, and input specific tag.

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

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

2017-02-01

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

Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons.

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Ren, Anjing; Zhang, Huan; Xie, Zhifang; Ma, Xianhua; Ji, Wenli; He, David Z Z; Yuan, Wenjun; Ding, Yu-Qiang; Zhang, Xiao-Hui; Zhang, Weiping J

2012-10-01

The mammalian hippocampus harbours neural circuitry that is crucial for associative learning and memory. The mechanisms that underlie the development and regulation of this complex circuitry are not fully understood. Our previous study established an essential role for the zinc finger protein Zbtb20 in the specification of CA1 field identity in the developing hippocampus. Here, we show that conditionally deleting Zbtb20 specifically in mature CA1 pyramidal neurons impaired hippocampus-dependent memory formation, without affecting hippocampal architecture or the survival, identity and basal excitatory synaptic activity of CA1 pyramidal neurons. We demonstrate that mature CA1-specific Zbtb20 knockout mice exhibited reductions in long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents. Furthermore, we show that activity-induced phosphorylation of ERK and CREB is impaired in the hippocampal CA1 of Zbtb20 mutant mice. Collectively, these results indicate that Zbtb20 in mature CA1 plays an important role in LTP and memory by regulating NMDAR activity, and activation of ERK and CREB.

Cannabinoids prevent the differential long-term effects of exposure to severe stress on hippocampal- and amygdala-dependent memory and plasticity.

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Shoshan, Noa; Segev, Amir; Abush, Hila; Mizrachi Zer-Aviv, Tomer; Akirav, Irit

2017-10-01

Exposure to excessive or uncontrolled stress is a major factor associated with various diseases including posttraumatic stress disorder (PTSD). The consequences of exposure to trauma are affected not only by aspects of the event itself, but also by the frequency and severity of trauma reminders. It was suggested that in PTSD, hippocampal-dependent memory is compromised while amygdala-dependent memory is strengthened. Several lines of evidence support the role of the endocannabinoid (eCB) system as a modulator of the stress response. In this study we aimed to examine cannabinoids modulation of the long-term effects (i.e., 1 month) of exposure to a traumatic event on memory and plasticity in the hippocampus and amygdala. Following exposure to the shock and reminders model of PTSD in an inhibitory avoidance light-dark apparatus rats demonstrated: (i) enhanced fear retrieval and impaired inhibitory extinction (Ext), (ii) no long-term potentiation (LTP) in the CA1, (iii) impaired hippocampal-dependent short-term memory in the object location task, (iv) enhanced LTP in the amygdala, and (v) enhanced amygdala-dependent conditioned taste aversion memory. The cannabinoid CB1/2 receptor agonist WIN55-212,2 (0.5mg/kg, i.p.) and the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3mg/kg, i.p.), administered 2 hr after shock exposure prevented these opposing effects on hippocampal- and amygdala-dependent processes. Moreover, the effects of WIN55-212,2 and URB597 on Ext and acoustic startle were prevented by co-administration of a low dose of the CB1 receptor antagonist AM251 (0.5mg/kg, i.p.), suggesting that the preventing effects of both drugs are mediated by CB1 receptors. Exposure to shock and reminders increased CB1 receptor levels in the CA1 and basolateral amygdala 1 month after shock exposure and this increase was also prevented by administering WIN55-212,2 or URB597. Taken together, these findings suggest the involvement of the eCB system, and specifically CB1

Rapamycin inhibits mTOR/p70S6K activation in CA3 region of the hippocampus of the rat and impairs long term memory.

Science.gov (United States)

Lana, D; Di Russo, J; Mello, T; Wenk, G L; Giovannini, M G

2017-01-01

The present study was aimed at establishing whether the mTOR pathway and its downstream effector p70S6K in CA3 pyramidal neurons are under the modulation of the cholinergic input to trigger the formation of long term memories, similar to what we demonstrated in CA1 hippocampus. We performed in vivo behavioral experiments using the step down inhibitory avoidance test in adult Wistar rats to evaluate memory formation under different conditions. We examined the effects of rapamycin, an inhibitor of mTORC1 formation, scopolamine, a muscarinic receptor antagonist or mecamylamine, a nicotinic receptor antagonist, on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition was conducted 30min after i.c.v. injection of rapamycin. Recall testing was performed 1h, 4h or 24h after acquisition. We found that (1) mTOR and p70S6K activation in CA3 pyramidal neurons were involved in long term memory formation; (2) rapamycin significantly inhibited mTOR and of p70S6K activation at 4h, and long term memory impairment 24h after acquisition; (3) scopolamine impaired short but not long term memory, with an early increase of mTOR/p70S6K activation at 1h followed by stabilization at longer times; (4) mecamylamine and scopolamine co-administration impaired short term memory at 1h and 4h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1h and 4h; (5) mecamylamine and scopolamine treatment did not impair long term memory formation; (6) unexpectedly, rapamycin increased mTORC2 activation in microglial cells. Our results demonstrate that in CA3 pyramidal neurons the mTOR/p70S6K pathway is under the modulation of the cholinergic system and is involved in long-term memory encoding, and are consistent with the hypothesis that the CA3 region of the hippocampus is involved in memory mechanisms based on rapid, one-trial object-place learning and recall. Furthermore, our results are in accordance with previous reports that selective

Aluminium chloride impairs long-term memory and downregulates cAMP-PKA-CREB signalling in rats.

Science.gov (United States)

Zhang, Lifeng; Jin, Cuihong; Lu, Xiaobo; Yang, Jinghua; Wu, Shengwen; Liu, Qiufang; Chen, Rong; Bai, Chunyu; Zhang, Di; Zheng, Linlin; Du, Yanqiu; Cai, Yuan

2014-09-02

Epidemiological investigations have indicated that aluminium (Al) is an important environmental neurotoxicant that may be involved in the aetiology of the cognitive dysfunction associated with neurodegenerative diseases. Additionally, exposure to Al is known to cause neurobehavioural abnormalities in animals. Previous studies demonstrated that Al impaired early-phase long-term potentiation (E-LTP) in vivo and in vitro. Our previous research revealed that Al could impair long-term memory via the impairment of late-phase long-term potentiation (L-LTP) in vivo. However, the exact mechanism by which Al impairs long-term memory has been poorly studied thus far. This study was designed not only to observe the effects of subchronic Al treatment on long-term memory and hippocampal ultrastructure but also to explore a possible underlying mechanism (involving the cAMP-PKA-CREB signalling pathway) in the hippocampus of rats.. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation for 3 weeks and then fed with distilled water containing 0, 0.2%, 0.4% or 0.6% Al chloride (AlCl3) for 3 postnatal months. The levels of Al in the blood and hippocampus were quantified by atomic absorption spectrophotometry. The shuttle-box test was performed to detect long-term memory. The hippocampus was collected for ultrastructure observation, and the level of cAMP-PKA-CREB signalling was examined. The results showed that the Al concentrations in the blood and hippocampus of Al-treated rats were higher than those of the control rats. Al may impair the long-term memory of rats. Hippocampal cAMP, cPKA, pCREB, BDNF and c-jun expression decreased significantly, and the neuronal and synaptic ultrastructure exhibited pathological changes after Al treatment. These results indicated that Al may induce long-term memory damage in rats by inhibiting cAMP-PKA-CREB signalling and altering the synaptic and neuronal ultrastructure in the hippocampus. Copyright

Aluminium chloride impairs long-term memory and downregulates cAMP-PKA-CREB signalling in rats

International Nuclear Information System (INIS)

Zhang, Lifeng; Jin, Cuihong; Lu, Xiaobo; Yang, Jinghua; Wu, Shengwen; Liu, Qiufang; Chen, Rong; Bai, Chunyu; Zhang, Di; Zheng, Linlin; Du, Yanqiu; Cai, Yuan

2014-01-01

Epidemiological investigations have indicated that aluminium (Al) is an important environmental neurotoxicant that may be involved in the aetiology of the cognitive dysfunction associated with neurodegenerative diseases. Additionally, exposure to Al is known to cause neurobehavioural abnormalities in animals. Previous studies demonstrated that Al impaired early-phase long-term potentiation (E-LTP) in vivo and in vitro. Our previous research revealed that Al could impair long-term memory via the impairment of late-phase long-term potentiation (L-LTP) in vivo. However, the exact mechanism by which Al impairs long-term memory has been poorly studied thus far. This study was designed not only to observe the effects of subchronic Al treatment on long-term memory and hippocampal ultrastructure but also to explore a possible underlying mechanism (involving the cAMP-PKA-CREB signalling pathway) in the hippocampus of rats.. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation for 3 weeks and then fed with distilled water containing 0, 0.2%, 0.4% or 0.6% Al chloride (AlCl 3 ) for 3 postnatal months. The levels of Al in the blood and hippocampus were quantified by atomic absorption spectrophotometry. The shuttle–box test was performed to detect long-term memory. The hippocampus was collected for ultrastructure observation, and the level of cAMP-PKA-CREB signalling was examined. The results showed that the Al concentrations in the blood and hippocampus of Al-treated rats were higher than those of the control rats. Al may impair the long-term memory of rats. Hippocampal cAMP, cPKA, pCREB, BDNF and c-jun expression decreased significantly, and the neuronal and synaptic ultrastructure exhibited pathological changes after Al treatment. These results indicated that Al may induce long-term memory damage in rats by inhibiting cAMP-PKA-CREB signalling and altering the synaptic and neuronal ultrastructure in the hippocampus

Early-life exposure to fibroblast growth factor-2 facilitates context-dependent long-term memory in developing rats.

Science.gov (United States)

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.

Hippocampus duality: Memory and novelty detection are subserved by distinct mechanisms.

Science.gov (United States)

Barbeau, Emmanuel J; Chauvel, Patrick; Moulin, Christopher J A; Regis, Jean; Liégeois-Chauvel, Catherine

2017-04-01

The hippocampus plays a pivotal role both in novelty detection and in long-term memory. The physiological mechanisms underlying these behaviors have yet to be understood in humans. We recorded intracerebral evoked potentials within the hippocampus of epileptic patients (n = 10) during both memory and novelty detection tasks (targets in oddball tasks). We found that memory and detection tasks elicited late local field potentials in the hippocampus during the same period, but of opposite polarity (negative during novelty detection tasks, positive during memory tasks, ∼260-600 ms poststimulus onset, P < 0.05). Critically, these potentials had maximal amplitude on the same contact in the hippocampus for each patient. This pattern did not depend on the task as different types of memory and novelty detection tasks were used. It did not depend on the novelty of the stimulus or the difficulty of the task either. Two different hypotheses are discussed to account for this result: it is either due to the activation of CA1 pyramidal neurons by two different pathways such as the monosynaptic and trisynaptic entorhinal-hippocampus pathways, or to the activation of different neuronal populations, that is, differing either functionally (e.g., novelty/familiarity neurons) or located in different regions of the hippocampus (e.g., CA1/subiculum). In either case, these activities may integrate the activity of two distinct large-scale networks implementing externally or internally oriented, mutually exclusive, brain states. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Hypocretin/orexin neurons contribute to hippocampus-dependent social memory and synaptic plasticity in mice.

Science.gov (United States)

Yang, Liya; Zou, Bende; Xiong, Xiaoxing; Pascual, Conrado; Xie, James; Malik, Adam; Xie, Julian; Sakurai, Takeshi; Xie, Xinmin Simon

2013-03-20

Hypocretin/orexin (Hcrt)-producing neurons in the lateral hypothalamus project throughout the brain, including to the hippocampus, where Hcrt receptors are widely expressed. Hcrt neurons activate these targets to orchestrate global arousal state, wake-sleep architecture, energy homeostasis, stress adaptation, and reward behaviors. Recently, Hcrt has been implicated in cognitive functions and social interaction. In the present study, we tested the hypothesis that Hcrt neurons are critical to social interaction, particularly social memory, using neurobehavioral assessment and electrophysiological approaches. The validated "two-enclosure homecage test" devices and procedure were used to test sociability, preference for social novelty (social novelty), and recognition memory. A conventional direct contact social test was conducted to corroborate the findings. We found that adult orexin/ataxin-3-transgenic (AT) mice, in which Hcrt neurons degenerate by 3 months of age, displayed normal sociability and social novelty with respect to their wild-type littermates. However, AT mice displayed deficits in long-term social memory. Nasal administration of exogenous Hcrt-1 restored social memory to an extent in AT mice. Hippocampal slices taken from AT mice exhibited decreases in degree of paired-pulse facilitation and magnitude of long-term potentiation, despite displaying normal basal synaptic neurotransmission in the CA1 area compared to wild-type hippocampal slices. AT hippocampi had lower levels of phosphorylated cAMP response element-binding protein (pCREB), an activity-dependent transcription factor important for synaptic plasticity and long-term memory storage. Our studies demonstrate that Hcrt neurons play an important role in the consolidation of social recognition memory, at least in part through enhancements of hippocampal synaptic plasticity and cAMP response element-binding protein phosphorylation.

Learning-dependent neurogenesis in the olfactory bulb determines long-term olfactory memory.

Science.gov (United States)

Sultan, S; Mandairon, N; Kermen, F; Garcia, S; Sacquet, J; Didier, A

2010-07-01

Inhibitory interneurons of the olfactory bulb are subjected to permanent adult neurogenesis. Their number is modulated by learning, suggesting that they could play a role in plastic changes of the bulbar network associated with olfactory memory. Adult male C57BL/6 mice were trained in an associative olfactory task, and we analyzed long-term retention of the task 5, 30, and 90 d post-training. In parallel, we assessed the fate of these newborn cells, mapped their distribution in the olfactory bulb and measured their functional implication using the immediate early gene Zif268. In a second set of experiments, we pharmacologically modulated glutamatergic transmission and using the same behavioral task assessed the consequences on memory retention and neurogenesis. Finally, by local infusion of an antimitotic drug, we selectively blocked neurogenesis during acquisition of the task and looked at the effects on memory retention. First we demonstrated that retrieval of an associative olfactory task recruits the newborn neurons in odor-specific areas of the olfactory bulb selected to survive during acquisition of the task and that it does this in a manner that depends on the strength of learning. We then demonstrated that acquisition is not dependent on neurogenesis if long-term retention of the task is abolished by blocking neurogenesis. Adult-born neurons are thus involved in changes in the neural representation of an odor; this underlies long-term olfactory memory as the strength of learning is linked to the duration of this memory. Neurogenesis thus plays a crucial role in long-term olfactory memory.

Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs.

Science.gov (United States)

Varela, Carmen; Weiss, Sarah; Meyer, Retsina; Halassa, Michael; Biedenkapp, Joseph; Wilson, Matthew A; Goosens, Ki Ann; Bendor, Daniel

2016-01-01

The hippocampus is critical for the storage of new autobiographical experiences as memories. Following an initial encoding stage in the hippocampus, memories undergo a process of systems-level consolidation, which leads to greater stability through time and an increased reliance on neocortical areas for retrieval. The extent to which the retrieval of these consolidated memories still requires the hippocampus is unclear, as both spared and severely degraded remote memory recall have been reported following post-training hippocampal lesions. One difficulty in definitively addressing the role of the hippocampus in remote memory retrieval is the precision with which the entire volume of the hippocampal region can be inactivated. To address this issue, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), a chemical-genetic tool capable of highly specific neuronal manipulation over large volumes of brain tissue. We find that remote (>7 weeks after acquisition), but not recent (1-2 days after acquisition) contextual fear memories can be recalled after injection of the DREADD agonist (CNO) in animals expressing the inhibitory DREADD in the entire hippocampus. Our data demonstrate a time-dependent role of the hippocampus in memory retrieval, supporting the standard model of systems consolidation.

Hippocampal-prefrontal connectivity predicts midfrontal oscillations and long-term memory performance

NARCIS (Netherlands)

Cohen, M.X.

2011-01-01

The hippocampus and prefrontal cortex interact to support working memory (WM) and long-term memory [1, 2 and 3]. Neurophysiologically, WM is thought to be subserved by reverberatory activity of distributed networks within the prefrontal cortex (PFC) [2, 4, 5, 6, 7 and 8], which become synchronized

Genetic disruption of the core circadian clock impairs hippocampus-dependent memory

OpenAIRE

2014-01-01

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 hippoca...

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

KAUST Repository

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

2016-01-01

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

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

KAUST Repository

Gao, Virginia

2016-07-12

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

Neurotrophins play differential roles in short and long-term recognition memory.

Science.gov (United States)

Callaghan, Charlotte K; Kelly, Aine M

2013-09-01

The neurotrophin family of proteins are believed to mediate various forms of synaptic plasticity in the adult brain. Here we have assessed the roles of these proteins in object recognition memory in the rat, using icv infusions of function-blocking antibodies or the tyrosine kinase antagonist, tyrphostin AG879, to block Trk receptors. We report that tyrphostin AG879 impairs both short-term and long-term recognition memory, indicating a requirement for Trk receptor activation in both processes. The effect of inhibition of each of the neurotrophins with activity-blocking neutralising antibodies was also tested. Treatment with anti-BDNF, anti-NGF or anti-NT4 had no effect on short-term memory, but blocked long-term recognition memory. Treatment with anti-NT3 had no effect on either process. We also assessed changes in expression of neurotrophins and their respective receptors in the hippocampus, dentate gyrus and perirhinal cortex over a 24 h period following training in the object recognition task. We observed time-dependent changes in expression of the Trk receptors and their ligands in the dentate gyrus and perirhinal cortex. The data are consistent with a pivotal role for neurotrophic factors in the expression of recognition memory. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of social instability stress in adolescence on long-term, not short-term, spatial memory performance.

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Green, Matthew R; McCormick, Cheryl M

2013-11-01

There is evidence that exposure to stressors in adolescence leads to lasting deficits on hippocampal-dependent tasks, but whether medial prefrontal cortical function is also impaired is unknown. We previously found that rats exposed to social instability stress in adolescence (SS; daily 1h isolation and subsequent change of cage partner between postnatal days 30 and 45) had impaired memory performance on a Spatial Object Location test and in memory for fear conditioning context, tasks that depend on the integrity of the hippocampus. Here we investigated whether impaired performance would be evident after adolescent SS in male rats on a different test of hippocampal function, spatial learning and memory in the Morris water maze (MWM) and on a working memory task for which performance depends on the integrity of the medial prefrontal cortex, the Delayed Alternation task (DAT). During MWM testing, SS rats showed greater improvements in performance across trials within days compared to control (CTL) rats, but showed less retention of learning between days (48 h) compared to CTL rats. Similarly, SS rats had impaired long-term memory in the Spatial Object Location test after a long delay (240 min), but not after shorter delays (15 or 60 min) compared to CTL rats. No group differences were observed on the DAT, which assessed working memory across brief delays (5-90 s). Thus, deficits in memory performance after chronic social stress in adolescence may be limited to long-term memory. Copyright © 2013 Elsevier B.V. All rights reserved.

Alternative conceptions of memory consolidation and the role of the hippocampus at the systems level in rodents.

Science.gov (United States)

Sutherland, R J; Lehmann, H

2011-06-01

We discuss very recent experiments with rodents addressing the idea that long-term memories initially depending on the hippocampus, over a prolonged period, become independent of it. No unambiguous recent evidence exists to substantiate that this occurs. Most experiments find that recent and remote memories are equally affected by hippocampus damage. Nearly all experiments that report spared remote memories suffer from two problems: retrieval could be based upon substantial regions of spared hippocampus and recent memory is tested at intervals that are of the same order of magnitude as cellular consolidation. Accordingly, we point the way beyond systems consolidation theories, both the Standard Model of Consolidation and the Multiple Trace Theory, and propose a simpler multiple storage site hypothesis. On this view, with event reiterations, different memory representations are independently established in multiple networks. Many detailed memories always depend on the hippocampus; the others may be established and maintained independently. Copyright © 2011 Elsevier Ltd. All rights reserved.

Context-specific activation of hippocampus and SN/VTA by reward is related to enhanced long-term memory for embedded objects.

Science.gov (United States)

Loh, Eleanor; Kumaran, Dharshan; Koster, Raphael; Berron, David; Dolan, Ray; Duzel, Emrah

2016-10-01

Animal studies indicate that hippocampal representations of environmental context modulate reward-related processing in the substantia nigra and ventral tegmental area (SN/VTA), a major origin of dopamine in the brain. Using functional magnetic resonance imaging (fMRI) in humans, we investigated the neural specificity of context-reward associations under conditions where the presence of perceptually similar neutral contexts imposed high demands on a putative hippocampal function, pattern separation. The design also allowed us to investigate how contextual reward enhances long-term memory for embedded neutral objects. SN/VTA activity underpinned specific context-reward associations in the face of perceptual similarity. A reward-related enhancement of long-term memory was restricted to the condition where the rewarding and the neutral contexts were perceptually similar, and in turn was linked to co-activation of the hippocampus (subfield DG/CA3) and SN/VTA. Thus, an ability of contextual reward to enhance memory for focal objects is closely linked to context-related engagement of hippocampal-SN/VTA circuitry. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval.

Science.gov (United States)

Vanelzakker, Michael B; Zoladz, Phillip R; Thompson, Vanessa M; Park, Collin R; Halonen, Joshua D; Spencer, Robert L; Diamond, David M

2011-01-01

We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 h later. Rat brains were extracted 30 min after the 24-h memory test trial for analysis of c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard); (2) Rats given cat exposure (Predator Stress) 30 min prior to training (Pre-Training Stress); (3) Rats given water exposure only (Water Yoked); and (4) Rats given no water exposure (Home Cage). The Standard trained group exhibited excellent 24 h memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS) compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval.

Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala and Striatum Following Long-Term Spatial Memory Retrieval

Directory of Open Access Journals (Sweden)

Michael B VanElzakker

2011-06-01

Full Text Available We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 hr later. Rat brains were extracted 30 min after the 24 hr memory test trial for analysis of c-fos mRNA. Four groups were tested: 1 Rats given standard training (Standard; 2 Rats given cat exposure (Predator Stress 30 min prior to training (Pre-Training Stress; 3 Rats given water exposure only (Water Yoked; and 4 Rats given no water exposure (Home Cage. The Standard trained group exhibited excellent 24 hr memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA. The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval.

Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval

Science.gov (United States)

VanElzakker, Michael B.; Zoladz, Phillip R.; Thompson, Vanessa M.; Park, Collin R.; Halonen, Joshua D.; Spencer, Robert L.; Diamond, David M.

2011-01-01

We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 h later. Rat brains were extracted 30 min after the 24-h memory test trial for analysis of c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard); (2) Rats given cat exposure (Predator Stress) 30 min prior to training (Pre-Training Stress); (3) Rats given water exposure only (Water Yoked); and (4) Rats given no water exposure (Home Cage). The Standard trained group exhibited excellent 24 h memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS) compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval. PMID:21738501

Short- and long-term memory: differential involvement of neurotransmitter systems and signal transduction cascades

Directory of Open Access Journals (Sweden)

MÔNICA R.M. VIANNA

2000-09-01

Full Text Available Since William James (1890 first distinguished primary from secondary memory, equivalent to short- and long-term memory, respectively, it has been assumed that short-term memory processes are in charge of cognition while long-term memory is being consolidated. From those days a major question has been whether short-term memory is merely a initial phase of long-term memory, or a separate phenomena. Recent experiments have shown that many treatments with specific molecular actions given into the hippocampus and related brain areas after one-trial avoidance learning can effectively cancel short-term memory without affecting long-term memory formation. This shows that short-term memory and long-term memory involve separate mechanisms and are independently processed. Other treatments, however, influence both memory types similarly, suggesting links between both at the receptor and at the post-receptor level, which should not be surprising as they both deal with nearly the same sensorimotor representations. This review examines recent advances in short- and long-term memory mechanisms based on the effect of intra-hippocampal infusion of drugs acting upon neurotransmitter and signal transduction systems on both memory types.

Two waves of proteasome-dependent protein degradation in the hippocampus are required for recognition memory consolidation.

Science.gov (United States)

Figueiredo, Luciana S; Dornelles, Arethuza S; Petry, Fernanda S; Falavigna, Lucio; Dargél, Vinicius A; Köbe, Luiza M; Aguzzoli, Cristiano; Roesler, Rafael; Schröder, Nadja

2015-04-01

Healthy neuronal function and synaptic modification require a concert of synthesis and degradation of proteins. Increasing evidence indicates that protein turnover mediated by proteasome activity is involved in long-term synaptic plasticity and memory. However, its role in different phases of memory remains debated, and previous studies have not examined the possible requirement of protein degradation in recognition memory. Here, we show that the proteasome inhibitor, lactacystin (LAC), infused into the CA1 area of the hippocampus at two specific time points during consolidation, impairs 24-retention of memory for object recognition in rats. Administration of LAC after retrieval did not affect retention. These findings provide the first evidence for a requirement of proteasome activity in recognition memory, indicate that protein degradation in the hippocampus is necessary during selective time windows of memory consolidation, and further our understanding of the role of protein turnover in memory formation. Copyright © 2015 Elsevier Inc. All rights reserved.

Uhrf2 deletion impairs the formation of hippocampus-dependent memory by changing the structure of the dentate gyrus.

Science.gov (United States)

Chen, Xiao-Rong; Sun, Shi-Cheng; Teng, Shuai-Wen; Li, Liang; Bie, Yi-Fan; Yu, Hui; Li, Da-Li; Chen, Zhe-Yu; Wang, Yue

2018-03-01

Ubiquitin-like with PHD and ring finger domains 2 (Uhrf2) is distributed in many brain regions, including the cortex and hippocampus. Decreased Uhrf2 expression is involved in neurodegenerative disease. A recent study showed Uhrf2 deletion impaired spatial memory; however, the mechanism remains elusive. In our study, we determined that Uhrf2 +/- and Uhrf2 -/- mice had significant learning and memory deficiencies in contextual fear conditioning (CFC) and the novel place recognition test but not in the novel object recognition test. Interestingly, there were no changes in the Uhrf2 protein levels in the hippocampus of C57BL6 mice after CFC training, which suggests Uhrf2 in adult mice may not be related to the formation of CFC long-term memory. Based on Nissl staining, Uhrf2 deletion caused neuropathological changes specifically in the crest of the dentate gyrus (DG), such as cell swelling, a vague outline and confused boundary; however, no changes were identified in the medial prefrontal cortex (mPFC). Transmission electron microscope assay further indicated a series of abnormal ultrastructure changes in neurons and glia in the DG crest. These results suggested that Uhrf2 deletion selectively blocked the development of the DG crest and impaired hippocampus-dependent learning and memory. Our study will facilitate a better understanding of the role of Uhrf2 protein in the central nervous system.

A Critical Role for the Nucleus Reuniens in Long-Term, But Not Short-Term Associative Recognition Memory Formation.

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Barker, Gareth R I; Warburton, Elizabeth Clea

2018-03-28

Recognition memory for single items requires the perirhinal cortex (PRH), whereas recognition of an item and its associated location requires a functional interaction among the PRH, hippocampus (HPC), and medial prefrontal cortex (mPFC). Although the precise mechanisms through which these interactions are effected are unknown, the nucleus reuniens (NRe) has bidirectional connections with each regions and thus may play a role in recognition memory. Here we investigated, in male rats, whether specific manipulations of NRe function affected performance of recognition memory for single items, object location, or object-in-place associations. Permanent lesions in the NRe significantly impaired long-term, but not short-term, object-in-place associative recognition memory, whereas single item recognition memory and object location memory were unaffected. Temporary inactivation of the NRe during distinct phases of the object-in-place task revealed its importance in both the encoding and retrieval stages of long-term associative recognition memory. Infusions of specific receptor antagonists showed that encoding was dependent on muscarinic and nicotinic cholinergic neurotransmission, whereas NMDA receptor neurotransmission was not required. Finally, we found that long-term object-in-place memory required protein synthesis within the NRe. These data reveal a specific role for the NRe in long-term associative recognition memory through its interactions with the HPC and mPFC, but not the PRH. The delay-dependent involvement of the NRe suggests that it is not a simple relay station between brain regions, but, rather, during high mnemonic demand, facilitates interactions between the mPFC and HPC, a process that requires both cholinergic neurotransmission and protein synthesis. SIGNIFICANCE STATEMENT Recognizing an object and its associated location, which is fundamental to our everyday memory, requires specific hippocampal-cortical interactions, potentially facilitated by the

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

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

2011-01-01

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

Pre- and long-term postoperative courses of hippocampus-associated memory impairment in epilepsy patients with antibody-associated limbic encephalitis and selective amygdalohippocampectomy.

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Hansen, Niels; Ernst, Leon; Rüber, Theodor; Widman, Guido; Becker, Albert J; Elger, Christian E; Helmstaedter, Christoph

2018-02-01

Limbic encephalitis (LE) is defined by mesiotemporal lobe structure abnormalities, seizures, memory, and psychiatric disturbances. This study aimed to identify the long-term clinical and neuropsychological outcome of selective amygdalohippocampectomy (sAH) in drug-resistant patients with temporal lobe epilepsy due to known or later diagnosed subacute LE not responding to immunotherapy associated with neuronal autoantibodies. In seven patients with temporal lobe epilepsy due to antibody positive LE (glutamic acid decarboxylase (GAD65): n=5; voltage-gated potassium channel complex (VGKC), N-methyl d-aspartate receptor (NMDAR): n=1; Ma-2/Ta: n=1) sAH (6 left, 1 right) was performed. Those patients underwent repeated electroencephalography (EEG) recordings, magnetic resonance imaging (MRI) volumetry of the amygdala and hippocampus, and neuropsychological examinations and were followed up for 6-7years on average. Verbal memory and figural memory were affected in 57% of patients at baseline and 71% at the last follow-up. At the last follow-up, 14% of the patients had declined in verbal memory and figural memory. We observed improved memory in 43% of patients regarding figural memory, but not in a single patient regarding verbal memory. Repeated evaluations across the individual courses reveal cognitive and MRI dynamics that appear to be unrelated to surgery and drug treatment. Three of the seven patients with LE with different antibodies (NMDAR: n=1, Ma-2/Ta: n=1 and GAD65: n=1) achieved persistent seizure freedom along with no accelerated memory decline after surgery. Two of the five GAD65-antibody patients positive with LE showed progressive memory decline and a long-term tendency to contralateral hippocampus atrophy. While memory demonstrated some decline in the long run, what is most important is that a progressive decline in memory is seldom found after sAH in patients with LE. Moreover, the dynamics in performance and MRI before and after surgery reveal disease

Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

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Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

2015-01-01

The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.

Fluoxetine Inhibits Natural Decay of Long-Term Memory via Akt/GSK-3β Signaling.

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Yi, Jee Hyun; Zhang, JiaBao; Ko, Sang Yoon; Kwon, Huiyoung; Jeon, Se Jin; Park, Se Jin; Jung, Jiwook; Kim, Byung C; Lee, Young Choon; Kim, Dong Hyun; Ryu, Jong Hoon

2018-02-09

Understanding the mechanisms underlying the natural decay of long-term memory can help us find means of extending the duration of long-term memory. However, the neurobiological processes involved in the decay of long-term memory are poorly understood. In the present study, we examined the effect of acute and chronic treatment of fluoxetine on natural decay of long-term memory and the possible mechanism. Late administration of fluoxetine prolonged the persistence of long-term memory in mice, as demonstrated by object location recognition and Barnes maze tests. Fluoxetine altered Akt/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling in the hippocampus. Late short- and long-term pharmacological inhibition of GSK-3β mimicked the effect of fluoxetine on memory persistence. Pharmacological inhibition of Akt blocked the effect of fluoxetine on memory persistence. Finally, late infusion of fluoxetine increased hippocampal long-term potentiation (LTP) and pharmacological inhibition of GSK-3β blocked the natural decline in LTP. These results demonstrate that GSK-3β might be a key molecule in memory decay process, and fluoxetine extends the period of long-term memory maintenance via Akt/GSK-3β signaling.

Spatial olfactory learning facilitates long-term depression in the hippocampus.

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André, Marion Agnès Emma; Manahan-Vaughan, Denise

2013-10-01

Recently, it has emerged that visual spatial exploration facilitates synaptic plasticity at different synapses within the trisynaptic network. Particularly striking is the finding that visuospatial contexts facilitate hippocampal long-term depression (LTD), raising the possibility that this form of plasticity may be important for memory formation. It is not known whether other sensory modalities elicit similar permissive effects on LTD. Here, we explored if spatial olfactory learning facilitates LTD in the hippocampus region of freely behaving rats. Patterned afferent stimulation of the Schaffer collaterals elicited short-term depression (STD) (<1 h) of evoked responses in the Stratum radiatum of the CA1 region. Coupling of this protocol with novel exploration of a spatial constellation of olfactory cues facilitated short-term depression into LTD that lasted for over 24 h. Facilitation of LTD did not occur when animals were re-exposed 1 week later to the same odors in the same spatial constellation. Evaluation of learning behavior revealed that 1 week after the 1st odor exposure, the animals remembered the odors and their relative positions. These data support that the hippocampus can use nonvisuospatial resources, and specifically can use spatial olfactory information, to facilitate LTD and to generate spatial representations. The data also support that a tight relationship exists between the processing of spatial contextual information and the expression of LTD in the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

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

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

2014-01-05

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

Significant long-term, but not short-term, hippocampal-dependent memory impairment in adult rats exposed to alcohol in early postnatal life.

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Goodfellow, Molly J; Lindquist, Derick H

2014-09-01

In rodents, ethanol exposure in early postnatal life is known to induce structural and functional impairments throughout the brain, including the hippocampus. Herein, rat pups were administered one of three ethanol doses over postnatal days (PD) 4-9, a period of brain development comparable to the third trimester of human pregnancy. As adults, control and ethanol rats were trained and tested in a variant of hippocampal-dependent one-trial context fear conditioning. In Experiment 1, subjects were placed into a novel context and presented with an immediate footshock (i.e., within ∼8 sec). When re-exposed to the same context 24 hr later low levels of conditioned freezing were observed. Context pre-exposure 24 hr prior to the immediate shock reversed the deficit in sham-intubated and unintubated control rats, enhancing freezing behavior during the context retention test. Even with context pre-exposure, however, significant dose-dependent reductions in contextual freezing were seen in ethanol rats. In Experiment 2, the interval between context pre-exposure and the immediate shock was shortened to 2 hr, in addition to the standard 24 hr. Ethanol rats trained with the 2 hr, but not 24 hr, interval displayed retention test freezing levels roughly equal to controls. Results suggest the ethanol rats can encode a short-term context memory and associate it with the aversive footshock 2 hr later. In the 24 hr ethanol rats the short-term context memory is poorly transferred or consolidated into long-term memory, we propose, impeding the memory's subsequent retrieval and association with shock. © 2014 Wiley Periodicals, Inc.

Resistance exercise improves hippocampus-dependent memory

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R.C. Cassilhas

2012-12-01

Full Text Available It has been demonstrated that resistance exercise improves cognitive functions in humans. Thus, an animal model that mimics this phenomenon can be an important tool for studying the underlying neurophysiological mechanisms. Here, we tested if an animal model for resistance exercise was able to improve the performance in a hippocampus-dependent memory task. In addition, we also evaluated the level of insulin-like growth factor 1/insulin growth factor receptor (IGF-1/IGF-1R, which plays pleiotropic roles in the nervous system. Adult male Wistar rats were divided into three groups (N = 10 for each group: control, SHAM, and resistance exercise (RES. The RES group was submitted to 8 weeks of progressive resistance exercise in a vertical ladder apparatus, while the SHAM group was left in the same apparatus without exercising. Analysis of a cross-sectional area of the flexor digitorum longus muscle indicated that this training period was sufficient to cause muscle fiber hypertrophy. In a step-through passive avoidance task (PA, the RES group presented a longer latency than the other groups on the test day. We also observed an increase of 43 and 94% for systemic and hippocampal IGF-1 concentration, respectively, in the RES group compared to the others. A positive correlation was established between PA performance and systemic IGF-1 (r = 0.46, P < 0.05. Taken together, our data indicate that resistance exercise improves the hippocampus-dependent memory task with a concomitant increase of IGF-1 level in the rat model. This model can be further explored to better understand the effects of resistance exercise on brain functions.

Endogenous BDNF is required for long-term memory formation in the rat parietal cortex.

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Alonso, Mariana; Bekinschtein, Pedro; Cammarota, Martín; Vianna, Monica R M; Izquierdo, Iván; Medina, Jorge H

2005-01-01

Information storage in the brain is a temporally graded process involving different memory phases as well as different structures in the mammalian brain. Cortical plasticity seems to be essential to store stable long-term memories, although little information is available at the moment regarding molecular and cellular events supporting memory consolidation in the neocortex. Brain-derived neurotrophic factor (BDNF) modulates both short-term synaptic function and activity-dependent synaptic plasticity in hippocampal and cortical neurons. We have recently demonstrated that endogenous BDNF in the hippocampus is involved in memory formation. Here we examined the role of BDNF in the parietal cortex (PCx) in short-term (STM) and long-term memory (LTM) formation of a one-trial fear-motivated learning task in rats. Bilateral infusions of function-blocking anti-BDNF antibody into the PCx impaired both STM and LTM retention scores and decreased the phosphorylation state of cAMP response element-binding protein (CREB). In contrast, intracortical administration of recombinant human BDNF facilitated LTM and increased CREB activation. Moreover, inhibitory avoidance training is associated with a rapid and transient increase in phospho-CREB/total CREB ratio in the PCx. Thus, our results indicate that endogenous BDNF is required for both STM and LTM formation of inhibitory avoidance learning, possibly involving CREB activation-dependent mechanisms. The present data support the idea that early sensory areas constitute important components of the networks subserving memory formation and that information processing in neocortex plays an important role in memory formation.

Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition.

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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.

Upregulation of CREB-mediated transcription enhances both short- and long-term memory.

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Suzuki, Akinobu; Fukushima, Hotaka; Mukawa, Takuya; Toyoda, Hiroki; Wu, Long-Jun; Zhao, Ming-Gao; Xu, Hui; Shang, Yuze; Endoh, Kengo; Iwamoto, Taku; Mamiya, Nori; Okano, Emiko; Hasegawa, Shunsuke; Mercaldo, Valentina; Zhang, Yue; Maeda, Ryouta; Ohta, Miho; Josselyn, Sheena A; Zhuo, Min; Kida, Satoshi

2011-06-15

Unraveling the mechanisms by which the molecular manipulation of genes of interest enhances cognitive function is important to establish genetic therapies for cognitive disorders. Although CREB is thought to positively regulate formation of long-term memory (LTM), gain-of-function effects of CREB remain poorly understood, especially at the behavioral level. To address this, we generated four lines of transgenic mice expressing dominant active CREB mutants (CREB-Y134F or CREB-DIEDML) in the forebrain that exhibited moderate upregulation of CREB activity. These transgenic lines improved not only LTM but also long-lasting long-term potentiation in the CA1 area in the hippocampus. However, we also observed enhanced short-term memory (STM) in contextual fear-conditioning and social recognition tasks. Enhanced LTM and STM could be dissociated behaviorally in these four lines of transgenic mice, suggesting that the underlying mechanism for enhanced STM and LTM are distinct. LTM enhancement seems to be attributable to the improvement of memory consolidation by the upregulation of CREB transcriptional activity, whereas higher basal levels of BDNF, a CREB target gene, predicted enhanced shorter-term memory. The importance of BDNF in STM was verified by microinfusing BDNF or BDNF inhibitors into the hippocampus of wild-type or transgenic mice. Additionally, increasing BDNF further enhanced LTM in one of the lines of transgenic mice that displayed a normal BDNF level but enhanced LTM, suggesting that upregulation of BDNF and CREB activity cooperatively enhances LTM formation. Our findings suggest that CREB positively regulates memory consolidation and affects memory performance by regulating BDNF expression.

PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.

Directory of Open Access Journals (Sweden)

Peter Serrano

2008-12-01

Full Text Available How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta, an autonomously active atypical protein kinase C (PKC isoform critical for the maintenance of long-term potentiation (LTP. PKMzeta maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH and basolateral amygdala (BLA on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMzeta activity. Similarly, PKMzeta inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMzeta inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise

PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.

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Serrano, Peter; Friedman, Eugenia L; Kenney, Jana; Taubenfeld, Stephen M; Zimmerman, Joshua M; Hanna, John; Alberini, Cristina; Kelley, Ann E; Maren, Stephen; Rudy, Jerry W; Yin, Jerry C P; Sacktor, Todd C; Fenton, André A

2008-12-23

How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta), an autonomously active atypical protein kinase C (PKC) isoform critical for the maintenance of long-term potentiation (LTP). PKMzeta maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP) by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH) and basolateral amygdala (BLA) on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMzeta activity. Similarly, PKMzeta inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMzeta inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US) associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise, or

Hippocampal size is related to short-term true and false memory, and right fusiform size is related to long-term true and false memory.

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Zhu, Bi; Chen, Chuansheng; Loftus, Elizabeth F; He, Qinghua; Lei, Xuemei; Dong, Qi; Lin, Chongde

2016-11-01

There is a keen interest in identifying specific brain regions that are related to individual differences in true and false memories. Previous functional neuroimaging studies showed that activities in the hippocampus, right fusiform gyrus, and parahippocampal gyrus were associated with true and false memories, but no study thus far has examined whether the structures of these brain regions are associated with short-term and long-term true and false memories. To address that question, the current study analyzed data from 205 healthy young adults, who had valid data from both structural brain imaging and a misinformation task. In the misinformation task, subjects saw the crime scenarios, received misinformation, and took memory tests about the crimes an hour later and again after 1.5 years. Results showed that bilateral hippocampal volume was associated with short-term true and false memories, whereas right fusiform gyrus volume and surface area were associated with long-term true and false memories. This study provides the first evidence for the structural neural bases of individual differences in short-term and long-term true and false memories.

Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory.

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Havekes, Robbert; Park, Alan J; Tolentino, Rosa E; Bruinenberg, Vibeke M; Tudor, Jennifer C; Lee, Yool; Hansen, Rolf T; Guercio, Leonardo A; Linton, Edward; Neves-Zaph, Susana R; Meerlo, Peter; Baillie, George S; Houslay, Miles D; Abel, Ted

2016-08-24

Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. Neurons exhibit localized signaling processes that enable biochemical cascades to be activated selectively in specific subcellular compartments. The

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

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

2009-01-01

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

Verbal Short-Term Memory Span in Children: Long-Term Modality Dependent Effects of Intrauterine Growth Restriction

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Geva, R.; Eshel, R.; Leitner, Y.; Fattal-Valevski, A.; Harel, S.

2008-01-01

Background: Recent reports showed that children born with intrauterine growth restriction (IUGR) are at greater risk of experiencing verbal short-term memory span (STM) deficits that may impede their learning capacities at school. It is still unknown whether these deficits are modality dependent. Methods: This long-term, prospective design study…

Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.

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Al Abed, Alice Shaam; Sellami, Azza; Brayda-Bruno, Laurent; Lamothe, Valérie; Noguès, Xavier; Potier, Mylène; Bennetau-Pelissero, Catherine; Marighetto, Aline

2016-07-01

Because estrogens have mostly been studied in gonadectomized females, effects of chronic exposure to environmental estrogens in the general population are underestimated. Estrogens can enhance hippocampus-dependent memory through the modulation of information storage. However, declarative memory, the hippocampus-dependent memory of facts and events, demands more than abilities to retain information. Specifically, memory of repetitive events of everyday life such as "where I parked" requires abilities to organize/update memories to prevent proactive interference from similar memories of previous "parking events". Whether such organizational processes are estrogen-sensitive is unknown. We here studied, in intact young and aged adult mice, drinking-water (1μM) estradiol effects on both retention and organizational components of hippocampus-dependent memory, using a radial-maze task of everyday-like memory. Demand on retention vs organization was manipulated by varying the time-interval separating repetitions of similar events. Estradiol increased performance in young and aged mice under minimized organizational demand, but failed to improve the age-associated memory impairment and diminished performance in young mice under high organizational demand. In fact, estradiol prolonged mnemonic retention of successive events without improving organization abilities, hence resulted in more proactive interference from irrelevant memories. c-Fos imaging of testing-induced brain activations showed that the deterioration of young memory was associated with dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our findings support the view that estradiol is promnesic but also reveal that such property can paradoxically impair memory. These findings have important outcomes regarding health issues relative to the impact of environmental estrogens in the general population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is the hippocampus necessary for visual and verbal binding in working memory?

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Baddeley, Alan; Allen, Richard; Vargha-Khadem, Faraneh

2010-03-01

A series of experiments test the recent claim that the hippocampus is necessary for the binding of features in working memory. Some potential limitations of studies underlying this claim are discussed, and an attempt is made to further test the hypothesis by studying a case of developmental amnesia whose extensively investigated pathology appears to be principally limited to the hippocampus, and who shows the expected deficit in episodic long-term memory. One series of experiments studied the short-term visual binding of color and shape under conditions ranging from simple presentation of colored objects through the more demanding task of combining the features when separated in space, or in time. A second set of experiments studied the capacity to use sentence structure to bind words into chunks in short-term verbal memory. Hippocampal pathology did not lead to a decrement on any of these tasks, suggesting that the hippocampus is not essential for short-term binding in working memory. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Impaired fear memory specificity associated with deficient endocannabinoid-dependent long-term plasticity.

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Lovelace, Jonathan W; Vieira, Philip A; Corches, Alex; Mackie, Ken; Korzus, Edward

2014-06-01

In addition to its central role in learning and memory, N-methyl D-aspartate receptor (NMDAR)-dependent signaling regulates central glutamatergic synapse maturation and has been implicated in schizophrenia. We have transiently induced NMDAR hypofunction in infant mice during postnatal days 7-11, followed by testing fear memory specificity and presynaptic plasticity in the prefrontal cortex (PFC) in adult mice. We show that transient NMDAR hypofunction during early brain development, coinciding with the maturation of cortical plasticity results in a loss of an endocannabinoid (eCB)-mediated form of long-term depression (eCB-LTD) at adult central glutamatergic synapses, while another form of presynaptic long-term depression mediated by the metabotropic glutamate receptor 2/3 (mGluR2/3-LTD) remains intact. Mice with this selective impairment of presynaptic plasticity also showed deficits in fear memory specificity. The observed deficit in cortical presynaptic plasticity may represent a neural maladaptation contributing to network instability and abnormal cognitive functioning.

The role of the BDNF Val66Met polymorphism in individual differences in long-term memory capacity.

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Montag, Christian; Felten, Andrea; Markett, Sebastian; Fischer, Luise; Winkel, Katja; Cooper, Andrew; Reuter, Martin

2014-12-01

The protein brain-derived neurotrophic factor (BDNF) plays an important role in diverse memory processes and is strongly expressed in the hippocampus. The hippocampus itself is a key structure involved in the processing of information from short-term to long-term memory. Due to the putative role of BDNF in memory consolidation, a prominent single nucleotide polymorphism (SNP) on the BDNF gene (BDNF Val66Met) was investigated in the context of long-term memory performance. N=138 students were presented with 40 words from 10 categories, each consisting of eight words such as 'fruits' or 'vehicles' in a memory recognition task (specifically the Deese-Roediger-McDermott Paradigm). Recognition performance was analyzed 25 min after the initial presentation of the word list and subsequently 1 week after the initial presentation. Overall, individual long-term memory performance immediately after learning the word list (T1) and performance 1 week later (T2) did not differ on the basis of the BDNF SNP, but an interaction effect of BDNF Val66Met by time-of-recall was found: Carriers of the Met66+ variant showed the strongest decline in hit rate performance over time.

Chewing Maintains Hippocampus-Dependent Cognitive Function.

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Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

2015-01-01

Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research.

The hippocampus remains activated over the long term for the retrieval of truly episodic memories.

Directory of Open Access Journals (Sweden)

Caroline Harand

Full Text Available The role of the hippocampus in declarative memory consolidation is a matter of intense debate. We investigated the neural substrates of memory retrieval for recent and remote information using functional magnetic resonance imaging (fMRI. 18 young, healthy participants learned a series of pictures. Then, during two fMRI recognition sessions, 3 days and 3 months later, they had to determine whether they recognized or not each picture using the "Remember/Know" procedure. Presentation of the same learned images at both delays allowed us to track the evolution of memories and distinguish consistently episodic memories from those that were initially episodic and then became familiar or semantic over time and were retrieved without any contextual detail. Hippocampal activation decreased over time for initially episodic, later semantic memories, but remained stable for consistently episodic ones, at least in its posterior part. For both types of memories, neocortical activations were observed at both delays, notably in the ventromedial prefrontal and anterior cingulate cortices. These activations may reflect a gradual reorganization of memory traces within neural networks. Our data indicate maintenance and strengthening of hippocampal and cortico-cortical connections in the consolidation and retrieval of episodic memories over time, in line with the Multiple Trace theory (Nadel and Moscovitch, 1997. At variance, memories becoming semantic over time consolidate through strengthening of cortico-cortical connections and progressive disengagement of the hippocampus.

Learning, memory and synaptic plasticity in hippocampus in rats exposed to sevoflurane.

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Xiao, Hongyan; Liu, Bing; Chen, Yali; Zhang, Jun

2016-02-01

Developmental exposure to volatile anesthetics has been associated with cognitive deficits at adulthood. Rodent studies have revealed impairments in performance in learning tasks involving the hippocampus. However, how the duration of anesthesia exposure impact on hippocampal synaptic plasticity, learning, and memory is as yet not fully elucidated. On postnatal day 7(P7), rat pups were divided into 3 groups: control group (n=30), 3% sevoflurane treatment for 1h (Sev 1h group, n=30) and 3% sevoflurane treatment for 6h (Sev 6h group, n=28). Following anesthesia, synaptic vesicle-associated proteins and dendrite spine density and synapse ultrastructure were measured using western blotting, Golgi staining, and transmission electron microscopy (TEM) on P21. In addition, the effects of sevoflurane treatment on long-term potentiation (LTP) and long-term depression (LTD), two molecular correlates of memory, were studied in CA1 subfields of the hippocampus, using electrophysiological recordings of field potentials in hippocampal slices on P35-42. Rats' neurocognitive performance was assessed at 2 months of age, using the Morris water maze and novel-object recognition tasks. Our results showed that neonatal exposure to 3% sevoflurane for 6h results in reduced spine density of apical dendrites along with elevated expression of synaptic vesicle-associated proteins (SNAP-25 and syntaxin), and synaptic ultrastructure damage in the hippocampus. The electrophysiological evidence indicated that hippocampal LTP, but not LTD, was inhibited and that learning and memory performance were impaired in two behavioral tasks in the Sev 6h group. In contrast, lesser structural and functional damage in the hippocampus was observed in the Sev 1h group. Our data showed that 6-h exposure of the developing brain to 3% sevoflurane could result in synaptic plasticity impairment in the hippocampus and spatial and nonspatial hippocampal-dependent learning and memory deficits. In contrast, shorter

Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

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Adriana eBarman

2014-04-01

Full Text Available The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT and the logical memory section of the Wechsler Memory Scale (WMS. Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e. the myopia risk allele showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point towards pleitropic effects of RASGRF1 genetic variations on complex neural function in humans.

Adverse effect of combination of chronic psychosocial stress and high fat diet on hippocampus-dependent memory in rats.

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Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A

2009-12-01

The combined effects of high fat diet (HFD) and chronic stress on the hippocampus-dependent spatial learning and memory were studied in rats using the radial arm water maze (RAWM). Chronic psychosocial stress and/or HFD were simultaneously administered for 3 months to young adult male Wister rats. In the RAWM, rats were subjected to 12 learning trials as well as short-term and long-term memory tests. This procedure was applied on a daily basis until the animal reaches days to criterion (DTC) in the 12th learning trial and in memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Groups were compared based on the number of errors per trial or test as well as on the DTC. Chronic stress, HFD and chronic stress/HFD animal groups showed impaired learning as indicated by committing significantly (Pchronic stress, HFD and chronic stress/HFD groups showed significantly impaired performance compared to control group. Additionally, the stress/HFD was the only group that showed significantly impaired performance in memory tests on the 5th training day, suggesting more severe memory impairment in that group. Furthermore, DTC value for above groups indicated that chronic stress or HFD, alone, resulted in a mild impairment of spatial memory, but the combination of chronic stress and HFD resulted in a more severe and long-lasting memory impairment. The data indicated that the combination of stress and HFD produced more deleterious effects on hippocampal cognitive function than either chronic stress or HFD alone.

SPIN90 Modulates Long-Term Depression and Behavioral Flexibility in the Hippocampus

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Dae Hwan Kim

2017-09-01

Full Text Available The importance of actin-binding proteins (ABPs in the regulation of synapse morphology and plasticity has been well established. SH3 protein interacting with Nck, 90 kDa (SPIN90, an Nck-interacting protein highly expressed in synapses, is essential for actin remodeling and dendritic spine morphology. Synaptic targeting of SPIN90 to spine heads or dendritic shafts depends on its phosphorylation state, leading to blockage of cofilin-mediated actin depolymerization and spine shrinkage. However, the physiological role of SPIN90 in long-term plasticity, learning and memory are largely unknown. In this study, we demonstrate that Spin90-knockout (KO mice exhibit substantial deficits in synaptic plasticity and behavioral flexibility. We found that loss of SPIN90 disrupted dendritic spine density in CA1 neurons of the hippocampus and significantly impaired long-term depression (LTD, leaving basal synaptic transmission and long-term potentiation (LTP intact. These impairments were due in part to deficits in AMPA receptor endocytosis and its pre-requisites, GluA1 dephosphorylation and postsynaptic density (PSD 95 phosphorylation, but also by an intrinsic activation of Akt-GSK3β signaling as a result of Spin90-KO. In accordance with these defects, mice lacking SPIN90 were found to carry significant deficits in object-recognition and behavioral flexibility, while learning ability was largely unaffected. Collectively, these findings demonstrate a novel modulatory role for SPIN90 in hippocampal LTD and behavioral flexibility.

Long Term Depression in Rat Hippocampus and the Effect of Ethanol during Fetal Life

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Olivier Pierrefiche

2017-11-01

Full Text Available Alcohol (ethanol disturbs cognitive functions including learning and memory in humans, non-human primates, and laboratory animals such as rodents. As studied in animals, cellular mechanisms for learning and memory include bidirectional synaptic plasticity, long-term potentiation (LTP, and long-term depression (LTD, primarily in the hippocampus. Most of the research in the field of alcohol has analyzed the effects of ethanol on LTP; however, with recent advances in the understanding of the physiological role of LTD in learning and memory, some authors have examined the effects of ethanol exposure on this particular signal. In the present review, I will focus on hippocampal LTD recorded in rodents and the effects of fetal alcohol exposure on this signal. A synthesis of the findings indicates that prenatal ethanol exposure disturbs LTD concurrently with LTP in offspring and that both glutamatergic and γ-aminobutyric acid (GABA neurotransmissions are altered and contribute to LTD disturbances. Although the ultimate mode of action of ethanol on these two transmitter systems is not yet clear, novel suggestions have recently appeared in the literature.

Long term effects of murine postnatal exposure to decabromodiphenyl ether (BDE-209) on learning and memory are dependent upon APOE polymorphism and age

DEFF Research Database (Denmark)

Reverte, Ingrid; Klein, Anders Bue; Domingo, José L

2014-01-01

exposure to BDE-209 induced long term effects in spatial learning, which were dependent upon age, sex and apoE genotype; these effects were more evident in apoE3 mice. BDNF levels were lower in the frontal cortex of apoE4 mice and higher in the hippocampus of exposed mice, independent of the genotype....... The results of the present study provide evidence of long-lasting effects in spatial learning and memory after early exposure to BDE-209. Developmental exposure to this neurotoxicant may contribute to cognitive decline and abnormal aging....... with varied vulnerability for the development of neurodegenerative diseases. On postnatal day 10, transgenic mice of both sexes carrying apoE2, apoE3 and apoE4 were orally exposed to 0, 10 or 30mg/kg of BDE-209. Spatial reference memory was assessed in a Morris Water Maze (MWM) task at 4 and 12months of age...

Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice.

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Camera, Daria; Coleman, Harold A; Parkington, Helena C; Jenkins, Trisha A; Pow, David V; Boase, Natasha; Kumar, Sharad; Poronnik, Philip

2016-04-15

The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4(+/-) mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4(+/+) and Nedd4(+/-) mice in terms of short-term spatial memory in a Y-maze test. Nedd4(+/-) mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes. Copyright © 2016 Elsevier B.V. All rights reserved.

Observation of long term potentiation in papain-based memory devices

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Bag, A.; Hota, Mrinal Kanti; Mallik, Sandipan B.; Maì ti, Chinmay Kumar

2014-01-01

Biological synaptic behavior in terms of long term potentiation has been observed in papain-based (plant protein) memory devices (memristors) for the first time. Improvement in long term potentiation depends on pulse amplitude and width (duration). Continuous/repetitive dc voltage sweep leads to an increase in memristor conductivity leading to a long term memory in the 'learning' processes.

Observation of long term potentiation in papain-based memory devices

KAUST Repository

Bag, A.

2014-06-01

Biological synaptic behavior in terms of long term potentiation has been observed in papain-based (plant protein) memory devices (memristors) for the first time. Improvement in long term potentiation depends on pulse amplitude and width (duration). Continuous/repetitive dc voltage sweep leads to an increase in memristor conductivity leading to a long term memory in the \\'learning\\' processes.

Anisomycin Injection in Area CA3 of the Hippocampus Impairs Both Short-Term and Long-Term Memories of Contextual Fear

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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…

Enhancement of long-term spatial memory in adult rats by the noncompetitive NMDA receptor antagonists, memantine and neramexane.

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Zoladz, Phillip R; Campbell, Adam M; Park, Collin R; Schaefer, Daniela; Danysz, Wojciech; Diamond, David M

2006-10-01

Memantine and neramexane are noncompetitive NMDA receptor antagonists which have been investigated for their promising effects in aiding memory in people with dementia. Memantine is approved for the treatment of Alzheimer's disease, and neramexane is currently under development for this indication. Therefore, the present study provided a comparative assessment of the effects of equimolar doses of memantine and neramexane on spatial (hippocampus-dependent) memory. Adult male rats were given only 3 training trials to learn the location of a hidden platform in a water maze. In control (vehicle-injected) rats, this minimal amount of training produced intact short-term (15 min), but poor long-term (24 h), memory. Pre-training administration of memantine or neramexane produced a dose-dependent enhancement of long-term memory. Pharmacokinetic experiments with equimolar doses of both agents indicated that lower plasma levels of neramexane were more effective than memantine at enhancing memory. The effective doses of both agents in the current study produced plasma levels (and extrapolated brain CSF levels) within a range of activity at NMDA receptors and plasma levels seen in patients with Alzheimer's disease. These findings provide support for the use of neramexane as a pharmacological intervention in the treatment of dementia.

Long term potentiation, but not depression, in interlamellar hippocampus CA1.

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Sun, Duk-Gyu; Kang, Hyeri; Tetteh, Hannah; Su, Junfeng; Lee, Jihwan; Park, Sung-Won; He, Jufang; Jo, Jihoon; Yang, Sungchil; Yang, Sunggu

2018-03-26

Synaptic plasticity in the lamellar CA3 to CA1 circuitry has been extensively studied while interlamellar CA1 to CA1 connections have not yet received much attention. One of our earlier studies demonstrated that axons of CA1 pyramidal neurons project to neighboring CA1 neurons, implicating information transfer along a longitudinal interlamellar network. Still, it remains unclear whether long-term synaptic plasticity is present within this longitudinal CA1 network. Here, we investigate long-term synaptic plasticity between CA1 pyramidal cells, using in vitro and in vivo extracellular recordings and 3D holography glutamate uncaging. We found that the CA1-CA1 network exhibits NMDA receptor-dependent long-term potentiation (LTP) without direction or layer selectivity. By contrast, we find no significant long-term depression (LTD) under various LTD induction protocols. These results implicate unique synaptic properties in the longitudinal projection suggesting that the interlamellar CA1 network could be a promising structure for hippocampus-related information processing and brain diseases.

Iron Loading Selectively Increases Hippocampal Levels of Ubiquitinated Proteins and Impairs Hippocampus-Dependent Memory.

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Figueiredo, Luciana Silva; de Freitas, Betânia Souza; Garcia, Vanessa Athaíde; Dargél, Vinícius Ayub; Köbe, Luiza Machado; Kist, Luiza Wilges; Bogo, Maurício Reis; Schröder, Nadja

2016-11-01

Alterations of brain iron levels have been observed in a number of neurodegenerative disorders. We have previously demonstrated that iron overload in the neonatal period results in severe and persistent memory deficits in the adulthood. Protein degradation mediated by the ubiquitin-proteasome system (UPS) plays a central regulatory role in several cellular processes. Impairment of the UPS has been implicated in the pathogenesis of neurodegenerative disorders. Here, we examined the effects of iron exposure in the neonatal period (12th-14th day of postnatal life) on the expression of proteasome β-1, β-2, and β-5 subunits, and ubiquitinated proteins in brains of 15-day-old rats, to evaluate the immediate effect of the treatment, and in adulthood to assess long-lasting effects. Two different memory types, emotionally motivated conditioning and object recognition were assessed in adult animals. We found that iron administered in the neonatal period impairs both emotionally motivated and recognition memory. Polyubiquitinated protein levels were increased in the hippocampus, but not in the cortex, of adult animals treated with iron. Gene expression of subunits β1 and β5 was affected by age, being higher in the early stages of development in the hippocampus, accompanied by an age-related increase in polyubiquitinated protein levels in adults. In the cortex, gene expression of the three proteasome subunits was significantly higher in adulthood than in the neonatal period. These findings suggest that expression of proteasome subunits and activity are age-dependently regulated. Iron exposure in the neonatal period produces long-lasting harmful effects on the UPS functioning, which may be related with iron-induced memory impairment.

Hippocampus-dependent spatial memory impairment due to molar tooth loss is ameliorated by an enriched environment.

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Kondo, Hiroko; Kurahashi, Minori; Mori, Daisuke; Iinuma, Mitsuo; Tamura, Yasuo; Mizutani, Kenmei; Shimpo, Kan; Sonoda, Shigeru; Azuma, Kagaku; Kubo, Kin-ya

2016-01-01

Teeth are crucial, not only for mastication, but for overall nutrition and general health, including cognitive function. Aged mice with chronic stress due to tooth loss exhibit impaired hippocampus-dependent learning and memory. Exposure to an enriched environment restores the reduced hippocampal function. Here, we explored the effects of an enriched environment on learning deficits and hippocampal morphologic changes in aged senescence-accelerated mouse strain P8 (SAMP8) mice with tooth loss. Eight-month-old male aged SAMP8 mice with molar intact or with molars removed were housed in either a standard environment or enriched environment for 3 weeks. The Morris water maze was performed for spatial memory test. The newborn cell proliferation, survival, and differentiation in the hippocampus were analyzed using 5-Bromodeoxyuridine (BrdU) immunohistochemical method. The hippocampal brain-derived neurotrophic factor (BDNF) levels were also measured. Mice with upper molars removed (molarless) exhibited a significant decline in the proliferation and survival of newborn cells in the dentate gyrus (DG) as well as in hippocampal BDNF levels. In addition, neuronal differentiation of newly generated cells was suppressed and hippocampus-dependent spatial memory was impaired. Exposure of molarless mice to an enriched environment attenuated the reductions in the hippocampal BDNF levels and neuronal differentiation, and partially improved the proliferation and survival of newborn cells, as well as the spatial memory ability. These findings indicated that an enriched environment could ameliorate the hippocampus-dependent spatial memory impairment induced by molar tooth loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

Contributions of Volumetrics of the Hippocampus and Thalamus to Verbal Memory in Temporal Lobe Epilepsy Patients

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Stewart, Christopher C.; Griffith, H. Randall; Okonkwo, Ozioma C.; Martin, Roy C.; Knowlton, Robert K.; Richardson, Elizabeth J.; Hermann, Bruce P.; Seidenberg, Michael

2009-01-01

Recent theories have posited that the hippocampus and thalamus serve distinct, yet related, roles in episodic memory. Whereas the hippocampus has been implicated in long-term memory encoding and storage, the thalamus, as a whole, has been implicated in the selection of items for subsequent encoding and the use of retrieval strategies. However,…

Differential role of calpain-dependent protein cleavage in intermediate and long-term operant memory in Aplysia.

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Lyons, Lisa C; Gardner, Jacob S; Lentsch, Cassidy T; Gandour, Catherine E; Krishnan, Harini C; Noakes, Eric J

2017-01-01

In addition to protein synthesis, protein degradation or protein cleavage may be necessary for intermediate (ITM) and long-term memory (LTM) to remove molecular constraints, facilitate persistent kinase activity and modulate synaptic plasticity. Calpains, a family of conserved calcium dependent cysteine proteases, modulate synaptic function through protein cleavage. We used the marine mollusk Aplysia californica to investigate the in vivo role of calpains during intermediate and long-term operant memory formation using the learning that food is inedible (LFI) paradigm. A single LFI training session, in which the animal associates a specific netted seaweed with the failure to swallow, generates short (30min), intermediate (4-6h) and long-term (24h) memory. Using the calpain inhibitors calpeptin and MDL-28170, we found that ITM requires calpain activity for induction and consolidation similar to the previously reported requirements for persistent protein kinase C activity in intermediate-term LFI memory. The induction of LTM also required calpain activity. In contrast to ITM, calpain activity was not necessary for the molecular consolidation of LTM. Surprisingly, six hours after LFI training we found that calpain activity was necessary for LTM, although this is a time at which neither persistent PKC activity nor protein synthesis is required for the maintenance of long-term LFI memory. These results demonstrate that calpains function in multiple roles in vivo during associative memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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Maher, Pamela; Akaishi, Tatsuhiro; Abe, Kazuho

2006-01-01

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

Physical exercise prevents short and long-term deficits on aversive and recognition memory and attenuates brain oxidative damage induced by maternal deprivation.

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Neves, Ben-Hur; Menezes, Jefferson; Souza, Mauren Assis; Mello-Carpes, Pâmela B

2015-12-01

It is known from previous research that physical exercise prevents long-term memory deficits induced by maternal deprivation in rats. But we could not assume similar effects of physical exercise on short-term memory, as short- and long-term memories are known to result from some different memory consolidation processes. Here we demonstrated that, in addition to long-term memory deficit, the short-term memory deficit resultant from maternal deprivation in object recognition and aversive memory tasks is also prevented by physical exercise. Additionally, one of the mechanisms by which the physical exercise influences the memory processes involves its effects attenuating the oxidative damage in the maternal deprived rats' hippocampus and prefrontal cortex.

GABAergic activities control spike timing- and frequency-dependent long-term depression at hippocampal excitatory synapses

Directory of Open Access Journals (Sweden)

Makoto Nishiyama

2010-06-01

Full Text Available GABAergic interneuronal network activities in the hippocampus control a variety of neural functions, including learning and memory, by regulating θ and γ oscillations. How these GABAergic activities at pre- and post-synaptic sites of hippocampal CA1 pyramidal cells differentially contribute to synaptic function and plasticity during their repetitive pre- and post-synaptic spiking at θ and γ oscillations is largely unknown. We show here that activities mediated by postsynaptic GABAARs and presynaptic GABABRs determine, respectively, the spike timing- and frequency-dependence of activity-induced synaptic modifications at Schaffer collateral-CA1 excitatory synapses. We demonstrate that both feedforward and feedback GABAAR-mediated inhibition in the postsynaptic cell controls the spike timing-dependent long-term depression of excitatory inputs (“e-LTD” at the θ frequency. We also show that feedback postsynaptic inhibition specifically causes e-LTD of inputs that induce small postsynaptic currents (<70 pA with LTP timing, thus enforcing the requirement of cooperativity for induction of long-term potentiation at excitatory inputs (“e-LTP”. Furthermore, under spike-timing protocols that induce e-LTP and e-LTD at excitatory synapses, we observed parallel induction of LTP and LTD at inhibitory inputs (“i-LTP” and “i-LTD” to the same postsynaptic cells. Finally, we show that presynaptic GABABR-mediated inhibition plays a major role in the induction of frequency-dependent e-LTD at α and β frequencies. These observations demonstrate the critical influence of GABAergic interneuronal network activities in regulating the spike timing and frequency dependences of long-term synaptic modifications in the hippocampus.

Calcium/Calmodulin-dependent Protein Kinase II is a Ubiquitous Molecule in Human Long-term Memory Synaptic Plasticity: A Systematic Review

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Ataei, Negar; Sabzghabaee, Ali Mohammad; Movahedian, Ahmad

2015-01-01

Background: Long-term memory is based on synaptic plasticity, a series of biochemical mechanisms include changes in structure and proteins of brain's neurons. In this article, we systematically reviewed the studies that indicate calcium/calmodulin kinase II (CaMKII) is a ubiquitous molecule among different enzymes involved in human long-term memory and the main downstream signaling pathway of long-term memory. Methods: All of the observational, case–control and review studies were considered and evaluated by the search engines PubMed, Cochrane Central Register of Controlled Trials and ScienceDirect Scopus between 1990 and February 2015. We did not carry out meta-analysis. Results: At the first search, it was fined 1015 articles which included “synaptic plasticity” OR “neuronal plasticity” OR “synaptic density” AND memory AND “molecular mechanism” AND “calcium/calmodulin-dependent protein kinase II” OR CaMKII as the keywords. A total of 335 articles were duplicates in the databases and eliminated. A total of 680 title articles were evaluated. Finally, 40 articles were selected as reference. Conclusions: The studies have shown the most important intracellular signal of long-term memory is calcium-dependent signals. Calcium linked calmodulin can activate CaMKII. After receiving information for learning and memory, CaMKII is activated by Glutamate, the most important neurotransmitter for memory-related plasticity. Glutamate activates CaMKII and it plays some important roles in synaptic plasticity modification and long-term memory. PMID:26445635

Nuclear protein phosphatase-1: an epigenetic regulator of fear memory and amygdala long-term potentiation.

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Koshibu, K; Gräff, J; Mansuy, I M

2011-01-26

Complex brain diseases and neurological disorders in human generally result from the disturbance of multiple genes and signaling pathways. These disturbances may derive from mutations, deletions, translocations or rearrangements of specific gene(s). However, over the past years, it has become clear that such disturbances may also derive from alterations in the epigenome affecting several genes simultaneously. Our work recently demonstrated that epigenetic mechanisms in the adult brain are in part regulated by protein phosphatase 1 (PP1), a protein Ser/Thr phosphatase that negatively regulates hippocampus-dependent long-term memory (LTM) and synaptic plasticity. PP1 is abundant in brain structures involved in emotional processing like the amygdala, it may therefore be involved in the regulation of fear memory, a form of memory related to post-traumatic stress disorder (PTSD) in human. Here, we demonstrate that PP1 is a molecular suppressor of fear memory and synaptic plasticity in the amygdala that can control chromatin remodeling in neurons. We show that the selective inhibition of the nuclear pool of PP1 in amygdala neurons significantly alters posttranslational modifications (PTMs) of histones and the expression of several memory-associated genes. These alterations correlate with enhanced fear memory, and with an increase in long-term potentiation (LTP) that is transcription-dependent. Our results underscore the importance of nuclear PP1 in the amygdala as an epigenetic regulator of emotional memory, and the relevance of protein phosphatases as potential targets for therapeutic treatment of brain disorders like PTSD. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Insulin signaling is acutely required for long-term memory in Drosophila.

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Chambers, Daniel B; Androschuk, Alaura; Rosenfelt, Cory; Langer, Steven; Harding, Mark; Bolduc, Francois V

2015-01-01

Memory formation has been shown recently to be dependent on energy status in Drosophila. A well-established energy sensor is the insulin signaling (InS) pathway. Previous studies in various animal models including human have revealed the role of insulin levels in short-term memory but its role in long-term memory remains less clear. We therefore investigated genetically the spatial and temporal role of InS using the olfactory learning and long-term memory model in Drosophila. We found that InS is involved in both learning and memory. InS in the mushroom body is required for learning and long-term memory whereas long-term memory specifically is impaired after InS signaling disruption in the ellipsoid body, where it regulates the level of p70s6k, a downstream target of InS and a marker of protein synthesis. Finally, we show also that InS is acutely required for long-term memory formation in adult flies.

Enhanced Long-Term and Impaired Short-Term Spatial Memory in GluA1 AMPA Receptor Subunit Knockout Mice: Evidence for a Dual-Process Memory Model

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

2009-01-01

The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of…

Combined lesions of hippocampus and subiculum Do not produce deficits in a nonspatial social olfactory memory task.

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Burton, S; Murphy, D; Qureshi, U; Sutton, P; O'Keefe, J

2000-07-15

Rats transmit information to each other about which foods are safe to eat. If a rat smells a food odor on the breath of another rat, it is subsequently more likely to eat that food than an alternative. Work by Galef et al. (1988) has shown that the observer rat forms an association between two olfactory stimuli on the breath of the demonstrator rat that has eaten the food, the food odor and carbon disulphide, which is normally present in the rat breath. Bunsey and Eichenbaum (1995) claimed that the hippocampus/subicular region is required for the long-term retention of this nonspatial form of associative memory on the basis that combined lesions of the hippocampus and subiculum produced a deficit, but lesions of either structure alone did not. We report here a failure to repeat this finding. Rats with either combined lesions of the hippocampus and subiculum or with amygdala lesions were tested on their ability to remember this association either immediately (testing short-term memory) or after a 24 hr delay (testing long-term memory). Neither lesion group exhibited significant memory deficits on this nonspatial associative task at either test interval. In contrast, a deficit was observed on a spatial memory task (forced-choice alternation t-maze) for animals with combined lesions of the hippocampus and subiculum. These results contradict the findings of Bunsey and Eichenbaum (1995) and support the idea that the hippocampus/subicular region is not required for this nonspatial associative memory.

Memory-Guided Attention: Independent Contributions of the Hippocampus and Striatum.

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Goldfarb, Elizabeth V; Chun, Marvin M; Phelps, Elizabeth A

2016-01-20

Memory can strongly influence how attention is deployed in future encounters. Though memory dependent on the medial temporal lobes has been shown to drive attention, how other memory systems could concurrently and comparably enhance attention is less clear. Here, we demonstrate that both reinforcement learning and context memory facilitate attention in a visual search task. Using functional magnetic resonance imaging, we dissociate the mechanisms by which these memories guide attention: trial by trial, the hippocampus (not the striatum) predicted attention benefits from context memory, while the striatum (not the hippocampus) predicted facilitation from rewarded stimulus-response associations. Responses in these regions were also distinctly correlated with individual differences in each type of memory-guided attention. This study provides novel evidence for the role of the striatum in guiding attention, dissociable from hippocampus-dependent context memory.

Spatial, contextual and working memory are not affected by the absence of mossy fiber long-term potentiation and depression

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Hensbroek, R.A.; Kamal, A.; Baars, A.M.; Verhage, M.; Spruijt, B.M.

2003-01-01

The mossy fibers of the hippocampus display NMDA-receptor independent long-term plasticity. A number of studies addressed the role of mossy fiber long-term plasticity in memory, but have provided contrasting results. Here, we have exploited a genetic model, the rab3A null-mutant, which is

Verbal short-term memory span in children: long-term modality dependent effects of intrauterine growth restriction.

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Geva, R; Eshel, R; Leitner, Y; Fattal-Valevski, A; Harel, S

2008-12-01

Recent reports showed that children born with intrauterine growth restriction (IUGR) are at greater risk of experiencing verbal short-term memory span (STM) deficits that may impede their learning capacities at school. It is still unknown whether these deficits are modality dependent. This long-term, prospective design study examined modality-dependent verbal STM functions in children who were diagnosed at birth with IUGR (n = 138) and a control group (n = 64). Their STM skills were evaluated individually at 9 years of age with four conditions of the Visual-Aural Digit Span Test (VADS; Koppitz, 1981): auditory-oral, auditory-written, visuospatial-oral and visuospatial-written. Cognitive competence was evaluated with the short form of the Wechsler Intelligence Scales for Children--revised (WISC-R95; Wechsler, 1998). We found IUGR-related specific auditory-oral STM deficits (p long-term relationship between prenatal aberrant head growth and auditory verbal STM deficits by the end of the first decade of life. Empirical, clinical and educational implications are presented.

Short-term Retention of Relational Memory in Amnesia Revisited: Accurate Performance Depends on Hippocampal Integrity

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Lydia T.S. Yee

2014-01-01

Full Text Available Traditionally, it has been proposed that the hippocampus and adjacent medial temporal lobe cortical structures are selectively critical for long-term declarative memory, which entails memory for inter-item and item-context relationships. Whether the hippocampus might also contribute to short-term retention of relational memory representations has remained controversial. In two experiments, we revisit this question by testing memory for relationships among items embedded in scenes using a standard working memory trial structure in which a sample stimulus is followed by a brief delay and the corresponding test stimulus. In each experimental block, eight trials using different exemplars of the same scene were presented. The exemplars contained the same items but with different spatial relationships among them. By repeating the pictures across trials, any potential contributions of item or scene memory to performance were minimized, and relational memory could be assessed more directly than has been done previously. When test displays were presented, participants indicated whether any of the item-location relationships had changed. Then, regardless of their responses (and whether any item did change its location, participants indicated on a forced-choice test, which item might have moved, guessing if necessary. Amnesic patients were impaired on the change detection test, and were frequently unable to specify the change after having reported correctly that a change had taken place. Comparison participants, by contrast, frequently identified the change even when they failed to report the mismatch, an outcome that speaks to the sensitivity of the change specification measure. These results confirm past reports of hippocampal contributions to short-term retention of relational memory representations, and suggest that the role of the hippocampus in memory has more to do with relational memory requirements than the length of a retention interval.

Long-Term Memory Performance in Adult ADHD.

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Skodzik, Timo; Holling, Heinz; Pedersen, Anya

2017-02-01

Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta-analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented.

Visual working memory buffers information retrieved from visual long-term memory.

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Fukuda, Keisuke; Woodman, Geoffrey F

2017-05-16

Human memory is thought to consist of long-term storage and short-term storage mechanisms, the latter known as working memory. Although it has long been assumed that information retrieved from long-term memory is represented in working memory, we lack neural evidence for this and need neural measures that allow us to watch this retrieval into working memory unfold with high temporal resolution. Here, we show that human electrophysiology can be used to track information as it is brought back into working memory during retrieval from long-term memory. Specifically, we found that the retrieval of information from long-term memory was limited to just a few simple objects' worth of information at once, and elicited a pattern of neurophysiological activity similar to that observed when people encode new information into working memory. Our findings suggest that working memory is where information is buffered when being retrieved from long-term memory and reconcile current theories of memory retrieval with classic notions about the memory mechanisms involved.

Short-term memory and long-term memory are still different.

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Norris, Dennis

2017-09-01

A commonly expressed view is that short-term memory (STM) is nothing more than activated long-term memory. If true, this would overturn a central tenet of cognitive psychology-the idea that there are functionally and neurobiologically distinct short- and long-term stores. Here I present an updated case for a separation between short- and long-term stores, focusing on the computational demands placed on any STM system. STM must support memory for previously unencountered information, the storage of multiple tokens of the same type, and variable binding. None of these can be achieved simply by activating long-term memory. For example, even a simple sequence of digits such as "1, 3, 1" where there are 2 tokens of the digit "1" cannot be stored in the correct order simply by activating the representations of the digits "1" and "3" in LTM. I also review recent neuroimaging data that has been presented as evidence that STM is activated LTM and show that these data are exactly what one would expect to see based on a conventional 2-store view. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

mTORC2 controls actin polymerization required for consolidation of long-term memory

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Huang, Wei; Zhu, Ping Jun; Zhang, Shixing; Zhou, Hongyi; Stoica, Loredana; Galiano, Mauricio; Krnjević, Krešimir; Roman, Gregg; Costa-Mattioli, Mauro

2013-01-01

A major goal of biomedical research has been the identification of molecular mechanisms that can enhance memory. Here we report a novel signaling pathway that regulates the conversion from short- to long-term memory. The mTOR complex 2 (mTORC2), which contains the key regulatory protein Rictor (Rapamycin-Insensitive Companion of mTOR), was discovered only recently, and little is known about its physiological role. We show that conditional deletion of rictor in the postnatal murine forebrain greatly reduces mTORC2 activity and selectively impairs both long-term memory (LTM) and the late (but not the early) phase of hippocampal long-term potentiation (LTP). Actin polymerization is reduced in the hippocampus of mTORC2-deficient mice and its restoration rescues both L-LTP and LTM. More importantly, a compound that selectively promotes mTORC2 activity converts early-LTP into late-LTP and enhances LTM. These findings indicate that mTORC2 could be a novel therapeutic target for the treatment of cognitive dysfunction. PMID:23455608

Neonatal hydrocortisone treatment related to 1H-MRS of the hippocampus and short-term memory at school age in preterm born children.

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Rademaker, Karin J; Rijpert, Maarten; Uiterwaal, Cuno S P M; Lieftink, Arno F; van Bel, Frank; Grobbee, Diederick E; de Vries, Linda S; Groenendaal, Floris

2006-02-01

Animal studies have shown that corticosteroids (dexamethasone) cause neuronal loss in the hippocampus and deficits in short term memory. Proton magnetic resonance spectroscopy can measure brain metabolites in vivo and give an indication of neuronal integrity. We investigated whether prolonged administration of hydrocortisone during the neonatal period for bronchopulmonary dysplasia (BPD) in preterm born children changes the metabolism in the hippocampus, measured at school age. Secondly, we investigated whether hippocampal metabolism and short-term memory and neurodevelopmental outcome are related. In this observational study 37 preterm born children (children were treated with hydrocortisone for BPD (starting dose 5 mg/kg/d tapered over a minimum period of 22 d, median duration 28 d) and 19 never received corticosteroids during the perinatal period. N-acetyl aspartate/ Choline + Creatine/phosphocreatine (NAA/(Cho + Cr)) ratios were determined. A 15-word recall memory test and an IQ measurement were obtained on the same day. Hydrocortisone treated children were younger, lighter and sicker than their nonsteroid treated counterparts. Mean NAA/(Cho + Cr) ratios in the hippocampus were not significantly different in the hydrocortisone group compared with the non-steroid group. Performance on the 15-word memory test and IQ were similar in the two groups. There was no relation between NAA/(Cho + Cr) ratios and memory nor between NAA/(Cho + Cr) ratios and IQ. We conclude that hydrocortisone in the mentioned dose, administered in the neonatal period for BPD, does not appear to have any long-term effects on memory and/or hippocampal metabolism.

Memory integration in amnesia: prior knowledge supports verbal short-term memory.

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Race, Elizabeth; Palombo, Daniela J; Cadden, Margaret; Burke, Keely; Verfaellie, Mieke

2015-04-01

Short-term memory (STM) and long-term memory (LTM) have traditionally been considered cognitively distinct. However, it is known that STM can improve when to-be-remembered information appears in contexts that make contact with prior knowledge, suggesting a more interactive relationship between STM and LTM. The current study investigated whether the ability to leverage LTM in support of STM critically depends on the integrity of the hippocampus. Specifically, we investigated whether the hippocampus differentially supports between-domain versus within-domain STM-LTM integration given prior evidence that the representational domain of the elements being integrated in memory is a critical determinant of whether memory performance depends on the hippocampus. In Experiment 1, we investigated hippocampal contributions to within-domain STM-LTM integration by testing whether immediate verbal recall of words improves in MTL amnesic patients when words are presented in familiar verbal contexts (meaningful sentences) compared to unfamiliar verbal contexts (random word lists). Patients demonstrated a robust sentence superiority effect, whereby verbal STM performance improved in familiar compared to unfamiliar verbal contexts, and the magnitude of this effect did not differ from that in controls. In Experiment 2, we investigated hippocampal contributions to between-domain STM-LTM integration by testing whether immediate verbal recall of digits improves in MTL amnesic patients when digits are presented in a familiar visuospatial context (a typical keypad layout) compared to an unfamiliar visuospatial context (a random keypad layout). Immediate verbal recall improved in both patients and controls when digits were presented in the familiar compared to the unfamiliar keypad array, indicating a preserved ability to integrate activated verbal information with stored visuospatial knowledge. Together, these results demonstrate that immediate verbal recall in amnesia can benefit from two

Memory Reactivation Enables Long-Term Prevention of Interference.

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Herszage, Jasmine; Censor, Nitzan

2017-05-22

The ability of the human brain to successively learn or perform two competing tasks constitutes a major challenge in daily function. Indeed, exposing the brain to two different competing memories within a short temporal offset can induce interference, resulting in deteriorated performance in at least one of the learned memories [1-4]. Although previous studies have investigated online interference and its effects on performance [5-13], whether the human brain can enable long-term prevention of future interference is unknown. To address this question, we utilized the memory reactivation-reconsolidation framework [2, 12] stemming from studies at the synaptic level [14-17], according to which reactivation of a memory enables its update. In a set of experiments, using the motor sequence learning task [18] we report that a unique pairing of reactivating the original memory (right hand) in synchrony with novel memory trials (left hand) prevented future interference between the two memories. Strikingly, these effects were long-term and observed a month following reactivation. Further experiments showed that preventing future interference was not due to practice per se, but rather specifically depended on a limited time window induced by reactivation of the original memory. These results suggest a mechanism according to which memory reactivation enables long-term prevention of interference, possibly by creating an updated memory trace integrating original and novel memories during the reconsolidation time window. The opportunity to induce a long-term preventive effect on memories may enable the utilization of strategies optimizing normal human learning, as well as recovery following neurological insults. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sleep-dependent directional coupling between human neocortex and hippocampus.

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Wagner, Tobias; Axmacher, Nikolai; Lehnertz, Klaus; Elger, Christian E; Fell, Jürgen

2010-02-01

Complex interactions between neocortex and hippocampus are the neural basis of memory formation. Two-step theories of memory formation suggest that initial encoding of novel information depends on the induction of rapid plasticity within the hippocampus, and is followed by a second sleep-dependent step of memory consolidation. These theories predict information flow from the neocortex into the hippocampus during waking state and in the reverse direction during sleep. However, experimental evidence that interactions between hippocampus and neocortex have a predominant direction which reverses during sleep rely on cross-correlation analysis of data from animal experiments and yielded inconsistent results. Here, we investigated directional coupling in intracranial EEG data from human subjects using a phase-modeling approach which is well suited to reveal functional interdependencies in oscillatory data. In general, we observed that the anterior hippocampus predominantly drives nearby and remote brain regions. Surprisingly, however, the influence of neocortical regions on the hippocampus significantly increased during sleep as compared to waking state. These results question the standard model of hippocampal-neocortical interactions and suggest that sleep-dependent consolidation is accomplished by an active retrieval of hippocampal information by the neocortex. Copyright 2009 Elsevier Srl. All rights reserved.

Role of the hippocampus in memory functioning: modern view

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D. O. Assonov

2017-12-01

Full Text Available The purpose of this review was to develop the comprehensive conception of the hippocampus role in the functioning of human memory, based on data obtained by analysis of the latest scientific literature on the topic and make recommendations for further ways of researches in this topic. The scientific literature of the last 5 years on the role of the hippocampus in memory functioning was analyzed. Based on the reviewed literature, we made the next conclusions: the hippocampus is an extremely important for memory structure with various connections for different types of memory; the hippocampus is affected by a variety of substances, most studied now are glucocorticosteroids, whose effect on memory differs depending on the start time of action; the hippocampus volume in mental disorders affecting memory is less than normal, which makes it an important diagnostic criterion; at the moment, various promising methods that can help in the therapy of PTSD, depression, phobias and other disorders associated with memory impairment and based on the knowledge of the hippocampus for the treatment of memory disorders are being developed. Based on these conclusions and data, which were analyzed, we offered the following recommendations: to implement the hippocampal function examination in the diagnostics of mental disorders, which are accompanied by a violation of its work; to use the size of the hippocampus as one of the prognostic factors for the severity of the memory-associated disorders and the therapy progress; to carefully investigate the difference in the effect of various psychotherapies and pharmacotherapies on the hippocampus to determine exactly which of the therapies is the most morphologically reasonable; to find out how significant the decrease in the hippocampal volume is for the memory functioning; to use pathogenetically and morphologically based methods to improve the function of the hippocampus in the treatment of disorders that are

DAT genotype modulates striatal processing and long-term memory for items associated with reward and punishment.

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Wittmann, Bianca C; Tan, Geoffrey C; Lisman, John E; Dolan, Raymond J; Düzel, Emrah

2013-09-01

Previous studies have shown that appetitive motivation enhances episodic memory formation via a network including the substantia nigra/ventral tegmental area (SN/VTA), striatum and hippocampus. This functional magnetic resonance imaging (fMRI) study now contrasted the impact of aversive and appetitive motivation on episodic long-term memory. Cue pictures predicted monetary reward or punishment in alternating experimental blocks. One day later, episodic memory for the cue pictures was tested. We also investigated how the neural processing of appetitive and aversive motivation and episodic memory were modulated by dopaminergic mechanisms. To that end, participants were selected on the basis of their genotype for a variable number of tandem repeat polymorphism of the dopamine transporter (DAT) gene. The resulting groups were carefully matched for the 5-HTTLPR polymorphism of the serotonin transporter gene. Recognition memory for cues from both motivational categories was enhanced in participants homozygous for the 10-repeat allele of the DAT, the functional effects of which are not known yet, but not in heterozygous subjects. In comparison with heterozygous participants, 10-repeat homozygous participants also showed increased striatal activity for anticipation of motivational outcomes compared to neutral outcomes. In a subsequent memory analysis, encoding activity in striatum and hippocampus was found to be higher for later recognized items in 10-repeat homozygotes compared to 9/10-repeat heterozygotes. These findings suggest that processing of appetitive and aversive motivation in the human striatum involve the dopaminergic system and that dopamine plays a role in memory for both types of motivational information. In accordance with animal studies, these data support the idea that encoding of motivational events depends on dopaminergic processes in the hippocampus. © 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

Conversion of short-term to long-term memory in the novel object recognition paradigm.

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Moore, Shannon J; Deshpande, Kaivalya; Stinnett, Gwen S; Seasholtz, Audrey F; Murphy, Geoffrey G

2013-10-01

It is well-known that stress can significantly impact learning; however, whether this effect facilitates or impairs the resultant memory depends on the characteristics of the stressor. Investigation of these dynamics can be confounded by the role of the stressor in motivating performance in a task. Positing a cohesive model of the effect of stress on learning and memory necessitates elucidating the consequences of stressful stimuli independently from task-specific functions. Therefore, the goal of this study was to examine the effect of manipulating a task-independent stressor (elevated light level) on short-term and long-term memory in the novel object recognition paradigm. Short-term memory was elicited in both low light and high light conditions, but long-term memory specifically required high light conditions during the acquisition phase (familiarization trial) and was independent of the light level during retrieval (test trial). Additionally, long-term memory appeared to be independent of stress-mediated glucocorticoid release, as both low and high light produced similar levels of plasma corticosterone, which further did not correlate with subsequent memory performance. Finally, both short-term and long-term memory showed no savings between repeated experiments suggesting that this novel object recognition paradigm may be useful for longitudinal studies, particularly when investigating treatments to stabilize or enhance weak memories in neurodegenerative diseases or during age-related cognitive decline. Copyright © 2013 Elsevier Inc. All rights reserved.

A single episode of high intensity sound inhibits long-term potentiation in the hippocampus of rats.

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de Deus, J L; Cunha, A O S; Terzian, A L; Resstel, L B; Elias, L L K; Antunes-Rodrigues, J; Almeida, S S; Leão, R M

2017-10-26

Exposure to loud sounds has become increasingly common. The most common consequences of loud sound exposure are deafness and tinnitus, but emotional and cognitive problems are also associated with loud sound exposure. Loud sounds can activate the hipothalamic-pituitary-adrenal axis resulting in the secretion of corticosterone, which affects hippocampal synaptic plasticity. Previously we have shown that long-term exposure to short episodes of high intensity sound inhibited hippocampal long-term potentiation (LTP) without affecting spatial learning and memory. Here we aimed to study the impact of short term loud sound exposure on hippocampal synaptic plasticity and function. We found that a single minute of 110 dB sound inhibits hippocampal Schaffer-CA1 LTP for 24 hours. This effect did not occur with an 80-dB sound exposure, was not correlated with corticosterone secretion and was also observed in the perforant-dentate gyrus synapse. We found that despite the deficit in the LTP these animals presented normal spatial learning and memory and fear conditioning. We conclude that a single episode of high-intensity sound impairs hippocampal LTP, without impairing memory and learning. Our results show that the hippocampus is very responsive to loud sounds which can have a potential, but not yet identified, impact on its function.

Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation.

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Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F

2015-02-01

Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

NEREC, an effective brain mapping protocol for combined language and long-term memory functions.

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Perrone-Bertolotti, Marcela; Girard, Cléa; Cousin, Emilie; Vidal, Juan Ricardo; Pichat, Cédric; Kahane, Philippe; Baciu, Monica

2015-12-01

Temporal lobe epilepsy can induce functional plasticity in temporoparietal networks involved in language and long-term memory processing. Previous studies in healthy subjects have revealed the relative difficulty for this network to respond effectively across different experimental designs, as compared to more reactive regions such as frontal lobes. For a protocol to be optimal for clinical use, it has to first show robust effects in a healthy cohort. In this study, we developed a novel experimental paradigm entitled NEREC, which is able to reveal the robust participation of temporoparietal networks in a uniquely combined language and memory task, validated in an fMRI study with healthy subjects. Concretely, NEREC is composed of two runs: (a) an intermixed language-memory task (confrontation naming associated with encoding in nonverbal items, NE) to map language (i.e., word retrieval and lexico-semantic processes) combined with simultaneous long-term verbal memory encoding (NE items named but also explicitly memorized) and (b) a memory retrieval task of items encoded during NE (word recognition, REC) intermixed with new items. Word recognition is based on both perceptual-semantic familiarity (feeling of 'know') and accessing stored memory representations (remembering). In order to maximize the remembering and recruitment of medial temporal lobe structures, we increased REC difficulty by changing the modality of stimulus presentation (from nonverbal during NE to verbal during REC). We report that (a) temporoparietal activation during NE was attributable to both lexico-semantic (language) and memory (episodic encoding and semantic retrieval) processes; that (b) encoding activated the left hippocampus, bilateral fusiform, and bilateral inferior temporal gyri; and that (c) task recognition (recollection) activated the right hippocampus and bilateral but predominant left fusiform gyrus. The novelty of this protocol consists of (a) combining two tasks in one (language

Long-Term Memory Search across the Visual Brain

Directory of Open Access Journals (Sweden)

Milan Fedurco

2012-01-01

Full Text Available Signal transmission from the human retina to visual cortex and connectivity of visual brain areas are relatively well understood. How specific visual perceptions transform into corresponding long-term memories remains unknown. Here, I will review recent Blood Oxygenation Level-Dependent functional Magnetic Resonance Imaging (BOLD fMRI in humans together with molecular biology studies (animal models aiming to understand how the retinal image gets transformed into so-called visual (retinotropic maps. The broken object paradigm has been chosen in order to illustrate the complexity of multisensory perception of simple objects subject to visual —rather than semantic— type of memory encoding. The author explores how amygdala projections to the visual cortex affect the memory formation and proposes the choice of experimental techniques needed to explain our massive visual memory capacity. Maintenance of the visual long-term memories is suggested to require recycling of GluR2-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR and β2-adrenoreceptors at the postsynaptic membrane, which critically depends on the catalytic activity of the N-ethylmaleimide-sensitive factor (NSF and protein kinase PKMζ.

Brief, pre-retrieval stress differentially influences long-term memory depending on sex and corticosteroid response.

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Zoladz, Phillip R; Kalchik, Andrea E; Hoffman, Mackenzie M; Aufdenkampe, Rachael L; Burke, Hanna M; Woelke, Sarah A; Pisansky, Julia M; Talbot, Jeffery N

2014-03-01

Previous work has indicated that stress generally impairs memory retrieval. However, little research has addressed discrepancies that exist in this line of work and the factors that could explain why stress can exert differential effects on retrieval processes. Therefore, we examined the influence of brief, pre-retrieval stress that was administered immediately before testing on long-term memory in males and females. Participants learned a list of 42 words varying in emotional valence and arousal. Following the learning phase, participants were given an immediate free recall test. Twenty-four hours later, participants submerged their non-dominant hand in a bath of ice cold (Stress) or warm (No Stress) water for 3 min. Immediately following this manipulation, participants' memory for the word list was assessed via free recall and recognition tests. We observed no group differences on short-term memory. However, male participants who showed a robust cortisol response to the stress exhibited enhanced long-term recognition memory, while male participants who demonstrated a blunted cortisol response to the stress exhibited impaired long-term recall and recognition memory. These findings suggest that the effects of brief, pre-retrieval stress on long-term memory are sex-specific and mediated by corticosteroid mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

Hippocampal Protein Kinase C Signaling Mediates the Short-Term Memory Impairment Induced by Delta9-Tetrahydrocannabinol.

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Busquets-Garcia, Arnau; Gomis-González, Maria; Salgado-Mendialdúa, Victòria; Galera-López, Lorena; Puighermanal, Emma; Martín-García, Elena; Maldonado, Rafael; Ozaita, Andrés

2018-04-01

Cannabis affects cognitive performance through the activation of the endocannabinoid system, and the molecular mechanisms involved in this process are poorly understood. Using the novel object-recognition memory test in mice, we found that the main psychoactive component of cannabis, delta9-tetrahydrocannabinol (THC), alters short-term object-recognition memory specifically involving protein kinase C (PKC)-dependent signaling. Indeed, the systemic or intra-hippocampal pre-treatment with the PKC inhibitors prevented the short-term, but not the long-term, memory impairment induced by THC. In contrast, systemic pre-treatment with mammalian target of rapamycin complex 1 inhibitors, known to block the amnesic-like effects of THC on long-term memory, did not modify such a short-term cognitive deficit. Immunoblot analysis revealed a transient increase in PKC signaling activity in the hippocampus after THC treatment. Thus, THC administration induced the phosphorylation of a specific Ser residue in the hydrophobic-motif at the C-terminal tail of several PKC isoforms. This significant immunoreactive band that paralleled cognitive performance did not match in size with the major PKC isoforms expressed in the hippocampus except for PKCθ. Moreover, THC transiently enhanced the phosphorylation of the postsynaptic calmodulin-binding protein neurogranin in a PKC dependent manner. These data demonstrate that THC alters short-term object-recognition memory through hippocampal PKC/neurogranin signaling.

Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies.

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Finsterwald, Charles; Alberini, Cristina M

2014-07-01

A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitary-adrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the formation of

Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies

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Finsterwald, Charles; Alberini, Cristina M.

2013-01-01

A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitaryadrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the effects of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the

Neurocomputational account of memory and perception: Thresholded and graded signals in the hippocampus.

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Elfman, Kane W; Aly, Mariam; Yonelinas, Andrew P

2014-12-01

Recent evidence suggests that the hippocampus, a region critical for long-term memory, also supports certain forms of high-level visual perception. A seemingly paradoxical finding is that, unlike the thresholded hippocampal signals associated with memory, the hippocampus produces graded, strength-based signals in perception. This article tests a neurocomputational model of the hippocampus, based on the complementary learning systems framework, to determine if the same model can account for both memory and perception, and whether it produces the appropriate thresholded and strength-based signals in these two types of tasks. The simulations showed that the hippocampus, and most prominently the CA1 subfield, produced graded signals when required to discriminate between highly similar stimuli in a perception task, but generated thresholded patterns of activity in recognition memory. A threshold was observed in recognition memory because pattern completion occurred for only some trials and completely failed to occur for others; conversely, in perception, pattern completion always occurred because of the high degree of item similarity. These results offer a neurocomputational account of the distinct hippocampal signals associated with perception and memory, and are broadly consistent with proposals that CA1 functions as a comparator of expected versus perceived events. We conclude that the hippocampal computations required for high-level perceptual discrimination are congruous with current neurocomputational models that account for recognition memory, and fit neatly into a broader description of the role of the hippocampus for the processing of complex relational information. © 2014 Wiley Periodicals, Inc.

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

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

2010-09-29

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

Long-term associative learning predicts verbal short-term memory performance.

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Jones, Gary; Macken, Bill

2018-02-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting.

A cost of long-term memory in Drosophila

OpenAIRE

Mery, Frederic; Kawecki, Tadeusz J.

2005-01-01

Two distinct forms of consolidated associative memory are known in Drosophila: long-term memory and so-called anesthesia-resistant memory. Long-term memory is more stable, but unlike anesthesia-resistant memory, its formation requires protein synthesis. We show that flies induced to form long-term memory become more susceptible to extreme stress (such as desiccation). In contrast, induction of anesthesia-resistant memory had no detectable effect on desiccation resistance. This finding may hel...

Requirement for nuclear calcium signaling in Drosophila long-term memory.

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Weislogel, Jan-Marek; Bengtson, C Peter; Müller, Michaela K; Hörtzsch, Jan N; Bujard, Martina; Schuster, Christoph M; Bading, Hilmar

2013-05-07

Calcium is used throughout evolution as an intracellular signal transducer. In the mammalian central nervous system, calcium mediates the dialogue between the synapse and the nucleus that is required for transcription-dependent persistent neuronal adaptations. A role for nuclear calcium signaling in similar processes in the invertebrate brain has yet to be investigated. Here, we show by in vivo calcium imaging of adult brain neurons of the fruit fly Drosophila melanogaster, that electrical foot shocks used in olfactory avoidance conditioning evoked transient increases in cytosolic and nuclear calcium concentrations in neurons. These calcium signals were detected in Kenyon cells of the flies' mushroom bodies, which are sites of learning and memory related to smell. Acute blockade of nuclear calcium signaling during conditioning selectively and reversibly abolished the formation of long-term olfactory avoidance memory, whereas short-term, middle-term, or anesthesia-resistant olfactory memory remained unaffected. Thus, nuclear calcium signaling is required in flies for the progression of memories from labile to transcription-dependent long-lasting forms. These results identify nuclear calcium as an evolutionarily conserved signal needed in both invertebrate and vertebrate brains for transcription-dependent memory consolidation.

The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory.

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Cicvaric, Ana; Yang, Jiaye; Krieger, Sigurd; Khan, Deeba; Kim, Eun-Jung; Dominguez-Rodriguez, Manuel; Cabatic, Maureen; Molz, Barbara; Acevedo Aguilar, Juan Pablo; Milicevic, Radoslav; Smani, Tarik; Breuss, Johannes M; Kerjaschki, Dontscho; Pollak, Daniela D; Uhrin, Pavel; Monje, Francisco J

2016-12-01

Podoplanin is a cell-surface glycoprotein constitutively expressed in the brain and implicated in human brain tumorigenesis. The intrinsic function of podoplanin in brain neurons remains however uncharacterized. Using an established podoplanin-knockout mouse model and electrophysiological, biochemical, and behavioral approaches, we investigated the brain neuronal role of podoplanin. Ex-vivo electrophysiology showed that podoplanin deletion impairs dentate gyrus synaptic strengthening. In vivo, podoplanin deletion selectively impaired hippocampus-dependent spatial learning and memory without affecting amygdala-dependent cued fear conditioning. In vitro, neuronal overexpression of podoplanin promoted synaptic activity and neuritic outgrowth whereas podoplanin-deficient neurons exhibited stunted outgrowth and lower levels of p-Ezrin, TrkA, and CREB in response to nerve growth factor (NGF). Surface Plasmon Resonance data further indicated a physical interaction between podoplanin and NGF. This work proposes podoplanin as a novel component of the neuronal machinery underlying neuritogenesis, synaptic plasticity, and hippocampus-dependent memory functions. The existence of a relevant cross-talk between podoplanin and the NGF/TrkA signaling pathway is also for the first time proposed here, thus providing a novel molecular complex as a target for future multidisciplinary studies of the brain function in the physiology and the pathology. Key messages Podoplanin, a protein linked to the promotion of human brain tumors, is required in vivo for proper hippocampus-dependent learning and memory functions. Deletion of podoplanin selectively impairs activity-dependent synaptic strengthening at the neurogenic dentate-gyrus and hampers neuritogenesis and phospho Ezrin, TrkA and CREB protein levels upon NGF stimulation. Surface plasmon resonance data indicates a physical interaction between podoplanin and NGF. On these grounds, a relevant cross-talk between podoplanin and NGF as well

Factors that Determine the Non-Linear Amygdala Influence on Hippocampus-Dependent Memory

OpenAIRE

Akirav, Irit; Richter-Levin, Gal

2006-01-01

Stressful experiences are known to either improve or impair hippocampal-dependent memory tasks and synaptic plasticity. These positive and negative effects of stress on the hippocampus have been largely documented, however little is known about the mechanism involved in the twofold influence of stress on hippocampal functioning and about what factors define an enhancing or inhibitory outcome. We have recently demonstrated that activation of the basolateral amygdala can produce a biphasic effe...

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

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

2018-02-23

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

Sex- and histamine-dependent long-term cognitive effects of methamphetamine exposure

NARCIS (Netherlands)

Acevedo, S.F.; de Esch, I.J.P.; Raber, J.

2007-01-01

As prenatal methamphetamine (MA) exposure results in long-term hippocampus-dependent cognitive deficits, the increased MA use in women of childbearing age is of great concern. As mice are most commonly used in genetic models, we started to study the potential effects of neonatal MA exposure in

The right hippocampus participates in short-term memory maintenance of object-location associations

NARCIS (Netherlands)

Piekema, C.; Kessels, R.P.C.; Mars, R.B.; Petersson, K.M.; Fernandez, G.S.E.

2006-01-01

Doubts have been cast on the strict dissociation between short- and long-term memory systems. Specifically, several neuroimaging studies have shown that the medial temporal lobe, a region almost invariably associated with long-term memory, is involved in active short-term memory maintenance.

The right hippocampus participates in short-term memory maintenance of object-location associations.

NARCIS (Netherlands)

Piekema, C.; Kessels, R.P.C.; Mars, R.B.; Petersson, K.M.; Fernandez, G.S.E.

2006-01-01

Doubts have been cast on the strict dissociation between short- and long-term memory systems. Specifically, several neuroimaging studies have shown that the medial temporal lobe, a region almost invariably associated with long-term memory, is involved in active short-term memory maintenance.

Stress within a Restricted Time Window Selectively Affects the Persistence of Long-Term Memory

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Fang, Qin; Chai, Ning; Zhao, Li-Yan; Xue, Yan-Xue; Luo, Yi-Xiao; Jian, Min; Han, Ying; Shi, Hai-Shui; Lu, Lin; Wu, Ping; Wang, Ji-Shi

2013-01-01

The effects of stress on emotional memory are distinct and depend on the stages of memory. Memory undergoes consolidation and reconsolidation after acquisition and retrieval, respectively. Stress facilitates the consolidation but disrupts the reconsolidation of emotional memory. Previous research on the effects of stress on memory have focused on long-term memory (LTM) formation (tested 24 h later), but the effects of stress on the persistence of LTM (tested at least 1 week later) are unclear. Recent findings indicated that the persistence of LTM requires late-phase protein synthesis in the dorsal hippocampus. The present study investigated the effect of stress (i.e., cold water stress) during the late phase after the acquisition and retrieval of contextual fear memory in rats. We found that stress and corticosterone administration during the late phase (12 h) after acquisition, referred to as late consolidation, selectively enhanced the persistence of LTM, whereas stress during the late phase (12 h) after retrieval, referred to as late reconsolidation, selectively disrupted the restabilized persistence of LTM. Moreover, the effects of stress on the persistence of LTM were blocked by the corticosterone synthesis inhibitor metyrapone, which was administered before stress, suggesting that the glucocorticoid system is involved in the effects of stress on the persistence of LTM. We conclude that stress within a restricted time window after acquisition or retrieval selectively affects the persistence of LTM and depends on the glucocorticoid system. PMID:23544051

Visual long-term memory for spatial frequency?

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Lages, Martin; Paul, Aileen

2006-06-01

It has been suggested that a visual long-term memory based on a sensory representation of the stimulus accounts for discrimination performance when the reference and the test stimuli are separated in time. Decision processes involved in setting response criteria, however, may also contribute to discrimination performance. In the present study, it is shown that under proper control, spatial frequency discrimination thresholds from a group of observers, each performing on a single trial, are significantly higher for a 2-h than for a 5-sec retention interval, whereas thresholds from individual observers performing in repeated trials with a 2-h retention interval are considerably lower. The results suggest that discrimination performance may depend on the retention of task-relevant information, such as a response criterion, rather than on visual memory of the stimulus. It is concluded that it is risky to postulate a high-fidelity long-term visual memory for spatial frequency on the basis of psychophysical group discrimination thresholds.

Mechanisms of translation control underlying long-lasting synaptic plasticity and the consolidation of long-term memory.

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Santini, Emanuela; Huynh, Thu N; Klann, Eric

2014-01-01

The complexity of memory formation and its persistence is a phenomenon that has been studied intensely for centuries. Memory exists in many forms and is stored in various brain regions. Generally speaking, memories are reorganized into broadly distributed cortical networks over time through systems level consolidation. At the cellular level, storage of information is believed to initially occur via altered synaptic strength by processes such as long-term potentiation. New protein synthesis is required for long-lasting synaptic plasticity as well as for the formation of long-term memory. The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of cap-dependent protein synthesis and is required for numerous forms of long-lasting synaptic plasticity and long-term memory. As such, the study of mTORC1 and protein factors that control translation initiation and elongation has enhanced our understanding of how the process of protein synthesis is regulated during memory formation. Herein we discuss the molecular mechanisms that regulate protein synthesis as well as pharmacological and genetic manipulations that demonstrate the requirement for proper translational control in long-lasting synaptic plasticity and long-term memory formation. © 2014 Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Christian Tetzlaff

2013-10-01

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

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

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

2013-10-01

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

Musical and Verbal Memory in Alzheimer's Disease: A Study of Long-Term and Short-Term Memory

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Menard, Marie-Claude; Belleville, Sylvie

2009-01-01

Musical memory was tested in Alzheimer patients and in healthy older adults using long-term and short-term memory tasks. Long-term memory (LTM) was tested with a recognition procedure using unfamiliar melodies. Short-term memory (STM) was evaluated with same/different judgment tasks on short series of notes. Musical memory was compared to verbal…

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

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

2017-03-29

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

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

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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.

Hippocampal long term memory: effect of the cholinergic system on local protein synthesis.

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Lana, Daniele; Cerbai, Francesca; Di Russo, Jacopo; Boscaro, Francesca; Giannetti, Ambra; Petkova-Kirova, Polina; Pugliese, Anna Maria; Giovannini, Maria Grazia

2013-11-01

The present study was aimed at establishing a link between the cholinergic system and the pathway of mTOR and its downstream effector p70S6K, likely actors in long term memory encoding. We performed in vivo behavioral experiments using the step down inhibitory avoidance test (IA) in adult Wistar rats to evaluate memory formation under different conditions, and immunohistochemistry on hippocampal slices to evaluate the level and the time-course of mTOR and p70S6K activation. We also examined the effect of RAPA, inhibitor of mTORC1 formation, and of the acetylcholine (ACh) muscarinic receptor antagonist scopolamine (SCOP) or ACh nicotinic receptor antagonist mecamylamine (MECA) on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition test was performed 30 min after i.c.v. injection of RAPA, a time sufficient for the drug to diffuse to CA1 pyramidal neurons, as demonstrated by MALDI-TOF-TOF imaging. Recall test was performed 1 h, 4 h or 24 h after acquisition. To confirm our results we performed in vitro experiments on live hippocampal slices: we evaluated whether stimulation of the cholinergic system with the cholinergic receptor agonist carbachol (CCh) activated the mTOR pathway and whether the administration of the above-mentioned antagonists together with CCh could revert this activation. We found that (1) mTOR and p70S6K activation in the hippocampus were involved in long term memory formation; (2) RAPA administration caused inhibition of mTOR activation at 1 h and 4 h and of p70S6K activation at 4 h, and long term memory impairment at 24 h after acquisition; (3) scopolamine treatment caused short but not long term memory impairment with an early increase of mTOR/p70S6K activation at 1 h followed by stabilization at longer times; (4) mecamylamine plus scopolamine treatment caused short term memory impairment at 1 h and 4 h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1 h and 4 h; (5

Modulation of working memory updating: Does long-term memory lexical association matter?

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Artuso, Caterina; Palladino, Paola

2016-02-01

The aim of the present study was to investigate how working memory updating for verbal material is modulated by enduring properties of long-term memory. Two coexisting perspectives that account for the relation between long-term representation and short-term performance were addressed. First, evidence suggests that performance is more closely linked to lexical properties, that is, co-occurrences within the language. Conversely, other evidence suggests that performance is linked more to long-term representations which do not entail lexical/linguistic representations. Our aim was to investigate how these two kinds of long-term memory associations (i.e., lexical or nonlexical) modulate ongoing working memory activity. Therefore, we manipulated (between participants) the strength of the association in letters based on either frequency of co-occurrences (lexical) or contiguity along the sequence of the alphabet (nonlexical). Results showed a cost in working memory updating for strongly lexically associated stimuli only. Our findings advance knowledge of how lexical long-term memory associations between consonants affect working memory updating and, in turn, contribute to the study of factors which impact the updating process across memory systems.

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

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Kutlu, Munir Gunes

2016-01-01

It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. PMID:27634143

Fast Weight Long Short-Term Memory

OpenAIRE

Keller, T. Anderson; Sridhar, Sharath Nittur; Wang, Xin

2018-01-01

Associative memory using fast weights is a short-term memory mechanism that substantially improves the memory capacity and time scale of recurrent neural networks (RNNs). As recent studies introduced fast weights only to regular RNNs, it is unknown whether fast weight memory is beneficial to gated RNNs. In this work, we report a significant synergy between long short-term memory (LSTM) networks and fast weight associative memories. We show that this combination, in learning associative retrie...

Differences in the verbal fluency, working memory and executive functions in alcoholics: Short-term vs. long-term abstainers.

Science.gov (United States)

Nowakowska-Domagała, Katarzyna; Jabłkowska-Górecka, Karolina; Mokros, Łukasz; Koprowicz, Jacek; Pietras, Tadeusz

2017-03-01

The aim of the study was to assess differences in verbal fluency, working memory and executive functions in two subgroups of alcohol-dependent patients, those undergoing short-term abstinence (STA) and those undergoing long-term abstinence (LTA), and to compare the level of cognitive functions in patients after long-term abstinence with healthy subjects. The study group consisted of 106 alcohol-dependent patients (53 immediately after drinking at least 3 days and 53 after at least one-year abstinence). The control group comprised 53 subjects, whose age, sex and education levels matched those of the patients in the experimental group. The dependence intensity was assessed using SADD and MAST scales. The neuropsychological assessment was based on the FAS Test, Stroop Test and TMT A&B Test. The results obtained for alcohol-dependent patients revealed significant disturbances of cognitive functions. Such results indicate the presence of severe frontal cerebral cortex dysfunctions. Frontal cortex dysfunctions affecting the verbal fluency and working memory subsystems and the executive functions also persisted during long-term abstinence periods. No significant correlations between the duration of dependence, quantity of alcohol consumed and efficiency of the working memory and executive functions were observed in alcohol-dependent subjects after short-term or long-term abstinence. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

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Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

2016-12-01

Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke–Korsakoff syndrome

Science.gov (United States)

Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

2016-01-01

Patients with severe Wernicke–Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation. PMID:27576603

Protein Phosphatase 1-Dependent Transcriptional Programs for Long-Term Memory and Plasticity

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Graff, Johannes; Koshibu, Kyoko; Jouvenceau, Anne; Dutar, Patrick; Mansuy, Isabelle M.

2010-01-01

Gene transcription is essential for the establishment and the maintenance of long-term memory (LTM) and for long-lasting forms of synaptic plasticity. The molecular mechanisms that control gene transcription in neuronal cells are complex and recruit multiple signaling pathways in the cytoplasm and the nucleus. Protein kinases (PKs) and…

A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus.

Science.gov (United States)

Hunter, B E; de Fiebre, C M; Papke, R L; Kem, W R; Meyer, E M

1994-02-28

Long-term potentiation (LTP) can be modulated by a number of neurotransmitter receptors including muscarinic and GABAergic receptor types. We have found that a novel nicotinic agonist, 2,4-dimethoxybenzylidene anabaseine (DMXB), facilitated the induction of LTP in the hippocampus in a dose-dependent and mecamylamine-sensitive manner. DMXB displaced high affinity nicotinic [125I]alpha-bungarotoxin and [3H]acetylcholine binding in rat brain. Xenopus oocyte studies demonstrated that DMXB has agonist activity at alpha 7 but not alpha 4/beta 2 nicotinic receptor subtypes. These results indicated that DMXB is a novel nicotinic agonist with apparent specificity for the alpha 7/alpha-bungarotoxin nicotinic receptor subtype and indicate that nicotinic receptor activation is capable of modulating the induction of long-term potentiation.

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

Science.gov (United States)

White, André O.; Wood, Marcelo A.

2013-01-01

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

What are the differences between long-term, short-term, and working memory?

OpenAIRE

Cowan, Nelson

2008-01-01

In the recent literature there has been considerable confusion about the three types of memory: long-term, short-term, and working memory. This chapter strives to reduce that confusion and makes up-to-date assessments of these types of memory. Long- and short-term memory could differ in two fundamental ways, with only short-term memory demonstrating (1) temporal decay and (2) chunk capacity limits. Both properties of short-term memory are still controversial but the current literature is rath...

PKA increases in the olfactory bulb act as unconditioned stimuli and provide evidence for parallel memory systems: pairing odor with increased PKA creates intermediate- and long-term, but not short-term, memories.

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Grimes, Matthew T; Harley, Carolyn W; Darby-King, Andrea; McLean, John H

2012-02-21

Neonatal odor-preference memory in rat pups is a well-defined associative mammalian memory model dependent on cAMP. Previous work from this laboratory demonstrates three phases of neonatal odor-preference memory: short-term (translation-independent), intermediate-term (translation-dependent), and long-term (transcription- and translation-dependent). Here, we use neonatal odor-preference learning to explore the role of olfactory bulb PKA in these three phases of mammalian memory. PKA activity increased normally in learning animals 10 min after a single training trial. Inhibition of PKA by Rp-cAMPs blocked intermediate-term and long-term memory, with no effect on short-term memory. PKA inhibition also prevented learning-associated CREB phosphorylation, a transcription factor implicated in long-term memory. When long-term memory was rescued through increased β-adrenoceptor activation, CREB phosphorylation was restored. Intermediate-term and long-term, but not short-term odor-preference memories were generated by pairing odor with direct PKA activation using intrabulbar Sp-cAMPs, which bypasses β-adrenoceptor activation. Higher levels of Sp-cAMPs enhanced memory by extending normal 24-h retention to 48-72 h. These results suggest that increased bulbar PKA is necessary and sufficient for the induction of intermediate-term and long-term odor-preference memory, and suggest that PKA activation levels also modulate memory duration. However, short-term memory appears to use molecular mechanisms other than the PKA/CREB pathway. These mechanisms, which are also recruited by β-adrenoceptor activation, must operate in parallel with PKA activation.

Cdk7 Is Required for Activity-Dependent Neuronal Gene Expression, Long-Lasting Synaptic Plasticity and Long-Term Memory

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Guiqin He

2017-11-01

Full Text Available In the brain, de novo gene expression driven by learning-associated neuronal activities is critical for the formation of long-term memories. However, the signaling machinery mediating neuronal activity-induced gene expression, especially the rapid transcription of immediate-early genes (IEGs remains unclear. Cyclin-dependent kinases (Cdks are a family of serine/threonine kinases that have been firmly established as key regulators of transcription processes underling coordinated cell cycle entry and sequential progression in nearly all types of proliferative cells. Cdk7 is a subunit of transcriptional initiation factor II-H (TFIIH and the only known Cdk-activating kinase (CAK in metazoans. Recent studies using a novel Cdk7 specific covalent inhibitor, THZ1, revealed important roles of Cdk7 in transcription regulation in cancer cells. However, whether Cdk7 plays a role in the regulation of transcription in neurons remains unknown. In this study, we present evidence demonstrating that, in post-mitotic neurons, Cdk7 activity is positively correlated with neuronal activities in cultured primary neurons, acute hippocampal slices and in the brain. Cdk7 inhibition by THZ1 significantly suppressed mRNA levels of IEGs, selectively impaired long-lasting synaptic plasticity induced by 4 trains of high frequency stimulation (HFS and prevented the formation of long-term memories.

On the relationship between short- and long-term memory

DEFF Research Database (Denmark)

Sørensen, Thomas Alrik

James (1890) divided memory into separate stores; primary and secondary – or short-term and long-term memory. The interaction between the two stores often assumes that information initially is represented in volatile short-term store before entering and consolidating in the more durable long-term......, accepted). Counter to popular beliefs this suggest that long-term memory precedes short-term memory and not vice versa....... memory system (e.g. Atkinson & Shiffrin, 1968). Short-term memory seems to provide a surprising processing bottleneck where only a very limited amount of information can be represented at any given moment (Miller, 1956; Cowan, 2001). A number of studies have investigated the nature of this processing...

A Protein Synthesis and Nitric Oxide-Dependent Presynaptic Enhancement in Persistent Forms of Long-Term Potentiation

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Johnstone, Victoria P. A.; Raymond, Clarke R.

2011-01-01

Long-term potentiation (LTP) is an important process underlying learning and memory in the brain. At CA3-CA1 synapses in the hippocampus, three discrete forms of LTP (LTP1, 2, and 3) can be differentiated on the basis of maintenance and induction mechanisms. However, the relative roles of pre- and post-synaptic expression mechanisms in LTP1, 2,…

Iron deficiency in infancy and neurocognitive functioning at 19 years: evidence of long-term deficits in executive function and recognition memory.

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Lukowski, Angela F; Koss, Marlene; Burden, Matthew J; Jonides, John; Nelson, Charles A; Kaciroti, Niko; Jimenez, Elias; Lozoff, Betsy

2010-04-01

Iron deficiency in infancy negatively impacts a variety of neurodevelopmental processes at the time of nutrient insufficiency, with persistent central nervous system alterations and deficits in behavioral functioning, despite iron therapy. In rodent models, early iron deficiency impairs the hippocampus and the dopamine system. We examined the possibility that young adults who had experienced chronic, severe, iron deficiency as infants would exhibit deficits on neurocognitive tests with documented frontostriatal (Trail Making Test, Intra-/Extra-dimensional Shift, Stockings of Cambridge, Spatial Working Memory, Rapid Visual Information Processing) and hippocampal specificity (Pattern Recognition Memory, Spatial Recognition Memory). Participants with chronic, severe iron deficiency in infancy performed less well on frontostriatal-mediated executive functions, including inhibitory control, set-shifting, and planning. Participants also exhibited impairment on a hippocampus-based recognition memory task. We suggest that these deficits may result from the long-term effects of early iron deficiency on the dopamine system, the hippocampus, and their interaction.

Distinct neural correlates of associative working memory and long-term memory encoding in the medial temporal lobe.

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Bergmann, Heiko C; Rijpkema, Mark; Fernández, Guillén; Kessels, Roy P C

2012-11-01

Increasing evidence suggests a role for the hippocampus not only in long-term memory (LTM) but also in relational working memory (WM) processes, challenging the view of the hippocampus as being solely involved in episodic LTM. However, hippocampal involvement reported in some neuroimaging studies using "classical" WM tasks may at least partly reflect incidental LTM encoding. To disentangle WM processing and LTM formation we administered a delayed-match-to-sample associative WM task in an event-related fMRI study design. Each trial of the WM task consisted of four pairs of faces and houses, which had to be maintained during a delay of 10 s. This was followed by a probe phase consisting of three consecutively presented pairs; for each pair participants were to indicate whether it matched one of the pairs of the encoding phase. After scanning, an unexpected recognition-memory (LTM) task was administered. Brain activity during encoding was analyzed based on WM and LTM performance. Hence, encoding-related activity predicting WM success in the absence of successful LTM formation could be isolated. Furthermore, regions critical for successful LTM formation for pairs previously correctly processed in WM were analyzed. Results showed that the left parahippocampal gyrus including the fusiform gyrus predicted subsequent accuracy on WM decisions. The right anterior hippocampus and left inferior frontal gyrus, in contrast, predicted successful LTM for pairs that were previously correctly classified in the WM task. Our results suggest that brain regions associated with higher-level visuo-perceptual processing are involved in successful associative WM encoding, whereas the anterior hippocampus and left inferior frontal gyrus are involved in successful LTM formation during incidental encoding. Copyright © 2012 Elsevier Inc. All rights reserved.

Long-term memory, sleep, and the spacing effect.

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Bell, Matthew C; Kawadri, Nader; Simone, Patricia M; Wiseheart, Melody

2014-01-01

Many studies have shown that memory is enhanced when study sessions are spaced apart rather than massed. This spacing effect has been shown to have a lasting benefit to long-term memory when the study phase session follows the encoding session by 24 hours. Using a spacing paradigm we examined the impact of sleep and spacing gaps on long-term declarative memory for Swahili-English word pairs by including four spacing delay gaps (massed, 12 hours same-day, 12 hours overnight, and 24 hours). Results showed that a 12-hour spacing gap that includes sleep promotes long-term memory retention similar to the 24-hour gap. The findings support the importance of sleep to the long-term benefit of the spacing effect.

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction.

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Kutlu, Munir Gunes; Gould, Thomas J

2016-10-01

It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. © 2016 Kutlu and Gould; Published by Cold Spring Harbor Laboratory Press.

Transcriptional regulation of long-term memory in the marine snail Aplysia

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Lee Yong-Seok

2008-06-01

Full Text Available Abstract Whereas the induction of short-term memory involves only covalent modifications of constitutively expressed preexisting proteins, the formation of long-term memory requires gene expression, new RNA, and new protein synthesis. On the cellular level, transcriptional regulation is thought to be the starting point for a series of molecular steps necessary for both the initiation and maintenance of long-term synaptic facilitation (LTF. The core molecular features of transcriptional regulation involved in the long-term process are evolutionally conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by the cyclic AMP response element binding protein (CREB acting in conjunction with different combinations of transcriptional factors is critical for the expression of many forms of long-term memory. In the marine snail Aplysia, the molecular mechanisms that underlie the storage of long-term memory have been extensively studied in the monosynaptic connections between identified sensory neuron and motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of serotonin (5-HT, a modulatory transmitter released by tail shocks, produces a transient facilitation mediated by the cAMP-dependent protein kinase leading to covalent modifications in the sensory neurons that results in an enhancement of transmitter release and a strengthening of synaptic connections lasting minutes. By contrast, repeated pulses of 5-hydroxytryptamine (5-HT induce a transcription- and translation-dependent long-term facilitation (LTF lasting more than 24 h and trigger the activation of a family of transcription factors in the presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition, we have recently identified novel transcription factors that modulate the expression of ApC/EBP and also are critically involved in LTF. In this review, we examine the roles of these transcription factors during consolidation of LTF induced

Transcriptional regulation of long-term memory in the marine snail Aplysia.

Science.gov (United States)

Lee, Yong-Seok; Bailey, Craig H; Kandel, Eric R; Kaang, Bong-Kiun

2008-06-17

Whereas the induction of short-term memory involves only covalent modifications of constitutively expressed preexisting proteins, the formation of long-term memory requires gene expression, new RNA, and new protein synthesis. On the cellular level, transcriptional regulation is thought to be the starting point for a series of molecular steps necessary for both the initiation and maintenance of long-term synaptic facilitation (LTF). The core molecular features of transcriptional regulation involved in the long-term process are evolutionally conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by the cyclic AMP response element binding protein (CREB) acting in conjunction with different combinations of transcriptional factors is critical for the expression of many forms of long-term memory. In the marine snail Aplysia, the molecular mechanisms that underlie the storage of long-term memory have been extensively studied in the monosynaptic connections between identified sensory neuron and motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of serotonin (5-HT), a modulatory transmitter released by tail shocks, produces a transient facilitation mediated by the cAMP-dependent protein kinase leading to covalent modifications in the sensory neurons that results in an enhancement of transmitter release and a strengthening of synaptic connections lasting minutes. By contrast, repeated pulses of 5-hydroxytryptamine (5-HT) induce a transcription- and translation-dependent long-term facilitation (LTF) lasting more than 24 h and trigger the activation of a family of transcription factors in the presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition, we have recently identified novel transcription factors that modulate the expression of ApC/EBP and also are critically involved in LTF. In this review, we examine the roles of these transcription factors during consolidation of LTF induced by different

Long-term pitch memory for music recordings is related to auditory working memory precision.

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Van Hedger, Stephen C; Heald, Shannon Lm; Nusbaum, Howard C

2018-04-01

Most individuals have reliable long-term memories for the pitch of familiar music recordings. This pitch memory (1) appears to be normally distributed in the population, (2) does not depend on explicit musical training and (3) only seems to be weakly related to differences in listening frequency estimates. The present experiment was designed to assess whether individual differences in auditory working memory could explain variance in long-term pitch memory for music recordings. In Experiment 1, participants first completed a musical note adjustment task that has been previously used to assess working memory of musical pitch. Afterward, participants were asked to judge the pitch of well-known music recordings, which either had or had not been shifted in pitch. We found that performance on the pitch working memory task was significantly related to performance in the pitch memory task using well-known recordings, even when controlling for overall musical experience and familiarity with each recording. In Experiment 2, we replicated these findings in a separate group of participants while additionally controlling for fluid intelligence and non-pitch-based components of auditory working memory. In Experiment 3, we demonstrated that participants could not accurately judge the pitch of unfamiliar recordings, suggesting that our method of pitch shifting did not result in unwanted acoustic cues that could have aided participants in Experiments 1 and 2. These results, taken together, suggest that the ability to maintain pitch information in working memory might lead to more accurate long-term pitch memory.

Accessing forgotten memory traces from long-term memory via visual movements

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Estela eCamara

2014-11-01

Full Text Available Because memory retrieval often requires overt responses, it is difficult to determine to what extend forgetting occurs as a problem in explicit accessing of long-term memory traces. In this study, we used eye-tracking measures in combination with a behavioural task that favoured high forgetting rates to investigate the existence of memory traces from long-term memory in spite of failure in accessing them consciously. In 2 experiments, participants were encouraged to encode a large set of sound-picture-location associations. In a later test, sounds were presented and participants were instructed to visually scan, before a verbal memory report, for the correct location of the associated pictures in an empty screen. We found the reactivation of associated memories by sound cues at test biased oculomotor behaviour towards locations congruent with memory representations, even when participants failed to consciously provide a memory report of it. These findings reveal the emergence of a memory-guided behaviour that can be used to map internal representations of forgotten memories from long-term memory.

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

Science.gov (United States)

White, André O; Wood, Marcelo A

2014-07-01

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

Retrosplenial Cortex and Long-Term Memory: Molecules to Behavior

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Travis P. Todd

2015-01-01

Full Text Available The retrosplenial cortex (RSC is reciprocally connected with the hippocampus and various parahippocampal cortical regions, suggesting that RSC is well-positioned to contribute to hippocampal-dependent memory. Consistent with this, substantial behavioral evidence indicates that RSC is essential for consolidating and/or retrieving contextual and spatial memories. In addition, there is growing evidence that RSC neurons undergo activity-dependent plastic changes during memory formation and retrieval. In this paper we review both the behavioral and cellular/molecular data and posit that the RSC has a particularly important role in the storage and retrieval of spatial and contextual memories perhaps due its involvement in binding together multiple cues in the environment. We identify remaining questions and avenues for future research that take advantage of emerging methods to selectively manipulate RSC neurons both spatially and temporally and to image the RSC in awake, behaving animals.

Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress.

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Maras, P M; Molet, J; Chen, Y; Rice, C; Ji, S G; Solodkin, A; Baram, T Z

2014-07-01

The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress.

Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress

Science.gov (United States)

Maras, P M; Molet, J; Chen, Y; Rice, C; Ji, S G; Solodkin, A; Baram, T Z

2014-01-01

The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress. PMID:24589888

Long-term associative learning predicts verbal short-term memory performance

OpenAIRE

Jones, Gary; Macken, Bill

2017-01-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term...

Long-term memory for instrumental responses does not undergo protein synthesis-dependent reconsolidation upon retrieval.

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Hernandez, Pepe J; Kelley, Ann E

2004-01-01

Recent evidence indicates that certain forms of memory, upon recall, may return to a labile state requiring the synthesis of new proteins in order to preserve or reconsolidate the original memory trace. While the initial consolidation of "instrumental memories" has been shown to require de novo protein synthesis in the nucleus accumbens, it is not known whether memories of this type undergo protein synthesis-dependent reconsolidation. Here we show that low doses of the protein synthesis inhibitor anisomycin (ANI; 5 or 20 mg/kg) administered systemically in rats immediately after recall of a lever-pressing task potently impaired performance on the following daily test sessions. We determined that the nature of this impairment was attributable to conditioned taste aversion (CTA) to the sugar reinforcer used in the task rather than to mnemonic or motoric impairments. However, by substituting a novel flavored reinforcer (chocolate pellets) prior to the administration of doses of ANI (150 or 210 mg/kg) previously shown to cause amnesia, a strong CTA to chocolate was induced sparing any aversion to sugar. Importantly, when sugar was reintroduced on the following session, we found that memory for the task was not significantly affected by ANI. Thus, these data suggest that memory for a well-learned instrumental response does not require protein synthesis-dependent reconsolidation as a means of long-term maintenance.

Developmental Dyslexia and Explicit Long-Term Memory

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Menghini, Deny; Carlesimo, Giovanni Augusto; Marotta, Luigi; Finzi, Alessandra; Vicari, Stefano

2010-01-01

The reduced verbal long-term memory capacities often reported in dyslexics are generally interpreted as a consequence of their deficit in phonological coding. The present study was aimed at evaluating whether the learning deficit exhibited by dyslexics was restricted only to the verbal component of the long-term memory abilities or also involved…

7,8-dihydroxyflavone, a TrkB receptor agonist, blocks long-term spatial memory impairment caused by immobilization stress in rats.

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Andero, Raül; Daviu, Núria; Escorihuela, Rosa Maria; Nadal, Roser; Armario, Antonio

2012-03-01

Post-traumatic stress disorder (PTSD) patients show cognitive deficits, but it is unclear whether these are a consequence of the pathology or a pre-existing factor of vulnerability to PTSD. Animal models may help to demonstrate whether or not exposure to certain stressors can actually induce long-lasting (LL; days) impairment of hippocampus-dependent memory tasks and to characterize neurobiological mechanisms. Adult male rats were exposed to 2-h immobilization on boards (IMO), a severe stressor, and spatial learning in the Morris water maze (MWM) was studied days later. Exposure to IMO did not modify learning or short-term memory in the MWM when learning started 3 or 9 days after IMO, but stressed rats did show impaired long-term memory at both times, in accordance with the severity of the stressor. New treatments to prevent PTSD symptoms are needed. Thus, considering the potential protective role of brain-derived neurotrophic factor (BDNF) on hippocampal function, 7,8-dihydroxyflavone (7,8-DHF), a recently characterized agonist of the BDNF receptor TrkB, was given before or after IMO in additional experiments. Again, exposure to IMO resulted in LL deficit in long-term memory, and such impairment was prevented by the administration of 7,8-DHF either 2 h prior IMO or 8 h after the termination of IMO. The finding that IMO-induced impairment of spatial memory was prevented by pharmacological potentiation of TrkB pathway with 7,8-DHF even when the drug was given 8 h after IMO suggests that IMO-induced impairment is likely to be a LL process that is strongly dependent on the integrity of the BDNF-TrkB system and is susceptible to poststress therapeutic interventions. 7,8-DHF may represent a new therapeutic approach for early treatment of subjects who have suffered traumatic experiences. Copyright © 2010 Wiley Periodicals, Inc.

Acute predator stress impairs the consolidation and retrieval of hippocampus-dependent memory in male and female rats.

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Park, Collin R; Zoladz, Phillip R; Conrad, Cheryl D; Fleshner, Monika; Diamond, David M

2008-04-01

We have studied the effects of an acute predator stress experience on spatial learning and memory in adult male and female Sprague-Dawley rats. All rats were trained to learn the location of a hidden escape platform in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. In the control (non-stress) condition, female rats were superior to the males in the accuracy and consistency of their spatial memory performance tested over multiple days of training. In the stress condition, rats were exposed to the cat for 30 min immediately before or after learning, or before the 24-h memory test. Predator stress dramatically increased corticosterone levels in males and females, with females exhibiting greater baseline and stress-evoked responses than males. Despite these sex differences in the overall magnitudes of corticosterone levels, there were significant sex-independent correlations involving basal and stress-evoked corticosterone levels, and memory performance. Most importantly, predator stress impaired short-term memory, as well as processes involved in memory consolidation and retrieval, in male and female rats. Overall, we have found that an intense, ethologically relevant stressor produced a largely equivalent impairment of memory in male and female rats, and sex-independent corticosterone-memory correlations. These findings may provide insight into commonalities in how traumatic stress affects the brain and memory in men and women.

Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis

International Nuclear Information System (INIS)

Kim, Joong-Sun; Lee, Hae-June; Kim, Jong-Choon

2008-01-01

Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis. (author)

Anisomycin administered in the olfactory bulb and dorsal hippocampus impaired social recognition memory consolidation in different time-points.

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Pena, R R; Pereira-Caixeta, A R; Moraes, M F D; Pereira, G S

2014-10-01

To identify an individual as familiar, rodents form a specific type of memory named social recognition memory. The olfactory bulb (OB) is an important structure for social recognition memory, while the hippocampus recruitment is still controversial. The present study was designed to elucidate the OB and the dorsal hippocampus contribution to the consolidation of social memory. For that purpose, we tested the effect of anisomycin (ANI), which one of the effects is the inhibition of protein synthesis, on the consolidation of social recognition memory. Swiss adult mice with cannulae implanted into the CA1 region of the dorsal hippocampus or into the OB were exposed to a juvenile during 5 min (training session; TR), and once again 1.5 h or 24 h later to test social short-term memory (S-STM) or social long-term memory (S-LTM), respectively. To study S-LTM consolidation, mice received intra-OB or intra-CA1 infusion of saline or ANI immediately, 3, 6 or 18 h after TR. ANI impaired S-LTM consolidation in the OB, when administered immediately or 6h after TR. In the dorsal hippocampus, ANI was amnesic only if administered 3 h after TR. Furthermore, the infusion of ANI in either OB or CA1, immediately after training, did not affect S-STM. Moreover, ANI administered into the OB did not alter the animal's performance in the buried food-finding task. Altogether, our results suggest the consolidation of S-LTM requires both OB and hippocampus participation, although in different time points. This study may help shedding light on the specific roles of the OB and dorsal hippocampus in social recognition memory. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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Hosono, Shouhei; Matsumoto, Yukihisa; Mizunami, Makoto

2016-01-01

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

Conceptual distinctiveness supports detailed visual long-term memory for real-world objects.

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Konkle, Talia; Brady, Timothy F; Alvarez, George A; Oliva, Aude

2010-08-01

Humans have a massive capacity to store detailed information in visual long-term memory. The present studies explored the fidelity of these visual long-term memory representations and examined how conceptual and perceptual features of object categories support this capacity. Observers viewed 2,800 object images with a different number of exemplars presented from each category. At test, observers indicated which of 2 exemplars they had previously studied. Memory performance was high and remained quite high (82% accuracy) with 16 exemplars from a category in memory, demonstrating a large memory capacity for object exemplars. However, memory performance decreased as more exemplars were held in memory, implying systematic categorical interference. Object categories with conceptually distinctive exemplars showed less interference in memory as the number of exemplars increased. Interference in memory was not predicted by the perceptual distinctiveness of exemplars from an object category, though these perceptual measures predicted visual search rates for an object target among exemplars. These data provide evidence that observers' capacity to remember visual information in long-term memory depends more on conceptual structure than perceptual distinctiveness. 2010 APA, all rights reserved

Role of the hippocampus in contextual modulation of fear extinction

Institute of Scientific and Technical Information of China (English)

Lingzhi Kong; Xihong Wu; Liang Li

2008-01-01

Fear extinction is an important form of emotional learning, and affects neural plasticity. Cue fear extinction is a classical form of inhibitory learning that can be used as an exposure-based treatment for phobia, because the long-term extinction memory produced during cue fear extinction can limit the over-expression of fear. The expression of this inhibitory memory partly depends on the context in which the extinction learning occurs. Studies such as transient inhibition, electrophysiology and brain imaging have proved that the hippocampus - an important structure in the limbic system - facilitates memory retrieval by contextual cues.Mediation of the hippocampus-medial prefrontal lobe circuit may be the neurobiological basis of this process.This article has reviewed the role of the hippocampus in the learning and retrieval of fear extinction.Contextual modulation of fear extinction may rely on a neural network consisting of the hippocampus, the medial prefrontal cortex and the amygdala.

The role of basolateral amygdala adrenergic receptors in hippocampus dependent spatial memory in rat

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Vafaei A.L.

2008-03-01

Full Text Available Background and the purpose of the study: There are extensive evidences indicating that the noradrenergic system of the basolateral nucleus of the amygdala (BLA is involved in memory processes. The present study investigated the role of the BLA adrenergic receptors (ARs in hippocampus dependent spatial memory in place avoidance task in male rat. Material and Methods: Long Evans rats (n=150 were trained to avoid footshock in a 60° segment while foraging for scattered food on a circular (80-cm diameter arena. The rats were injected bilaterally in the BLA specific ARS (Adrenergic receptors agonist norepinephrine (NE, 0.5 and 1 µg/µl and specific β-ARs antagonist propranolol (PRO, 0.5 and 1 µg/µl before acquisition, after training or before retrieval of the place avoidance task. Control rats received vehicle at the same volume. The learning in a single 30-min session was assessed 24h later by a 30-min extinction trial in which the time to first entrance and the number of entrances to the shocked area measured the avoidance memory. Results: Acquisition and consolidation were enhanced and impaired significantly by NE and PRO when the drugs were injected 10 min before or immediately after training, respectively. In contrast, neither NE nor PRO influenced animal performances when injected before retention testing. Conclusion: Findings of this study indicates that adrenergic system of the BLA plays an important role in regulation of memory storage and show further evidences for the opinion that the BLA plays an important role in integrating hormonal and neurotransmitter influences on memory storage.

Pre-training administration of tianeptine, but not propranolol, protects hippocampus-dependent memory from being impaired by predator stress.

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Campbell, Adam M; Park, Collin R; Zoladz, Phillip R; Muñoz, Carmen; Fleshner, Monika; Diamond, David M

2008-02-01

Extensive research has shown that the antidepressant tianeptine blocks the adverse effects of chronic stress on hippocampal functioning. The current series of experiments extended this area of investigation by examining the influence of tianeptine on acute stress-induced impairments of spatial (hippocampus-dependent) memory. Tianeptine (10 mg/kg, ip) administered to adult male rats before, but not after, water maze training blocked the amnestic effects of predator stress (occurring between training and retrieval) on memory. The protective effects of tianeptine on memory occurred in rats which had extensive pre-stress training, as well as in rats which had only a single day of training. Tianeptine blocked stress effects on memory without altering the stress-induced increase in corticosterone levels. Propranolol, a beta-adrenergic receptor antagonist (5 and 10 mg/kg, ip), in contrast, did not block stress-induced amnesia. These findings indicate that treatment with tianeptine, unlike propanolol, provides an effective means with which to block the adverse effects of stress on cognitive functions of the hippocampus.

Hyperfunction of muscarinic receptor maintains long-term memory in 5-HT4 receptor knock-out mice.

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Luis Segu

Full Text Available Patients suffering from dementia of Alzheimer's type express less serotonin 4 receptors (5-HTR(4, but whether an absence of these receptors modifies learning and memory is unexplored. In the spatial version of the Morris water maze, we show that 5-HTR(4 knock-out (KO and wild-type (WT mice performed similarly for spatial learning, short- and long-term retention. Since 5-HTR(4 control mnesic abilities, we tested whether cholinergic system had circumvented the absence of 5-HTR(4. Inactivating muscarinic receptor with scopolamine, at an ineffective dose (0.8 mg/kg to alter memory in WT mice, decreased long-term but not short-term memory of 5-HTR(4 KO mice. Other changes included decreases in the activity of choline acetyltransferase (ChAT, the required enzyme for acetylcholine synthesis, in the septum and the dorsal hippocampus in 5-HTR(4 KO under baseline conditions. Training- and scopolamine-induced increase and decrease, respectively in ChAT activity in the septum in WT mice were not detected in the 5-HTR(4 KO animals. Findings suggest that adaptive changes in cholinergic systems may circumvent the absence of 5-HTR(4 to maintain long-term memory under baseline conditions. In contrast, despite adaptive mechanisms, the absence of 5-HTR(4 aggravates scopolamine-induced memory impairments. The mechanisms whereby 5-HTR(4 mediate a tonic influence on ChAT activity and muscarinic receptors remain to be determined.

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

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Makoto Mizunami

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

Effects of postnatal malnutrition and senescence on learning, long-term memory, and extinction in the rat.

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Martínez, Yvonne; Díaz-Cintra, Sofía; León-Jacinto, Uriel; Aguilar-Vázquez, Azucena; Medina, Andrea C; Quirarte, Gina L; Prado-Alcalá, Roberto A

2009-10-12

There is a wealth of information indicating that the hippocampal formation is important for learning and memory consolidation. The hippocampus is very sensitive to ageing and developmentally stressful factors such as prenatal malnutrition, which produces anatomical alterations of hippocampal pyramidal cells as well as impaired spatial learning. On the other hand, there are no reports about differential effects of postnatal malnutrition, installed at birth and maintained all through life in young and aged rats, on learning and memory of active avoidance, a task with an important procedural component. We now report that learning and long-term retention of this task were impaired in young malnourished animals, but not in young control, senile control, and senile malnourished Sprague-Dawley rats; young and senile rats were 90 and 660 days of age, respectively. Extinction tests showed, however, that long-term memory of the malnourished groups and senile control animals is impaired as compared with the young control animals. These data strongly suggest that the learning and long-term retention impairments seen in the young animals were due to postnatal malnutrition; in the senile groups, this cognitive alteration did not occur, probably because ageing itself is an important factor that enables the brain to engage in compensatory mechanisms that reduce the effects of malnutrition. Nonetheless, ageing and malnutrition, conditions known to produce anatomic and functional hippocampal alterations, impede the maintenance of long-term memory, as seen during the extinction test.

Effects of Sleep Deprivation and Aging on Long-Term and Remote Memory in Mice

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Vecsey, Christopher G.; Park, Alan J.; Khatib, Nora; Abel, Ted

2015-01-01

Sleep deprivation (SD) following hippocampus-dependent learning in young mice impairs memory when tested the following day. Here, we examined the effects of SD on remote memory in both young and aged mice. In young mice, we found that memory is still impaired 1 mo after training. SD also impaired memory in aged mice 1 d after training, but, by a…

Long-term memory traces for language sounds are highly context-sensitive: an MEG/ERF study

DEFF Research Database (Denmark)

Nielsen, Andreas Højlund; Gebauer, Line; Mcgregor, William

impact on the proposed long-term memory traces for native phonological categories. In order to generate different MMF responses to the same language sound contrast depending on the phonetic context, these long-term memory traces must thus be context-sensitive themselves or exist as separate traces...

Long-term memory and volatility clustering in high-frequency price changes

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oh, Gabjin; Kim, Seunghwan; Eom, Cheoljun

2008-02-01

We studied the long-term memory in diverse stock market indices and foreign exchange rates using Detrended Fluctuation Analysis (DFA). For all high-frequency market data studied, no significant long-term memory property was detected in the return series, while a strong long-term memory property was found in the volatility time series. The possible causes of the long-term memory property were investigated using the return data filtered by the AR(1) model, reflecting the short-term memory property, the GARCH(1,1) model, reflecting the volatility clustering property, and the FIGARCH model, reflecting the long-term memory property of the volatility time series. The memory effect in the AR(1) filtered return and volatility time series remained unchanged, while the long-term memory property diminished significantly in the volatility series of the GARCH(1,1) filtered data. Notably, there is no long-term memory property, when we eliminate the long-term memory property of volatility by the FIGARCH model. For all data used, although the Hurst exponents of the volatility time series changed considerably over time, those of the time series with the volatility clustering effect removed diminish significantly. Our results imply that the long-term memory property of the volatility time series can be attributed to the volatility clustering observed in the financial time series.

What are the differences between long-term, short-term, and working memory?

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Cowan, Nelson

2008-01-01

In the recent literature there has been considerable confusion about the three types of memory: long-term, short-term, and working memory. This chapter strives to reduce that confusion and makes up-to-date assessments of these types of memory. Long- and short-term memory could differ in two fundamental ways, with only short-term memory demonstrating (1) temporal decay and (2) chunk capacity limits. Both properties of short-term memory are still controversial but the current literature is rather encouraging regarding the existence of both decay and capacity limits. Working memory has been conceived and defined in three different, slightly discrepant ways: as short-term memory applied to cognitive tasks, as a multi-component system that holds and manipulates information in short-term memory, and as the use of attention to manage short-term memory. Regardless of the definition, there are some measures of memory in the short term that seem routine and do not correlate well with cognitive aptitudes and other measures (those usually identified with the term "working memory") that seem more attention demanding and do correlate well with these aptitudes. The evidence is evaluated and placed within a theoretical framework depicted in Fig. 1.

Long-term social recognition memory is mediated by oxytocin-dependent synaptic plasticity in the medial amygdala.

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Gur, Rotem; Tendler, Alex; Wagner, Shlomo

2014-09-01

Recognition of specific individuals is fundamental to mammalian social behavior and is mediated in most mammals by the main and accessory olfactory systems. Both these systems innervate the medial amygdala (MeA), where activity of the neuropeptide oxytocin is thought to mediate social recognition memory (SRM). The specific contribution of the MeA to SRM formation and the specific actions of oxytocin in the MeA are unknown. We used the social discrimination test to evaluate short-term and long-term SRM in adult Sprague-Dawley male rats (n = 38). The role of protein synthesis in the MeA was investigated by local application of the protein synthesis blocker anisomycin (n = 11). Synaptic plasticity was assessed in vivo by recording the MeA evoked field potential responses to stimulation of the main (n = 21) and accessory (n = 56) olfactory bulbs before and after theta burst stimulation. Intracerebroventricular administration of saline, oxytocin, or oxytocin receptor antagonist was used to measure the effect of oxytocin on synaptic plasticity. Anisomycin application to the MeA prevented the formation of long-term SRM. In addition, the responses of MeA neurons underwent long-term depression (LTD) after theta burst stimulation of the accessory olfactory bulb, but not the main accessory bulb, in an oxytocin-dependent manner. No LTD was found in socially isolated rats, which are known to lack long-term SRM. Finally, accessory olfactory bulb stimulation before SRM acquisition blocked long-term SRM, supporting the involvement of LTD in the MeA in formation of long-term SRM. Our results indicate that long-term SRM in rats involves protein synthesis and oxytocin-dependent LTD in the MeA. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Protein Synthesis-Dependent Long-Term Memory Induced by One Single Associative Training Trial in the Parasitic Wasp Lariophagus distinguendus

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Steidle, Johannes L. M.; Collatz, Jana; Muller, Caroline

2006-01-01

Protein synthesis-dependent long-term memory in Apis mellifera and Drosophila melanogaster is formed after multiple trainings that are spaced in time. The parasitic wasp Lariophagus distinguendus remarkably differs from these species. It significantly responds to the artificial odor furfurylheptanoate (FFH) in olfactometer experiments, when this…

The Working Memory and Dorsolateral Prefrontal-Hippocampal Functional Connectivity Changes in Long-Term Survival Breast Cancer Patients Treated with Tamoxifen

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Chen, Xingui; Tao, Longxiang; Li, Jingjing; Wu, Jiaonan; Zhu, Chunyan; Yu, Fengqiong; Zhang, Lei; Zhang, Jingjie; Qiu, Bensheng; Yu, Yongqiang; He, Xiaoxuan

2017-01-01

Abstract Background: Tamoxifen is the most widely used drug for treating patients with estrogen receptor-sensitive breast cancer. There is evidence that breast cancer patients treated with tamoxifen exhibit cognitive dysfunction. However, the underlying neural mechanism remains unclear. The present study aimed to investigate the neural mechanisms underlying working memory deficits in combination with functional connectivity changes in premenopausal women with breast cancer who received long-term tamoxifen treatment. Methods: A total of 31 premenopausal women with breast cancer who received tamoxifen and 32 matched healthy control participants were included. The participants completed n-back tasks and underwent resting-state functional magnetic resonance imaging, which measure working memory performance and brain functional connectivity, respectively. A seed-based functional connectivity analysis within the whole brain was conducted, for which the dorsolateral prefrontal cortex was chosen as the seed region. Results: Our results indicated that the tamoxifen group had significant deficits in working memory and general executive function performance and significantly lower functional connectivity of the right dorsolateral prefrontal cortex with the right hippocampus compared with the healthy controls. There were no significant changes in functional connectivity in the left dorsolateral prefrontal cortex within the whole brain between the tamoxifen group and healthy controls. Moreover, significant correlations were found in the tamoxifen group between the functional connectivity strength of the dorsolateral prefrontal cortex with the right hippocampus and decreased working memory performance. Conclusion: This study demonstrates that the prefrontal cortex and hippocampus may be affected by tamoxifen treatment, supporting an antagonistic role of tamoxifen in the long-term treatment of breast cancer patients. PMID:28177081

Long-Term Treatment with Paroxetine Increases Verbal Declarative Memory and Hippocampal Volume in Posttraumatic Stress Disorder

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Vermetten, Eric; Vythilingam, Meena; Southwick, Steven M.; Charney, Dennis S.; Bremner, J. Douglas

2011-01-01

Background Animal studies have shown that stress is associated with damage to the hippocampus, inhibition of neurogenesis, and deficits in hippocampal-based memory dysfunction. Studies in patients with posttraumatic stress disorder (PTSD) found deficits in hippocampal-based declarative verbal memory and smaller hippocampal volume, as measured with magnetic resonance imaging (MRI). Recent preclinical evidence has shown that selective serotonin reuptake inhibitors promote neurogenesis and reverse the effects of stress on hippocampal atrophy. This study assessed the effects of long-term treatment with paroxetine on hippocampal volume and declarative memory performance in PTSD. Methods Declarative memory was assessed with the Wechsler Memory Scale–Revised and Selective Reminding Test before and after 9–12 months of treatment with paroxetine in PTSD. Hippocampal volume was measured with MRI. Of the 28 patients who started the protocol, 23 completed the full course of treatment and neuropsychological testing. Twenty patients were able to complete MRI imaging. Results Patients with PTSD showed a significant improvement in PTSD symptoms with treatment. Treatment resulted in significant improvements in verbal declarative memory and a 4.6% increase in mean hippocampal volume. Conclusions These findings suggest that long-term treatment with paroxetine is associated with improvement of verbal declarative memory deficits and an increase in hippocampal volume in PTSD. PMID:14512209

Acute stress does not impair long-term memory retrieval in older people.

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Pulopulos, Matias M; Almela, Mercedes; Hidalgo, Vanesa; Villada, Carolina; Puig-Perez, Sara; Salvador, Alicia

2013-09-01

Previous studies have shown that stress-induced cortisol increases impair memory retrieval in young people. This effect has not been studied in older people; however, some findings suggest that age-related changes in the brain can affect the relationships between acute stress, cortisol and memory in older people. Our aim was to investigate the effects of acute stress on long-term memory retrieval in healthy older people. To this end, 76 participants from 56 to 76 years old (38 men and 38 women) were exposed to an acute psychosocial stressor or a control task. After the stress/control task, the recall of pictures, words and stories learned the previous day was assessed. There were no differences in memory retrieval between the stress and control groups on any of the memory tasks. In addition, stress-induced cortisol response was not associated with memory retrieval. An age-related decrease in cortisol receptors and functional changes in the amygdala and hippocampus could underlie the differences observed between the results from this study and those found in studies performed with young people. Copyright © 2013 Elsevier Inc. All rights reserved.

Stimulus Intensity-dependent Modulations of Hippocampal Long-term Potentiation by Basolateral Amygdala Priming

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Zexuan eLi

2012-05-01

Full Text Available There is growing realization that the relationship between memory and stress/emotionality is complicated, and may include both memory enhancing and memory impairing aspects. It has been suggested that the underlying mechanisms involve amygdalar modulation of hippocampal synaptic plasticity, such as long-term potentiation (LTP. We recently reported that while in CA1 basolateral amygdala (BLA priming impaired theta stimulation induced LTP, it enhanced LTP in the dentate gyrus (DG. However, emotional and stressfull experiences were found to activate synaptic plasticity within the BLA, rasing the possibility that BLA modulation of other brain regions may be altered as well, as it may depend on the way the BLA is activated or is responding. In previous studies BLA priming stimulation was relatively weak (1V, 50 µs pulse duration. In the present study we assessed the effects of two stronger levels of BLA priming stimulation (1V or 2V, 100 µs pulse duration on LTP induction in hippocampal DG and CA1, in anesthetized rats. Results show that 1V-BLA priming stimulation enhanced but 2V-BLA priming stimulation impaired DG LTP; however, both levels of BLA priming stimulation impaired CA1 LTP, suggesting that modulation of hippocampal synaptic plasticity by amygdala is dependent on the degree of amygdala activation. These findings suggest that plasticity induced within the amygdala, by stressful experiences induces a form of metaplasticity that would alter the way the amygdala may modulate memory-related processes in other brain areas, such as the hippocampus.

Rapid effects of estrogens on short-term memory: Possible mechanisms.

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Paletta, Pietro; Sheppard, Paul A S; Matta, Richard; Ervin, Kelsy S J; Choleris, Elena

2018-06-01

Estrogens affect learning and memory through rapid and delayed mechanisms. Here we review studies on rapid effects on short-term memory. Estradiol rapidly improves social and object recognition memory, spatial memory, and social learning when administered systemically. The dorsal hippocampus mediates estrogen rapid facilitation of object, social and spatial short-term memory. The medial amygdala mediates rapid facilitation of social recognition. The three estrogen receptors, α (ERα), β (ERβ) and the G-protein coupled estrogen receptor (GPER) appear to play different roles depending on the task and brain region. Both ERα and GPER agonists rapidly facilitate short-term social and object recognition and spatial memory when administered systemically or into the dorsal hippocampus and facilitate social recognition in the medial amygdala. Conversely, only GPER can facilitate social learning after systemic treatment and an ERβ agonist only rapidly improved short-term spatial memory when given systemically or into the hippocampus, but also facilitates social recognition in the medial amygdala. Investigations into the mechanisms behind estrogens' rapid effects on short term memory showed an involvement of the extracellular signal-regulated kinase (ERK) and the phosphoinositide 3-kinase (PI3K) kinase pathways. Recent evidence also showed that estrogens interact with the neuropeptide oxytocin in rapidly facilitating social recognition. Estrogens can increase the production and/or release of oxytocin and other neurotransmitters, such as dopamine and acetylcholine. Therefore, it is possible that estrogens' rapid effects on short-term memory may occur through the regulation of various neurotransmitters, although more research is need on these interactions as well as the mechanisms of estrogens' actions on short-term memory. Copyright © 2018 Elsevier Inc. All rights reserved.

GABA-Mediated Presynaptic Inhibition Is Required for Precision of Long-Term Memory

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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…

Medial prefrontal cortex dopamine controls the persistent storage of aversive memories

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Gonzalez, María C.; Kramar, Cecilia P.; Tomaiuolo, Micol; Katche, Cynthia; Weisstaub, Noelia; Cammarota, Martín; Medina, Jorge H.

2014-01-01

Medial prefrontal cortex (mPFC) is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-term aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 h later. Our results indicate that besides its well-known participation in retrieval and early consolidation, mPFC also modulates the endurance of long-lasting aversive memories regardless of whether formation of the aversive mnemonic trace requires the participation of the hippocampus. PMID:25506318

Critical Role of Endoplasmic Reticulum Stress in Chronic Intermittent Hypoxia-Induced Deficits in Synaptic Plasticity and Long-Term Memory.

Science.gov (United States)

Xu, Lin-Hao; Xie, Hui; Shi, Zhi-Hui; Du, Li-Da; Wing, Yun-Kwok; Li, Albert M; Ke, Ya; Yung, Wing-Ho

2015-09-20

This study examined the role of endoplasmic reticulum (ER) stress in mediating chronic intermittent hypoxia (IH)-induced neurocognitive deficits. We designed experiments to demonstrate that ER stress is initiated in the hippocampus under chronic IH and determined its role in apoptotic cell death, impaired synaptic structure and plasticity, and memory deficits. Two weeks of IH disrupted ER fine structure and upregulated ER stress markers, glucose-regulated protein 78, caspase-12, and C/EBP homologous protein, in the hippocampus, which could be suppressed by ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid. Meanwhile, ER stress induced apoptosis via decreased Bcl-2, promoted reactive oxygen species production, and increased malondialdehyde formation and protein carbonyl, as well as suppressed mitochondrial function. These effects were largely prevented by ER stress inhibitors. On the other hand, suppression of oxidative stress could reduce ER stress. In addition, the length of the synaptic active zone and number of mature spines were reduced by IH. Long-term recognition memory and spatial memory were also impaired, which was accompanied by reduced long-term potentiation in the Schaffer collateral pathway. These effects were prevented by coadministration of the TUDCA. These results show that ER stress plays a critical role in underlying memory deficits in obstructive sleep apnea (OSA)-associated IH. Attenuators of ER stress may serve as novel adjunct therapeutic agents for ameliorating OSA-induced neurocognitive impairment.

Competitive short-term and long-term memory processes in spatial habituation.

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Sanderson, David J; Bannerman, David M

2011-04-01

Exposure to a spatial location leads to habituation of exploration such that, in a novelty preference test, rodents subsequently prefer exploring a novel location to the familiar location. According to Wagner's (1981) theory of memory, short-term and long-term habituation are caused by separate and sometimes opponent processes. In the present study, this dual-process account of memory was tested. Mice received a series of exposure training trials to a location before receiving a novelty preference test. The novelty preference was greater when tested after a short, rather than a long, interval. In contrast, the novelty preference was weaker when exposure training trials were separated by a short, rather than a long interval. Furthermore, it was found that long-term habituation was determined by the independent effects of the amount of exposure training and the number of exposure training trials when factors such as the intertrial interval and the cumulative intertrial interval were controlled. A final experiment demonstrated that a long-term reduction of exploration could be caused by a negative priming effect due to associations formed during exploration. These results provide evidence against a single-process account of habituation and suggest that spatial habituation is determined by both short-term, recency-based memory and long-term, incrementally strengthened memory.

Synaptic plasticity, memory and the hippocampus: a neural network approach to causality.

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Neves, Guilherme; Cooke, Sam F; Bliss, Tim V P

2008-01-01

Two facts about the hippocampus have been common currency among neuroscientists for several decades. First, lesions of the hippocampus in humans prevent the acquisition of new episodic memories; second, activity-dependent synaptic plasticity is a prominent feature of hippocampal synapses. Given this background, the hypothesis that hippocampus-dependent memory is mediated, at least in part, by hippocampal synaptic plasticity has seemed as cogent in theory as it has been difficult to prove in practice. Here we argue that the recent development of transgenic molecular devices will encourage a shift from mechanistic investigations of synaptic plasticity in single neurons towards an analysis of how networks of neurons encode and represent memory, and we suggest ways in which this might be achieved. In the process, the hypothesis that synaptic plasticity is necessary and sufficient for information storage in the brain may finally be validated.

Working memory, long-term memory and language processing : issues and future directions

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Collette, Fabienne; Van der Linden, Martial; Poncelet, Martine

2000-01-01

We examined different views of the relationships between working memory, long-term memory and language processing : working memory considered as a gateway between sensory input and long-term memory or rather as a workspace; working memory considered as not strictly tied to any particular cognitive system (and consequently viewed as separated from the language system) or rather as drawing on the operation and storage capacities of a subset of components involved in language processing. It is a...

Dietary Reversal Ameliorates Short- and Long-Term Memory Deficits Induced by High-fat Diet Early in Life.

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Catrina Sims-Robinson

Full Text Available A high-fat diet (HFD, one of the major factors contributing to metabolic syndrome, which is associated with an increased risk of neurodegenerative diseases, leads to insulin resistance and cognitive impairment. It is not known whether these alterations are improved with dietary intervention. To investigate the long-term impact of a HFD on hippocampal insulin signaling and memory, C57BL6 mice were placed into one of three groups based on the diet: a standard diet (control, a HFD, or a HFD for 16 weeks and then the standard diet for 8 weeks (HF16. HFD-induced impairments in glucose tolerance and hippocampal insulin signaling occurred concurrently with deficits in both short- and long-term memory. Furthermore, these conditions were improved with dietary intervention; however, the HFD-induced decrease in insulin receptor expression in the hippocampus was not altered with dietary intervention. Our results demonstrate that memory deficits due to the consumption of a HFD at an early age are reversible.

Context-dependent memory following recurrent hypoglycaemia in non-diabetic rats is mediated via glucocorticoid signalling in the dorsal hippocampus.

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Osborne, Danielle M; O'Leary, Kelsey E; Fitzgerald, Dennis P; George, Alvin J; Vidal, Michael M; Anderson, Brian M; McNay, Ewan C

2017-01-01

Recurrent hypoglycaemia is primarily caused by repeated over-administration of insulin to patients with diabetes. Although cognition is impaired during hypoglycaemia, restoration of euglycaemia after recurrent hypoglycaemia is associated with improved hippocampally mediated memory. Recurrent hypoglycaemia alters glucocorticoid secretion in response to hypoglycaemia; glucocorticoids are well established to regulate hippocampal processes, suggesting a possible mechanism for recurrent hypoglycaemia modulation of subsequent cognition. We tested the hypothesis that glucocorticoids within the dorsal hippocampus might mediate the impact of recurrent hypoglycaemia on hippocampal cognitive processes. We characterised changes in the dorsal hippocampus at several time points to identify specific mechanisms affected by recurrent hypoglycaemia, using a well-validated 3 day model of recurrent hypoglycaemia either alone or with intrahippocampal delivery of glucocorticoid (mifepristone) and mineralocorticoid (spironolactone) receptor antagonists prior to each hypoglycaemic episode. Recurrent hypoglycaemia enhanced learning and also increased hippocampal expression of glucocorticoid receptors, serum/glucocorticoid-regulated kinase 1, cyclic AMP response element binding (CREB) phosphorylation, and plasma membrane levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptors. Both hippocampus-dependent memory enhancement and the molecular changes were reversed by glucocorticoid receptor antagonist treatment. These results indicate that increased glucocorticoid signalling during recurrent hypoglycaemia produces several changes in the dorsal hippocampus that are conducive to enhanced hippocampus-dependent contextual learning. These changes appear to be adaptive, and in addition to supporting cognition may reduce damage otherwise caused by repeated exposure to severe hypoglycaemia.

PKA Increases in the Olfactory Bulb Act as Unconditioned Stimuli and Provide Evidence for Parallel Memory Systems: Pairing Odor with Increased PKA Creates Intermediate- and Long-Term, but Not Short-Term, Memories

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Grimes, Matthew T.; Harley, Carolyn W.; Darby-King, Andrea; McLean, John H.

2012-01-01

Neonatal odor-preference memory in rat pups is a well-defined associative mammalian memory model dependent on cAMP. Previous work from this laboratory demonstrates three phases of neonatal odor-preference memory: short-term (translation-independent), intermediate-term (translation-dependent), and long-term (transcription- and…

GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories.

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Hardt, Oliver; Nader, Karim; Wang, Yu-Tian

2014-01-05

The molecular processes involved in establishing long-term potentiation (LTP) have been characterized well, but the decay of early and late LTP (E-LTP and L-LTP) is poorly understood. We review recent advances in describing the mechanisms involved in maintaining LTP and homeostatic plasticity. We discuss how these phenomena could relate to processes that might underpin the loss of synaptic potentiation over time, and how they might contribute to the forgetting of short-term and long-term memories. We propose that homeostatic downscaling mediates the loss of E-LTP, and that metaplastic parameters determine the decay rate of L-LTP, while both processes require the activity-dependent removal of postsynaptic GluA2-containing AMPA receptors.

Andra long term memory project - 59277

International Nuclear Information System (INIS)

Charton, Patrick; Boissier, Fabrice; Martin, Guillaume

2012-01-01

Document available in abstract form only. Full text of publication follows: Long term memory of repositories is required by safety, reversibility and social expectations. Thus Andra has implemented since 2010 a long-term memory project to reinforce and diversify its current arrangements in this field, as well as to explore opportunities to extend memory keeping over thousands years. The project includes opportunity studies of dedicated facilities. The 'Ecotheque' and 'Geotheque' projects contribute to memory respectively through environmental and geological samples preservation. The options of creating (i) an archive centre for Andra's interim and permanent archives, (ii) an artist center to study the contribution of arts to memory preservation, (iii) a museum of radioactive waste disposal history and technology (radium industry..., sea disposal, current solutions...) are considered. Other studies provided by the project examine our heritage. This includes the continuity of languages and symbolic systems, the continuity of writing and engraving methods, the archaeology of landscapes (memory of the earths evolution, multi-century memory of industrial and agricultural landscapes), the archaeology practices (how might a future archaeologist be interested in our current activity?), the preservation of historical sites and industrial memory, the continuity of institutional organizations, the memory and history of science evolution as well as broad history

Context Dependent Effects of Ventral Tegmental Area Inactivation on Spatial Working Memory

OpenAIRE

Martig, Adria K.; Jones, Graham L.; Smith, Kelsey E.; Mizumori, Sheri J.Y.

2009-01-01

Rats were tested on a hippocampus dependent win-shift working memory task in familiar or novel environments after receiving bilateral ventral tegmental area infusions of baclofen. Baclofen infusion disrupted working memory performance in both familiar and novel environments. In addition, baclofen infusion selectively disrupted short-term working memory in the novel environment. This experiment confirms selective ventral tegmental area support of accurate performance during a context dependent...

The interaction of short-term and long-term memory in phonetic category formation

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Harnsberger, James D.

2002-05-01

This study examined the role that short-term memory capacity plays in the relationship between novel stimuli (e.g., non-native speech sounds, native nonsense words) and phonetic categories in long-term memory. Thirty native speakers of American English were administered five tests: categorial AXB discrimination using nasal consonants from Malayalam; categorial identification, also using Malayalam nasals, which measured the influence of phonetic categories in long-term memory; digit span; nonword span, a short-term memory measure mediated by phonetic categories in long-term memory; and paired-associate word learning (word-word and word-nonword pairs). The results showed that almost all measures were significantly correlated with one another. The strongest predictor for the discrimination and word-nonword learning results was nonword (r=+0.62) and digit span (r=+0.51), respectively. When the identification test results were partialed out, only nonword span significantly correlated with discrimination. The results show a strong influence of short-term memory capacity on the encoding of phonetic detail within phonetic categories and suggest that long-term memory representations regulate the capacity of short-term memory to preserve information for subsequent encoding. The results of this study will also be discussed with regards to resolving the tension between episodic and abstract models of phonetic category structure.

Cognitive and functional correlates of accelerated long-term forgetting in temporal lobe epilepsy.

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Audrain, Samantha; McAndrews, Mary P

2018-03-30

While we know that hippocampal dysfunction is responsible for the memory deficits that patients with temporal lobe epilepsy exhibit at relatively short study-test delays, the role of this region in accelerated long-term forgetting (ALF) is not yet clear. In the present study, we probed the role of the hippocampus in ALF by directly comparing memory for associations to memory that could be supported by item recognition during a forced choice recognition task over delays ranging from 15-min to 72-h. We additionally examined resting-state functional connectivity between the hippocampus and cortical regions known to be involved in processing these types of stimuli, as well as the relationship between ALF and various clinical variables including structural abnormality in the hippocampus, lateralization of epileptic focus, presence of seizures across the retention period, and standardized composite memory scores. We found evidence of accelerated forgetting for item stimuli (but not associative stimuli) by 6 h post-learning, which became statistically reliable by 72-h. This finding suggests that unlike controls, patients were unable to utilize novelty to reject the incorrect object-scene pair. While none of the examined clinical variables were related to long-term forgetting, reduced resting-state functional connectivity between the affected anterior hippocampus and unaffected lateral temporal cortex predicted forgetting of item stimuli over the 72-h delay. Implications for the role of the hippocampus in accelerated long-term forgetting, and existing theories of systems consolidation in this context are discussed. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

The histone deacetylase HDAC4 regulates long-term memory in Drosophila.

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

2013-01-01

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

NMDA and kainate receptor expression, long-term potentiation, and neurogenesis in the hippocampus of long-lived Ames dwarf mice.

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Sharma, Sunita; Darland, Diane; Lei, Saobo; Rakoczy, Sharlene; Brown-Borg, Holly M

2012-06-01

In the current study, we investigated changes in N-methyl D-aspartate (NMDA) and kainate receptor expression, long-term potentiation (LTP), and neurogenesis in response to neurotoxic stress in long-living Ames dwarf mice. We hypothesized that Ames dwarf mice have enhanced neurogenesis that enables retention of spatial learning and memory with age and promotes neurogenesis in response to injury. Levels of the NMDA receptors (NR)1, NR2A, NR2B, and the kainate receptor (KAR)2 were increased in Ames dwarf mice, relative to wild-type littermates. Quantitative assessment of the excitatory postsynaptic potential in Schaffer collaterals in hippocampal slices from Ames dwarf mice showed an increased response in high-frequency induced LTP over time compared with wild type. Kainic acid (KA) injection was used to promote neurotoxic stress-induced neurogenesis. KA mildly increased the number of doublecortin-positive neurons in wild-type mice, but the response was significantly enhanced in the Ames dwarf mice. Collectively, these data support our hypothesis that the enhanced learning and memory associated with the Ames dwarf mouse may be due to elevated levels of NMDA and KA receptors in hippocampus and their ability to continue producing new neurons in response to neuronal damage.

The hippocampus supports multiple cognitive processes through relational binding and comparison

Directory of Open Access Journals (Sweden)

Rosanna Kathleen Olsen

2012-05-01

Full Text Available It has been well established that the hippocampus plays a pivotal role in explicit long-term recognition memory. However, findings from amnesia, lesion and recording studies with non-human animals, eye-movement recording studies, and functional neuroimaging have recently converged upon a similar message: the functional reach of the hippocampus extends far beyond explicit recognition memory. Damage to the hippocampus affects performance on a number of cognitive tasks including recognition memory after short and long delays and visual discrimination. Additionally, with the advent of neuroimaging techniques that have fine spatial and temporal resolution, findings have emerged that show the elicitation of hippocampal responses within the first few hundred milliseconds of stimulus/task onset. These responses occur for novel and previously viewed information during a time when perceptual processing is traditionally thought to occur, and long before overt recognition responses are made. We propose that the hippocampus is obligatorily involved in the binding of disparate elements across both space and time, and in the comparison of such relational memory representations. Furthermore, the hippocampus supports relational binding and comparison with or without conscious awareness for the relational representations that are formed, retrieved and/or compared. It is by virtue of these basic binding and comparison functions that the reach of the hippocampus extends beyond long-term recognition memory and underlies task performance in multiple cognitive domains.

Reactivations of emotional memory in the hippocampus-amygdala system during sleep.

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Girardeau, Gabrielle; Inema, Ingrid; Buzsáki, György

2017-11-01

The consolidation of context-dependent emotional memory requires communication between the hippocampus and the basolateral amygdala (BLA), but the mechanisms of this process are unknown. We recorded neuronal ensembles in the hippocampus and BLA while rats learned the location of an aversive air puff on a linear track, as well as during sleep before and after training. We found coordinated reactivations between the hippocampus and the BLA during non-REM sleep following training. These reactivations peaked during hippocampal sharp wave-ripples (SPW-Rs) and involved a subgroup of BLA cells positively modulated during hippocampal SPW-Rs. Notably, reactivation was stronger for the hippocampus-BLA correlation patterns representing the run direction that involved the air puff than for the 'safe' direction. These findings suggest that consolidation of contextual emotional memory occurs during ripple-reactivation of hippocampus-amygdala circuits.

Altered Effective Connectivity of Hippocampus-Dependent Episodic Memory Network in mTBI Survivors

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Hao Yan

2016-01-01

Full Text Available Traumatic brain injuries (TBIs are generally recognized to affect episodic memory. However, less is known regarding how external force altered the way functionally connected brain structures of the episodic memory system interact. To address this issue, we adopted an effective connectivity based analysis, namely, multivariate Granger causality approach, to explore causal interactions within the brain network of interest. Results presented that TBI induced increased bilateral and decreased ipsilateral effective connectivity in the episodic memory network in comparison with that of normal controls. Moreover, the left anterior superior temporal gyrus (aSTG, the concept forming hub, left hippocampus (the personal experience binding hub, and left parahippocampal gyrus (the contextual association hub were no longer network hubs in TBI survivors, who compensated for hippocampal deficits by relying more on the right hippocampus (underlying perceptual memory and the right medial frontal gyrus (MeFG in the anterior prefrontal cortex (PFC. We postulated that the overrecruitment of the right anterior PFC caused dysfunction of the strategic component of episodic memory, which caused deteriorating episodic memory in mTBI survivors. Our findings also suggested that the pattern of brain network changes in TBI survivors presented similar functional consequences to normal aging.

Down-Regulation of Neuregulin1/ErbB4 Signaling in the Hippocampus Is Critical for Learning and Memory.

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Tian, Jia; Geng, Fei; Gao, Feng; Chen, Yi-Hua; Liu, Ji-Hong; Wu, Jian-Lin; Lan, Yu-Jie; Zeng, Yuan-Ning; Li, Xiao-Wen; Yang, Jian-Ming; Gao, Tian-Ming

2017-08-01

Hippocampal function is important for learning and memory, and dysfunction of the hippocampus has been linked to the pathophysiology of neuropsychiatric diseases such as schizophrenia. Neuregulin1 (NRG1) and ErbB4, two susceptibility genes for schizophrenia, reportedly modulate long-term potentiation (LTP) at hippocampal Schaffer collateral (SC)-CA1 synapses. However, little is known regarding the contribution of hippocampal NRG1/ErbB4 signaling to learning and memory function. Here, quantitative real-time PCR and Western blotting were used to assess the mRNA and protein levels of NRG1 and ErbB4. Pharmacological and genetic approaches were used to manipulate NRG1/ErbB4 signaling, following which learning and memory behaviors were evaluated using the Morris water maze, Y-maze test, and the novel object recognition test. Spatial learning was found to reduce hippocampal NRG1 and ErbB4 expression. The blockade of NRG1/ErbB4 signaling in hippocampal CA1, either by neutralizing endogenous NRG1 or inhibiting/ablating ErbB4 receptor activity, enhanced hippocampus-dependent spatial learning, spatial working memory, and novel object recognition memory. Accordingly, administration of exogenous NRG1 impaired those functions. More importantly, the specific ablation of ErbB4 in parvalbumin interneurons also improved learning and memory performance. The manipulation of NRG1/ErbB4 signaling in the present study revealed that NRG1/ErbB4 activity in the hippocampus is critical for learning and memory. These findings might provide novel insights on the pathophysiological mechanisms of schizophrenia and a new target for the treatment of Alzheimer's disease, which is characterized by a progressive decline in cognitive function.

Neural bases of orthographic long-term memory and working memory in dysgraphia.

Science.gov (United States)

Rapp, Brenda; Purcell, Jeremy; Hillis, Argye E; Capasso, Rita; Miceli, Gabriele

2016-02-01

Spelling a word involves the retrieval of information about the word's letters and their order from long-term memory as well as the maintenance and processing of this information by working memory in preparation for serial production by the motor system. While it is known that brain lesions may selectively affect orthographic long-term memory and working memory processes, relatively little is known about the neurotopographic distribution of the substrates that support these cognitive processes, or the lesions that give rise to the distinct forms of dysgraphia that affect these cognitive processes. To examine these issues, this study uses a voxel-based mapping approach to analyse the lesion distribution of 27 individuals with dysgraphia subsequent to stroke, who were identified on the basis of their behavioural profiles alone, as suffering from deficits only affecting either orthographic long-term or working memory, as well as six other individuals with deficits affecting both sets of processes. The findings provide, for the first time, clear evidence of substrates that selectively support orthographic long-term and working memory processes, with orthographic long-term memory deficits centred in either the left posterior inferior frontal region or left ventral temporal cortex, and orthographic working memory deficits primarily arising from lesions of the left parietal cortex centred on the intraparietal sulcus. These findings also contribute to our understanding of the relationship between the neural instantiation of written language processes and spoken language, working memory and other cognitive skills. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Working memory and the hippocampus.

Science.gov (United States)

Baddeley, Alan; Jarrold, Christopher; Vargha-Khadem, Faraneh

2011-12-01

A number of studies suggest an important role for the hippocampus in tasks involving visuospatial or relational working memory. We test the generality of this proposal across tasks using a battery designed to investigate the various components of working memory, studying the working memory performance of Jon, who shows a bilateral reduction in hippocampal volume of approximately 50%, comparing him to a group of 48 college students. We measure performance on four complex working memory span measures based on combining visuospatial and verbal storage with visuospatial or verbal concurrent processing as well as measuring Jon's ability to carry out the component storage and processing aspects of these tasks. Jon performed at a consistently high level across our range of tasks. Possible reasons for the apparent disparity between our own findings and earlier studies showing a hippocampal deficit are discussed in terms of both the potential differences in the demands placed on relational memory and of the proposed distinction between egocentric and allocentric visuospatial processing.

Post-learning stress enhances long-term memory and differentially influences memory in females depending on menstrual stage.

Science.gov (United States)

Zoladz, Phillip R; Peters, David M; Cadle, Chelsea E; Kalchik, Andrea E; Aufdenkampe, Rachael L; Dailey, Alison M; Brown, Callie M; Scharf, Amanda R; Earley, McKenna B; Knippen, Courtney L; Rorabaugh, Boyd R

2015-09-01

Most work has shown that post-learning stress enhances long-term memory; however, there have been recent inconsistencies in this literature. The purpose of the present study was to examine further the effects of post-learning stress on long-term memory and to explore any sex differences that may exist. Male and female participants learned a list of 42 words that varied in emotional valence and arousal level. Following encoding, participants completed a free recall assessment and then submerged their hand into a bath of ice cold (stress) or lukewarm (no stress) water for 3 min. The next day, participants were given free recall and recognition tests. Stressed participants recalled more words than non-stressed participants 24h after learning. Stress also enhanced female participants' recall of arousing words when they were in the follicular, but not luteal, phase. These findings replicate previous work examining post-learning stress effects on memory and implicate the involvement of sex-related hormones in such effects. Copyright © 2015 Elsevier B.V. All rights reserved.

The influence of propofol anesthesia exposure on nonaversive memory retrieval and expression of molecules involved in memory process in the dorsal hippocampus in peripubertal rats.

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Pavković, Željko; Milanović, Desanka; Ruždijić, Sabera; Kanazir, Selma; Pešić, Vesna

2018-06-01

The effects of anesthetic drugs on postoperative cognitive function in children are not well defined and have not been experimentally addressed. The present study aimed to examine the influence of propofol anesthesia exposure on nonaversive hippocampus-dependent learning and biochemical changes involved in memory process in the dorsal hippocampus, in peripubertal rats as the rodent model of periadolescence. The intersession spatial habituation and the novel object recognition tasks were used to assess spatial and nonspatial, nonaversive hippocampus-dependent learning. The exposure to anesthesia was performed after comparably long acquisition phases in both tasks. Behavioral testing lasted for 2 consecutive days (24-hour retention period). Changes in the expression of molecules involved in memory retrieval/reconsolidation were examined in the dorsal hippocampus by Western blot and immunohistochemistry, at the time of behavioral testing. Exposure to propofol anesthesia resulted in inappropriate assessment of spatial novelty at the beginning of the test session and affected continuation of acquisition in the spatial habituation test. The treatment did not affect recognition of the novel object at the beginning of the test session but it attenuated overall preference to novelty, reflecting retrieval of a weak memory. The expression of phosphorylated extracellular signal-regulated kinase 2 (involved in memory retrieval) was decreased while the level of phosphorylated Ca 2+ /calmodulin-dependent protein kinase IIα and early growth response protein 1 (involved in memory reconsolidation) was increased in the dorsal hippocampus. The level of Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog B (neuronal activity indicator) was increased in the dorsal dentate gyrus. Enhanced exploratory activity was still evident in the propofol anesthesia exposure (PAE) group 48 hour after the treatment in both tasks. In peripubertal rats, propofol anesthesia exposure

Inhibition of protein kinase A activity interferes with long-term, but not short-term, memory of conditioned taste aversions.

Science.gov (United States)

Koh, Ming Teng; Thiele, Todd E; Bernstein, Ilene L

2002-12-01

The present experiments examined whether inhibition of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) activity interferes with conditioned taste aversion (CTA) memories. Rats were centrally infused with the selective PKA inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPS) before conditioning. Direct infusions of Rp-cAMPS into the amygdala showed no interference with short-term memory but did show significant attenuation of long-term memory and more rapid extinction. Results suggest that PKA activity is involved in the consolidation of long-term memory of CTAs, and that the amygdala may be 1 site that is important for this activity.

Long-Term Memory and Learning

Science.gov (United States)

Crossland, John

2011-01-01

The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

The histone deacetylase HDAC4 regulates long-term memory in Drosophila.

Directory of Open Access Journals (Sweden)

Helen L Fitzsimons

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

Interaction between the Basolateral Amygdala and Dorsal Hippocampus Is Critical for Cocaine Memory Reconsolidation and Subsequent Drug Context-Induced Cocaine-Seeking Behaviorin Rats

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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…

Sucrose and naltrexone prevent increased pain sensitivity and impaired long-term memory induced by repetitive neonatal noxious stimulation: Role of BDNF and β-endorphin.

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Nuseir, Khawla Q; Alzoubi, Karem H; Alhusban, Ahmed; Bawaane, Areej; Al-Azzani, Mohammed; Khabour, Omar F

2017-10-01

Pain in neonates is associated with short and long-term adverse outcomes. Data demonstrated that long-term consequences of untreated pain are linked to the plasticity of the neonate's brain. Sucrose is effective and safe for reducing painful procedures from single events. However, the mechanism of sucrose-induced analgesia is not fully understood. The role of the opioid system in this analgesia using the opioid receptor antagonist Naltrexone was investigated, plus the long-term effects on learning and memory formation during adulthood. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution and/or naltrexone were administered before the pricks. All treatments started on day one of birth and continued for two weeks. At the end of 8weeks, behavioral studies were conducted to test spatial learning and memory using radial arm water maze (RAWM), and pain threshold via foot-withdrawal response to a hot plate. The hippocampus was dissected; levels of brain derived neurotrophic factor (BDNF) and endorphins were assessed using ELISA. Acute repetitive neonatal pain increased pain sensitivity later in life, while naltrexone with sucrose decreased pain sensitivity. Naltrexone and/or sucrose prevented neonatal pain induced impairment of long-term memory, while neonatal pain decreased levels of BDNF in the hippocampus; this decrease was averted by sucrose and naltrexone. Sucrose with naltrexone significantly increased β-endorphin levels in noxiously stimulated rats. In conclusion, naltrexone and sucrose can reverse increased pain sensitivity and impaired long-term memory induced by acute repetitive neonatal pain probably by normalizing BDNF expression and increasing β-endorphin levels. Copyright © 2017 Elsevier Inc. All rights reserved.

C. elegans positive butanone learning, short-term, and long-term associative memory assays.

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Kauffman, Amanda; Parsons, Lance; Stein, Geneva; Wills, Airon; Kaletsky, Rachel; Murphy, Coleen

2011-03-11

The memory of experiences and learned information is critical for organisms to make choices that aid their survival. C. elegans navigates its environment through neuron-specific detection of food and chemical odors, and can associate nutritive states with chemical odors, temperature, and the pathogenicity of a food source. Here, we describe assays of C. elegans associative learning and short- and long-term associative memory. We modified an aversive olfactory learning paradigm to instead produce a positive response; the assay involves starving ~400 worms, then feeding the worms in the presence of the AWC neuron-sensed volatile chemoattractant butanone at a concentration that elicits a low chemotactic index (similar to Toroyama et al.). A standard population chemotaxis assay1 tests the worms' attraction to the odorant immediately or minutes to hours after conditioning. After conditioning, wild-type animals' chemotaxis to butanone increases ~0.6 Chemotaxis Index units, its "Learning Index". Associative learning is dependent on the presence of both food and butanone during training. Pairing food and butanone for a single conditioning period ("massed training") produces short-term associative memory that lasts ~2 hours. Multiple conditioning periods with rest periods between ("spaced training") yields long-term associative memory (long-term memory across species. Our protocol also includes image analysis methods for quick and accurate determination of chemotaxis indices. High-contrast images of animals on chemotaxis assay plates are captured and analyzed by worm counting software in MatLab. The software corrects for uneven background using a morphological tophat transformation. Otsu's method is then used to determine a threshold to separate worms from the background. Very small particles are removed automatically and larger non-worm regions (plate edges or agar punches) are removed by manual selection. The software then estimates the size of single worm by ignoring

Long Term Memory for Noise: Evidence of Robust Encoding of Very Short Temporal Acoustic Patterns.

Science.gov (United States)

Viswanathan, Jayalakshmi; Rémy, Florence; Bacon-Macé, Nadège; Thorpe, Simon J

2016-01-01

Recent research has demonstrated that humans are able to implicitly encode and retain repeating patterns in meaningless auditory noise. Our study aimed at testing the robustness of long-term implicit recognition memory for these learned patterns. Participants performed a cyclic/non-cyclic discrimination task, during which they were presented with either 1-s cyclic noises (CNs) (the two halves of the noise were identical) or 1-s plain random noises (Ns). Among CNs and Ns presented once, target CNs were implicitly presented multiple times within a block, and implicit recognition of these target CNs was tested 4 weeks later using a similar cyclic/non-cyclic discrimination task. Furthermore, robustness of implicit recognition memory was tested by presenting participants with looped (shifting the origin) and scrambled (chopping sounds into 10- and 20-ms bits before shuffling) versions of the target CNs. We found that participants had robust implicit recognition memory for learned noise patterns after 4 weeks, right from the first presentation. Additionally, this memory was remarkably resistant to acoustic transformations, such as looping and scrambling of the sounds. Finally, implicit recognition of sounds was dependent on participant's discrimination performance during learning. Our findings suggest that meaningless temporal features as short as 10 ms can be implicitly stored in long-term auditory memory. Moreover, successful encoding and storage of such fine features may vary between participants, possibly depending on individual attention and auditory discrimination abilities. Significance Statement Meaningless auditory patterns could be implicitly encoded and stored in long-term memory.Acoustic transformations of learned meaningless patterns could be implicitly recognized after 4 weeks.Implicit long-term memories can be formed for meaningless auditory features as short as 10 ms.Successful encoding and long-term implicit recognition of meaningless patterns may

Autobiographical Memory Deficits in Alcohol-Dependent Patients with Short- and Long-Term Abstinence.

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Nandrino, Jean-Louis; El Haj, Mohamad; Torre, Julie; Naye, Delphine; Douchet, Helyette; Danel, Thierry; Cottençin, Oliver

2016-04-01

Autobiographical memory (AM) enables the storage and retrieval of life experiences that allow individuals to build their sense of identity. Several AM impairments have been described in patients with alcohol abuse disorders without assessing whether such deficits can be recovered. This cross-sectional study aimed to identify whether the semantic (SAM) and episodic (EAM) dimensions of AM are affected in individuals with alcohol dependence after short-term abstinence (STA) or long-term abstinence (LTA). A second aim of this study was to examine the factors that could disrupt the efficiency of semantic and episodic AM (the impact of depression severity, cognitive functions, recent or early traumatic events, and drinking history variables). After clinical and cognitive evaluations (alcohol consumption, depression, anxiety, IQ, memory performance), AM was assessed with the Autobiographical Memory Interview in patients with recent (between 4 and 6 weeks) and longer (at least 6 months) abstinence. Participants were asked to retrieve the number and nature of traumatic or painful life experiences in recent or early life periods (using the Childhood Traumatic Events Scale). The 2 abstinent groups had lower global EAM and SAM scores than the control group. These scores were comparable for both abstinent groups. For childhood events, no significant differences were observed in SAM for both groups compared with control participants. For early adulthood and recent events, both STA and LTA groups had lower scores on both SAM and EAM. Moreover, there was a negative correlation between the length of substance consumption and SAM scores. This study highlighted a specific AM disorder in both episodic and semantic dimensions. These deficits remained after 6 months of abstinence. This AM impairment may be explained by compromised encoding and consolidation of memories during bouts of drinking. Copyright © 2016 by the Research Society on Alcoholism.

Distinct behavioral consequences of short-term and prolonged GABAergic depletion in prefrontal cortex and dorsal hippocampus

Directory of Open Access Journals (Sweden)

Judith M. Reichel

2015-01-01

Full Text Available GABAergic interneurons are essential for a functional equilibrium between excitatory and inhibitory impulses throughout the CNS. Disruption of this equilibrium can lead to various neurological or neuropsychiatric disorders such as epileptic seizures or schizophrenia. Schizophrenia itself is clinically defined by negative- (e.g. depression and positive- (e.g. hallucinations symptoms as well as cognitive dysfunction. GABAergic interneurons are proposed to play a central role in the etiology and progression of schizophrenia; however, the specific mechanisms and the time-line of symptom development as well as the distinct involvement of cortical and hippocampal GABAergic interneurons in the etiology of schizophrenia-related symptoms are still not conclusively resolved.Previous work demonstrated that GABAergic interneurons can be selectively depleted in adult mice by means of saporin-conjugated anti-vesicular GABA transporter antibodies (SAVAs in vitro and in vivo. Given their involvement in Schizophrenia-related disease etiology, we ablated GABAergic interneurons in the medial prefrontal cortex (mPFC and dorsal hippocampus (dHPC in adult male C57BL/6N mice. Subsequently we assessed alterations in anxiety, sensory processing, hyperactivity and cognition after long-term (>14 days and short-term (< 14 days GABAergic depletion. Long-term GABAergic depletion in the mPFC resulted in a decrease in sensorimotor-gating and impairments in cognitive flexibility. Notably, the same treatment at the level of the dHPC completely abolished spatial learning capabilities. Short-term GABAergic depletion in the dHPC revealed a transient hyperactive phenotype as well as marked impairments regarding the acquisition of a spatial memory. In contrast, recall of a spatial memory was not affected by the same intervention. These findings emphasize the importance of functional local GABAergic networks for the encoding but not the recall of hippocampus-dependent spatial memories.

When is the hippocampus involved in recognition memory?

OpenAIRE

Barker, Gareth R. I.; Warburton, Elizabeth C.

2011-01-01

The role of the hippocampus in recognition memory is controversial. Recognition memory judgments may be made using different types of information, including object familiarity, an object's spatial location, or when an object was encountered. Experiment 1 examined the role of the hippocampus in recognition memory tasks that required the animals to use these different types of mnemonic information. Rats with bilateral cytotoxic lesions in the hippocampus or perirhinal or prefrontal cortex were ...

Differential functions of NR2A and NR2B in short-term and long-term memory in rats.

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Jung, Ye-Ha; Suh, Yoo-Hun

2010-08-23

N-methyl-D-aspartate receptors (NMDARs) are glutamate receptors implicated in synaptic plasticity and memory function. The specific functions of NMDA receptor subunits NR2A and NR2B have not yet been fully determined in the different types of memory. Nine Wistar rats (8-weeks-old) were subjected to the Morris water maze task to evaluate the memory behaviorally. Quantitative analysis of NR1, NR2A, and NR2B levels in the right and left forebrain of rats was performed and subunit associations with different types of memory were investigated using the Morris water maze task. Right forebrain NR2A expression was significantly increased and correlated with faster escape time onto a hidden platform, indicating involvement of short-term memory, because of the training time interval. Right forebrain NR2B expression was positively associated with long-term memory lasting 24-h (h). In the left forebrain, NR2B expression was positively related to 72-h long-term memory. In conclusion, the functions of NR2A and NR2B receptors were differentially specialized in short-term and long-term memory, depending on the right or left forebrain.

Effect of zinc supplementation of pregnant rats on short-term and long-term memory of their offspring

International Nuclear Information System (INIS)

Ali, M.A.; Ghotbeddin, Z.; Parham, G.H.

2007-01-01

To see the dose dependent effects of zinc chloride on the short-term and long-term memory in a shuttle box (rats). Six pair adult wistar rats were taken for this experiment. One group of pregnant rats received a daily oral dose of 20 mg/kg Zn as zinc chloride and the remaining groups received a daily oral dose of (30, 50, 70,100 mg/kg) zinc chloride for two weeks by gavage. One month after birth, a shuttle box was used to test short-term and long-term memory. Two criteria were considered to behavioral test, including latency in entering dark chamber and time spent in the dark chamber. This experiment showed that oral administration of ZnCl/sub 2/ with (20, 30, 50 mg/kg/day) doses after 2 weeks at the stage of pregnancy, can improve the working memory of their offspring (p<0.05). Where as ZnCl/sub 2/ with 30 mg/kg/day dose has been more effective than other doses (p<0.001). But rat which received ZnCl/sub 2/ with 100 mg/kg/day at the stage of pregnancy, has shown significant impairment in working (short-term) memory of their offspring (p<0.05) and there was no significant difference in reference (long-term) memory 3 for any of groups. This study has demonstrated that zinc chloride consumption with 30 mg/kg/day dose for two weeks at the stage of pregnancy in rats, has positive effect on short-term memory on their offspring. But consumption of enhanced zinc 100 mg/kg/day in pregnant rats can cause short-term memory impairment. On the other hand, zinc supplementation such as zinc chloride has no effect on long-term memory. (author)

A lower ratio of omega-6 to omega-3 fatty acids predicts better hippocampus-dependent spatial memory and cognitive status in older adults.

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Andruchow, Nadia D; Konishi, Kyoko; Shatenstein, Bryna; Bohbot, Véronique D

2017-10-01

Evidence from several cross-sectional studies indicates that an increase in omega-6 to omega-3 fatty acids (FAs) may negatively affect cognition in old age. The hippocampus is among the first neural structures affected by age and atrophy in this brain region is associated with cognitive decline. Therefore, we hypothesized that a lower omega-6:3 FA ratio would predict better hippocampus-dependent spatial memory, and a higher general cognitive status. Fifty-two healthy older adults completed a Food Frequency Questionnaire, the Montreal Cognitive Assessment test (MoCA; a test of global cognition) and virtual navigation tasks that assess navigational strategies and spatial memory. In this cross-sectional study, a lower ratio of omega-6 to omega-3 FA intake strongly predicted more accurate hippocampus-dependent spatial memory and faster learning on our virtual navigation tasks, as well as higher cognitive status overall. These results may help elucidate why certain dietary patterns with a lower omega-6:3 FA ratio, like the Mediterranean diet, are associated with reduced risk of cognitive decline. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Basal Ganglia Activity Mirrors a Benefit of Action and Reward on Long-Lasting Event Memory.

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Koster, Raphael; Guitart-Masip, Marc; Dolan, Raymond J; Düzel, Emrah

2015-12-01

The expectation of reward is known to enhance a consolidation of long-term memory for events. We tested whether this effect is driven by positive valence or action requirements tied to expected reward. Using a functional magnetic resonance imaging (fMRI) paradigm in young adults, novel images predicted gain or loss outcomes, which in turn were either obtained or avoided by action or inaction. After 24 h, memory for these images reflected a benefit of action as well as a congruence of action requirements and valence, namely, action for reward and inaction for avoidance. fMRI responses in the hippocampus, a region known to be critical for long-term memory function, reflected the anticipation of inaction. In contrast, activity in the putamen mirrored the congruence of action requirement and valence, whereas other basal ganglia regions mirrored overall action benefits on long-lasting memory. The findings indicate a novel type of functional division between the hippocampus and the basal ganglia in the motivational regulation of long-term memory consolidation, which favors remembering events that are worth acting for. © The Author 2015. Published by Oxford University Press.

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

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Jiang, Haiteng; van Gerven, Marcel A J; Jensen, Ole

2015-03-01

It has been proposed that long-term memory encoding is not only dependent on engaging task-relevant regions but also on disengaging task-irrelevant regions. In particular, oscillatory alpha activity has been shown to be involved in shaping the functional architecture of the working brain because it reflects the functional disengagement of specific regions in attention and memory tasks. We here ask if such allocation of resources by alpha oscillations generalizes to long-term memory encoding in a cross-modal setting in which we acquired the ongoing brain activity using magnetoencephalography. Participants were asked to encode pictures while ignoring simultaneously presented words and vice versa. We quantified the brain activity during rehearsal reflecting subsequent memory in the different attention conditions. The key finding was that successful long-term memory encoding is reflected by alpha power decreases in the sensory region of the to-be-attended modality and increases in the sensory region of the to-be-ignored modality to suppress distraction during rehearsal period. Our results corroborate related findings from attention studies by demonstrating that alpha activity is also important for the allocation of resources during long-term memory encoding in the presence of distracters.

Implicit short- and long-term memory direct our gaze in visual search.

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Kruijne, Wouter; Meeter, Martijn

2016-04-01

Visual attention is strongly affected by the past: both by recent experience and by long-term regularities in the environment that are encoded in and retrieved from memory. In visual search, intertrial repetition of targets causes speeded response times (short-term priming). Similarly, targets that are presented more often than others may facilitate search, even long after it is no longer present (long-term priming). In this study, we investigate whether such short-term priming and long-term priming depend on dissociable mechanisms. By recording eye movements while participants searched for one of two conjunction targets, we explored at what stages of visual search different forms of priming manifest. We found both long- and short- term priming effects. Long-term priming persisted long after the bias was present, and was again found even in participants who were unaware of a color bias. Short- and long-term priming affected the same stage of the task; both biased eye movements towards targets with the primed color, already starting with the first eye movement. Neither form of priming affected the response phase of a trial, but response repetition did. The results strongly suggest that both long- and short-term memory can implicitly modulate feedforward visual processing.

Hippocampus is place of interaction between unconscious and conscious memories.

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Marc Alain Züst

Full Text Available Recent evidence suggests that humans can form and later retrieve new semantic relations unconsciously by way of hippocampus-the key structure also recruited for conscious relational (episodic memory. If the hippocampus subserves both conscious and unconscious relational encoding/retrieval, one would expect the hippocampus to be place of unconscious-conscious interactions during memory retrieval. We tested this hypothesis in an fMRI experiment probing the interaction between the unconscious and conscious retrieval of face-associated information. For the establishment of unconscious relational memories, we presented subliminal (masked combinations of unfamiliar faces and written occupations ("actor" or "politician". At test, we presented the former subliminal faces, but now supraliminally, as cues for the reactivation of the unconsciously associated occupations. We hypothesized that unconscious reactivation of the associated occupation-actor or politician-would facilitate or inhibit the subsequent conscious retrieval of a celebrity's occupation, which was also actor or politician. Depending on whether the reactivated unconscious occupation was congruent or incongruent to the celebrity's occupation, we expected either quicker or delayed conscious retrieval process. Conscious retrieval was quicker in the congruent relative to a neutral baseline condition but not delayed in the incongruent condition. fMRI data collected during subliminal face-occupation encoding confirmed previous evidence that the hippocampus was interacting with neocortical storage sites of semantic knowledge to support relational encoding. fMRI data collected at test revealed that the facilitated conscious retrieval was paralleled by deactivations in the hippocampus and neocortical storage sites of semantic knowledge. We assume that the unconscious reactivation has pre-activated overlapping relational representations in the hippocampus reducing the neural effort for conscious

Anticipatory eye movements and long-term memory in early infancy.

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Wong-Kee-You, Audrey M B; Adler, Scott A

2016-11-01

Advances in our understanding of long-term memory in early infancy have been made possible by studies that have used the Rovee-Collier's mobile conjugate reinforcement paradigm and its variants. One function that has been attributed to long-term memory is the formation of expectations (Rovee-Collier & Hayne, 1987); consequently, a long-term memory representation should be established during expectation formation. To examine this prediction and potentially open the door on a new paradigm for exploring infants' long-term memory, using the Visual Expectation Paradigm (Haith, Hazan, & Goodman, 1988), 3-month-old infants were trained to form an expectation for predictable color and spatial information of picture events and emit anticipatory eye movements to those events. One day later, infants' anticipatory eye movements decreased in number relative to the end of training when the predictable colors were changed but not when the spatial location of the predictable color events was changed. These findings confirm that information encoded during expectation formation are stored in long-term memory, as hypothesized by Rovee-Collier and colleagues. Further, this research suggests that eye movements are potentially viable measures of long-term memory in infancy, providing confirmatory evidence for early mnemonic processes. © 2016 Wiley Periodicals, Inc.

Nicotine Modulates the Long-Lasting Storage of Fear Memory

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Lima, Ramon H.; Radiske, Andressa; Kohler, Cristiano A.; Gonzalez, Maria Carolina; Bevilaqua, Lia R.; Rossato, Janine I.; Medina, Jorge H.; Cammarota, Martin

2013-01-01

Late post-training activation of the ventral tegmental area (VTA)-hippocampus dopaminergic loop controls the entry of information into long-term memory (LTM). Nicotinic acetylcholine receptors (nAChR) modulate VTA function, but their involvement in LTM storage is unknown. Using pharmacological and behavioral tools, we found that…

The evidence for hippocampal long-term potentiation as a basis of memory for simple tasks

Directory of Open Access Journals (Sweden)

Iván Izquierdo

2008-03-01

Full Text Available Long-term potentiation (LTP is the enhancement of postsynaptic responses for hours, days or weeks following the brief repetitive afferent stimulation of presynaptic afferents. It has been proposed many times over the last 30 years to be the basis of long-term memory. Several recent findings finally supported this hypothesis: a memory formation of one-trial avoidance learning depends on a series of molecular steps in the CA1 region of the hippocampus almost identical to those of LTP in the same region; bhippocampal LTP in this region accompanies memory formation of that task and of another similar task. However, CA1 LTP and the accompanying memory processes can be dissociated, and in addition plastic events in several other brain regions(amygdala, entorhinal cortex, parietal cortex are also necessary for memory formation of the one-trial task, and perhaps of many others.A potenciação de longa duração (LTP é o aumento de respostas pós-sinápticas durante horas, dias ou semanas após a breve estimulação repetitiva de aferentes pre-sinápticos. Foi proposto durante 30 anos ser a base da memória de longa duração. Vários achados recentes finalmente apoiaram esta hipótese: a a formação da memória de esquiva inibitória adquirida numa sessão depende de uma cadeia de processos moleculares na região CA1 do hipocampo quase idêntica à da LTP nessa mesma região; b LTP hipocampal nessa região acompanha a formação da memóría dessa tarefa e de outra semelhante. No entanto, a LTP de CA1 e os processos de memória podem ser dissociados e, fora disso, processos plásticos em outras regiões cerebrais (amígdala, córtex entorrinal, córtex parietal também são necessários para a formação da memória da tarefa de uma sessão e talvez de muitas outras.

Stress, memory, and the hippocampus.

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Wingenfeld, Katja; Wolf, Oliver T

2014-01-01

Stress hormones, i.e. cortisol in human and cortisone in rodents, influence a wide range of cognitive functions, including hippocampus-based declarative memory performance. Cortisol enhances memory consolidation, but impairs memory retrieval. In this context glucocorticoid receptor sensitivity and hippocampal integrity play an important role. This review integrates findings on the relationships between the hypothalamus-pituitary-adrenal (HPA) axis, one of the main coordinators of the stress response, hippocampus, and memory. Findings obtained in healthy participants will be compared with selected mental disorders, including major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD). These disorders are characterized by alterations of the HPA axis and hippocampal dysfunctions. Interestingly, the acute effects of stress hormones on memory in psychiatric patients are different from those found in healthy humans. While cortisol administration has failed to affect memory retrieval in patients with MDD, patients with PTSD and BPD have been found to show enhanced rather than impaired memory retrieval after hydrocortisone. This indicates an altered sensitivity to stress hormones in these mental disorders. © 2014 S. Karger AG, Basel

About sleep's role in memory.

Science.gov (United States)

Rasch, Björn; Born, Jan

2013-04-01

Over more than a century of research has established the fact that sleep benefits the retention of memory. In this review we aim to comprehensively cover the field of "sleep and memory" research by providing a historical perspective on concepts and a discussion of more recent key findings. Whereas initial theories posed a passive role for sleep enhancing memories by protecting them from interfering stimuli, current theories highlight an active role for sleep in which memories undergo a process of system consolidation during sleep. Whereas older research concentrated on the role of rapid-eye-movement (REM) sleep, recent work has revealed the importance of slow-wave sleep (SWS) for memory consolidation and also enlightened some of the underlying electrophysiological, neurochemical, and genetic mechanisms, as well as developmental aspects in these processes. Specifically, newer findings characterize sleep as a brain state optimizing memory consolidation, in opposition to the waking brain being optimized for encoding of memories. Consolidation originates from reactivation of recently encoded neuronal memory representations, which occur during SWS and transform respective representations for integration into long-term memory. Ensuing REM sleep may stabilize transformed memories. While elaborated with respect to hippocampus-dependent memories, the concept of an active redistribution of memory representations from networks serving as temporary store into long-term stores might hold also for non-hippocampus-dependent memory, and even for nonneuronal, i.e., immunological memories, giving rise to the idea that the offline consolidation of memory during sleep represents a principle of long-term memory formation established in quite different physiological systems.

Associative recognition and the hippocampus: differential effects of hippocampal lesions on object-place, object-context and object-place-context memory.

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Langston, Rosamund F; Wood, Emma R

2010-10-01

The hippocampus is thought to be required for the associative recognition of objects together with the spatial or temporal contexts in which they occur. However, recent data showing that rats with fornix lesions perform as well as controls in an object-place task, while being impaired on an object-place-context task (Eacott and Norman (2004) J Neurosci 24:1948-1953), suggest that not all forms of context-dependent associative recognition depend on the integrity of the hippocampus. To examine the role of the hippocampus in context-dependent recognition directly, the present study tested the effects of large, selective, bilateral hippocampus lesions in rats on performance of a series of spontaneous recognition memory tasks: object recognition, object-place recognition, object-context recognition and object-place-context recognition. Consistent with the effects of fornix lesions, animals with hippocampus lesions were impaired only on the object-place-context task. These data confirm that not all forms of context-dependent associative recognition are mediated by the hippocampus. Subsequent experiments suggested that the object-place task does not require an allocentric representation of space, which could account for the lack of impairment following hippocampus lesions. Importantly, as the object-place-context task has similar spatial requirements, the selective deficit in object-place-context recognition suggests that this task requires hippocampus-dependent neural processes distinct from those required for allocentric spatial memory, or for object memory, object-place memory or object-context memory. Two possibilities are that object, place, and context information converge only in the hippocampus, or that recognition of integrated object-place-context information requires a hippocampus-dependent mode of retrieval, such as recollection. © 2009 Wiley-Liss, Inc.

Involvement Of BDNF In Age-Dependent Alterations In The Hippocampus

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Oliver Von Bohlen Und Halbach

2010-08-01

Full Text Available It is known since a long time that the hippocampus is sensitive to aging. Thus, there is a reduction in the hippocampal volume during aging. This age-related volume reduction is paralleled by behavioral and functional deficits in hippocampus-dependent learning and memory tasks. This age-related volume reduction of the hippocampus is not a consequence of an age-related loss of hippocampal neurons. The morphological changes associated with aging include reductions in the branching pattern of dendrites, as well as reductions in spine-densities, reductions in the densities of fibers projecting into the hippocampus as well as declines in the rate of neurogenesis. It is very unlikely that a single factor or a single class of molecules is responsible for all these age-related morphological changes in the hippocampus. Nevertheless, it would be of advantage to identify possible neuromodulators or neuropeptides that may contribute to these age-related changes. In this context, growth factors may play an important role in the maintenance of the postnatal hippocampal architecture. In this review it is hypothesized that brain-derived neurotrophic factor (BDNF is a factor critically involved in the regulation of age-related processes in the hippocampus. Moreover, evidences suggest that disturbances in the BDNF-system also affect hippocampal dysfunctions, as e.g. seen in major depression or in Alzheimer disease.

Amygdala modulation of memory-related processes in the hippocampus: potential relevance to PTSD.

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Tsoory, M M; Vouimba, R M; Akirav, I; Kavushansky, A; Avital, A; Richter-Levin, G

2008-01-01

A key assumption in the study of stress-induced cognitive and neurobiological modifications is that alterations in hippocampal functioning after stress are due to an excessive activity exerted by the amygdala on the hippocampus. Research so far focused on stress-induced impairment of hippocampal plasticity and memory but an exposure to stress may simultaneously also result in strong emotional memories. In fact, under normal conditions emotionally charged events are better remembered compared with neutral ones. Results indicate that under these conditions there is an increase in activity within the amygdala that may lead to memory of a different quality. Studying the way emotionality activates the amygdala and the functional impact of this activation we found that the amygdala modulates memory-related processes in other brain areas, such as the hippocampus. However, this modulation is complex, involving both enhancing and suppressing effects, depending on the way the amygdala is activated and the hippocampal subregion examined. The current review summarizes our findings and attempts to put them in context with the impact of an exposure to a traumatic experience, in which there is a mixture of a strong memory of some aspects of the experience but impaired memory of other aspects of that experience. Toward that end, we have recently developed an animal model for the induction of predisposition to stress-related disorders, focusing on the consequences of exposure to stressors during juvenility on the ability to cope with stress in adulthood. Exposing juvenile-stressed rats to an additional stressful challenge in adulthood revealed their impairment to cope with stress and resulted in significant elevation of the amygdala. Interestingly, and similar to our electrophysiological findings, differential effects were observed between the impact of the emotional challenge on CA1 and dentate gyrus subregions of the hippocampus. Taken together, the results indicate that long-term

About Sleep's Role in Memory

Science.gov (United States)

2013-01-01

Over more than a century of research has established the fact that sleep benefits the retention of memory. In this review we aim to comprehensively cover the field of “sleep and memory” research by providing a historical perspective on concepts and a discussion of more recent key findings. Whereas initial theories posed a passive role for sleep enhancing memories by protecting them from interfering stimuli, current theories highlight an active role for sleep in which memories undergo a process of system consolidation during sleep. Whereas older research concentrated on the role of rapid-eye-movement (REM) sleep, recent work has revealed the importance of slow-wave sleep (SWS) for memory consolidation and also enlightened some of the underlying electrophysiological, neurochemical, and genetic mechanisms, as well as developmental aspects in these processes. Specifically, newer findings characterize sleep as a brain state optimizing memory consolidation, in opposition to the waking brain being optimized for encoding of memories. Consolidation originates from reactivation of recently encoded neuronal memory representations, which occur during SWS and transform respective representations for integration into long-term memory. Ensuing REM sleep may stabilize transformed memories. While elaborated with respect to hippocampus-dependent memories, the concept of an active redistribution of memory representations from networks serving as temporary store into long-term stores might hold also for non-hippocampus-dependent memory, and even for nonneuronal, i.e., immunological memories, giving rise to the idea that the offline consolidation of memory during sleep represents a principle of long-term memory formation established in quite different physiological systems. PMID:23589831

Role of Proteasome-Dependent Protein Degradation in Long-Term Operant Memory in "Aplysia"

Science.gov (United States)

Lyons, Lisa C.; Gardner, Jacob S.; Gandour, Catherine E.; Krishnan, Harini C.

2017-01-01

We investigated the in vivo role of protein degradation during intermediate (ITM) and long-term memory (LTM) in "Aplysia" using an operant learning paradigm. The proteasome inhibitor MG-132 inhibited the induction and molecular consolidation of LTM with no effect on ITM. Remarkably, maintenance of steady-state protein levels through…

Binaural auditory beats affect long-term memory.

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Garcia-Argibay, Miguel; Santed, Miguel A; Reales, José M

2017-12-08

The presentation of two pure tones to each ear separately with a slight difference in their frequency results in the perception of a single tone that fluctuates in amplitude at a frequency that equals the difference of interaural frequencies. This perceptual phenomenon is known as binaural auditory beats, and it is thought to entrain electrocortical activity and enhance cognition functions such as attention and memory. The aim of this study was to determine the effect of binaural auditory beats on long-term memory. Participants (n = 32) were kept blind to the goal of the study and performed both the free recall and recognition tasks after being exposed to binaural auditory beats, either in the beta (20 Hz) or theta (5 Hz) frequency bands and white noise as a control condition. Exposure to beta-frequency binaural beats yielded a greater proportion of correctly recalled words and a higher sensitivity index d' in recognition tasks, while theta-frequency binaural-beat presentation lessened the number of correctly remembered words and the sensitivity index. On the other hand, we could not find differences in the conditional probability for recall given recognition between beta and theta frequencies and white noise, suggesting that the observed changes in recognition were due to the recollection component. These findings indicate that the presentation of binaural auditory beats can affect long-term memory both positively and negatively, depending on the frequency used.

Long-term memory of hierarchical relationships in free-living greylag geese.

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Weiss, Brigitte M; Scheiber, Isabella B R

2013-01-01

Animals may memorise spatial and social information for many months and even years. Here, we investigated long-term memory of hierarchically ordered relationships, where the position of a reward depended on the relationship of a stimulus relative to other stimuli in the hierarchy. Seventeen greylag geese (Anser anser) had been trained on discriminations between successive pairs of five or seven implicitly ordered colours, where the higher ranking colour in each pair was rewarded. Geese were re-tested on the task 2, 6 and 12 months after learning the dyadic colour relationships. They chose the correct colour above chance at all three points in time, whereby performance was better in colour pairs at the beginning or end of the colour series. Nonetheless, they also performed above chance on internal colour pairs, which is indicative of long-term memory for quantitative differences in associative strength and/or for relational information. There were no indications for a decline in performance over time, indicating that geese may remember dyadic relationships for at least 6 months and probably well over 1 year. Furthermore, performance in the memory task was unrelated to the individuals' sex and their performance while initially learning the dyadic colour relationships. We discuss possible functions of this long-term memory in the social domain.

Interplay of hippocampus and prefrontal cortex in memory

Science.gov (United States)

Preston, Alison R.; Eichenbaum, Howard

2013-01-01

Recent studies on the hippocampus and the prefrontal cortex have considerably advanced our understanding of the distinct roles of these brain areas in the encoding and retrieval of memories, and of how they interact in the prolonged process by which new memories are consolidated into our permanent storehouse of knowledge. These studies have led to a new model of how the hippocampus forms and replays memories and how the prefrontal cortex engages representations of the meaningful contexts in which related memories occur, as well as how these areas interact during memory retrieval. Furthermore, they have provided new insights into how interactions between the hippocampus and prefrontal cortex support the assimilation of new memories into pre-existing networks of knowledge, called schemas, and how schemas are modified in this process as the foundation of memory consolidation. PMID:24028960

Retrospective attention in short-term memory has a lasting effect on long-term memory across age.

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Strunk, Jonathan; Morgan, Lauren; Reaves, Sarah; Verhaeghen, Paul; Duarte, Audrey

2018-04-13

Declines in both short- and long-term memory are typical of healthy aging. Recent findings suggest that retrodictive attentional cues ("retro-cues") that indicate the location of to-be-probed items in short-term memory (STM) have a lasting impact on long-term memory (LTM) performance in young adults. Whether older adults can also use retro-cues to facilitate both STM and LTM is unknown. Young and older adults performed a visual STM task in which spatially informative retro-cues or non-informative neutral-cues were presented during STM maintenance of real-world objects. We tested participants' memory at both STM and LTM delays for objects that were previously cued with retrodictive or neutral cues during STM order to measure the lasting impact of retrospective attention on LTM. Older adults showed reduced STM and LTM capacity compared to young adults. However, they showed similar magnitude retro-cue memory benefits as young adults at both STM and LTM delays. To the best of our knowledge, this is the first study to investigate whether retro-cues in STM facilitate the encoding of objects into LTM such that they are more likely to be subsequently retrieved by older adults. Our results support the idea that retrospective attention can be an effective means by which older adults can improve their short and long-term memory performance, even in the context of reduced memory capacity.

Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory

KAUST Repository

Tadi, Monika; Allaman, Igor; Lengacher, Sylvain; Grenningloh, Gabriele; Magistretti, Pierre J.

2015-01-01

We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory

KAUST Repository

Tadi, Monika

2015-10-29

We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

Randomized controlled trial evaluating the temporal effects of high-intensity exercise on learning, short-term and long-term memory, and prospective memory.

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Frith, Emily; Sng, Eveleen; Loprinzi, Paul D

2017-11-01

The broader purpose of this study was to examine the temporal effects of high-intensity exercise on learning, short-term and long-term retrospective memory and prospective memory. Among a sample of 88 young adult participants, 22 were randomized into one of four different groups: exercise before learning, control group, exercise during learning, and exercise after learning. The retrospective assessments (learning, short-term and long-term memory) were assessed using the Rey Auditory Verbal Learning Test. Long-term memory including a 20-min and 24-hr follow-up assessment. Prospective memory was assessed using a time-based procedure by having participants contact (via phone) the researchers at a follow-up time period. The exercise stimulus included a 15-min bout of progressive maximal exertion treadmill exercise. High-intensity exercise prior to memory encoding (vs. exercise during memory encoding or consolidation) was effective in enhancing long-term memory (for both 20-min and 24-h follow-up assessments). We did not observe a differential temporal effect of high-intensity exercise on short-term memory (immediate post-memory encoding), learning or prospective memory. The timing of high-intensity exercise may play an important role in facilitating long-term memory. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Acutely increasing δGABAA receptor activity impairs memory and inhibits synaptic plasticity in the hippocampus

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Paul David Whissell

2013-09-01

Full Text Available Extrasynaptic γ-aminobutyric acid type A (GABAA receptors that contain the δ subunit (δGABAA receptors are expressed in several brain regions including the dentate gyrus (DG and CA1 subfields of the hippocampus. Drugs that increase δGABAA receptor activity have been proposed as treatments for a variety of disorders including insomnia, epilepsy and chronic pain. Also, long-term pretreatment with the δGABAA receptor–preferring agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP enhances discrimination memory and increases neurogenesis in the DG. Despite the potential therapeutic benefits of such treatments, the effects of acutely increasing δGABAA receptor activity on memory behaviors remain unknown. Here, we studied the effects of THIP (4 mg/kg, i.p. on memory performance in wild-type (WT and δGABAA receptor null mutant (Gabrd–/– mice. Additionally, the effects of THIP on long-term potentiation (LTP, a molecular correlate of memory, were studied within the DG and CA1 subfields of the hippocampus using electrophysiological recordings of field potentials in hippocampal slices. The results showed that THIP impaired performance in the Morris water maze, contextual fear conditioning and object recognition tasks in WT mice but not Gabrd–/– mice. Furthermore, THIP inhibited LTP in hippocampal slices from WT but not Gabrd–/– mice, an effect that was blocked by GABAA receptor antagonist bicuculline. Thus, acutely increasing δGABAA receptor activity impairs memory behaviors and inhibits synaptic plasticity. These results have important implications for the development of therapies aimed at increasing δGABAA receptor activity.

Acutely increasing δGABAA receptor activity impairs memory and inhibits synaptic plasticity in the hippocampus

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Whissell, Paul D.; Eng, Dave; Lecker, Irene; Martin, Loren J.; Wang, Dian-Shi; Orser, Beverley A.

2013-01-01

Extrasynaptic γ-aminobutyric acid type A (GABAA) receptors that contain the δ subunit (δGABAA receptors) are expressed in several brain regions including the dentate gyrus (DG) and CA1 subfields of the hippocampus. Drugs that increase δGABAA receptor activity have been proposed as treatments for a variety of disorders including insomnia, epilepsy and chronic pain. Also, long-term pretreatment with the δGABAA receptor–preferring agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) enhances discrimination memory and increases neurogenesis in the DG. Despite the potential therapeutic benefits of such treatments, the effects of acutely increasing δGABAA receptor activity on memory behaviors remain unknown. Here, we studied the effects of THIP (4 mg/kg, i.p.) on memory performance in wild-type (WT) and δGABAA receptor null mutant (Gabrd−/−) mice. Additionally, the effects of THIP on long-term potentiation (LTP), a molecular correlate of memory, were studied within the DG and CA1 subfields of the hippocampus using electrophysiological recordings of field potentials in hippocampal slices. The results showed that THIP impaired performance in the Morris water maze, contextual fear conditioning and object recognition tasks in WT mice but not Gabrd−/− mice. Furthermore, THIP inhibited LTP in hippocampal slices from WT but not Gabrd−/− mice, an effect that was blocked by GABAA receptor antagonist bicuculline. Thus, acutely increasing δGABAA receptor activity impairs memory behaviors and inhibits synaptic plasticity. These results have important implications for the development of therapies aimed at increasing δGABAA receptor activity. PMID:24062648

Long-term memory of hierarchical relationships in free-living greylag geese

NARCIS (Netherlands)

Weiss, Brigitte M.; Scheiber, Isabella B. R.

Animals may memorise spatial and social information for many months and even years. Here, we investigated long-term memory of hierarchically ordered relationships, where the position of a reward depended on the relationship of a stimulus relative to other stimuli in the hierarchy. Seventeen greylag

Depletion of serotonin selectively impairs short-term memory without affecting long-term memory in odor learning in the terrestrial slug Limax valentianus.

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Shirahata, Takaaki; Tsunoda, Makoto; Santa, Tomofumi; Kirino, Yutaka; Watanabe, Satoshi

2006-01-01

The terrestrial slug Limax is able to acquire short-term and long-term memories during aversive odor-taste associative learning. We investigated the effect of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on memory. Behavioral studies indicated that 5,7-DHT impaired short-term memory but not long-term memory. HPLC (high-performance liquid chromatography) analysis revealed that 5,7-DHT significantly reduced serotonin content in the central nervous system. The present study suggests that acquisition, retention, and/or retrieval of short-term memory involves serotonin, and neither acquisition nor retrieval of long-term memory requires serotonin at a level as high as that required for short-term memory.

The hippocampus and visual perception

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Lee, Andy C. H.; Yeung, Lok-Kin; Barense, Morgan D.

2012-01-01

In this review, we will discuss the idea that the hippocampus may be involved in both memory and perception, contrary to theories that posit functional and neuroanatomical segregation of these processes. This suggestion is based on a number of recent neuropsychological and functional neuroimaging studies that have demonstrated that the hippocampus is involved in the visual discrimination of complex spatial scene stimuli. We argue that these findings cannot be explained by long-term memory or working memory processing or, in the case of patient findings, dysfunction beyond the medial temporal lobe (MTL). Instead, these studies point toward a role for the hippocampus in higher-order spatial perception. We suggest that the hippocampus processes complex conjunctions of spatial features, and that it may be more appropriate to consider the representations for which this structure is critical, rather than the cognitive processes that it mediates. PMID:22529794

The hippocampus and visual perception

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Andy C. H. Lee

2012-04-01

Full Text Available In this review, we will discuss the idea that the hippocampus may be involved in both memory and perception, contrary to theories that posit functional and neuroanatomical segregation of these processes. This suggestion is based on a number of recent neuropsychological and functional neuroimaging studies that have demonstrated that the hippocampus is involved in the visual discrimination of complex spatial scene stimuli. We argue that these findings cannot be explained by long-term memory or working memory processing or, in the case of patient findings, dysfunction beyond the medial temporal lobe. Instead, these studies point towards a role for the hippocampus in higher-order spatial perception. We suggest that the hippocampus processes complex conjunctions of spatial features, and that it may be more appropriate to consider the representations for which this structure is critical, rather than the cognitive processes that it mediates.

Merging of long-term memories in an insect.

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Hunt, Kathryn L; Chittka, Lars

2015-03-16

Research on comparative cognition has largely focused on successes and failures of animals to solve certain cognitive tasks, but in humans, memory errors can be more complex than simple failures to retrieve information [1, 2]. The existence of various types of "false memories," in which individuals remember events that they have never actually encountered, are now well established in humans [3, 4]. We hypothesize that such systematic memory errors may be widespread in animals whose natural lifestyle involves the processing and recollection of memories for multiple stimuli [5]. We predict that memory traces for various stimuli may "merge," such that features acquired in distinct bouts of training are combined in an animal's mind, so that stimuli that have never been viewed before, but are a combination of the features presented in training, may be chosen during recall. We tested this using bumblebees, Bombus terrestris. When individuals were first trained to a solid single-colored stimulus followed by a black and white (b/w)-patterned stimulus, a subsequent preference for the last entrained stimulus was found in both short-term- and long-term-memory tests. However, when bees were first trained to b/w-patterned stimuli followed by solid single-colored stimuli and were tested in long-term-memory tests 1 or 3 days later, they only initially preferred the most recently rewarded stimulus, and then switched their preference to stimuli that combined features from the previous color and pattern stimuli. The observed merging of long-term memories is thus similar to the memory conjunction error found in humans [6]. Copyright © 2015 Elsevier Ltd. All rights reserved.

Short-term memory to long-term memory transition in a nanoscale memristor.

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Chang, Ting; Jo, Sung-Hyun; Lu, Wei

2011-09-27

"Memory" is an essential building block in learning and decision-making in biological systems. Unlike modern semiconductor memory devices, needless to say, human memory is by no means eternal. Yet, forgetfulness is not always a disadvantage since it releases memory storage for more important or more frequently accessed pieces of information and is thought to be necessary for individuals to adapt to new environments. Eventually, only memories that are of significance are transformed from short-term memory into long-term memory through repeated stimulation. In this study, we show experimentally that the retention loss in a nanoscale memristor device bears striking resemblance to memory loss in biological systems. By stimulating the memristor with repeated voltage pulses, we observe an effect analogous to memory transition in biological systems with much improved retention time accompanied by additional structural changes in the memristor. We verify that not only the shape or the total number of stimuli is influential, but also the time interval between stimulation pulses (i.e., the stimulation rate) plays a crucial role in determining the effectiveness of the transition. The memory enhancement and transition of the memristor device was explained from the microscopic picture of impurity redistribution and can be qualitatively described by the same equations governing biological memories. © 2011 American Chemical Society

Consolidation of long-term memory: Evidence and alternatives.

NARCIS (Netherlands)

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

2004-01-01

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

Protein kinase M ζ and the maintenance of long-term memory.

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Zhang, Yang; Zong, Wei; Zhang, Lei; Ma, Yuanye; Wang, Jianhong

2016-10-01

Although various molecules have been found to mediate the processes of memory acquisition and consolidation, the molecular mechanism to maintain memory still remains elusive. In recent years, a molecular pathway focusing on protein kinase Mζ (PKMζ) has become of interest to researchers because of its potential role in long-term memory maintenance. PKMζ is an isoform of protein kinase C (PKC) and has a related structure that influences its function in maintaining memory. Considerable evidence has been gathered on PKMζ activity, including loss of function studies using PKMζ inhibitors, such as PKMζ inhibitory peptide (ZIP), suggesting PKMζ plays an important role in long-term memory maintenance. This review provides an overview of the role of PKMζ in long-term memory and outlines the molecular structure of PKMζ, the molecular mechanism of PKMζ in long-term memory maintenance and future directions of PKMζ research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Select overexpression of homer1a in dorsal hippocampus impairs spatial working memory

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Tansu Celikel

2007-10-01

Full Text Available Long Homer proteins forge assemblies of signaling components involved in glutamate receptor signaling in postsynaptic excitatory neurons, including those underlying synaptic transmission and plasticity. The short immediate-early gene (IEG Homer1a can dynamically uncouple these physical associations by functional competition with long Homer isoforms. To examine the consequences of Homer1amediated uncoupling for synaptic plasticity and behavior, we generated forebrain-specific tetracycline (tet controlled expression of Venus-tagged Homer1a (H1aV in mice. We report that sustained overexpression of H1aV impaired spatial working but not reference memory. Most notably, a similar impairment was observed when H1aV expression was restricted to the dorsal hippocampus (HP, which identifies this structure as the principal cortical area for spatial working memory. Interestingly, H1aV overexpression also abolished maintenance of CA3-CA1 long-term potentiation (LTP. These impairments, generated by sustained high Homer1a levels, identify a requirement for long Homer forms in synaptic plasticity and temporal encoding of spatial memory.

Memory Vocabulary Learning Strategies and Long-Term Retention ...

African Journals Online (AJOL)

The present study was an attempt to compare the impact of teaching through memory strategies, where students were taught the meaning of new vocabulary items by giving them synonyms, antonyms, definitions and mini-contexts. The results were reflected in the students' short-term and long-term memory retention.

Incidental biasing of attention from visual long-term memory.

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Fan, Judith E; Turk-Browne, Nicholas B

2016-06-01

Holding recently experienced information in mind can help us achieve our current goals. However, such immediate and direct forms of guidance from working memory are less helpful over extended delays or when other related information in long-term memory is useful for reaching these goals. Here we show that information that was encoded in the past but is no longer present or relevant to the task also guides attention. We examined this by associating multiple unique features with novel shapes in visual long-term memory (VLTM), and subsequently testing how memories for these objects biased the deployment of attention. In Experiment 1, VLTM for associated features guided visual search for the shapes, even when these features had never been task-relevant. In Experiment 2, associated features captured attention when presented in isolation during a secondary task that was completely unrelated to the shapes. These findings suggest that long-term memory enables a durable and automatic type of memory-based attentional control. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Evidences of the role of the rodent hippocampus in the non-spatial recognition memory.

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Yi, Jee Hyun; Park, Hye Jin; Kim, Byeong C; Kim, Dong Hyun; Ryu, Jong Hoon

2016-01-15

The hippocampus is a key region responsible for processing spatial information. However, the role of the hippocampus in non-spatial recognition memory is still controversial. In the present study, we performed hippocampal lesioning to address this controversy. The hippocampi of mice were disrupted with bilateral cytotoxic lesions, and standard object recognition (non-spatial) and object location recognition (spatial) were tested. In the habituation period, mice with hippocampal lesions needed a significantly longer time to fully habituate to the test box. Interestingly, after 4 days of habituation (insufficient habituation), the recognition index was similar in the sham and hippocampal lesion groups. However, exploration time was significantly shorter in mice with hippocampal lesions compared with that in control mice. Interestingly, if mice were subjected to a 10-days-long period of habituation (full habituation), the recognition index was significantly lower in mice with hippocampal lesions compared with that in control mice; however, total exploration time was similar in both groups. Furthermore, the object recognition test after full habituation occluded hippocampal long-term potentiation, a cellular model of memory. These results indicate that sufficient habituation is required to observe the effects of hippocampal lesions on object recognition memory. Copyright © 2015 Elsevier B.V. All rights reserved.

A phenomenological memristor model for short-term/long-term memory

International Nuclear Information System (INIS)

Chen, Ling; Li, Chuandong; Huang, Tingwen; Ahmad, Hafiz Gulfam; Chen, Yiran

2014-01-01

Memristor is considered to be a natural electrical synapse because of its distinct memory property and nanoscale. In recent years, more and more similar behaviors are observed between memristors and biological synapse, e.g., short-term memory (STM) and long-term memory (LTM). The traditional mathematical models are unable to capture the new emerging behaviors. In this article, an updated phenomenological model based on the model of the Hewlett–Packard (HP) Labs has been proposed to capture such new behaviors. The new dynamical memristor model with an improved ion diffusion term can emulate the synapse behavior with forgetting effect, and exhibit the transformation between the STM and the LTM. Further, this model can be used in building new type of neural networks with forgetting ability like biological systems, and it is verified by our experiment with Hopfield neural network. - Highlights: • We take the Fick diffusion and the Soret diffusion into account in the ion drift theory. • We develop a new model based on the old HP model. • The new model can describe the forgetting effect and the spike-rate-dependent property of memristor. • The new model can solve the boundary effect of all window functions discussed in [13]. • A new Hopfield neural network with the forgetting ability is built by the new memristor model

Contributions of the Nucleus Accumbens Shell in Mediating the Enhancement in Memory Following Noradrenergic Activation of Either the Amygdala or Hippocampus

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Erin C. Kerfoot

2018-02-01

Full Text Available The nucleus accumbens shell is a site of converging inputs during memory processing for emotional events. The accumbens receives input from the nucleus of the solitary tract (NTS regarding changes in peripheral autonomic functioning following emotional arousal. The shell also receives input from the amygdala and hippocampus regarding affective and contextual attributes of new learning experiences. The successful encoding of affect or context is facilitated by activating noradrenergic systems in either the amygdala or hippocampus. Recent findings indicate that memory enhancement produced by activating NTS neurons, is attenuated by suppressing accumbens functioning after learning. This finding illustrates the significance of the shell in integrating information from the periphery to modulate memory for arousing events. However, it is not known if the accumbens shell plays an equally important role in consolidating information that is initially processed in the amygdala and hippocampus. The present study determined if the convergence of inputs from these limbic regions within the nucleus accumbens contributes to successful encoding of emotional events into memory. Male Sprague-Dawley rats received bilateral cannula implants 2 mm above the accumbens shell and a second bilateral implant 2 mm above either the amygdala or hippocampus. The subjects were trained for 6 days to drink from a water spout. On day 7, a 0.35 mA footshock was initiated as the rat approached the spout and was terminated once the rat escaped into a white compartment. Subjects were then given intra-amygdala or hippocampal infusions of PBS or a dose of norepinephrine (0.2 μg previously shown to enhance memory. Later, all subjects were given intra-accumbens infusion of muscimol to functionally inactivate the shell. Muscimol inactivation of the accumbens shell was delayed to allow sufficient time for norepinephrine to activate intracellular cascades that lead to long-term synaptic

Contributions of the Nucleus Accumbens Shell in Mediating the Enhancement in Memory Following Noradrenergic Activation of Either the Amygdala or Hippocampus.

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Kerfoot, Erin C; Williams, Cedric L

2018-01-01

The nucleus accumbens shell is a site of converging inputs during memory processing for emotional events. The accumbens receives input from the nucleus of the solitary tract (NTS) regarding changes in peripheral autonomic functioning following emotional arousal. The shell also receives input from the amygdala and hippocampus regarding affective and contextual attributes of new learning experiences. The successful encoding of affect or context is facilitated by activating noradrenergic systems in either the amygdala or hippocampus. Recent findings indicate that memory enhancement produced by activating NTS neurons, is attenuated by suppressing accumbens functioning after learning. This finding illustrates the significance of the shell in integrating information from the periphery to modulate memory for arousing events. However, it is not known if the accumbens shell plays an equally important role in consolidating information that is initially processed in the amygdala and hippocampus. The present study determined if the convergence of inputs from these limbic regions within the nucleus accumbens contributes to successful encoding of emotional events into memory. Male Sprague-Dawley rats received bilateral cannula implants 2 mm above the accumbens shell and a second bilateral implant 2 mm above either the amygdala or hippocampus. The subjects were trained for 6 days to drink from a water spout. On day 7, a 0.35 mA footshock was initiated as the rat approached the spout and was terminated once the rat escaped into a white compartment. Subjects were then given intra-amygdala or hippocampal infusions of PBS or a dose of norepinephrine (0.2 μg) previously shown to enhance memory. Later, all subjects were given intra-accumbens infusion of muscimol to functionally inactivate the shell. Muscimol inactivation of the accumbens shell was delayed to allow sufficient time for norepinephrine to activate intracellular cascades that lead to long-term synaptic modifications

Depletion of Serotonin Selectively Impairs Short-Term Memory without Affecting Long-Term Memory in Odor Learning in the Terrestrial Slug "Limax Valentianus"

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Santa, Tomofumi; Kirino, Yutaka; Watanabe, Satoshi; Shirahata, Takaaki; Tsunoda, Makoto

2006-01-01

The terrestrial slug "Limax" is able to acquire short-term and long-term memories during aversive odor-taste associative learning. We investigated the effect of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on memory. Behavioral studies indicated that 5,7-DHT impaired short-term memory but not long-term memory. HPLC…

Repeated Neck Restraint Stress Bidirectionally Modulates Excitatory Transmission in the Dentate Gyrus and Performance in a Hippocampus-dependent Memory Task.

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Spyrka, Jadwiga; Hess, Grzegorz

2018-05-21

The consequences of stress depend on characteristics of the stressor, including the duration of exposure, severity, and predictability. Exposure of mice to repeated neck restraint has been shown to bidirectionally modulate the potential for long-term potentiation (LTP) in the dentate gyrus (DG) in a manner dependent on the number of restraint repetitions, but the influence of repeated brief neck restraint on electrophysiology of single DG neurons has not yet been investigated. Here, we aimed at finding the effects of 1, 3, 7, 14, or 21 daily neck restraint sessions lasting 10 min on electrophysiological characteristics of DG granule cells as well as excitatory and inhibitory synaptic inputs to these neurons. While the excitability of DG granule cells and inhibitory synaptic transmission were unchanged, neck restraint decreased the frequency of spontaneous excitatory currents after three repetitions but enhanced it after 14 and 21 repetitions. The consequences of repeated neck restraint on hippocampus-dependent memory were investigated using the object location test (OLT). Neck restraint stress impaired cognitive performance in the OLT after three repetitions but improved it after 14 and 21 repetitions. Mice subjected to three neck restraint sessions displayed an increase in the measures of depressive and anxiety-like behaviors, however, prolongation of the exposure to neck restraint resulted in a gradual decline in the intensity of these measures. These data indicate that stress imposed by an increasing number of repeated neck restraint episodes bidirectionally modulates both excitatory synaptic transmission in the DG and cognitive performance in the object location memory task. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Long-Term Fault Memory: A New Time-Dependent Recurrence Model for Large Earthquake Clusters on Plate Boundaries

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Salditch, L.; Brooks, E. M.; Stein, S.; Spencer, B. D.; Campbell, M. R.

2017-12-01

A challenge for earthquake hazard assessment is that geologic records often show large earthquakes occurring in temporal clusters separated by periods of quiescence. For example, in Cascadia, a paleoseismic record going back 10,000 years shows four to five clusters separated by approximately 1,000 year gaps. If we are still in the cluster that began 1700 years ago, a large earthquake is likely to happen soon. If the cluster has ended, a great earthquake is less likely. For a Gaussian distribution of recurrence times, the probability of an earthquake in the next 50 years is six times larger if we are still in the most recent cluster. Earthquake hazard assessments typically employ one of two recurrence models, neither of which directly incorporate clustering. In one, earthquake probability is time-independent and modeled as Poissonian, so an earthquake is equally likely at any time. The fault has no "memory" because when a prior earthquake occurred has no bearing on when the next will occur. The other common model is a time-dependent earthquake cycle in which the probability of an earthquake increases with time until one happens, after which the probability resets to zero. Because the probability is reset after each earthquake, the fault "remembers" only the last earthquake. This approach can be used with any assumed probability density function for recurrence times. We propose an alternative, Long-Term Fault Memory (LTFM), a modified earthquake cycle model where the probability of an earthquake increases with time until one happens, after which it decreases, but not necessarily to zero. Hence the probability of the next earthquake depends on the fault's history over multiple cycles, giving "long-term memory". Physically, this reflects an earthquake releasing only part of the elastic strain stored on the fault. We use the LTFM to simulate earthquake clustering along the San Andreas Fault and Cascadia. In some portions of the simulated earthquake history, events would

Reconsolidation of long-term memory in Aplysia.

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Cai, Diancai; Pearce, Kaycey; Chen, Shanping; Glanzman, David L

2012-10-09

When an animal is reminded of a prior experience and shortly afterward treated with a protein synthesis inhibitor, the consolidated memory for the experience can be disrupted; by contrast, protein synthesis inhibition without prior reminding commonly does not disrupt long-term memory [1-3]. Such results imply that the reminding triggers reconsolidation of the memory. Here, we asked whether the behavioral and synaptic changes associated with the memory for long-term sensitization (LTS) of the siphon-withdrawal reflex in the marine snail Aplysia californica [4, 5] could undergo reconsolidation. In support of this idea, we found that when sensitized animals were given abbreviated reminder sensitization training 48-96 hr after the original sensitization training, followed by treatment with the protein synthesis inhibitor anisomycin, LTS was disrupted. We also found that long-term (≥ 24 hr) facilitation (LTF) [6], which can be induced in the monosynaptic connection between Aplysia sensory and motor neurons in dissociated cell culture by multiple spaced pulses of the endogenous facilitatory transmitter serotonin (5-HT) [7, 8], could be eliminated by treating the synapses with one reminder pulse of 5-HT, followed by anisomycin, at 48 hr after the original training. Our results provide a simple model system for understanding the synaptic basis of reconsolidation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Visual working memory is more tolerant than visual long-term memory.

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Schurgin, Mark W; Flombaum, Jonathan I

2018-05-07

Human visual memory is tolerant, meaning that it supports object recognition despite variability across encounters at the image level. Tolerant object recognition remains one capacity in which artificial intelligence trails humans. Typically, tolerance is described as a property of human visual long-term memory (VLTM). In contrast, visual working memory (VWM) is not usually ascribed a role in tolerant recognition, with tests of that system usually demanding discriminatory power-identifying changes, not sameness. There are good reasons to expect that VLTM is more tolerant; functionally, recognition over the long-term must accommodate the fact that objects will not be viewed under identical conditions; and practically, the passive and massive nature of VLTM may impose relatively permissive criteria for thinking that two inputs are the same. But empirically, tolerance has never been compared across working and long-term visual memory. We therefore developed a novel paradigm for equating encoding and test across different memory types. In each experiment trial, participants saw two objects, memory for one tested immediately (VWM) and later for the other (VLTM). VWM performance was better than VLTM and remained robust despite the introduction of image and object variability. In contrast, VLTM performance suffered linearly as more variability was introduced into test stimuli. Additional experiments excluded interference effects as causes for the observed differences. These results suggest the possibility of a previously unidentified role for VWM in the acquisition of tolerant representations for object recognition. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Recent memory for socially transmitted food preferences in rats does not depend on the hippocampus.

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Thapa, Rajat; Sparks, Fraser T; Hanif, Wahab; Gulbrandsen, Tine; Sutherland, Robert J

2014-10-01

The standard model of systems consolidation holds that the hippocampus (HPC) is involved only in the initial storage and retrieval of a memory. With time hippocampal-neocortical interactions slowly strengthen the neocortical memory, ultimately enabling retrieval of the memory without the HPC. Key support for this idea comes from experiments measuring memory recall in the socially-transmitted food preference (STFP) task in rats. HPC damage within a day or two of STFP learning can abolish recall, but similar damage five or more days after learning has no effect. We hypothesize that disruption of cellular consolidation outside the HPC could contribute to the amnesia with recent memories, perhaps playing a more important role than the loss of HPC. This view predicts that intraHPC infusion of Tetrodotoxin (TTX), which can block conduction of action potentials from the lesion sites, will block the retrograde amnesia in the STFP task. Here we confirm the previously reported retrograde amnesia with neurotoxic HPC damage within the first day after learning, but show that co-administration of TTX with the neurotoxin blocks the retrograde amnesia despite very extensive HPC damage. These results indicate that HPC damage disrupts cellular consolidation of the recent memory elsewhere; STFP memory may not ever depend on the HPC. Copyright © 2014 Elsevier Inc. All rights reserved.

Acutely increasing δGABA(A) receptor activity impairs memory and inhibits synaptic plasticity in the hippocampus.

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Whissell, Paul D; Eng, Dave; Lecker, Irene; Martin, Loren J; Wang, Dian-Shi; Orser, Beverley A

2013-01-01

Extrasynaptic γ-aminobutyric acid type A (GABA(A)) receptors that contain the δ subunit (δGABA(A) receptors) are expressed in several brain regions including the dentate gyrus (DG) and CA1 subfields of the hippocampus. Drugs that increase δGABA(A) receptor activity have been proposed as treatments for a variety of disorders including insomnia, epilepsy and chronic pain. Also, long-term pretreatment with the δGABA(A) receptor-preferring agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) enhances discrimination memory and increases neurogenesis in the DG. Despite the potential therapeutic benefits of such treatments, the effects of acutely increasing δGABA(A) receptor activity on memory behaviors remain unknown. Here, we studied the effects of THIP (4 mg/kg, i.p.) on memory performance in wild-type (WT) and δGABA(A) receptor null mutant (Gabrd(-/-)) mice. Additionally, the effects of THIP on long-term potentiation (LTP), a molecular correlate of memory, were studied within the DG and CA1 subfields of the hippocampus using electrophysiological recordings of field potentials in hippocampal slices. The results showed that THIP impaired performance in the Morris water maze, contextual fear conditioning and object recognition tasks in WT mice but not Gabrd(-/-) mice. Furthermore, THIP inhibited LTP in hippocampal slices from WT but not Gabrd(-/-) mice, an effect that was blocked by GABA(A) receptor antagonist bicuculline. Thus, acutely increasing δGABA(A) receptor activity impairs memory behaviors and inhibits synaptic plasticity. These results have important implications for the development of therapies aimed at increasing δGABA(A) receptor activity.

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

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

2018-03-19

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

Deficits in verbal long-term memory and learning in children with poor phonological short-term memory skills.

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Gathercole, Susan E; Briscoe, Josie; Thorn, Annabel; Tiffany, Claire

2008-03-01

Possible links between phonological short-term memory and both longer term memory and learning in 8-year-old children were investigated in this study. Performance on a range of tests of long-term memory and learning was compared for a group of 16 children with poor phonological short-term memory skills and a comparison group of children of the same age with matched nonverbal reasoning abilities but memory scores in the average range. The low-phonological-memory group were impaired on longer term memory and learning tasks that taxed memory for arbitrary verbal material such as names and nonwords. However, the two groups performed at comparable levels on tasks requiring the retention of visuo-spatial information and of meaningful material and at carrying out prospective memory tasks in which the children were asked to carry out actions at a future point in time. The results are consistent with the view that poor short-term memory function impairs the longer-term retention and ease of learning of novel verbal material.

Abstract memory representations in the ventromedial prefrontal cortex and hippocampus support concept generalization.

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Bowman, Caitlin R; Zeithamova, Dagmar

2018-02-07

to arise through integration across events supported by the ventromedial prefrontal cortex (VMPFC) and hippocampus. The current study combined formal categorization models with fMRI data analysis to show that the VMPFC and anterior hippocampus represent abstract prototype information during concept generalization, contributing novel evidence of generalized concept representations in the brain. Results indicate that VMPFC-hippocampal memory integration mechanisms contribute to knowledge generalization across multiple cognitive domains, with the degree of abstraction of memory representations varying along the long axis of the hippocampus. Copyright © 2018 the authors.

Leptin attenuates the detrimental effects of β-amyloid on spatial memory and hippocampal later-phase long term potentiation in rats.

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Tong, Jia-Qing; Zhang, Jun; Hao, Ming; Yang, Ju; Han, Yu-Fei; Liu, Xiao-Jie; Shi, Hui; Wu, Mei-Na; Liu, Qing-Song; Qi, Jin-Shun

2015-07-01

β-Amyloid (Aβ) is the main component of amyloid plaques developed in the brain of patients with Alzheimer's disease (AD). The increasing burden of Aβ in the cortex and hippocampus is closely correlated with memory loss and cognition deficits in AD. Recently, leptin, a 16kD peptide derived mainly from white adipocyte tissue, has been appreciated for its neuroprotective function, although less is known about the effects of leptin on spatial memory and synaptic plasticity. The present study investigated the neuroprotective effects of leptin against Aβ-induced deficits in spatial memory and in vivo hippocampal late-phase long-term potentiation (L-LTP) in rats. Y maze spontaneous alternation was used to assess short term working memory, and the Morris water maze task was used to assess long term reference memory. Hippocampal field potential recordings were performed to observe changes in L-LTP. We found that chronically intracerebroventricular injection of leptin (1μg) effectively alleviated Aβ1-42 (20μg)-induced spatial memory impairments of Y maze spontaneous alternation and Morris water maze. In addition, chronic administration of leptin also reversed Aβ1-42-induced suppression of in vivo hippocampal L-LTP in rats. Together, these results suggest that chronic leptin treatments reversed Aβ-induced deficits in learning and memory and the maintenance of L-LTP. Copyright © 2015 Elsevier Inc. All rights reserved.

Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups.

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Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

2016-06-01

Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2'-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits.

Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory.

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Monika Tadi

Full Text Available We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4, alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

Long-Term Memory Biases Auditory Spatial Attention

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Zimmermann, Jacqueline F.; Moscovitch, Morris; Alain, Claude

2017-01-01

Long-term memory (LTM) has been shown to bias attention to a previously learned visual target location. Here, we examined whether memory-predicted spatial location can facilitate the detection of a faint pure tone target embedded in real world audio clips (e.g., soundtrack of a restaurant). During an initial familiarization task, participants…

Transfer of Information from Short- to Long-Term Memory

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Modigliani, Vito; Seamon, John G.

1974-01-01

The present study examined current hypotheses concerning information transfer from short-term memory (STM) to long-term memory (LTM) using a Peterson STM task with word triplets presented over retention intervals of 0, 3, 6, 9, and 18 sec. (Editor)

Marijuana effects on long-term memory assessment and retrieval.

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Darley, C F; Tinklenberg, J R; Roth, W T; Vernon, S; Kopell, B S

1977-05-09

The ability of 16 college-educated male subjects to recall from long-term memory a series of common facts was tested during intoxication with marijuana extract calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol and during placebo conditions. The subjects' ability to assess their memory capabilities was then determined by measuring how certain they were about the accuracy of their recall performance and by having them predict their performance on a subsequent recognition test involving the same recall items. Marijuana had no effect on recall or recognition performance. These results do not support the view that marijuana provides access to facts in long-term storage which are inaccessible during non-intoxication. During both marijuana and placebo conditions, subjects could accurately predict their recognition memory performance. Hence, marijuana did not alter the subjects' ability to accurately assess what information resides in long-term memory even though they did not have complete access to that information.

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

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Orjon Rroji

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

The relationship between NMDA receptors and microwave-induced learning and memory impairment: a long-term observation on Wistar rats.

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Wang, Hui; Peng, Ruiyun; Zhao, Li; Wang, Shuiming; Gao, Yabing; Wang, Lifeng; Zuo, Hongyan; Dong, Ji; Xu, Xinping; Zhou, Hongmei; Su, Zhentao

2015-03-01

Abstract Purpose: To investigate whether high power microwave could cause continuous disorders to learning and memory in Wistar rats and to explore the underlying mechanisms. Eighty Wistar rats were exposed to a 2.856 GHz pulsed microwave source at a power density of 0 mW/cm(2) and 50 mW/cm(2) microwave for 6 min. The spatial memory ability, the structure of the hippocampus, contents of amino acids neurotransmitters in hippocampus and the expression of N-methyl-D-aspartic acid receptors (NMDAR) subunit 1, 2A and 2B (NR1, NR2A and NR2B) were detected at 1, 3, 6, 9, 12 and 18 months after microwave exposure. Our results showed that the microwave-exposed rats showed consistent deficiencies in spatial learning and memory. The level of amino acid neurotransmitters also decreased after microwave radiation. The ratio of glutamate (Glu) and gammaaminobutyric acid (GABA) significantly decreased at 6 months. Besides, the hippocampus showed varying degrees of degeneration of neurons, increased postsynaptic density and blurred synaptic clefts in the exposure group. The NR1 and NR2B expression showed a significant decrease, especially the NR2B expression. This study indicated that the content of amino acids neurotransmitters, the expression of NMDAR subunits and the variation of hippocampal structure might contribute to the long-term cognitive impairment after microwave exposure.

Hippocampus at 25

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Eichenbaum, Howard; Amaral, David G.; Buffalo, Elizabeth A.; Buzsáki, György; Cohen, Neal; Davachi, Lila; Frank, Loren; Heckers, Stephan; Morris, Richard G. M.; Moser, Edvard I.; Nadel, Lynn; O'Keefe, John; Preston, Alison; Ranganath, Charan; Silva, Alcino; Witter, Menno

2017-01-01

The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories. PMID:27399159

Enhanced hippocampal long-term potentiation and fear memory in Btbd9 mutant mice.

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Mark P DeAndrade

Full Text Available Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS, a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS.

Enhanced hippocampal long-term potentiation and fear memory in Btbd9 mutant mice.

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DeAndrade, Mark P; Zhang, Li; Doroodchi, Atbin; Yokoi, Fumiaki; Cheetham, Chad C; Chen, Huan-Xin; Roper, Steven N; Sweatt, J David; Li, Yuqing

2012-01-01

Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS), a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS.

Infants long-term memory for complex music

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Ilari, Beatriz; Polka, Linda; Costa-Giomi, Eugenia

2002-05-01

In this study we examined infants' long-term memory for two complex pieces of music. A group of thirty 7.5 month-old infants was exposed daily to one short piano piece (i.e., either the Prelude or the Forlane by Maurice Ravel) for ten consecutive days. Following the 10-day exposure period there was a two-week retention period in which no exposure to the piece occurred. After the retention period, infants were tested on the Headturn Preference Procedure. At test, 8 different excerpts of the familiar piece were mixed with 8 different foil excerpts of the unfamiliar one. Infants showed a significant preference for the familiar piece of music. A control group of fifteen nonexposed infants was also tested and showed no preferences for either piece of music. These results suggest that infants in the exposure group retained the familiar music in their long-term memory. This was demonstrated by their ability to discriminate between the different excerpts of both the familiar and the unfamiliar pieces of music, and by their preference for the familiar piece. Confirming previous findings (Jusczyk and Hohne, 1993; Saffran et al., 2000), in this study we suggest that infants can retain complex pieces of music in their long-term memory for two weeks.

Effects of Acute Exercise on Long-Term Memory

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Labban, Jeffrey D.; Etnier, Jennifer L.

2011-01-01

In this study, we tested the effect of acute exercise on long-term memory, specifically the timing of exercise relative to the memory challenge. We assessed memory via paragraph recall, in which participants listened to two paragraphs (exposure) and recounted them following a 35-min delay. Participants (n = 48) were randomly assigned to one of…

Word Length Effects in Long-Term Memory

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Tehan, Gerald; Tolan, Georgina Anne

2007-01-01

The word length effect has been a central feature of theorising about immediate memory. The notion that short-term memory traces rapidly decay unless refreshed by rehearsal is based primarily upon the finding that serial recall for short words is better than that for long words. The decay account of the word length effect has come under pressure…

Rhythmic Working Memory Activation in the Human Hippocampus

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Marcin Leszczyński

2015-11-01

Full Text Available Working memory (WM maintenance is assumed to rely on a single sustained process throughout the entire maintenance period. This assumption, although fundamental, has never been tested. We used intracranial electroencephalography (EEG recordings from the human hippocampus in two independent experiments to investigate the neural dynamics underlying WM maintenance. We observed periodic fluctuations between two different oscillatory regimes: Periods of “memory activation” were reflected by load-dependent alpha power reductions and lower levels of cross-frequency coupling (CFC. They occurred interleaved with periods characterized by load-independent high levels of alpha power and CFC. During memory activation periods, a relevant CFC parameter (load-dependent changes of the peak modulated frequency correlated with individual WM capacity. Fluctuations between these two periods predicted successful performance and were locked to the phase of endogenous delta oscillations. These results show that hippocampal maintenance is a dynamic rather than constant process and depends critically on a hierarchy of oscillations.

THEORETICAL REVIEW The Hippocampus, Time, and Memory Across Scales

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Howard, Marc W.; Eichenbaum, Howard

2014-01-01

A wealth of experimental studies with animals have offered insights about how neural networks within the hippocampus support the temporal organization of memories. These studies have revealed the existence of “time cells” that encode moments in time, much as the well-known “place cells” map locations in space. Another line of work inspired by human behavioral studies suggests that episodic memories are mediated by a state of temporal context that changes gradually over long time scales, up to at least a few thousand seconds. In this view, the “mental time travel” hypothesized to support the experience of episodic memory corresponds to a “jump back in time” in which a previous state of temporal context is recovered. We suggest that these 2 sets of findings could be different facets of a representation of temporal history that maintains a record at the last few thousand seconds of experience. The ability to represent long time scales comes at the cost of discarding precise information about when a stimulus was experienced—this uncertainty becomes greater for events further in the past. We review recent computational work that describes a mechanism that could construct such a scale-invariant representation. Taken as a whole, this suggests the hippocampus plays its role in multiple aspects of cognition by representing events embedded in a general spatiotemporal context. The representation of internal time can be useful across nonhippocampal memory systems. PMID:23915126

Subthreshold pharmacological and genetic approaches to analyzing CaV2.1-mediated NMDA receptor signaling in short-term memory.

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Takahashi, Eiki; Niimi, Kimie; Itakura, Chitoshi

2010-10-25

Ca(V)2.1 is highly expressed in the nervous system and plays an essential role in the presynaptic modulation of neurotransmitter release machinery. Recently, the antiepileptic drug levetiracetam was reported to inhibit presynaptic Ca(V)2.1 functions, reducing glutamate release in the hippocampus, although the precise physiological role of Ca(V)2.1-regulated synaptic functions in cognitive performance at the system level remains unknown. This study examined whether Ca(V)2.1 mediates hippocampus-dependent spatial short-term memory using the object location and Y-maze tests, and perirhinal cortex-dependent nonspatial short-term memory using the object recognition test, via a combined pharmacological and genetic approach. Heterozygous rolling Nagoya (rol/+) mice carrying the Ca(V)2.1alpha(1) mutation had normal spatial and nonspatial short-term memory. A 100mg/kg dose of levetiracetam, which is ineffective in wild-type controls, blocked spatial short-term memory in rol/+ mice. At 5mg/kg, the N-methyl-D-aspartate (NMDA) receptor blocker (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), which is ineffective in wild-type controls, also blocked the spatial short-term memory in rol/+ mice. Furthermore, a combination of subthreshold doses of levetiracetam (25 mg/kg) and CPP (2.5mg/kg) triggered a spatial short-term memory deficit in rol/+ mice, but not in wild-type controls. Similar patterns of nonspatial short-term memory were observed in wild-type and rol/+ mice when injected with levetiracetam (0-300 mg/kg). These results indicate that Ca(V)2.1-mediated NMDA receptor signaling is critical in hippocampus-dependent spatial short-term memory and differs in various regions. The combination subthreshold pharmacological and genetic approach presented here is easily performed and can be used to study functional signaling pathways in neuronal circuits. Copyright © 2010 Elsevier B.V. All rights reserved.

Long-term olfactory memories are stabilised via protein synthesis in Camponotus fellah ants

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Guerrieri, Fernando Javier; D'Ettorre, Patrizia; Deveaud, J-M.

2011-01-01

-chain hydrocarbons, one paired with sucrose and the other with quinine solution. Differential conditioning leads to the formation of a long-term memory retrievable at least 72¿h after training. Long-term memory consolidation was impaired by the ingestion of cycloheximide, a protein synthesis blocker, prior...... to conditioning. Cycloheximide did not impair acquisition of either short-term memory (10¿min) or early and late mid-term memories (1 or 12¿h). These results show that, upon olfactory learning, ants form different memories with variable molecular bases. While short- and mid-term memories do not require protein...... synthesis, long-term memories are stabilised via protein synthesis. Our behavioural protocol opens interesting research avenues to explore the cellular and molecular bases of olfactory learning and memory in ants....

The hippocampus, time and working memory.

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Rawlins, J N; Tsaltas, E

1983-12-01

Rats were trained on a discrete trial working memory leverpress alternation task, following hippocampal lesions (HC), cortical control lesions (CC) or sham operations (SO). Each trial consisted of a forced information response, for which a randomly selected lever was presented followed by a free choice stage, when both levers were presented. The rats were rewarded for pressing the lever which had not been presented at the information stage. When the information response was not rewarded, all rats learnt the task equally well at IRIs of up to 12.75 sec. When the information response was rewarded, the HC rats showed impaired choice accuracy. The extent of this impairment depended on the IRI, being greatest at long IRIs, and least at short ones. Varying the number of leverpresses required to complete the information response affected choice accuracy equivalently in all groups: all rats chose significantly less accurately when only one leverpress was required than when ten leverpresses were required. There was no interaction between the lesion treatments and the information response requirements. It was concluded that both the length of the IRI and the occurrence of events during the IRI determine the extent of the hippocampal lesion-induced performance deficit in working memory tasks. It is proposed that hippocampal damage disrupts an intermediate-term, high-capacity memory buffer, but leaves both a residual short-term memory system and the long-term retention of associations unaffected. This proposal leads to the prediction that reference memory tasks should also be affected by hippocampal lesions when a delay is introduced between making a response and being rewarded for doing so.

Frequency-dependent glycinergic inhibition modulates plasticity in hippocampus.

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Keck, Tara; Lillis, Kyle P; Zhou, Yu-Dong; White, John A

2008-07-16

Previous studies have demonstrated the presence of functional glycine receptors (GlyRs) in hippocampus. In this work, we examine the baseline activity and activity-dependent modulation of GlyRs in region CA1. We find that strychnine-sensitive GlyRs are open in the resting CA1 pyramidal cell, creating a state of tonic inhibition that "shunts" the magnitude of EPSPs evoked by electrical stimulation of the Schaffer collateral inputs. This GlyR-mediated shunting conductance is independent of the presynaptic stimulation rate; however, pairs of presynaptic and postsynaptic action potentials, repeated at frequencies above 5 Hz, reduce the GlyR-mediated conductance and increase peak EPSP magnitudes to levels at least 20% larger than those seen with presynaptic stimulation alone. We refer to this phenomenon as rate-dependent efficacy (RDE). Exogenous GlyR agonists (glycine, taurine) block RDE by preventing the closure of postsynaptic GlyRs. The GlyR antagonist strychnine blocks postsynaptic GlyRs under all conditions, occluding RDE. During RDE, GlyRs are less responsive to local glycine application, suggesting that a reduction in the number or sensitivity of membrane-inserted GlyRs underlies RDE. By extending the RDE induction protocol to include 500 paired presynaptic and postsynaptic spikes, we can induce long-term synaptic depression (LTD). Manipulations that lead to reduced functionality of GlyRs, either pharmacologically or through RDE, also lead to increased LTD. This result suggests that RDE contributes to long-term synaptic plasticity in the hippocampus.

Investigations into the involvement of NMDA mechanisms in recognition memory.

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Warburton, E Clea; Barker, Gareth R I; Brown, Malcom W

2013-11-01

This review will focus on evidence showing that NMDA receptor neurotransmission is critical for synaptic plasticity processes within brain regions known to be necessary for the formation of object recognition memories. The aim will be to provide evidence concerning NMDA mechanisms related to recognition memory processes and show that recognition memory for objects, places or associations between objects and places depends on NMDA neurotransmission within the perirhinal cortex, temporal association cortex medial prefrontal cortex and hippocampus. Administration of the NMDA antagonist AP5, selectively into each of these brain regions has revealed that the extent of the involvement NMDA receptors appears dependent on the type of information required to solve the recognition memory task; thus NMDA receptors in the perirhinal cortex are crucial for the encoding of long-term recognition memory for objects, and object-in-place associations, but not for short-term recognition memory or for retrieval. In contrast the hippocampus and medial prefrontal cortex are required for both long-term and short-term recognition memory for places or associations between objects and places, or for recognition memory tasks that have a temporal component. Such studies have therefore confirmed that the multiple brain regions make distinct contributions to recognition memory but in addition that more than one synaptic plasticity process must be involved. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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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

Long-term effects of interference on short-term memory performance in the rat.

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Missaire, Mégane; Fraize, Nicolas; Joseph, Mickaël Antoine; Hamieh, Al Mahdy; Parmentier, Régis; Marighetto, Aline; Salin, Paul Antoine; Malleret, Gaël

2017-01-01

A distinction has always been made between long-term and short-term memory (also now called working memory, WM). The obvious difference between these two kinds of memory concerns the duration of information storage: information is supposedly transiently stored in WM while it is considered durably consolidated into long-term memory. It is well acknowledged that the content of WM is erased and reset after a short time, to prevent irrelevant information from proactively interfering with newly stored information. In the present study, we used typical WM radial maze tasks to question the brief lifespan of spatial WM content in rodents. Groups of rats were submitted to one of two different WM tasks in a radial maze: a WM task involving the repetitive presentation of a same pair of arms expected to induce a high level of proactive interference (PI) (HIWM task), or a task using a different pair in each trial expected to induce a low level of PI (LIWM task). Performance was effectively lower in the HIWM group than in LIWM in the final trial of each training session, indicative of a "within-session/short-term" PI effect. However, we also observed a different "between-session/long-term" PI effect between the two groups: while performance of LIWM trained rats remained stable over days, the performance of HIWM rats dropped after 10 days of training, and this impairment was visible from the very first trial of the day, hence not attributable to within-session PI. We also showed that a 24 hour-gap across training sessions known to allow consolidation processes to unfold, was a necessary and sufficient condition for the long-term PI effect to occur. These findings suggest that in the HIWM task, WM content was not entirely reset between training sessions and that, in specific conditions, WM content can outlast its purpose by being stored more permanently, generating a long-term deleterious effect of PI. The alternative explanation is that WM content could be transferred and stored

Long-term effects of interference on short-term memory performance in the rat.

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Mégane Missaire

Full Text Available A distinction has always been made between long-term and short-term memory (also now called working memory, WM. The obvious difference between these two kinds of memory concerns the duration of information storage: information is supposedly transiently stored in WM while it is considered durably consolidated into long-term memory. It is well acknowledged that the content of WM is erased and reset after a short time, to prevent irrelevant information from proactively interfering with newly stored information. In the present study, we used typical WM radial maze tasks to question the brief lifespan of spatial WM content in rodents. Groups of rats were submitted to one of two different WM tasks in a radial maze: a WM task involving the repetitive presentation of a same pair of arms expected to induce a high level of proactive interference (PI (HIWM task, or a task using a different pair in each trial expected to induce a low level of PI (LIWM task. Performance was effectively lower in the HIWM group than in LIWM in the final trial of each training session, indicative of a "within-session/short-term" PI effect. However, we also observed a different "between-session/long-term" PI effect between the two groups: while performance of LIWM trained rats remained stable over days, the performance of HIWM rats dropped after 10 days of training, and this impairment was visible from the very first trial of the day, hence not attributable to within-session PI. We also showed that a 24 hour-gap across training sessions known to allow consolidation processes to unfold, was a necessary and sufficient condition for the long-term PI effect to occur. These findings suggest that in the HIWM task, WM content was not entirely reset between training sessions and that, in specific conditions, WM content can outlast its purpose by being stored more permanently, generating a long-term deleterious effect of PI. The alternative explanation is that WM content could be

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

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

2018-03-01

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

The roles of long-term phonotactic and lexical prosodic knowledge in phonological short-term memory.

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Tanida, Yuki; Ueno, Taiji; Lambon Ralph, Matthew A; Saito, Satoru

2015-04-01

Many previous studies have explored and confirmed the influence of long-term phonological representations on phonological short-term memory. In most investigations, phonological effects have been explored with respect to phonotactic constraints or frequency. If interaction between long-term memory and phonological short-term memory is a generalized principle, then other phonological characteristics-that is, suprasegmental aspects of phonology-should also exert similar effects on phonological short-term memory. We explored this hypothesis through three immediate serial-recall experiments that manipulated Japanese nonwords with respect to lexical prosody (pitch-accent type, reflecting suprasegmental characteristics) as well as phonotactic frequency (reflecting segmental characteristics). The results showed that phonotactic frequency affected the retention not only of the phonemic sequences, but also of pitch-accent patterns, when participants were instructed to recall both the phoneme sequence and accent pattern of nonwords. In addition, accent pattern typicality influenced the retention of the accent pattern: Typical accent patterns were recalled more accurately than atypical ones. These results indicate that both long-term phonotactic and lexical prosodic knowledge contribute to phonological short-term memory performance.

Early exposure to volatile anesthetics impairs long-term associative learning and recognition memory.

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Bradley H Lee

Full Text Available Anesthetic exposure early in life affects neural development and long-term cognitive function, but our understanding of the types of memory that are altered is incomplete. Specific cognitive tests in rodents that isolate different memory processes provide a useful approach for gaining insight into this issue.Postnatal day 7 (P7 rats were exposed to either desflurane or isoflurane at 1 Minimum Alveolar Concentration for 4 h. Acute neuronal death was assessed 12 h later in the thalamus, CA1-3 regions of hippocampus, and dentate gyrus. In separate behavioral experiments, beginning at P48, subjects were evaluated in a series of object recognition tests relying on associative learning, as well as social recognition.Exposure to either anesthetic led to a significant increase in neuroapoptosis in each brain region. The extent of neuronal death did not differ between groups. Subjects were unaffected in simple tasks of novel object and object-location recognition. However, anesthetized animals from both groups were impaired in allocentric object-location memory and a more complex task requiring subjects to associate an object with its location and contextual setting. Isoflurane exposure led to additional impairment in object-context association and social memory.Isoflurane and desflurane exposure during development result in deficits in tasks relying on associative learning and recognition memory. Isoflurane may potentially cause worse impairment than desflurane.

Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models

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Choi, Catherine H.; Schoenfeld, Brian P.; Bell, Aaron J.; Hinchey, Joseph; Rosenfelt, Cory; Gertner, Michael J.; Campbell, Sean R.; Emerson, Danielle; Hinchey, Paul; Kollaros, Maria; Ferrick, Neal J.; Chambers, Daniel B.; Langer, Steven; Sust, Steven; Malik, Aatika; Terlizzi, Allison M.; Liebelt, David A.; Ferreiro, David; Sharma, Ali; Koenigsberg, Eric; Choi, Richard J.; Louneva, Natalia; Arnold, Steven E.; Featherstone, Robert E.; Siegel, Steven J.; Zukin, R. Suzanne; McDonald, Thomas V.; Bolduc, Francois V.; Jongens, Thomas A.; McBride, Sean M. J.

2016-01-01

Fragile X is the most common monogenic disorder associated with intellectual disability (ID) and autism spectrum disorders (ASD). Additionally, many patients are afflicted with executive dysfunction, ADHD, seizure disorder and sleep disturbances. Fragile X is caused by loss of FMRP expression, which is encoded by the FMR1 gene. Both the fly and mouse models of fragile X are also based on having no functional protein expression of their respective FMR1 homologs. The fly model displays well defined cognitive impairments and structural brain defects and the mouse model, although having subtle behavioral defects, has robust electrophysiological phenotypes and provides a tool to do extensive biochemical analysis of select brain regions. Decreased cAMP signaling has been observed in samples from the fly and mouse models of fragile X as well as in samples derived from human patients. Indeed, we have previously demonstrated that strategies that increase cAMP signaling can rescue short term memory in the fly model and restore DHPG induced mGluR mediated long term depression (LTD) in the hippocampus to proper levels in the mouse model (McBride et al., 2005; Choi et al., 2011, 2015). Here, we demonstrate that the same three strategies used previously with the potential to be used clinically, lithium treatment, PDE-4 inhibitor treatment or mGluR antagonist treatment can rescue long term memory in the fly model and alter the cAMP signaling pathway in the hippocampus of the mouse model. PMID:27445731

Chronic traumatic stress impairs memory in mice: Potential roles of acetylcholine, neuroinflammation and corticotropin releasing factor expression in the hippocampus.

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Bhakta, Ami; Gavini, Kartheek; Yang, Euitaek; Lyman-Henley, Lani; Parameshwaran, Kodeeswaran

2017-09-29

Chronic stress in humans can result in multiple adverse psychiatric and neurobiological outcomes, including memory deficits. These adverse outcomes can be more severe if each episode of stress is very traumatic. When compared to acute or short term stress relatively little is known about the effects of chronic traumatic stress on memory and molecular changes in hippocampus, a brain area involved in memory processing. Here we studied the effects of chronic traumatic stress in mice by exposing them to adult Long Evan rats for 28 consecutive days and subsequently analyzing behavioral outcomes and the changes in the hippocampus. Results show that stressed mice developed memory deficits when assayed with radial arm maze tasks. However, chronic traumatic stress did not induce anxiety, locomotor hyperactivity or anhedonia. In the hippocampus of stressed mice interleukin-1β protein expression was increased along with decreased corticotropin releasing hormone (CRH) gene expression. Furthermore, there was a reduction in acetylcholine levels in the hippocampus of stressed mice. There were no changes in brain derived neurotrophic factor (BDNF) or nerve growth factor (NGF) levels in the hippocampus of stressed mice. Gene expression of immediate early genes (Zif268, Arc, C-Fos) as well as glucocorticoid and mineralocorticoid receptors were also not affected by chronic stress. These data demonstrate that chronic traumatic stress followed by a recovery period might lead to development of resilience resulting in the development of selected, most vulnerable behavioral alterations and molecular changes in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

Short-term memory for spatial, sequential and duration information.

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Manohar, Sanjay G; Pertzov, Yoni; Husain, Masud

2017-10-01

Space and time appear to play key roles in the way that information is organized in short-term memory (STM). Some argue that they are crucial contexts within which other stored features are embedded, allowing binding of information that belongs together within STM. Here we review recent behavioral, neurophysiological and imaging studies that have sought to investigate the nature of spatial, sequential and duration representations in STM, and how these might break down in disease. Findings from these studies point to an important role of the hippocampus and other medial temporal lobe structures in aspects of STM, challenging conventional accounts of involvement of these regions in only long-term memory.

Using electrophysiology to demonstrate that cueing affects long-term memory storage over the short term.

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Maxcey, Ashleigh M; Fukuda, Keisuke; Song, Won S; Woodman, Geoffrey F

2015-10-01

As researchers who study working memory, we often assume that participants keep a representation of an object in working memory when we present a cue that indicates that the object will be tested in a couple of seconds. This intuitively accounts for how well people can remember a cued object, relative to their memory for that same object presented without a cue. However, it is possible that this superior memory does not purely reflect storage of the cued object in working memory. We tested the hypothesis that cues presented during a stream of objects, followed by a short retention interval and immediate memory test, can change how information is handled by long-term memory. We tested this hypothesis by using a family of frontal event-related potentials believed to reflect long-term memory storage. We found that these frontal indices of long-term memory were sensitive to the task relevance of objects signaled by auditory cues, even when the objects repeated frequently, such that proactive interference was high. Our findings indicate the problematic nature of assuming process purity in the study of working memory, and demonstrate that frequent stimulus repetitions fail to isolate the role of working memory mechanisms.

Assessing the associative deficit of older adults in long-term and short-term/working memory.

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Chen, Tina; Naveh-Benjamin, Moshe

2012-09-01

Older adults exhibit a deficit in associative long-term memory relative to younger adults. However, the literature is inconclusive regarding whether this deficit is attenuated in short-term/working memory. To elucidate the issue, three experiments assessed younger and older adults' item and interitem associative memory and the effects of several variables that might potentially contribute to the inconsistent pattern of results in previous studies. In Experiment 1, participants were tested on item and associative recognition memory with both long-term and short-term retention intervals in a single, continuous recognition paradigm. There was an associative deficit for older adults in the short-term and long-term intervals. Using only short-term intervals, Experiment 2 utilized mixed and blocked test designs to examine the effect of test event salience. Blocking the test did not attenuate the age-related associative deficit seen in the mixed test blocks. Finally, an age-related associative deficit was found in Experiment 3, under both sequential and simultaneous presentation conditions. Even while accounting for some methodological issues, the associative deficit of older adults is evident in short-term/working memory.

BDNF Variants May Modulate Long-Term Visual Memory Performance in a Healthy Cohort.

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Avgan, Nesli; Sutherland, Heidi G; Spriggens, Lauren K; Yu, Chieh; Ibrahim, Omar; Bellis, Claire; Haupt, Larisa M; Shum, David H K; Griffiths, Lyn R

2017-03-17

Brain-derived neurotrophic factor (BDNF) is involved in numerous cognitive functions including learning and memory. BDNF plays an important role in synaptic plasticity in humans and rats with BDNF shown to be essential for the formation of long-term memories. We previously identified a significant association between the BDNF Val66Met polymorphism (rs6265) and long-term visual memory ( p -value = 0.003) in a small cohort ( n = 181) comprised of healthy individuals who had been phenotyped for various aspects of memory function. In this study, we have extended the cohort to 597 individuals and examined multiple genetic variants across both the BDNF and BDNF-AS genes for association with visual memory performance as assessed by the Wechsler Memory Scale-Fourth Edition subtests Visual Reproduction I and II (VR I and II). VR I assesses immediate visual memory, whereas VR II assesses long-term visual memory. Genetic association analyses were performed for 34 single nucleotide polymorphisms genotyped on Illumina OmniExpress BeadChip arrays with the immediate and long-term visual memory phenotypes. While none of the BDNF and BDNF-AS variants were shown to be significant for immediate visual memory, we found 10 variants (including the Val66Met polymorphism ( p -value = 0.006)) that were nominally associated, and three variants (two variants in BDNF and one variant in the BDNF-AS locus) that were significantly associated with long-term visual memory. Our data therefore suggests a potential role for BDNF , and its anti-sense transcript BDNF-AS , in long-term visual memory performance.

BDNF Variants May Modulate Long-Term Visual Memory Performance in a Healthy Cohort

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Nesli Avgan

2017-03-01

Full Text Available Brain-derived neurotrophic factor (BDNF is involved in numerous cognitive functions including learning and memory. BDNF plays an important role in synaptic plasticity in humans and rats with BDNF shown to be essential for the formation of long-term memories. We previously identified a significant association between the BDNF Val66Met polymorphism (rs6265 and long-term visual memory (p-value = 0.003 in a small cohort (n = 181 comprised of healthy individuals who had been phenotyped for various aspects of memory function. In this study, we have extended the cohort to 597 individuals and examined multiple genetic variants across both the BDNF and BDNF-AS genes for association with visual memory performance as assessed by the Wechsler Memory Scale—Fourth Edition subtests Visual Reproduction I and II (VR I and II. VR I assesses immediate visual memory, whereas VR II assesses long-term visual memory. Genetic association analyses were performed for 34 single nucleotide polymorphisms genotyped on Illumina OmniExpress BeadChip arrays with the immediate and long-term visual memory phenotypes. While none of the BDNF and BDNF-AS variants were shown to be significant for immediate visual memory, we found 10 variants (including the Val66Met polymorphism (p-value = 0.006 that were nominally associated, and three variants (two variants in BDNF and one variant in the BDNF-AS locus that were significantly associated with long-term visual memory. Our data therefore suggests a potential role for BDNF, and its anti-sense transcript BDNF-AS, in long-term visual memory performance.