c-Rel, an NF-[kappa]B Family Transcription Factor, Is Required for Hippocampal Long-Term Synaptic Plasticity and Memory Formation

ERIC Educational Resources Information Center

Ahn, Hyung Jin; Hernandez, Caterina M.; Levenson, Jonathan M.; Lubin, Farah D.; Liou, Hsiou-Chi; Sweatt, J. David

2008-01-01

Transcription is a critical component for consolidation of long-term memory. However, relatively few transcriptional mechanisms have been identified for the regulation of gene expression in memory formation. In the current study, we investigated the activity of one specific member of the NF-[kappa]B transcription factor family, c-Rel, during…

Context Memory Formation Requires Activity-Dependent Protein Degradation in the Hippocampus

ERIC Educational Resources Information Center

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

2017-01-01

Numerous studies have indicated that the consolidation of contextual fear memories supported by an aversive outcome like footshock requires de novo protein synthesis as well as protein degradation mediated by the ubiquitin-proteasome system (UPS). Context memory formed in the absence of an aversive stimulus by simple exposure to a novel…

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

PubMed

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

2018-03-01

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

Fasting launches CRTC to facilitate long-term memory formation in Drosophila.

PubMed

Hirano, Yukinori; Masuda, Tomoko; Naganos, Shintaro; Matsuno, Motomi; Ueno, Kohei; Miyashita, Tomoyuki; Horiuchi, Junjiro; Saitoe, Minoru

2013-01-25

Canonical aversive long-term memory (LTM) formation in Drosophila requires multiple spaced trainings, whereas appetitive LTM can be formed after a single training. Appetitive LTM requires fasting prior to training, which increases motivation for food intake. However, we found that fasting facilitated LTM formation in general; aversive LTM formation also occurred after single-cycle training when mild fasting was applied before training. Both fasting-dependent LTM (fLTM) and spaced training-dependent LTM (spLTM) required protein synthesis and cyclic adenosine monophosphate response element-binding protein (CREB) activity. However, spLTM required CREB activity in two neural populations--mushroom body and DAL neurons--whereas fLTM required CREB activity only in mushroom body neurons. fLTM uses the CREB coactivator CRTC, whereas spLTM uses the coactivator CBP. Thus, flies use distinct LTM machinery depending on their hunger state.

The epigenetic basis of memory formation and storage.

PubMed

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

2014-01-01

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

Medial prefrontal cortex dopamine controls the persistent storage of aversive memories

PubMed Central

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

Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway

PubMed Central

Gao, Jun; Joseph, Nadine; Xie, Zhigang; Zhou, Ying; Durak, Omer; Zhang, Lei; Zhu, J. Julius; Clauser, Karl R.; Carr, Steven A.; Tsai, Li-Huei

2011-01-01

Memory formation is modulated by pre- and post-synaptic signaling events in neurons. The neuronal protein kinase Cyclin-Dependent Kinase 5 (Cdk5) phosphorylates a variety of synaptic substrates and is implicated in memory formation. It has also been shown to play a role in homeostatic regulation of synaptic plasticity in cultured neurons. Surprisingly, we found that Cdk5 loss of function in hippocampal circuits results in severe impairments in memory formation and retrieval. Moreover, Cdk5 loss of function in the hippocampus disrupts cAMP signaling due to an aberrant increase in phosphodiesterase (PDE) proteins. Dysregulation of cAMP is associated with defective CREB phosphorylation and disrupted composition of synaptic proteins in Cdk5-deficient mice. Rolipram, a PDE4 inhibitor that prevents cAMP depletion, restores synaptic plasticity and memory formation in Cdk5-deficient mice. Collectively, our results demonstrate a critical role for Cdk5 in the regulation of cAMP-mediated hippocampal functions essential for synaptic plasticity and memory formation. PMID:21984943

Myosin II Motor Activity in the Lateral Amygdala Is Required for Fear Memory Consolidation

ERIC Educational Resources Information Center

Gavin, Cristin F.; Rubio, Maria D.; Young, Erica; Miller, Courtney; Rumbaugh, Gavin

2012-01-01

Learning induces dynamic changes to the actin cytoskeleton that are required to support memory formation. However, the molecular mechanisms that mediate filamentous actin (F-actin) dynamics during learning and memory are poorly understood. Myosin II motors are highly expressed in actin-rich growth structures including dendritic spines, and we have…

p300/CBP Histone Acetyltransferase Activity Is Required for Newly Acquired and Reactivated Fear Memories in the Lateral Amygdala

ERIC Educational Resources Information Center

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

2013-01-01

Modifications in chromatin structure have been widely implicated in memory and cognition, most notably using hippocampal-dependent memory paradigms including object recognition, spatial memory, and contextual fear memory. Relatively little is known, however, about the role of chromatin-modifying enzymes in amygdala-dependent memory formation.…

HDAC3 and the Molecular Brake Pad Hypothesis

PubMed Central

McQuown, Susan C.; Wood, Marcelo A.

2011-01-01

Successful transcription of specific genes required for long-term memory processes involves the orchestrated effort of not only transcription factors, but also very specific enzymatic protein complexes that modify chromatin structure. Chromatin modification has been identified as a pivotal molecular mechanism underlying certain forms of synaptic plasticity and memory. The best-studied form of chromatin modification in the learning and memory field is histone acetylation, which is regulated by histone acetyltransferases and histone deacetylases (HDACs). HDAC inhibitors have been shown to strongly enhance long-term memory processes, and recent work has aimed to identify contributions of individual HDACs. In this review, we focus on HDAC3 and discuss its recently defined role as a negative regulator of long-term memory formation. HDAC3 is part of a corepressor complex and has direct interactions with class II HDACs that may be important for its molecular and behavioral consequences. And last, we propose the “molecular brake pad” hypothesis of HDAC function. The HDACs and associated corepressor complexes may function in neurons, in part, as “molecular brake pads.” HDACs are localized to promoters of active genes and act as a persistent clamp that requires strong activity-dependent signaling to temporarily release these complexes (or brake pads) to activate gene expression required for long-term memory formation. Thus, HDAC inhibition removes the “molecular brake pads” constraining the processes necessary for long-term memory and results in strong, persistent memory formation. PMID:21521655

SODR Memory Control Buffer Control ASIC

NASA Technical Reports Server (NTRS)

Hodson, Robert F.

1994-01-01

The Spacecraft Optical Disk Recorder (SODR) is a state of the art mass storage system for future NASA missions requiring high transmission rates and a large capacity storage system. This report covers the design and development of an SODR memory buffer control applications specific integrated circuit (ASIC). The memory buffer control ASIC has two primary functions: (1) buffering data to prevent loss of data during disk access times, (2) converting data formats from a high performance parallel interface format to a small computer systems interface format. Ten 144 p in, 50 MHz CMOS ASIC's were designed, fabricated and tested to implement the memory buffer control function.

Astrocyte glycogen and lactate: New insights into learning and memory mechanisms.

PubMed

Alberini, Cristina M; Cruz, Emmanuel; Descalzi, Giannina; Bessières, Benjamin; Gao, Virginia

2018-06-01

Memory, the ability to retain learned information, is necessary for survival. Thus far, molecular and cellular investigations of memory formation and storage have mainly focused on neuronal mechanisms. In addition to neurons, however, the brain comprises other types of cells and systems, including glia and vasculature. Accordingly, recent experimental work has begun to ask questions about the roles of non-neuronal cells in memory formation. These studies provide evidence that all types of glial cells (astrocytes, oligodendrocytes, and microglia) make important contributions to the processing of encoded information and storing memories. In this review, we summarize and discuss recent findings on the critical role of astrocytes as providers of energy for the long-lasting neuronal changes that are necessary for long-term memory formation. We focus on three main findings: first, the role of glucose metabolism and the learning- and activity-dependent metabolic coupling between astrocytes and neurons in the service of long-term memory formation; second, the role of astrocytic glucose metabolism in arousal, a state that contributes to the formation of very long-lasting and detailed memories; and finally, in light of the high energy demands of the brain during early development, we will discuss the possible role of astrocytic and neuronal glucose metabolisms in the formation of early-life memories. We conclude by proposing future directions and discussing the implications of these findings for brain health and disease. Astrocyte glycogenolysis and lactate play a critical role in memory formation. Emotionally salient experiences form strong memories by recruiting astrocytic β2 adrenergic receptors and astrocyte-generated lactate. Glycogenolysis and astrocyte-neuron metabolic coupling may also play critical roles in memory formation during development, when the energy requirements of brain metabolism are at their peak. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2015-10-01

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

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

PubMed

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

2017-11-01

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

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

PubMed

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

2015-12-01

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

Metaplasticity contributes to memory formation in the hippocampus.

PubMed

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

2018-05-16

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

AMPK Signaling in the Dorsal Hippocampus Negatively Regulates Contextual Fear Memory Formation

PubMed Central

Han, Ying; Luo, Yixiao; Sun, Jia; Ding, Zengbo; Liu, Jianfeng; Yan, Wei; Jian, Min; Xue, Yanxue; Shi, Jie; Wang, Ji-Shi; Lu, Lin

2016-01-01

Both the formation of long-term memory (LTM) and dendritic spine growth that serves as a physical basis for the long-term storage of information require de novo protein synthesis. Memory formation also critically depends on transcription. Adenosine monophosphate-activated protein kinase (AMPK) is a transcriptional regulator that has emerged as a major energy sensor that maintains cellular energy homeostasis. However, still unknown is its role in memory formation. In the present study, we found that AMPK is primarily expressed in neurons in the hippocampus, and then we demonstrated a time-dependent decrease in AMPK activity and increase in mammalian target of rapamycin complex 1 (mTORC1) activity after contextual fear conditioning in the CA1 but not CA3 area of the dorsal hippocampus. Using pharmacological methods and adenovirus gene transfer to bidirectionally regulate AMPK activity, we found that increasing AMPK activity in the CA1 impaired the formation of long-term fear memory, and decreasing AMPK activity enhanced fear memory formation. These findings were associated with changes in the phosphorylation of AMPK and p70s6 kinase (p70s6k) and expression of BDNF and membrane GluR1 and GluR2 in the CA1. Furthermore, the prior administration of an mTORC1 inhibitor blocked the enhancing effect of AMPK inhibition on fear memory formation, suggesting that this negative regulation of contextual fear memory by AMPK in the CA1 depends on the mTORC1 signaling pathway. Finally, we found that AMPK activity regulated hippocampal spine growth associated with memory formation. In summary, our results indicate that AMPK is a key negative regulator of plasticity and fear memory formation. PMID:26647974

Growth Factor Signaling and Memory Formation: Temporal and Spatial Integration of a Molecular Network

ERIC Educational Resources Information Center

Kopec, Ashley M.; Carew, Thomas J.

2013-01-01

Growth factor (GF) signaling is critically important for developmental plasticity. It also plays a crucial role in adult plasticity, such as that required for memory formation. Although different GFs interact with receptors containing distinct types of kinase domains, they typically signal through converging intracellular cascades (e.g.,…

Dopaminergic neurons write and update memories with cell-type-specific rules

PubMed Central

Aso, Yoshinori; Rubin, Gerald M

2016-01-01

Associative learning is thought to involve parallel and distributed mechanisms of memory formation and storage. In Drosophila, the mushroom body (MB) is the major site of associative odor memory formation. Previously we described the anatomy of the adult MB and defined 20 types of dopaminergic neurons (DANs) that each innervate distinct MB compartments (Aso et al., 2014a, 2014b). Here we compare the properties of memories formed by optogenetic activation of individual DAN cell types. We found extensive differences in training requirements for memory formation, decay dynamics, storage capacity and flexibility to learn new associations. Even a single DAN cell type can either write or reduce an aversive memory, or write an appetitive memory, depending on when it is activated relative to odor delivery. Our results show that different learning rules are executed in seemingly parallel memory systems, providing multiple distinct circuit-based strategies to predict future events from past experiences. DOI: http://dx.doi.org/10.7554/eLife.16135.001 PMID:27441388

Requirement of the Combination of Mushroom Body ? Lobe and a/ß Lobes for the Retrieval of Both Aversive and Appetitive Early Memories in "Drosophila"

ERIC Educational Resources Information Center

Xie, Zhiyong; Huang, Cheng; Ci, Bo; Lianzhang, Wang; Zhong, Yi

2013-01-01

Extensive studies of "Drosophila" mushroom body in formation and retrieval of olfactory memories allow us to delineate the functional logic for memory storage and retrieval. Currently, there is a questionable disassociation of circuits for memory storage and retrieval during "Drosophila" olfactory memory processing. Formation…

Learning and memory: Steroids and epigenetics.

PubMed

Colciago, Alessandra; Casati, Lavinia; Negri-Cesi, Paola; Celotti, Fabio

2015-06-01

Memory formation and utilization is a complex process involving several brain structures in conjunction as the hippocampus, the amygdala and the adjacent cortical areas, usually defined as medial temporal lobe structures (MTL). The memory processes depend on the formation and modulation of synaptic connectivity affecting synaptic strength, synaptic plasticity and synaptic consolidation. The basic neurocognitive mechanisms of learning and memory are shortly recalled in the initial section of this paper. The effect of sex hormones (estrogens, androgens and progesterone) and of adrenocortical steroids on several aspects of memory processes are then analyzed on the basis of animal and human studies. A specific attention has been devoted to the different types of steroid receptors (membrane or nuclear) involved and on local metabolic transformations when required. The review is concluded by a short excursus on the steroid activated epigenetic mechanisms involved in memory formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Subliminal encoding and flexible retrieval of objects in scenes.

PubMed

Wuethrich, Sergej; Hannula, Deborah E; Mast, Fred W; Henke, Katharina

2018-04-27

Our episodic memory stores what happened when and where in life. Episodic memory requires the rapid formation and flexible retrieval of where things are located in space. Consciousness of the encoding scene is considered crucial for episodic memory formation. Here, we question the necessity of consciousness and hypothesize that humans can form unconscious episodic memories. Participants were presented with subliminal scenes, i.e., scenes invisible to the conscious mind. The scenes displayed objects at certain locations for participants to form unconscious object-in-space memories. Later, the same scenes were presented supraliminally, i.e., visibly, for retrieval testing. Scenes were presented absent the objects and rotated by 90°-270° in perspective to assess the representational flexibility of unconsciously formed memories. During the test phase, participants performed a forced-choice task that required them to place an object in one of two highlighted scene locations and their eye movements were recorded. Evaluation of the eye tracking data revealed that participants remembered object locations unconsciously, irrespective of changes in viewing perspective. This effect of gaze was related to correct placements of objects in scenes, and an intuitive decision style was necessary for unconscious memories to influence intentional behavior to a significant degree. We conclude that conscious perception is not mandatory for spatial episodic memory formation. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

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

PubMed

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

2015-07-15

Regulated expression and secretion of BDNF, which activates TrkB receptor signaling, is known to play a critical role in cognition. Identification of additional modulators of cognitive behavior that regulate activity-dependent BDNF secretion and/or potentiate TrkB receptor signaling would therefore be of considerable interest. In this study, we show in the adult mouse hippocampus that expression of the granin family gene Vgf and secretion of its C-terminal VGF-derived peptide TLQP-62 are required for fear memory formation. We found that hippocampal VGF expression and TLQP-62 levels were transiently induced after fear memory training and that sequestering secreted TLQP-62 peptide in the hippocampus immediately after training impaired memory formation. Reduced VGF expression was found to impair learning-evoked Rac1 induction and phosphorylation of the synaptic plasticity markers cofilin and synapsin in the adult mouse hippocampus. Moreover, TLQP-62 induced acute, transient activation of the TrkB receptor and subsequent CREB phosphorylation in hippocampal slice preparations and its administration immediately after training enhanced long-term memory formation. A critical role of BDNF-TrkB signaling as a downstream effector in VGF/TLQP-62-mediated memory consolidation was further revealed by posttraining activation of BDNF-TrkB signaling, which rescued impaired fear memory resulting from hippocampal administration of anti-VGF antibodies or germline VGF ablation in mice. We propose that VGF is a critical component of a positive BDNF-TrkB regulatory loop and, upon its induced expression by memory training, the TLQP-62 peptide rapidly reinforces BDNF-TrkB signaling, regulating hippocampal memory consolidation. Identification of the cellular and molecular mechanisms that regulate long-term memory formation and storage may provide alternative treatment modalities for degenerative and neuropsychiatric memory disorders. The neurotrophin BDNF plays a prominent role in cognitive function, and rapidly and robustly induces expression of VGF, a secreted neuronal peptide precursor. VGF knock-out mice have impaired fear and spatial memory. Our study shows that VGF and VGF-derived peptide TLQP-62 are transiently induced after fear memory training, leading to increased BDNF/TrkB signaling, and that sequestration of hippocampal TLQP-62 immediately after training impairs memory formation. We propose that TLQP-62 is a critical component of a positive regulatory loop that is induced by memory training, rapidly reinforces BDNF-TrkB signaling, and is required for hippocampal memory consolidation. Copyright © 2015 the authors 0270-6474/15/3510344-14$15.00/0.

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

PubMed Central

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

2015-01-01

Regulated expression and secretion of BDNF, which activates TrkB receptor signaling, is known to play a critical role in cognition. Identification of additional modulators of cognitive behavior that regulate activity-dependent BDNF secretion and/or potentiate TrkB receptor signaling would therefore be of considerable interest. In this study, we show in the adult mouse hippocampus that expression of the granin family gene Vgf and secretion of its C-terminal VGF-derived peptide TLQP-62 are required for fear memory formation. We found that hippocampal VGF expression and TLQP-62 levels were transiently induced after fear memory training and that sequestering secreted TLQP-62 peptide in the hippocampus immediately after training impaired memory formation. Reduced VGF expression was found to impair learning-evoked Rac1 induction and phosphorylation of the synaptic plasticity markers cofilin and synapsin in the adult mouse hippocampus. Moreover, TLQP-62 induced acute, transient activation of the TrkB receptor and subsequent CREB phosphorylation in hippocampal slice preparations and its administration immediately after training enhanced long-term memory formation. A critical role of BDNF-TrkB signaling as a downstream effector in VGF/TLQP-62-mediated memory consolidation was further revealed by posttraining activation of BDNF-TrkB signaling, which rescued impaired fear memory resulting from hippocampal administration of anti-VGF antibodies or germline VGF ablation in mice. We propose that VGF is a critical component of a positive BDNF-TrkB regulatory loop and, upon its induced expression by memory training, the TLQP-62 peptide rapidly reinforces BDNF-TrkB signaling, regulating hippocampal memory consolidation. SIGNIFICANCE STATEMENT Identification of the cellular and molecular mechanisms that regulate long-term memory formation and storage may provide alternative treatment modalities for degenerative and neuropsychiatric memory disorders. The neurotrophin BDNF plays a prominent role in cognitive function, and rapidly and robustly induces expression of VGF, a secreted neuronal peptide precursor. VGF knock-out mice have impaired fear and spatial memory. Our study shows that VGF and VGF-derived peptide TLQP-62 are transiently induced after fear memory training, leading to increased BDNF/TrkB signaling, and that sequestration of hippocampal TLQP-62 immediately after training impairs memory formation. We propose that TLQP-62 is a critical component of a positive regulatory loop that is induced by memory training, rapidly reinforces BDNF-TrkB signaling, and is required for hippocampal memory consolidation. PMID:26180209

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

PubMed Central

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

2016-01-01

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

NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors

PubMed Central

Hawk, Joshua D.; Bookout, Angie L.; Poplawski, Shane G.; Bridi, Morgan; Rao, Allison J.; Sulewski, Michael E.; Kroener, Brian T.; Manglesdorf, David J.; Abel, Ted

2012-01-01

The formation of a long-lasting memory requires a transcription-dependent consolidation period that converts a short-term memory into a long-term memory. Nuclear receptors compose a class of transcription factors that regulate diverse biological processes, and several nuclear receptors have been implicated in memory formation. Here, we examined the potential contribution of nuclear receptors to memory consolidation by measuring the expression of all 49 murine nuclear receptors after learning. We identified 13 nuclear receptors with increased expression after learning, including all 3 members of the Nr4a subfamily. These CREB-regulated Nr4a genes encode ligand-independent “orphan” nuclear receptors. We found that blocking NR4A activity in memory-supporting brain regions impaired long-term memory but did not impact short-term memory in mice. Further, expression of Nr4a genes increased following the memory-enhancing effects of histone deacetylase (HDAC) inhibitors. Blocking NR4A signaling interfered with the ability of HDAC inhibitors to enhance memory. These results demonstrate that the Nr4a gene family contributes to memory formation and is a promising target for improving cognitive function. PMID:22996661

The effect of rearing environment on memory formation.

PubMed

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

2018-05-22

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

NMDA Receptor- and ERK-Dependent Histone Methylation Changes in the Lateral Amygdala Bidirectionally Regulate Fear Memory Formation

ERIC Educational Resources Information Center

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

2014-01-01

It is well established that fear memory formation requires de novo gene transcription in the amygdala. We provide evidence that epigenetic mechanisms in the form of histone lysine methylation in the lateral amygdala (LA) are regulated by NMDA receptor (NMDAR) signaling and involved in gene transcription changes necessary for fear memory…

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

PubMed

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

2015-10-22

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

Transgenic Mice Expressing an Inhibitory Truncated Form of p300 Exhibit Long-Term Memory Deficits

ERIC Educational Resources Information Center

Oliveira, Ana M. M.; Wood, Marcelo A.; McDonough, Conor B.; Abel, Ted

2007-01-01

The formation of many forms of long-term memory requires several molecular mechanisms including regulation of gene expression. The mechanisms directing transcription require not only activation of individual transcription factors but also recruitment of transcriptional coactivators. CBP and p300 are transcriptional coactivators that interact with…

Cyclic Nucleotide-Gated Channels, Calmodulin, Adenylyl Cyclase, and Calcium/Calmodulin-Dependent Protein Kinase II Are Required for Late, but Not Early, Long-Term Memory Formation in the Honeybee

ERIC Educational Resources Information Center

Matsumoto, Yukihisa; Sandoz, Jean-Christophe; Devaud, Jean-Marc; Lormant, Flore; Mizunami, Makoto; Giurfa, Martin

2014-01-01

Memory is a dynamic process that allows encoding, storage, and retrieval of information acquired through individual experience. In the honeybee "Apis mellifera," olfactory conditioning of the proboscis extension response (PER) has shown that besides short-term memory (STM) and mid-term memory (MTM), two phases of long-term memory (LTM)…

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

PubMed

White, André O; Wood, Marcelo A

2014-07-01

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

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

PubMed Central

White, André O.; Wood, Marcelo A.

2013-01-01

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

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

PubMed

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.

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

PubMed

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

2018-02-23

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

Hippocampal-dependent memory in the plus-maze discriminative avoidance task: The role of spatial cues and CA1 activity.

PubMed

Leão, Anderson H F F; Medeiros, André M; Apolinário, Gênedy K S; Cabral, Alícia; Ribeiro, Alessandra M; Barbosa, Flávio F; Silva, Regina H

2016-05-01

The plus-maze discriminative avoidance task (PMDAT) has been used to investigate interactions between aversive memory and an anxiety-like response in rodents. Suitable performance in this task depends on the activity of the basolateral amygdala, similar to other aversive-based memory tasks. However, the role of spatial cues and hippocampal-dependent learning in the performance of PMDAT remains unknown. Here, we investigated the role of proximal and distal cues in the retrieval of this task. Animals tested under misplaced proximal cues had diminished performance, and animals tested under both misplaced proximal cues and absent distal cues could not discriminate the aversive arm. We also assessed the role of the dorsal hippocampus (CA1) in this aversive memory task. Temporary bilateral inactivation of dorsal CA1 was conducted with muscimol (0.05 μg, 0.1 μg, and 0.2 μg) prior to the training session. While the acquisition of the task was not altered, muscimol impaired the performance in the test session and reduced the anxiety-like response in the training session. We also performed a spreading analysis of a fluorophore-conjugated muscimol to confirm selective inhibition of CA1. In conclusion, both distal and proximal cues are required to retrieve the task, with the latter being more relevant to spatial orientation. Dorsal CA1 activity is also required for aversive memory formation in this task, and interfered with the anxiety-like response as well. Importantly, both effects were detected by different parameters in the same paradigm, endorsing the previous findings of independent assessment of aversive memory and anxiety-like behavior in the PMDAT. Taken together, these findings suggest that the PMDAT probably requires an integration of multiple systems for memory formation, resembling an episodic-like memory rather than a pure conditioning behavior. Furthermore, the concomitant and independent assessment of emotionality and memory in rodents is relevant to elucidate how these memory systems interact during aversive memory formation. Thus, the PMDAT can be useful for studying hippocampal-dependent memory when it involves emotional content. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-12-06

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

CASK and CaMKII function in the mushroom body α'/β' neurons during Drosophila memory formation.

PubMed

Malik, Bilal R; Gillespie, John Michael; Hodge, James J L

2013-01-01

Ca(2+)/CaM serine/threonine kinase II (CaMKII) is a central molecule in mechanisms of synaptic plasticity and memory. A vital feature of CaMKII in plasticity is its ability to switch to a calcium (Ca(2+)) independent constitutively active state after autophosphorylation at threonine 287 (T287). A second pair of sites, T306 T307 in the calmodulin (CaM) binding region once autophosphorylated, prevent subsequent CaM binding and inactivates the kinase during synaptic plasticity and memory. Recently a synaptic molecule called Ca(2+)/CaM-dependent serine protein kinase (CASK) has been shown to control both sets of CaMKII autophosphorylation events and hence is well poised to be a key regulator of memory. We show deletion of full length CASK or just its CaMK-like and L27 domains disrupts middle-term memory (MTM) and long-term memory (LTM), with CASK function in the α'/β' subset of mushroom body neurons being required for memory. Likewise directly changing the levels of CaMKII autophosphorylation in these neurons removed MTM and LTM. The requirement of CASK and CaMKII autophosphorylation was not developmental as their manipulation just in the adult α'/β' neurons was sufficient to remove memory. Overexpression of CASK or CaMKII in the α'/β' neurons also occluded MTM and LTM. Overexpression of either Drosophila or human CASK in the α'/β' neurons of the CASK mutant completely rescued memory, confirming that CASK signaling in α'/β' neurons is necessary and sufficient for Drosophila memory formation and that the neuronal function of CASK is conserved between Drosophila and human. At the cellular level CaMKII overexpression in the α'/β' neurons increased activity dependent Ca(2+) responses while reduction of CaMKII decreased it. Likewise reducing CASK or directly expressing a phosphomimetic CaMKII T287D transgene in the α'/β' similarly decreased Ca(2+) signaling. Our results are consistent with CASK regulating CaMKII autophosphorylation in a pathway required for memory formation that involves activity dependent changes in Ca(2+) signaling in the α'/β' neurons.

Endogenous BDNF Is Required for Long-Term Memory Formation in the Rat Parietal Cortex

ERIC Educational Resources Information Center

Alonso, Mariana; Bekinschtein, Pedro, Cammarota, Martin; Vianna, Monica R. M.; Izquierdo, Ivan; 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…

Memory, reconsolidation and extinction in Lymnaea require the soma of RPeD1.

PubMed

Sangha, Susan; Varshney, Nishi; Fras, Mary; Smyth, Kim; Rosenegger, David; Parvez, Kashif; Sadamoto, Hisayo; Lukowiak, Ken

2004-01-01

The central pattern generator (CPG) that drives aerial respiratory behaviour in Lymnaea consists of 3 neurons. One of these, RPeD1--the cell that initiates activity in the circuit, plays an absolutely necessary role as a site for memory formation, memory reconsolidation, and extinction. Using an operant conditioning training procedure that results in a long-term non-declarative memory (LTM), we decrease the occurrence of aerial respiratory behaviour. Since snails can still breathe cutaneously learning this procedure is not harmful. Concomitant with behavioural memory are changes in the spiking activity of RPeD1. Going beyond neural correlates of memory we directly show that RPeD1 is a necessary site for LTM formation. Expanding on this finding we show that this neuron is also a necessary site for memory reconsolidation and 'Pavlovian' extinction. As far as we can determine, this is the first time a single neuron has been shown to be a necessary site for these different aspects memory. RPeD1 is thus a key neuron mediating different hierarchical aspects of memory. We are now in a position to determine the necessary neuronal, molecular and proteomic events in this neuron that are causal to memory formation, reconsolidation and extinction.

Early Growth Response Gene 1 ("EGR-1") Is Required for New and Reactivated Fear Memories in the Lateral Amygdala

ERIC Educational Resources Information Center

Maddox, Stephanie A.; Monsey, Melissa S.; Schafe, Glenn E.

2011-01-01

The immediate-early gene early growth response gene-1 (EGR-1, zif-268) has been extensively studied in synaptic plasticity and memory formation in a variety of memory systems. However, a convincing role for EGR-1 in amygdala-dependent memory consolidation processes has yet to emerge. In the present study, we have examined the role of EGR-1 in the…

A model for memory systems based on processing modes rather than consciousness.

PubMed

Henke, Katharina

2010-07-01

Prominent models of human long-term memory distinguish between memory systems on the basis of whether learning and retrieval occur consciously or unconsciously. Episodic memory formation requires the rapid encoding of associations between different aspects of an event which, according to these models, depends on the hippocampus and on consciousness. However, recent evidence indicates that the hippocampus mediates rapid associative learning with and without consciousness in humans and animals, for long-term and short-term retention. Consciousness seems to be a poor criterion for differentiating between declarative (or explicit) and non declarative (or implicit) types of memory. A new model is therefore required in which memory systems are distinguished based on the processing operations involved rather than by consciousness.

SNAP-25 in hippocampal CA3 region is required for long-term memory formation

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

Hou Qiuling; Gao Xiang; Lu Qi

SNAP-25 is a synaptosomal protein of 25 kDa, a key component of synaptic vesicle-docking/fusion machinery, and plays a critical role in exocytosis and neurotransmitter release. We previously reported that SNAP-25 in the hippocampal CA1 region is involved in consolidation of contextual fear memory and water-maze spatial memory (Hou et al. European J Neuroscience, 20: 1593-1603, 2004). SNAP-25 is expressed not only in the CA1 region, but also in the CA3 region, and the SNAP-25 mRNA level in the CA3 region is higher than in the CA1 region. Here, we provide evidence that SNAP-25 in the CA3 region is also involvedmore » in learning/memory. Intra-CA3 infusion of SNAP-25 antisense oligonucleotide impaired both long-term contextual fear memory and water-maze spatial memory, with short-term memory intact. Furthermore, the SNAP-25 antisense oligonucleotide suppressed the long-term potentiation (LTP) of field excitatory post-synaptic potential (fEPSP) in the mossy-fiber pathway (DG-CA3 pathway), with no effect on paired-pulse facilitation of the fEPSP. These results are consistent with the notion that SNAP-25 in the hippocampal CA3 region is required for long-term memory formation.« less

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

PubMed

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

2010-09-29

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

Cell-Type-Specific Transcriptome Analysis in the Drosophila Mushroom Body Reveals Memory-Related Changes in Gene Expression.

PubMed

Crocker, Amanda; Guan, Xiao-Juan; Murphy, Coleen T; Murthy, Mala

2016-05-17

Learning and memory formation in Drosophila rely on a network of neurons in the mushroom bodies (MBs). Whereas numerous studies have delineated roles for individual cell types within this network in aspects of learning or memory, whether or not these cells can also be distinguished by the genes they express remains unresolved. In addition, the changes in gene expression that accompany long-term memory formation within the MBs have not yet been studied by neuron type. Here, we address both issues by performing RNA sequencing on single cell types (harvested via patch pipets) within the MB. We discover that the expression of genes that encode cell surface receptors is sufficient to identify cell types and that a subset of these genes, required for sensory transduction in peripheral sensory neurons, is not only expressed within individual neurons of the MB in the central brain, but is also critical for memory formation. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2017-01-01

Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on β-adrenergic receptors (βARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms. Specifically, using behavioral pharmacology and biochemistry in adult rats, we determined that βAR activity during, but not after PTC training initiates the activation of two plasticity-related targets: AMPA receptors (AMPARs) for memory acquisition and short-term memory and extracellular regulated kinase (ERK) for consolidating the learned association into a long-term memory. These findings reveal that βAR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations. PMID:27762270

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

PubMed

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

2017-03-01

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

A Transcription Factor-Binding Domain of the Coactivator CBP Is Essential for Long-Term Memory and the Expression of Specific Target Genes

ERIC Educational Resources Information Center

Oliveira, Ana M. M.; Brindle, Paul K.; Abel, Ted; Wood, Marcelo A.; Attner, Michelle A.

2006-01-01

Transcriptional activation is a key process required for long-term memory formation. Recently, the transcriptional coactivator CREB-binding protein (CBP) was shown to be critical for hippocampus-dependent long-term memory and hippocampal synaptic plasticity. As a coactivator with intrinsic histone acetyltransferase activity, CBP interacts with…

CD22 is required for formation of memory B cell precursors within germinal centers.

PubMed

Chappell, Craig P; Draves, Kevin E; Clark, Edward A

2017-01-01

CD22 is a BCR co-receptor that regulates B cell signaling, proliferation and survival and is required for T cell-independent Ab responses. To investigate the role of CD22 during T cell-dependent (TD) Ab responses and memory B cell formation, we analyzed Ag-specific B cell responses generated by wild-type (WT) or CD22-/- B cells following immunization with a TD Ag. CD22-/- B cells mounted normal early Ab responses yet failed to generate either memory B cells or long-lived plasma cells, whereas WT B cells formed both populations. Surprisingly, B cell expansion and germinal center (GC) differentiation were comparable between WT and CD22-/- B cells. CD22-/- B cells, however, were significantly less capable of generating a population of CXCR4hiCD38hi GC B cells, which we propose represent memory B cell precursors within GCs. These results demonstrate a novel role for CD22 during TD humoral responses evident during primary GC formation and underscore that CD22 functions not only during B cell maturation but also during responses to both TD and T cell-independent antigens.

CD22 is required for formation of memory B cell precursors within germinal centers

PubMed Central

Chappell, Craig P.; Draves, Kevin E.

2017-01-01

CD22 is a BCR co-receptor that regulates B cell signaling, proliferation and survival and is required for T cell-independent Ab responses. To investigate the role of CD22 during T cell-dependent (TD) Ab responses and memory B cell formation, we analyzed Ag-specific B cell responses generated by wild-type (WT) or CD22-/- B cells following immunization with a TD Ag. CD22-/- B cells mounted normal early Ab responses yet failed to generate either memory B cells or long-lived plasma cells, whereas WT B cells formed both populations. Surprisingly, B cell expansion and germinal center (GC) differentiation were comparable between WT and CD22-/- B cells. CD22-/- B cells, however, were significantly less capable of generating a population of CXCR4hiCD38hi GC B cells, which we propose represent memory B cell precursors within GCs. These results demonstrate a novel role for CD22 during TD humoral responses evident during primary GC formation and underscore that CD22 functions not only during B cell maturation but also during responses to both TD and T cell-independent antigens. PMID:28346517

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

PubMed

Centeno, Tonatiuh Pena; Shomroni, Orr; Hennion, Magali; Halder, Rashi; Vidal, Ramon; Rahman, Raza-Ur; Bonn, Stefan

2016-10-11

Recent evidence suggests that the formation and maintenance of memory requires epigenetic changes. In an effort to understand the spatio-temporal extent of learning and memory-related epigenetic changes we have charted genome-wide histone and DNA methylation profiles, in two different brain regions, two cell types, and three time-points, before and after learning. In this data descriptor we provide detailed information on data generation, give insights into the rationale of experiments, highlight necessary steps to assess data quality, offer guidelines for future use of the data and supply ready-to-use code to replicate the analysis results. The data provides a blueprint of the gene regulatory network underlying short- and long-term memory formation and maintenance. This 'healthy' gene regulatory network of learning can now be compared to changes in neurological or psychiatric diseases, providing mechanistic insights into brain disorders and highlighting potential therapeutic avenues.

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

PubMed

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 nucleus reuniens (NRe) of the thalamus. However, the role of the NRe itself in associative recognition memory is unknown. Here, we reveal the crucial role of the NRe in encoding and retrieval of long-term object-in-place memory, but not for remembrance of an individual object or individual location and such involvement is cholinergic receptor and protein synthesis dependent. This is the first demonstration that the NRe is a key node within an associative recognition memory network and is not just a simple relay for information within the network. Rather, we argue, the NRe actively modulates information processing during long-term associative memory formation. Copyright © 2018 the authors 0270-6474/18/383208-10$15.00/0.

Trace and Contextual Fear Conditioning Require Neural Activity and NMDA Receptor-Dependent Transmission in the Medial Prefrontal Cortex

ERIC Educational Resources Information Center

Gilmartin, Marieke R.; Helmstetter, Fred J.

2010-01-01

The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a…

Hippocampal Metaplasticity Is Required for the Formation of Temporal Associative Memories

PubMed Central

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

2014-01-01

Metaplasticity regulates the threshold for modification of synaptic strength and is an important regulator of learning rules; however, it is not known whether these cellular mechanisms for homeostatic regulation of synapses contribute to particular forms of learning. Conditional ablation of mGluR5 in CA1 pyramidal neurons resulted in the inability of low-frequency trains of afferent activation to prime synapses for subsequent theta burst potentiation. Priming-induced metaplasticity requires mGluR5-mediated mobilization of endocannabinoids during the priming train to induce long-term depression of inhibition (I-LTD). Mice lacking priming-induced plasticity had no deficit in spatial reference memory tasks, but were impaired in an associative task with a temporal component. Conversely, enhancing endocannabinoid signaling facilitated temporal associative memory acquisition and, after training animals in these tasks, ex vivo I-LTD was partially occluded and theta burst LTP was enhanced. Together, these results suggest a link between metaplasticity mechanisms in the hippocampus and the formation of temporal associative memories. PMID:25505329

Role of Immediate-Early Genes in Synaptic Plasticity and Neuronal Ensembles Underlying the Memory Trace

PubMed Central

Minatohara, Keiichiro; Akiyoshi, Mika; Okuno, Hiroyuki

2016-01-01

In the brain, neuronal gene expression is dynamically changed in response to neuronal activity. In particular, the expression of immediate-early genes (IEGs) such as egr-1, c-fos, and Arc is rapidly and selectively upregulated in subsets of neurons in specific brain regions associated with learning and memory formation. IEG expression has therefore been widely used as a molecular marker for neuronal populations that undergo plastic changes underlying formation of long-term memory. In recent years, optogenetic and pharmacogenetic studies of neurons expressing c-fos or Arc have revealed that, during learning, IEG-positive neurons encode and store information that is required for memory recall, suggesting that they may be involved in formation of the memory trace. However, despite accumulating evidence for the role of IEGs in synaptic plasticity, the molecular and cellular mechanisms associated with this process remain unclear. In this review, we first summarize recent literature concerning the role of IEG-expressing neuronal ensembles in organizing the memory trace. We then focus on the physiological significance of IEGs, especially Arc, in synaptic plasticity, and describe our hypotheses about the importance of Arc expression in various types of input-specific circuit reorganization. Finally, we offer perspectives on Arc function that would unveil the role of IEG-expressing neurons in the formation of memory traces in the hippocampus and other brain areas. PMID:26778955

Protein Phosphatase-1 Inhibitor-2 Is a Novel Memory Suppressor.

PubMed

Yang, Hongtian; Hou, Hailong; Pahng, Amanda; Gu, Hua; Nairn, Angus C; Tang, Ya-Ping; Colombo, Paul J; Xia, Houhui

2015-11-11

Reversible phosphorylation, a fundamental regulatory mechanism required for many biological processes including memory formation, is coordinated by the opposing actions of protein kinases and phosphatases. Type I protein phosphatase (PP1), in particular, has been shown to constrain learning and memory formation. However, how PP1 might be regulated in memory is still not clear. Our previous work has elucidated that PP1 inhibitor-2 (I-2) is an endogenous regulator of PP1 in hippocampal and cortical neurons (Hou et al., 2013). Contrary to expectation, our studies of contextual fear conditioning and novel object recognition in I-2 heterozygous mice suggest that I-2 is a memory suppressor. In addition, lentiviral knock-down of I-2 in the rat dorsal hippocampus facilitated memory for tasks dependent on the hippocampus. Our data indicate that I-2 suppresses memory formation, probably via negatively regulating the phosphorylation of cAMP/calcium response element-binding protein (CREB) at serine 133 and CREB-mediated gene expression in dorsal hippocampus. Surprisingly, the data from both biochemical and behavioral studies suggest that I-2, despite its assumed action as a PP1 inhibitor, is a positive regulator of PP1 function in memory formation. We found that inhibitor-2 acts as a memory suppressor through its positive functional influence on type I protein phosphatase (PP1), likely resulting in negative regulation of cAMP/calcium response element-binding protein (CREB) and CREB-activated gene expression. Our studies thus provide an interesting example of a molecule with an in vivo function that is opposite to its in vitro function. PP1 plays critical roles in many essential physiological functions such as cell mitosis and glucose metabolism in addition to its known role in memory formation. PP1 pharmacological inhibitors would thus not be able to serve as good therapeutic reagents because of its many targets. However, identification of PP1 inhibitor-2 as a critical contributor to suppression of memory formation by PP1 may provide a novel therapeutic target for memory-related diseases. Copyright © 2015 the authors 0270-6474/15/3515082-06$15.00/0.

Imprinting: When Early Life Memories Make Food Smell Bad.

PubMed

Rayes, Diego; Alkema, Mark J

2016-05-09

A recent study has found that pathogen exposure early in the life of the nematode Caenorhabditis elegans leads to a long-lasting aversion that requires distinct sets of neurons for the formation and retrieval of the imprinted memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-04-07

Metabolic homeostasis is regulated by the brain, but whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help in balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipid levels. Importantly, this function of metabolic learning requires not only the mushroom body but also the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting that the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate that the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis.

CASK and CaMKII function in the mushroom body α′/β′ neurons during Drosophila memory formation

PubMed Central

Malik, Bilal R.; Gillespie, John Michael; Hodge, James J. L.

2013-01-01

Ca2+/CaM serine/threonine kinase II (CaMKII) is a central molecule in mechanisms of synaptic plasticity and memory. A vital feature of CaMKII in plasticity is its ability to switch to a calcium (Ca2+) independent constitutively active state after autophosphorylation at threonine 287 (T287). A second pair of sites, T306 T307 in the calmodulin (CaM) binding region once autophosphorylated, prevent subsequent CaM binding and inactivates the kinase during synaptic plasticity and memory. Recently a synaptic molecule called Ca2+/CaM-dependent serine protein kinase (CASK) has been shown to control both sets of CaMKII autophosphorylation events and hence is well poised to be a key regulator of memory. We show deletion of full length CASK or just its CaMK-like and L27 domains disrupts middle-term memory (MTM) and long-term memory (LTM), with CASK function in the α′/β′ subset of mushroom body neurons being required for memory. Likewise directly changing the levels of CaMKII autophosphorylation in these neurons removed MTM and LTM. The requirement of CASK and CaMKII autophosphorylation was not developmental as their manipulation just in the adult α′/β′ neurons was sufficient to remove memory. Overexpression of CASK or CaMKII in the α′/β′ neurons also occluded MTM and LTM. Overexpression of either Drosophila or human CASK in the α′/β′ neurons of the CASK mutant completely rescued memory, confirming that CASK signaling in α′/β′ neurons is necessary and sufficient for Drosophila memory formation and that the neuronal function of CASK is conserved between Drosophila and human. At the cellular level CaMKII overexpression in the α′/β′ neurons increased activity dependent Ca2+ responses while reduction of CaMKII decreased it. Likewise reducing CASK or directly expressing a phosphomimetic CaMKII T287D transgene in the α′/β′ similarly decreased Ca2+ signaling. Our results are consistent with CASK regulating CaMKII autophosphorylation in a pathway required for memory formation that involves activity dependent changes in Ca2+ signaling in the α′/β′ neurons. PMID:23543616

The Cambridge Car Memory Test: a task matched in format to the Cambridge Face Memory Test, with norms, reliability, sex differences, dissociations from face memory, and expertise effects.

PubMed

Dennett, Hugh W; McKone, Elinor; Tavashmi, Raka; Hall, Ashleigh; Pidcock, Madeleine; Edwards, Mark; Duchaine, Bradley

2012-06-01

Many research questions require a within-class object recognition task matched for general cognitive requirements with a face recognition task. If the object task also has high internal reliability, it can improve accuracy and power in group analyses (e.g., mean inversion effects for faces vs. objects), individual-difference studies (e.g., correlations between certain perceptual abilities and face/object recognition), and case studies in neuropsychology (e.g., whether a prosopagnosic shows a face-specific or object-general deficit). Here, we present such a task. Our Cambridge Car Memory Test (CCMT) was matched in format to the established Cambridge Face Memory Test, requiring recognition of exemplars across view and lighting change. We tested 153 young adults (93 female). Results showed high reliability (Cronbach's alpha = .84) and a range of scores suitable both for normal-range individual-difference studies and, potentially, for diagnosis of impairment. The mean for males was much higher than the mean for females. We demonstrate independence between face memory and car memory (dissociation based on sex, plus a modest correlation between the two), including where participants have high relative expertise with cars. We also show that expertise with real car makes and models of the era used in the test significantly predicts CCMT performance. Surprisingly, however, regression analyses imply that there is an effect of sex per se on the CCMT that is not attributable to a stereotypical male advantage in car expertise.

DNA methylation mediates neural processing after odor learning in the honeybee

PubMed Central

Biergans, Stephanie D.; Claudianos, Charles; Reinhard, Judith; Galizia, C. Giovanni

2017-01-01

DNA methyltransferases (Dnmts) - epigenetic writers catalyzing the transfer of methyl-groups to cytosine (DNA methylation) – regulate different aspects of memory formation in many animal species. In honeybees, Dnmt activity is required to adjust the specificity of olfactory reward memories and bees’ relearning capability. The physiological relevance of Dnmt-mediated DNA methylation in neural networks, however, remains unknown. Here, we investigated how Dnmt activity impacts neuroplasticity in the bees’ primary olfactory center, the antennal lobe (AL) an equivalent of the vertebrate olfactory bulb. The AL is crucial for odor discrimination, an indispensable process in forming specific odor memories. Using pharmacological inhibition, we demonstrate that Dnmt activity influences neural network properties during memory formation in vivo. We show that Dnmt activity promotes fast odor pattern separation in trained bees. Furthermore, Dnmt activity during memory formation increases both the number of responding glomeruli and the response magnitude to a novel odor. These data suggest that Dnmt activity is necessary for a form of homoeostatic network control which might involve inhibitory interneurons in the AL network. PMID:28240742

Semantic-episodic interactions in the neuropsychology of disbelief.

PubMed

Ladowsky-Brooks, Ricki; Alcock, James E

2007-03-01

The purpose of this paper is to outline ways in which characteristics of memory functioning determine truth judgements regarding verbally transmitted information. Findings on belief formation from several areas of psychology were reviewed in order to identify general principles that appear to underlie the designation of information in memory as "true" or "false". Studies on belief formation have demonstrated that individuals have a tendency to encode information as "true" and that an additional encoding step is required to tag information as "false". This additional step can involve acquisition and later recall of semantic-episodic associations between message content and contextual cues that signal that information is "false". Semantic-episodic interactions also appear to prevent new information from being accepted as "true" through encoding bias or the assignment of a "false" tag to data that is incompatible with prior knowledge. It is proposed that truth judgements are made through a combined weighting of the reliability of the information source and the compatibility of this information with already stored data. This requires interactions in memory. Failure to integrate different types of memories, such as semantic and episodic memories, can arise from mild hippocampal dysfunction and might result in delusions.

Rapid Encoding of New Memories by Individual Neurons in the Human Brain

PubMed Central

Ison, Matias J.; Quian Quiroga, Rodrigo; Fried, Itzhak

2015-01-01

Summary The creation of memories about real-life episodes requires rapid neuronal changes that may appear after a single occurrence of an event. How is such demand met by neurons in the medial temporal lobe (MTL), which plays a fundamental role in episodic memory formation? We recorded the activity of MTL neurons in neurosurgical patients while they learned new associations. Pairs of unrelated pictures, one of a person and another of a place, were used to construct a meaningful association modeling the episodic memory of meeting a person in a particular place. We found that a large proportion of responsive MTL neurons expanded their selectivity to encode these specific associations within a few trials: cells initially responsive to one picture started firing to the associated one but not to others. Our results provide a plausible neural substrate for the inception of associations, which are crucial for the formation of episodic memories. PMID:26139375

Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory.

PubMed

Lubin, Farah D; Roth, Tania L; Sweatt, J David

2008-10-15

Long-term memory formation requires selective changes in gene expression. Here, we determined the contribution of chromatin remodeling to learning-induced changes in brain-derived neurotrophic factor (bdnf) gene expression in the adult hippocampus. Contextual fear learning induced differential regulation of exon-specific bdnf mRNAs (I, IV, VI, IX) that was associated with changes in bdnf DNA methylation and altered local chromatin structure. Infusions of zebularine (a DNA methyltransferase inhibitor) significantly altered bdnf DNA methylation and triggered changes in exon-specific bdnf mRNA levels, indicating that altered DNA methylation is sufficient to drive differential bdnf transcript regulation in the hippocampus. In addition, NMDA receptor blockade prevented memory-associated alterations in bdnf DNA methylation, resulting in a block of altered bdnf gene expression in hippocampus and a deficit in memory formation. These results suggest epigenetic modification of the bdnf gene as a mechanism for isoform-specific gene readout during memory consolidation.

Epigenetic mechanisms of memory formation and reconsolidation.

PubMed

Jarome, Timothy J; Lubin, Farah D

2014-11-01

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

Epigenetic Mechanisms of Memory Formation and Reconsolidation

PubMed Central

Jarome, Timothy J.; Lubin, Farah D.

2014-01-01

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

Social Memory Formation Rapidly and Differentially Affects the Motivation and Performance of Vocal Communication Signals in the Bengalese Finch (Lonchura striata var. domestica).

PubMed

Toccalino, Danielle C; Sun, Herie; Sakata, Jon T

2016-01-01

Cognitive processes like the formation of social memories can shape the nature of social interactions between conspecifics. Male songbirds use vocal signals during courtship interactions with females, but the degree to which social memory and familiarity influences the likelihood and structure of male courtship song remains largely unknown. Using a habituation-dishabituation paradigm, we found that a single, brief (<30 s) exposure to a female led to the formation of a short-term memory for that female: adult male Bengalese finches were significantly less likely to produce courtship song to an individual female when re-exposed to her 5 min later (i.e., habituation). Familiarity also rapidly decreased the duration of courtship songs but did not affect other measures of song performance (e.g., song tempo and the stereotypy of syllable structure and sequencing). Consistent with a contribution of social memory to the decrease in courtship song with repeated exposures to the same female, the likelihood that male Bengalese finches produced courtship song increased when they were exposed to a different female (i.e., dishabituation). Three consecutive exposures to individual females also led to the formation of a longer-term memory that persisted over days. Specifically, when courtship song production was assessed 2 days after initial exposures to females, males produced fewer and shorter courtship songs to familiar females than to unfamiliar females. Measures of song performance, however, were not different between courtship songs produced to familiar and unfamiliar females. The formation of a longer-term memory for individual females seemed to require at least three exposures because males did not differentially produce courtship song to unfamiliar females and females that they had been exposed to only once or twice. Taken together, these data indicate that brief exposures to individual females led to the rapid formation and persistence of social memories and support the existence of distinct mechanisms underlying the motivation to produce and the performance of courtship song.

Durable fear memories require PSD-95

PubMed Central

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

2014-01-01

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

Durable fear memories require PSD-95.

PubMed

Fitzgerald, P J; Pinard, C R; Camp, M C; Feyder, M; Sah, A; Bergstrom, H C; Graybeal, C; Liu, Y; Schlüter, O M; Grant, S G; Singewald, N; Xu, W; Holmes, A

2015-07-01

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

Kinase Activity in the Olfactory Bulb Is Required for Odor Memory Consolidation

ERIC Educational Resources Information Center

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

2018-01-01

Long-term fear memory formation in the hippocampus and neocortex depends upon brain-derived neurotrophic factor (BDNF) signaling after acquisition. Incremental, appetitive odor discrimination learning is thought to depend substantially on the differentiation of adult-born neurons within the olfactory bulb (OB)--a process that is closely associated…

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

PubMed

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

2014-12-10

Metaplasticity regulates the threshold for modification of synaptic strength and is an important regulator of learning rules; however, it is not known whether these cellular mechanisms for homeostatic regulation of synapses contribute to particular forms of learning. Conditional ablation of mGluR5 in CA1 pyramidal neurons resulted in the inability of low-frequency trains of afferent activation to prime synapses for subsequent theta burst potentiation. Priming-induced metaplasticity requires mGluR5-mediated mobilization of endocannabinoids during the priming train to induce long-term depression of inhibition (I-LTD). Mice lacking priming-induced plasticity had no deficit in spatial reference memory tasks, but were impaired in an associative task with a temporal component. Conversely, enhancing endocannabinoid signaling facilitated temporal associative memory acquisition and, after training animals in these tasks, ex vivo I-LTD was partially occluded and theta burst LTP was enhanced. Together, these results suggest a link between metaplasticity mechanisms in the hippocampus and the formation of temporal associative memories. Copyright © 2014 the authors 0270-6474/14/3416762-12$15.00/0.

Flashbulb Memories

PubMed Central

Hirst, William; Phelps, Elizabeth A.

2015-01-01

We review and analyze the key theories, debates, findings, and omissions of the existing literature on flashbulb memories (FBMs), including what factors affect their formation, retention, and degree of confidence. We argue that FBMs do not require special memory mechanisms and are best characterized as involving both forgetting and mnemonic distortions, despite a high level of confidence. Factual memories for FBM-inducing events generally follow a similar pattern. Although no necessary and sufficient factors straightforwardly account for FBM retention, media attention particularly shapes memory for the events themselves. FBMs are best characterized in term of repetitions, even of mnemonic distortions, whereas event memories evidence corrections. The bearing of this literature on social identity and traumatic memories is also discussed. PMID:26997762

Human aging reduces the neurobehavioral influence of motivation on episodic memory.

PubMed

Geddes, Maiya R; Mattfeld, Aaron T; Angeles, Carlo de Los; Keshavan, Anisha; Gabrieli, John D E

2018-05-01

The neural circuitry mediating the influence of motivation on long-term declarative or episodic memory formation is delineated in young adults, but its status is unknown in healthy aging. We examined the effect of reward and punishment anticipation on intentional declarative memory formation for words using an event-related functional magnetic resonance imaging (fMRI) monetary incentive encoding task in twenty-one younger and nineteen older adults. At 24-hour memory retrieval testing, younger adults were significantly more likely to remember words associated with motivational cues than neutral cues. Motivational enhancement of memory in younger adults occurred only for recollection ("remember" responses) and not for familiarity ("familiar" responses). Older adults had overall diminished memory and did not show memory gains in association with motivational cues. Memory encoding associated with monetary rewards or punishments activated motivational (substantia nigra/ventral tegmental area) and memory-related (hippocampus) brain regions in younger, but not older, adults during the target word periods. In contrast, older and younger adults showed similar activation of these brain regions during the anticipatory motivational cue interval. In a separate monetary incentive delay task that did not require learning, we found evidence for relatively preserved striatal reward anticipation in older adults. This supports a potential dissociation between incidental and intentional motivational processes in healthy aging. The finding that motivation to obtain rewards and avoid punishments had reduced behavioral and neural influence on intentional episodic memory formation in older compared to younger adults is relevant to life-span theories of cognitive aging including the dopaminergic vulnerability hypothesis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Synaptic Ensemble Underlying the Selection and Consolidation of Neuronal Circuits during Learning.

PubMed

Hoshiba, Yoshio; Wada, Takeyoshi; Hayashi-Takagi, Akiko

2017-01-01

Memories are crucial to the cognitive essence of who we are as human beings. Accumulating evidence has suggested that memories are stored as a subset of neurons that probably fire together in the same ensemble. Such formation of cell ensembles must meet contradictory requirements of being plastic and responsive during learning, but also stable in order to maintain the memory. Although synaptic potentiation is presumed to be the cellular substrate for this process, the link between the two remains correlational. With the application of the latest optogenetic tools, it has been possible to collect direct evidence of the contributions of synaptic potentiation in the formation and consolidation of cell ensemble in a learning task specific manner. In this review, we summarize the current view of the causative role of synaptic plasticity as the cellular mechanism underlying the encoding of memory and recalling of learned memories. In particular, we will be focusing on the latest optoprobe developed for the visualization of such "synaptic ensembles." We further discuss how a new synaptic ensemble could contribute to the formation of cell ensembles during learning and memory. With the development and application of novel research tools in the future, studies on synaptic ensembles will pioneer new discoveries, eventually leading to a comprehensive understanding of how the brain works.

A Novel Cysteine-Rich Neurotrophic Factor in "Aplysia" Facilitates Growth, MAPK Activation, and Long-Term Synaptic Facilitation

ERIC Educational Resources Information Center

Pu, Lu; Kopec, Ashley M.; Boyle, Heather D.; Carew, Thomas J.

2014-01-01

Neurotrophins are critically involved in developmental processes such as neuronal cell survival, growth, and differentiation, as well as in adult synaptic plasticity contributing to learning and memory. Our previous studies examining neurotrophins and memory formation in "Aplysia" showed that a TrkB ligand is required for MAPK…

Hippocampal contributions to recollection in retrograde and anterograde amnesia.

PubMed

Gilboa, Asaf; Winocur, Gordon; Rosenbaum, R Shayna; Poreh, Amir; Gao, Fuqiang; Black, Sandra E; Westmacott, Robyn; Moscovitch, Morris

2006-01-01

Lesions restricted to the hippocampal formation and/or extended hippocampal system (hippocampal formation, fornix, mammillary bodies, and anterior thalamic nuclei) can disrupt conscious recollection in anterograde amnesia, while leaving familiarity-based memory relatively intact. Familiarity may be supported by extra-hippocampal medial temporal lobe (MTL) structures. Within-task dissociations in recognition memory best exemplify this distinction in anterograde amnesia. The authors report for the first time comparable dissociations within recognition memory in retrograde amnesia. An amnesic patient (A.D.) with bilateral fornix and septal nuclei lesions failed to recognize details pertaining to personal past events only when recollection was required, during recognition of episodic details. His intact recognition of generic and semantic details pertaining to the same events was ascribed to intact familiarity processes. Recollective processes in the controls were reflected by asymmetrical Receiver's Operating Characteristic curves, whereas the patient's Receiver's Operating Characteristic was symmetrical, suggesting that his inferior recognition performance on episodic details was reliant on familiarity processes. Anterograde and retrograde memories were equally affected, with no temporal gradient for retrograde memories. By comparison, another amnesic person (K.C.) with extensive MTL damage (involving extra-hippocampal MTL structures in addition to hippocampal and fornix lesions) had very poor recognition and no recollection of either episodic or generic/semantic details. These data suggest that the extended hippocampal system is required to support recollection for both anterograde and retrograde memories, regardless of their age.

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

PubMed Central

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 formation of strong long-term memories because the activation of hippocampal GRs after learning is coupled to the recruitment of the growth and pro-survival BDNF/cAMP response element-binding protein (CREB) pathway, which is well-know to be a general mechanism required for long-term memory formation. We will then speculate about how these results may explain the negative effects of traumatic or chronic stress on memory and cognitive functions. PMID:24113652

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

PubMed

Zhou, Heng; Zhou, Qixin; Xu, Lin

2016-10-01

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

Latent memory facilitates relearning through molecular signaling mechanisms that are distinct from original learning.

PubMed

Menges, Steven A; Riepe, Joshua R; Philips, Gary T

2015-09-01

A highly conserved feature of memory is that it can exist in a latent, non-expressed state which is revealed during subsequent learning by its ability to significantly facilitate (savings) or inhibit (latent inhibition) subsequent memory formation. Despite the ubiquitous nature of latent memory, the mechanistic nature of the latent memory trace and its ability to influence subsequent learning remains unclear. The model organism Aplysia californica provides the unique opportunity to make strong links between behavior and underlying cellular and molecular mechanisms. Using Aplysia, we have studied the mechanisms of savings due to latent memory for a prior, forgotten experience. We previously reported savings in the induction of three distinct temporal domains of memory: short-term (10min), intermediate-term (2h) and long-term (24h). Here we report that savings memory formation utilizes molecular signaling pathways that are distinct from original learning: whereas the induction of both original intermediate- and long-term memory in naïve animals requires mitogen activated protein kinase (MAPK) activation and ongoing protein synthesis, 2h savings memory is not disrupted by inhibitors of MAPK or protein synthesis, and 24h savings memory is not dependent on MAPK activation. Collectively, these findings reveal that during forgetting, latent memory for the original experience can facilitate relearning through molecular signaling mechanisms that are distinct from original learning. Copyright © 2015 Elsevier Inc. All rights reserved.

LRP8-Reelin-regulated Neuronal (LRN) Enhancer Signature Underlying Learning and Memory Formation

PubMed Central

Telese, Francesca; Ma, Qi; Perez, Patricia Montilla; Notani, Dimple; Oh, Soohwan; Li, Wenbo; Comoletti, Davide; Ohgi, Kenneth A.; Taylor, Havilah; Rosenfeld, Michael G.

2015-01-01

Summary One of the exceptional properties of the brain is its ability to acquire new knowledge through learning and to store that information through memory. The epigenetic mechanisms linking changes in neuronal transcriptional programs to behavioral plasticity remain largely unknown. Here, we identify the epigenetic signature of the neuronal enhancers required for transcriptional regulation of synaptic plasticity genes during memory formation, linking this to Reelin signaling. The binding of Reelin to its receptor, LRP8, triggers activation of this cohort of LRP8-Reelin-regulated-Neuronal (LRN) enhancers that serve as the ultimate convergence point of a novel synapse-to-nucleus pathway. Reelin simultaneously regulates NMDA-receptor transmission, which reciprocally permits the required, γ-secretase-dependent cleavage of LRP8, revealing an unprecedented role for its intracellular domain in the regulation of synaptically generated signals. These results uncover an in vivo enhancer code serving as a critical molecular component of cognition and relevant to psychiatric disorders linked to defects in Reelin signaling. PMID:25892301

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

PubMed

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

2015-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

Engrams and Circuits Crucial for Systems Consolidation of a Memory

PubMed Central

Kitamura, Takashi; Ogawa, Sachie K.; Roy, Dheeraj S.; Okuyama, Teruhiro; Morrissey, Mark D.; Smith, Lillian M.; Redondo, Roger L.; Tonegawa, Susumu

2017-01-01

Episodic memories initially require rapid synaptic plasticity within the hippocampus for their formation and are gradually consolidated in neocortical networks for permanent storage. However, the engrams and circuits that support neocortical memory consolidation remain unknown. We found that neocortical prefrontal memory engram cells, critical for remote contextual fear memory, were rapidly generated during initial learning via inputs from both hippocampal-entorhinal cortex and basolateral amygdala. After their generation, the prefrontal engram cells, with support from hippocampal memory engram cells, became functionally mature with time. Whereas hippocampal engram cells gradually became silent with time, engram cells in the basolateral amygdala, which were necessary for fear memory, are maintained. Our data provide new insights into the functional reorganization of engrams and circuits underlying systems consolidation of memory. PMID:28386011

mTORC1 controls long-term memory retrieval.

PubMed

Pereyra, Magdalena; Katche, Cynthia; de Landeta, Ana Belén; Medina, Jorge H

2018-06-08

Understanding how stored information emerges is a main question in the neurobiology of memory that is now increasingly gaining attention. However, molecular events underlying this memory stage, including involvement of protein synthesis, are not well defined. Mammalian target of rapamycin complex 1 (mTORC1), a central regulator of protein synthesis, has been implicated in synaptic plasticity and is required for memory formation. Using inhibitory avoidance (IA), we evaluated the role of mTORC1 in memory retrieval. Infusion of a selective mTORC1 inhibitor, rapamycin, into the dorsal hippocampus 15 or 40 min but not 3 h before testing at 24 h reversibly disrupted memory expression even in animals that had already expressed IA memory. Emetine, a general protein synthesis inhibitor, provoked a similar impairment. mTORC1 inhibition did not interfere with short-term memory retrieval. When infused before test at 7 or 14 but not at 28 days after training, rapamycin impaired memory expression. mTORC1 blockade in retrosplenial cortex, another structure required for IA memory, also impaired memory retention. In addition, pretest intrahippocampal rapamycin infusion impaired object location memory retrieval. Our results support the idea that ongoing protein synthesis mediated by activation of mTORC1 pathway is necessary for long but not for short term memory.

DNA methylation in memory formation: Emerging insights

PubMed Central

Heyward, Frankie D.; Sweatt, J. David

2016-01-01

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

TRPC3 channels critically regulate hippocampal excitability and contextual fear memory.

PubMed

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

2015-03-15

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

Voluntary Running Depreciates the Requirement of Ca[superscript 2+]-Stimulated cAMP Signaling in Synaptic Potentiation and Memory Formation

ERIC Educational Resources Information Center

Zheng, Fei; Zhang, Ming; Ding, Qi; Sethna, Ferzin; Yan, Lily; Moon, Changjong; Yang, Miyoung; Wang, Hongbing

2016-01-01

Mental health and cognitive functions are influenced by both genetic and environmental factors. Although having active lifestyle with physical exercise improves learning and memory, how it interacts with the specific key molecular regulators of synaptic plasticity is largely unknown. Here, we examined the effects of voluntary running on long-term…

Social Memory Formation Rapidly and Differentially Affects the Motivation and Performance of Vocal Communication Signals in the Bengalese Finch (Lonchura striata var. domestica)

PubMed Central

Toccalino, Danielle C.; Sun, Herie; Sakata, Jon T.

2016-01-01

Cognitive processes like the formation of social memories can shape the nature of social interactions between conspecifics. Male songbirds use vocal signals during courtship interactions with females, but the degree to which social memory and familiarity influences the likelihood and structure of male courtship song remains largely unknown. Using a habituation-dishabituation paradigm, we found that a single, brief (<30 s) exposure to a female led to the formation of a short-term memory for that female: adult male Bengalese finches were significantly less likely to produce courtship song to an individual female when re-exposed to her 5 min later (i.e., habituation). Familiarity also rapidly decreased the duration of courtship songs but did not affect other measures of song performance (e.g., song tempo and the stereotypy of syllable structure and sequencing). Consistent with a contribution of social memory to the decrease in courtship song with repeated exposures to the same female, the likelihood that male Bengalese finches produced courtship song increased when they were exposed to a different female (i.e., dishabituation). Three consecutive exposures to individual females also led to the formation of a longer-term memory that persisted over days. Specifically, when courtship song production was assessed 2 days after initial exposures to females, males produced fewer and shorter courtship songs to familiar females than to unfamiliar females. Measures of song performance, however, were not different between courtship songs produced to familiar and unfamiliar females. The formation of a longer-term memory for individual females seemed to require at least three exposures because males did not differentially produce courtship song to unfamiliar females and females that they had been exposed to only once or twice. Taken together, these data indicate that brief exposures to individual females led to the rapid formation and persistence of social memories and support the existence of distinct mechanisms underlying the motivation to produce and the performance of courtship song. PMID:27378868

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains.

PubMed

Sudhakaran, Indulekha P; Ramaswami, Mani

2017-05-04

Long-term and short-term memories differ primarily in the duration of their retention. At a molecular level, long-term memory (LTM) is distinguished from short-term memory (STM) by its requirement for new gene expression. In addition to transcription (nuclear gene expression) the translation of stored mRNAs is necessary for LTM formation. The mechanisms and functions for temporal and spatial regulation of mRNAs required for LTM is a major contemporary problem, of interest from molecular, cell biological, neurobiological and clinical perspectives. This review discusses primary evidence in support for translational regulatory events involved in LTM and a model in which different phases of translation underlie distinct phases of consolidation of memories. However, it focuses largely on mechanisms of memory persistence and the role of prion-like domains in this defining aspect of long-term memory. We consider primary evidence for the concept that Cytoplasmic Polyadenylation Element Binding (CPEB) protein enables the persistence of formed memories by transforming in prion-like manner from a soluble monomeric state to a self-perpetuating and persistent polymeric translationally active state required for maintaining persistent synaptic plasticity. We further discuss prion-like domains prevalent on several other RNA-binding proteins involved in neuronal translational control underlying LTM. Growing evidence indicates that such RNA regulatory proteins are components of mRNP (RiboNucleoProtein) granules. In these proteins, prion-like domains, being intrinsically disordered, could mediate weak transient interactions that allow the assembly of RNP granules, a source of silenced mRNAs whose translation is necessary for LTM. We consider the structural bases for RNA granules formation as well as functions of disordered domains and discuss how these complicate the interpretation of existing experimental data relevant to general mechanisms by which prion-domain containing RBPs function in synapse specific plasticity underlying LTM.

Arbitrary and semantic associations in subjective memory impairment and amnestic mild cognitive impairment among Taiwanese individuals: A cross-sectional study.

PubMed

Chang, Hsin-Te; Chen, Ta-Fu; Cheng, Ting-Wen; Lai, Ya-Mei; Hua, Mau-Sun

2018-05-01

Researchers have recently proposed a preclinical stage of dementia of Alzheimer's type (DAT), referred to as subjective memory impairment (SMI), with the aim of developing methods for the early detection of DAT and subsequent intervention. It has been proposed that the objective memory functions of individuals with SMI are normal; however, arbitrary and semantic associations are both used to describe the processes of memory. No previous studies have investigated these processes among individuals with SMI. Cross-sectional analysis was used to compare the memory function of individuals with SMI, amnestic mild cognitive impairment (aMCI), or DAT. One hundred and eighty-three participants were recruited from the Memory Clinic of National Taiwan University Hospital and communities in northern Taiwan, including individuals with no memory complaints (HC, n = 30) and individuals with SMI (n = 61), aMCI-single domain (n = 24), aMCI-multiple domain (n = 33), or DAT (n = 35). The Word Sequence Learning Test (WSLT) was used to assess the formation of arbitrary associations and the Logical Memory subtest of the Wechsler Memory Scale-Third Edition was used to assess the formation of semantic associations. Compared to the HC group, the SMI group performed poorly only on the WSLT, whereas the other groups performed poorly on both of the memory tasks. This study demonstrated that SMI individuals tend to perform poorly in the formation of arbitrary associations. Our findings suggest that tasks requiring arbitrary associations may provide greater sensitivity in the detection cognitive changes associated with preclinical DAT. Copyright © 2017. Published by Elsevier B.V.

Subliminally and Supraliminally Acquired Long-Term Memories Jointly Bias Delayed Decisions.

PubMed

Ruch, Simon; Herbert, Elizabeth; Henke, Katharina

2017-01-01

Common wisdom and scientific evidence suggest that good decisions require conscious deliberation. But growing evidence demonstrates that not only conscious but also unconscious thoughts influence decision-making. Here, we hypothesize that both consciously and unconsciously acquired memories guide decisions. Our experiment measured the influence of subliminally and supraliminally presented information on delayed (30-40 min) decision-making. Participants were presented with subliminal pairs of faces and written occupations for unconscious encoding. Following a delay of 20 min, participants consciously (re-)encoded the same faces now presented supraliminally along with either the same written occupations, occupations congruous to the subliminally presented occupations (same wage-category), or incongruous occupations (opposite wage-category). To measure decision-making, participants viewed the same faces again (with occupations absent) and decided on the putative income of each person: low, low-average, high-average, or high. Participants were encouraged to decide spontaneously and intuitively. Hence, the decision task was an implicit or indirect test of relational memory. If conscious thought alone guided decisions (= H 0 ), supraliminal information should determine decision outcomes independently of the encoded subliminal information. This was, however, not the case. Instead, both unconsciously and consciously encoded memories influenced decisions: identical unconscious and conscious memories exerted the strongest bias on income decisions, while both incongruous and congruous (i.e., non-identical) subliminally and supraliminally formed memories canceled each other out leaving no bias on decisions. Importantly, the increased decision bias following the formation of identical unconscious and conscious memories and the reduced decision bias following to the formation of non-identical memories were determined relative to a control condition, where conscious memory formation alone could influence decisions. In view of the much weaker representational strength of subliminally vs. supraliminally formed memories, their long-lasting impact on decision-making is noteworthy.

Subliminally and Supraliminally Acquired Long-Term Memories Jointly Bias Delayed Decisions

PubMed Central

Ruch, Simon; Herbert, Elizabeth; Henke, Katharina

2017-01-01

Common wisdom and scientific evidence suggest that good decisions require conscious deliberation. But growing evidence demonstrates that not only conscious but also unconscious thoughts influence decision-making. Here, we hypothesize that both consciously and unconsciously acquired memories guide decisions. Our experiment measured the influence of subliminally and supraliminally presented information on delayed (30–40 min) decision-making. Participants were presented with subliminal pairs of faces and written occupations for unconscious encoding. Following a delay of 20 min, participants consciously (re-)encoded the same faces now presented supraliminally along with either the same written occupations, occupations congruous to the subliminally presented occupations (same wage-category), or incongruous occupations (opposite wage-category). To measure decision-making, participants viewed the same faces again (with occupations absent) and decided on the putative income of each person: low, low-average, high-average, or high. Participants were encouraged to decide spontaneously and intuitively. Hence, the decision task was an implicit or indirect test of relational memory. If conscious thought alone guided decisions (= H0), supraliminal information should determine decision outcomes independently of the encoded subliminal information. This was, however, not the case. Instead, both unconsciously and consciously encoded memories influenced decisions: identical unconscious and conscious memories exerted the strongest bias on income decisions, while both incongruous and congruous (i.e., non-identical) subliminally and supraliminally formed memories canceled each other out leaving no bias on decisions. Importantly, the increased decision bias following the formation of identical unconscious and conscious memories and the reduced decision bias following to the formation of non-identical memories were determined relative to a control condition, where conscious memory formation alone could influence decisions. In view of the much weaker representational strength of subliminally vs. supraliminally formed memories, their long-lasting impact on decision-making is noteworthy. PMID:28955268

KCNQ Channels Regulate Age-Related Memory Impairment

PubMed Central

Cavaliere, Sonia; Malik, Bilal R.; Hodge, James J. L.

2013-01-01

In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ) when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment. PMID:23638087

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

PubMed Central

Phan, Mimi L.; Bieszczad, Kasia M.

2016-01-01

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

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

PubMed

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

2014-07-01

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

CREB regulates memory allocation in the insular cortex

PubMed Central

Sano, Yoshitake; Shobe, Justin L.; Zhou, Miou; Huang, Shan; Shuman, Tristan; Cai, Denise J.; Golshani, Peyman; Kamata, Masakazu; Silva, Alcino J.

2016-01-01

Summary The molecular and cellular mechanisms of memory storage have attracted a great deal of attention. By comparison, little is known about memory allocation, the process that determines which specific neurons in a neural network will store a given memory [1, 2]. Previous studies demonstrated that memory allocation is not random in the amygdala; these studies showed that amygdala neurons with higher levels of the cAMP response element binding protein (CREB) are more likely to be recruited into encoding and storing fear memory [3–6]. To determine whether specific mechanisms also regulate memory allocation in other brain regions, and whether CREB also has a role in this process, we studied insular cortical memory representations for conditioned taste aversion (CTA). In this task, an animal learns to associate a taste (CS) with the experience of malaise (such as that induced by LiCl; US). The insular cortex is required for CTA memory formation and retrieval [7–12]. CTA learning activates a subpopulation of neurons in this structure [13–15], and the insular cortex and the basolateral amygdala (BLA) interact during CTA formation [16, 17]. Here, we used a combination of approaches, including viral vector transfections of insular cortex, arc Fluorescence In Situ Hybridization (FISH) and Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system, to show that CREB levels determine which insular cortical neurons go on to encode a given conditioned taste memory. PMID:25454591

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

PubMed Central

Hung, Hui-Chi; Hsiao, Ya-Hsin

2015-01-01

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

YAdumper: extracting and translating large information volumes from relational databases to structured flat files.

PubMed

Fernández, José M; Valencia, Alfonso

2004-10-12

Downloading the information stored in relational databases into XML and other flat formats is a common task in bioinformatics. This periodical dumping of information requires considerable CPU time, disk and memory resources. YAdumper has been developed as a purpose-specific tool to deal with the integral structured information download of relational databases. YAdumper is a Java application that organizes database extraction following an XML template based on an external Document Type Declaration. Compared with other non-native alternatives, YAdumper substantially reduces memory requirements and considerably improves writing performance.

The hippocampus and inferential reasoning: building memories to navigate future decisions

PubMed Central

Zeithamova, Dagmar; Schlichting, Margaret L.; Preston, Alison R.

2012-01-01

A critical aspect of inferential reasoning is the ability to form relationships between items or events that were not experienced together. This review considers different perspectives on the role of the hippocampus in successful inferential reasoning during both memory encoding and retrieval. Intuitively, inference can be thought of as a logical process by which elements of individual existing memories are retrieved and recombined to answer novel questions. Such flexible retrieval is sub-served by the hippocampus and is thought to require specialized hippocampal encoding mechanisms that discretely code events such that event elements are individually accessible from memory. In addition to retrieval-based inference, recent research has also focused on hippocampal processes that support the combination of information acquired across multiple experiences during encoding. This mechanism suggests that by recalling past events during new experiences, connections can be created between newly formed and existing memories. Such hippocampally mediated memory integration would thus underlie the formation of networks of related memories that extend beyond direct experience to anticipate future judgments about the relationships between items and events. We also discuss integrative encoding in the context of emerging evidence linking the hippocampus to the formation of schemas as well as prospective theories of hippocampal function that suggest memories are actively constructed to anticipate future decisions and actions. PMID:22470333

The development of neural correlates for memory formation

PubMed Central

Ofen, Noa

2012-01-01

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

PKA and PKC Are Required for Long-Term but Not Short-Term in Vivo Operant Memory in "Aplysia"

ERIC Educational Resources Information Center

Michel, Maximilian; Green, Charity L.; Lyons, Lisa C.

2011-01-01

We investigated the involvement of PKA and PKC signaling in a negatively reinforced operant learning paradigm in "Aplysia", learning that food is inedible (LFI). In vivo injection of PKA or PKC inhibitors blocked long-term LFI memory formation. Moreover, a persistent phase of PKA activity, although not PKC activity, was necessary for long-term…

Intrahippocampal Glutamine Administration Inhibits mTORC1 Signaling and Impairs Long-Term Memory

ERIC Educational Resources Information Center

Rozas, Natalia S.; Redell, John B.; Pita-Almenar, Juan D.; McKenna, James, III.; Moore, Anthony N.; Gambello, Michael J.; Dash, Pramod K.

2015-01-01

The mechanistic Target of Rapamycin Complex 1 (mTORC1), a key regulator of protein synthesis and cellular growth, is also required for long-term memory formation. Stimulation of mTORC1 signaling is known to be dependent on the availability of energy and growth factors, as well as the presence of amino acids. In vitro studies using serum- and amino…

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

PubMed Central

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

2011-01-01

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

Interaction between basal ganglia and limbic circuits in learning and memory processes.

PubMed

Calabresi, Paolo; Picconi, Barbara; Tozzi, Alessandro; Ghiglieri, Veronica

2016-01-01

Hippocampus and striatum play distinctive roles in memory processes since declarative and non-declarative memory systems may act independently. However, hippocampus and striatum can also be engaged to function in parallel as part of a dynamic system to integrate previous experience and adjust behavioral responses. In these structures the formation, storage, and retrieval of memory require a synaptic mechanism that is able to integrate multiple signals and to translate them into persistent molecular traces at both the corticostriatal and hippocampal/limbic synapses. The best cellular candidate for this complex synthesis is represented by long-term potentiation (LTP). A common feature of LTP expressed in these two memory systems is the critical requirement of convergence and coincidence of glutamatergic and dopaminergic inputs to the dendritic spines of the neurons expressing this form of synaptic plasticity. In experimental models of Parkinson's disease abnormal accumulation of α-synuclein affects these two memory systems by altering two major synaptic mechanisms underlying cognitive functions in cholinergic striatal neurons, likely implicated in basal ganglia dependent operative memory, and in the CA1 hippocampal region, playing a central function in episodic/declarative memory processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Satb2 determines miRNA expression and long-term memory in the adult central nervous system.

PubMed

Jaitner, Clemens; Reddy, Chethan; Abentung, Andreas; Whittle, Nigel; Rieder, Dietmar; Delekate, Andrea; Korte, Martin; Jain, Gaurav; Fischer, Andre; Sananbenesi, Farahnaz; Cera, Isabella; Singewald, Nicolas; Dechant, Georg; Apostolova, Galina

2016-11-29

SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.

From antenna to antenna: lateral shift of olfactory memory recall by honeybees.

PubMed

Rogers, Lesley J; Vallortigara, Giorgio

2008-06-04

Honeybees, Apis mellifera, readily learn to associate odours with sugar rewards and we show here that recall of the olfactory memory, as demonstrated by the bee extending its proboscis when presented with the trained odour, involves first the right and then the left antenna. At 1-2 hour after training using both antennae, recall is possible mainly when the bee uses its right antenna but by 6 hours after training a lateral shift has occurred and the memory can now be recalled mainly when the left antenna is in use. Long-term memory one day after training is also accessed mainly via the left antenna. This time-dependent shift from right to left antenna is also seen as side biases in responding to odour presented to the bee's left or right side. Hence, not only are the cellular events of memory formation similar in bees and vertebrate species but also the lateralized networks involved may be similar. These findings therefore seem to call for remarkable parallel evolution and suggest that the proper functioning of memory formation in a bilateral animal, either vertebrate or invertebrate, requires lateralization of processing.

Memory modification as an outcome variable in anxiety disorder treatment.

PubMed

Tryon, Warren W; McKay, Dean

2009-05-01

Learning and memory are interdependent processes. Memories are learned, and cumulative learning requires memory. It is generally accepted that learning contributes to psychopathology and consequently to pertinent memory formation. Neuroscience and psychological research have established that memory is an active reconstructive process that is influenced by thoughts, feelings, and behaviors including post-event information. Recent research on the treatment of anxiety disorders using medications (i.e., d-cyclcloserine) to alter neurological systems associated with memory used in conjunction with behavior therapy suggests that memory is part of a central mechanism in the etiology and maintenance of these conditions. The main thesis of this article is that learning-based interventions create new memories that may modify existing ones. This raises the possibility of using such memory modifications to measure intervention outcome. A connectionist context for understanding this phenomenon and informing intervention is provided, with specific reference to post-traumatic stress disorder, obsessive-compulsive disorder, and generalized anxiety disorder. Recommendations for future research examining the role of memory change in treatment outcome are suggested.

Engrams and circuits crucial for systems consolidation of a memory.

PubMed

Kitamura, Takashi; Ogawa, Sachie K; Roy, Dheeraj S; Okuyama, Teruhiro; Morrissey, Mark D; Smith, Lillian M; Redondo, Roger L; Tonegawa, Susumu

2017-04-07

Episodic memories initially require rapid synaptic plasticity within the hippocampus for their formation and are gradually consolidated in neocortical networks for permanent storage. However, the engrams and circuits that support neocortical memory consolidation have thus far been unknown. We found that neocortical prefrontal memory engram cells, which are critical for remote contextual fear memory, were rapidly generated during initial learning through inputs from both the hippocampal-entorhinal cortex network and the basolateral amygdala. After their generation, the prefrontal engram cells, with support from hippocampal memory engram cells, became functionally mature with time. Whereas hippocampal engram cells gradually became silent with time, engram cells in the basolateral amygdala, which were necessary for fear memory, were maintained. Our data provide new insights into the functional reorganization of engrams and circuits underlying systems consolidation of memory. Copyright © 2017, American Association for the Advancement of Science.

Reward signal in a recurrent circuit drives appetitive long-term memory formation.

PubMed

Ichinose, Toshiharu; Aso, Yoshinori; Yamagata, Nobuhiro; Abe, Ayako; Rubin, Gerald M; Tanimoto, Hiromu

2015-11-17

Dopamine signals reward in animal brains. A single presentation of a sugar reward to Drosophila activates distinct subsets of dopamine neurons that independently induce short- and long-term olfactory memories (STM and LTM, respectively). In this study, we show that a recurrent reward circuit underlies the formation and consolidation of LTM. This feedback circuit is composed of a single class of reward-signaling dopamine neurons (PAM-α1) projecting to a restricted region of the mushroom body (MB), and a specific MB output cell type, MBON-α1, whose dendrites arborize that same MB compartment. Both MBON-α1 and PAM-α1 neurons are required during the acquisition and consolidation of appetitive LTM. MBON-α1 additionally mediates the retrieval of LTM, which is dependent on the dopamine receptor signaling in the MB α/β neurons. Our results suggest that a reward signal transforms a nascent memory trace into a stable LTM using a feedback circuit at the cost of memory specificity.

Brain STAT5 signaling modulates learning and memory formation.

PubMed

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

2018-06-01

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

Nuclear factor kappa B-dependent Zif268 expression in hippocampus is required for recognition memory in mice.

PubMed

Zalcman, Gisela; Federman, Noel; de la Fuente, Verónica; Romano, Arturo

2015-03-01

Long-term memory formation requires gene expression after acquisition of new information. The first step in the regulation of gene expression is the participation of transcription factors (TFs) such as nuclear factor kappa B (NF-кB), which are present before the neuronal activity induced by training. It was proposed that the activation of these types of TFs allows a second step in gene regulation by induction of immediate-early genes (IEGs) whose protein products are, in turn, TFs. Between these IEGs, zif268 has been found to play a critical role in long-term memory formation and reprocessing after retrieval. Here we found in mice hippocampus that, on one hand, NF-кB was activated 45 min after training in a novel object recognition (NOR) task and that inhibiting NF-кB immediately after training by intrahippocampal administration of NF-кB Decoy DNA impaired NOR memory consolidation. On the other hand, Zif268 protein expression was induced 45 min after NOR training and the administration of DNA antisense to its mRNA post-training impaired recognition memory. Finally, we found that the inhibition of NF-кB by NF-кB Decoy DNA reduced significantly the training-induced Zif268 increment, indicating that NF-кB is involved in the regulation of Zif268 expression. Thus, the present results support the involvement of NF-кB activity-dependent Zif268 expression in the hippocampus during recognition memory consolidation. Copyright © 2015 Elsevier Inc. All rights reserved.

Monitoring supports performance in a dual-task paradigm involving a risky decision-making task and a working memory task

PubMed Central

Gathmann, Bettina; Schiebener, Johannes; Wolf, Oliver T.; Brand, Matthias

2015-01-01

Performing two cognitively demanding tasks at the same time is known to decrease performance. The current study investigates the underlying executive functions of a dual-tasking situation involving the simultaneous performance of decision making under explicit risk and a working memory task. It is suggested that making a decision and performing a working memory task at the same time should particularly require monitoring—an executive control process supervising behavior and the state of processing on two tasks. To test the role of a supervisory/monitoring function in such a dual-tasking situation we investigated 122 participants with the Game of Dice Task plus 2-back task (GDT plus 2-back task). This dual task requires participants to make decisions under risk and to perform a 2-back working memory task at the same time. Furthermore, a task measuring a set of several executive functions gathered in the term concept formation (Modified Card Sorting Test, MCST) and the newly developed Balanced Switching Task (BST), measuring monitoring in particular, were used. The results demonstrate that concept formation and monitoring are involved in the simultaneous performance of decision making under risk and a working memory task. In particular, the mediation analysis revealed that BST performance partially mediates the influence of MCST performance on the GDT plus 2-back task. These findings suggest that monitoring is one important subfunction for superior performance in a dual-tasking situation including decision making under risk and a working memory task. PMID:25741308

Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance

PubMed Central

Liston, Conor; Cichon, Joseph M; Jeanneteau, Freddy; Jia, Zhengping; Chao, Moses V; Gan, Wen-Biao

2013-01-01

Excessive glucocorticoid exposure during chronic stress causes synapse loss and learning impairment. Under normal physiological conditions, glucocorticoid activity oscillates in synchrony with the circadian rhythm. Whether and how endogenous glucocorticoid oscillations modulate synaptic plasticity and learning is unknown. Here we show that circadian glucocorticoid peaks promote postsynaptic dendritic spine formation in the mouse cortex after motor skill learning, whereas troughs are required for stabilizing newly formed spines that are important for long-term memory retention. Conversely, chronic and excessive exposure to glucocorticoids eliminates learning-associated new spines and disrupts previously acquired memories. Furthermore, we show that glucocorticoids promote rapid spine formation through a non-transcriptional mechanism by means of the LIM kinase–cofilin pathway and increase spine elimination through transcriptional mechanisms involving mineralocorticoid receptor activation. Together, these findings indicate that tightly regulated circadian glucocorticoid oscillations are important for learning-dependent synaptic formation and maintenance. They also delineate a new signaling mechanism underlying these effects. PMID:23624512

Memory Systems Do Not Divide on Consciousness: Reinterpreting Memory in Terms of Activation and Binding

PubMed Central

Reder, Lynne M.; Park, Heekyeong; Kieffaber, Paul D.

2009-01-01

There is a popular hypothesis that performance on implicit and explicit memory tasks reflects 2 distinct memory systems. Explicit memory is said to store those experiences that can be consciously recollected, and implicit memory is said to store experiences and affect subsequent behavior but to be unavailable to conscious awareness. Although this division based on awareness is a useful taxonomy for memory tasks, the authors review the evidence that the unconscious character of implicit memory does not necessitate that it be treated as a separate system of human memory. They also argue that some implicit and explicit memory tasks share the same memory representations and that the important distinction is whether the task (implicit or explicit) requires the formation of a new association. The authors review and critique dissociations from the behavioral, amnesia, and neuroimaging literatures that have been advanced in support of separate explicit and implicit memory systems by highlighting contradictory evidence and by illustrating how the data can be accounted for using a simple computational memory model that assumes the same memory representation for those disparate tasks. PMID:19210052

Dopamine D1/D5 receptors in the dorsal hippocampus are required for the acquisition and expression of a single trial cocaine-associated memory.

PubMed

Kramar, Cecilia P; Barbano, M Flavia; Medina, Jorge H

2014-12-01

The role of the hippocampus in memory supporting associative learning between contexts and unconditioned stimuli is well documented. Hippocampal dopamine neurotransmission modulates synaptic plasticity and memory processing of fear-motivated and spatial learning tasks. Much less is known about the involvement of the hippocampus and its D1/D5 dopamine receptors in the acquisition, consolidation and expression of memories for drug-associated experiences, more particularly, in the processing of single pairing cocaine conditioned place preference (CPP) training. To determine the temporal dynamics of cocaine CPP memory formation, we trained rats in a one-pairing CPP paradigm and tested them at different time intervals after conditioning. The cocaine-associated memory lasted 24 h but not 72 h. Then, we bilaterally infused the dorsal hippocampus with the GABA A receptor agonist muscimol or the D1/D5 dopamine receptor antagonist SCH 23390 at different stages to evaluate the mechanisms involved in the acquisition, consolidation or expression of cocaine CPP memory. Blockade of D1/D5 dopamine receptors at the moment of training impaired the acquisition of cocaine CPP memories, without having any effect when administered immediately or 12 h after training. The expression of cocaine CPP memory was also affected by the administration of SCH 23390 at the moment of the test. Conversely, muscimol impaired the consolidation of cocaine CPP memory only when administered 12 h post conditioning. These findings suggests that dopaminergic inputs to the dorsal hippocampus are required for the acquisition and expression of one trial cocaine-associated memory while neural activity of this structure is required for the late consolidation of these types of memories. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

Goodman, Jarid; Packard, Mark G

2015-11-01

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

mTOR referees memory and disease through mRNA repression and competition.

PubMed

Raab-Graham, Kimberly F; Niere, Farr

2017-06-01

Mammalian target of rapamycin (mTOR) activity is required for memory and is dysregulated in disease. Activation of mTOR promotes protein synthesis; however, new studies are demonstrating that mTOR activity also represses the translation of mRNAs. Almost three decades ago, Kandel and colleagues hypothesised that memory was due to the induction of positive regulators and removal of negative constraints. Are these negative constraints repressed mRNAs that code for proteins that block memory formation? Herein, we will discuss the mRNAs coded by putative memory suppressors, how activation/inactivation of mTOR repress protein expression at the synapse, how mTOR activity regulates RNA binding proteins, mRNA stability, and translation, and what the possible implications of mRNA repression are to memory and neurodegenerative disorders. © 2017 Federation of European Biochemical Societies.

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

PubMed

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

2014-03-01

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

The Construction of Semantic Memory: Grammar-Based Representations Learned from Relational Episodic Information

PubMed Central

Battaglia, Francesco P.; Pennartz, Cyriel M. A.

2011-01-01

After acquisition, memories underlie a process of consolidation, making them more resistant to interference and brain injury. Memory consolidation involves systems-level interactions, most importantly between the hippocampus and associated structures, which takes part in the initial encoding of memory, and the neocortex, which supports long-term storage. This dichotomy parallels the contrast between episodic memory (tied to the hippocampal formation), collecting an autobiographical stream of experiences, and semantic memory, a repertoire of facts and statistical regularities about the world, involving the neocortex at large. Experimental evidence points to a gradual transformation of memories, following encoding, from an episodic to a semantic character. This may require an exchange of information between different memory modules during inactive periods. We propose a theory for such interactions and for the formation of semantic memory, in which episodic memory is encoded as relational data. Semantic memory is modeled as a modified stochastic grammar, which learns to parse episodic configurations expressed as an association matrix. The grammar produces tree-like representations of episodes, describing the relationships between its main constituents at multiple levels of categorization, based on its current knowledge of world regularities. These regularities are learned by the grammar from episodic memory information, through an expectation-maximization procedure, analogous to the inside–outside algorithm for stochastic context-free grammars. We propose that a Monte-Carlo sampling version of this algorithm can be mapped on the dynamics of “sleep replay” of previously acquired information in the hippocampus and neocortex. We propose that the model can reproduce several properties of semantic memory such as decontextualization, top-down processing, and creation of schemata. PMID:21887143

The full-length form of the Drosophila amyloid precursor protein is involved in memory formation.

PubMed

Bourdet, Isabelle; Preat, Thomas; Goguel, Valérie

2015-01-21

The APP plays a central role in AD, a pathology that first manifests as a memory decline. Understanding the role of APP in normal cognition is fundamental in understanding the progression of AD, and mammalian studies have pointed to a role of secreted APPα in memory. In Drosophila, we recently showed that APPL, the fly APP ortholog, is required for associative memory. In the present study, we aimed to characterize which form of APPL is involved in this process. We show that expression of a secreted-APPL form in the mushroom bodies, the center for olfactory memory, is able to rescue the memory deficit caused by APPL partial loss of function. We next assessed the impact on memory of the Drosophila α-secretase kuzbanian (KUZ), the enzyme initiating the nonamyloidogenic pathway that produces secreted APPLα. Strikingly, KUZ overexpression not only failed to rescue the memory deficit caused by APPL loss of function, it exacerbated this deficit. We further show that in addition to an increase in secreted-APPL forms, KUZ overexpression caused a decrease of membrane-bound full-length species that could explain the memory deficit. Indeed, we observed that transient expression of a constitutive membrane-bound mutant APPL form is sufficient to rescue the memory deficit caused by APPL reduction, revealing for the first time a role of full-length APPL in memory formation. Our data demonstrate that, in addition to secreted APPL, the noncleaved form is involved in memory, raising the possibility that secreted and full-length APPL act together in memory processes. Copyright © 2015 the authors 0270-6474/15/351043-09$15.00/0.

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

Jones, J.P.; Bangs, A.L.; Butler, P.L.

Hetero Helix is a programming environment which simulates shared memory on a heterogeneous network of distributed-memory computers. The machines in the network may vary with respect to their native operating systems and internal representation of numbers. Hetero Helix presents a simple programming model to developers, and also considers the needs of designers, system integrators, and maintainers. The key software technology underlying Hetero Helix is the use of a compiler'' which analyzes the data structures in shared memory and automatically generates code which translates data representations from the format native to each machine into a common format, and vice versa. Themore » design of Hetero Helix was motivated in particular by the requirements of robotics applications. Hetero Helix has been used successfully in an integration effort involving 27 CPUs in a heterogeneous network and a body of software totaling roughly 100,00 lines of code. 25 refs., 6 figs.« less

RNP-Granule Assembly via Ataxin-2 Disordered Domains Is Required for Long-Term Memory and Neurodegeneration.

PubMed

Bakthavachalu, Baskar; Huelsmeier, Joern; Sudhakaran, Indulekha P; Hillebrand, Jens; Singh, Amanjot; Petrauskas, Arnas; Thiagarajan, Devasena; Sankaranarayanan, M; Mizoue, Laura; Anderson, Eric N; Pandey, Udai Bhan; Ross, Eric; VijayRaghavan, K; Parker, Roy; Ramaswami, Mani

2018-05-16

Human Ataxin-2 is implicated in the cause and progression of amyotrophic lateral sclerosis (ALS) and type 2 spinocerebellar ataxia (SCA-2). In Drosophila, a conserved atx2 gene is essential for animal survival as well as for normal RNP-granule assembly, translational control, and long-term habituation. Like its human homolog, Drosophila Ataxin-2 (Atx2) contains polyQ repeats and additional intrinsically disordered regions (IDRs). We demonstrate that Atx2 IDRs, which are capable of mediating liquid-liquid phase transitions in vitro, are essential for efficient formation of neuronal mRNP assemblies in vivo. Remarkably, ΔIDR mutants that lack neuronal RNP granules show normal animal development, survival, and fertility. However, they show defects in long-term memory formation/consolidation as well as in C9ORF72 dipeptide repeat or FUS-induced neurodegeneration. Together, our findings demonstrate (1) that higher-order mRNP assemblies contribute to long-term neuronal plasticity and memory, and (2) that a targeted reduction in RNP-granule formation efficiency can alleviate specific forms of neurodegeneration. Copyright © 2018 Elsevier Inc. All rights reserved.

Parametric and genetic analysis of Drosophila appetitive long-term memory and sugar motivation.

PubMed

Colomb, J; Kaiser, L; Chabaud, M-A; Preat, T

2009-06-01

Distinct forms of memory can be highlighted using different training protocols. In Drosophila olfactory aversive learning, one conditioning session triggers memory formation independently of protein synthesis, while five spaced conditioning sessions lead to the formation of long-term memory (LTM), a long-lasting memory dependent on de novo protein synthesis. In contrast, one session of odour-sugar association appeared sufficient for the fly to form LTM. We designed and tuned an apparatus that facilitates repeated discriminative conditioning by alternate presentations of two odours, one being associated with sugar, as well as a new paradigm to test sugar responsiveness (SR). Our results show that both SR and short-term memory (STM) scores increase with starvation length before conditioning. The protein dependency of appetitive LTM is independent of the repetition and the spacing of training sessions, on the starvation duration and on the strength of the unconditioned stimulus. In contrast to a recent report, our test measures an abnormal SR of radish mutant flies, which might initiate their STM and LTM phenotypes. In addition, our work shows that crammer and tequila mutants, which are deficient for aversive LTM, present both an SR and an appetitive STM defect. Using the MB247-P[switch] system, we further show that tequila is required in the adult mushroom bodies for normal sugar motivation.

Voluntary running depreciates the requirement of Ca2+-stimulated cAMP signaling in synaptic potentiation and memory formation

PubMed Central

Zheng, Fei; Zhang, Ming; Ding, Qi; Sethna, Ferzin; Yan, Lily; Moon, Changjong; Yang, Miyoung

2016-01-01

Mental health and cognitive functions are influenced by both genetic and environmental factors. Although having active lifestyle with physical exercise improves learning and memory, how it interacts with the specific key molecular regulators of synaptic plasticity is largely unknown. Here, we examined the effects of voluntary running on long-term potentiation (LTP) and memory formation in mice lacking type 1 adenylyl cyclase (AC1), a neurospecific synaptic enzyme that contributes to Ca2+-stimulated cAMP production. Following 1 mo of voluntary running-wheel exercise, the impaired LTP and object recognition memory in AC1 knockout (KO) mice were significantly attenuated. Running up-regulated exon II mRNA level of BDNF (brain-derived neurotrophic factor), though it failed to increase exon I and IV mRNAs in the hippocampus of AC1 KO mice. Intrahippocampal infusion of recombinant BDNF was sufficient to rescue LTP and object recognition memory defects in AC1 KO mice. Therefore, voluntary running and exogenous BDNF application overcome the defective Ca2+-stimulated cAMP signaling. Our results also demonstrate that alteration in Ca2+-stimulated cAMP can affect the molecular outcome of physical exercise. PMID:27421897

Memory, language, and ageing.

PubMed Central

Burke, D M; Mackay, D G

1997-01-01

This overview provides both theoretical and empirical reasons for emphasizing practice and familiar skills as a practical strategy for enhancing cognitive functioning in old age. Our review of empirical research on age-related changes in memory and language reveals a consistent pattern of spared and impaired abilities in normal old age. Relatively preserved in old age is memory performance involving highly practised skills and familiar information, including factual, semantic and autobiographical information. Relatively impaired in old age is memory performance that requires the formation of new connections, for example, recall of recent autobiographical experiences, new facts or the source of newly acquired facts. This pattern of impaired new learning versus preserved old learning cuts across distinctions between semantic memory, episodic memory, explicit memory and perhaps also implicit memory. However, familiar verbal information is not completely preserved when accessed on the output side rather than the input side: aspects of language production, namely word finding and spelling, exhibit significant age-related declines. This emerging pattern of preserved and impaired abilities presents a fundamental challenge for theories of cognitive ageing, which must explain why some aspects of language and memory are more vulnerable to the effects of ageing than others. Information-universal theories, involving mechanisms such as general slowing that are independent of the type or structure of the information being processed, require additional mechanisms to account for this pattern of cognitive aging. Information-specific theories, where the type or structure of the postulated memory units can influence the effects of cognitive ageing, are able to account for this emerging pattern, but in some cases require further development to account for comprehensive cognitive changes such as general slowing. PMID:9460069

Look before you leap: sensory memory improves decision making.

PubMed

Vlassova, Alexandra; Pearson, Joel

2013-09-01

Simple decisions require the processing and evaluation of perceptual and cognitive information, the formation of a decision, and often the execution of a motor response. This process involves the accumulation of evidence over time until a particular choice reaches a decision threshold. Using a random-dot-motion stimulus, we showed that simply delaying responses after the stimulus offset can almost double accuracy, even in the absence of new incoming visual information. However, under conditions in which the otherwise blank interval was filled with a sensory mask or concurrent working memory load was high, performance gains were lost. Further, memory and perception showed equivalent rates of evidence accumulation, suggesting a high-capacity memory store. We propose an account of continued evidence accumulation by sequential sampling from a simultaneously decaying memory trace. Memories typically decay with time, hence immediate inquiry trumps later recall from memory. However, the results we report here show the inverse: Inspecting a memory trumps viewing the actual object.

Rapid Consolidation to a radish and Protein Synthesis-Dependent Long-Term Memory after Single-Session Appetitive Olfactory Conditioning in Drosophila

PubMed Central

Krashes, Michael J.; Waddell, Scott

2008-01-01

In Drosophila, formation of aversive olfactory long-term memory (LTM) requires multiple training sessions pairing odor and electric shock punishment with rest intervals. In contrast, here we show that a single 2 min training session pairing odor with a more ethologically relevant sugar reinforcement forms long-term appetitive memory that lasts for days. Appetitive LTM has some mechanistic similarity to aversive LTM in that it can be disrupted by cycloheximide, the dCreb2-b transcriptional repressor, and the crammer and tequila LTM-specific mutations. However, appetitive LTM is completely disrupted by the radish mutation that apparently represents a distinct mechanistic phase of consolidated aversive memory. Furthermore, appetitive LTM requires activity in the dorsal paired medial neuron and mushroom body α′ β′ neuron circuit during the first hour after training and mushroom body αβ neuron output during retrieval, suggesting that appetitive middle-term memory and LTM are mechanistically linked. Last, experiments feeding and/or starving flies after training reveals a critical motivational drive that enables appetitive LTM retrieval. PMID:18354013

PKMζ Maintains Drug Reward and Aversion Memory in the Basolateral Amygdala and Extinction Memory in the Infralimbic Cortex

PubMed Central

He, Ying-Ying; Xue, Yan-Xue; Wang, Ji-shi; Fang, Qin; Liu, Jian-Feng; Xue, Li-Fen; Lu, Lin

2011-01-01

The intense associative memories that develop between drug-paired contextual cues and rewarding stimuli or the drug withdrawal-associated aversive feeling have been suggested to contribute to the high rate of relapse. Various studies have elucidated the mechanisms underlying the formation and expression of drug-related cue memories, but how this mechanism is maintained is unknown. Protein kinase M ζ (PKMζ) was recently shown to be necessary and sufficient for long-term potentiation maintenance and memory storage. In the present study, we used conditioned place preference (CPP) and aversion (CPA) to examine whether PKMζ maintains both morphine-associated reward memory and morphine withdrawal-associated aversive memory in the basolateral amygdala (BLA). We also investigate the role of PKMζ in the infralimbic cortex in the extinction memory of morphine reward-related cues and morphine withdrawal-related aversive cues. We found that intra-BLA but not central nucleus of the amygdala injection of the selective PKMζ inhibitor ZIP 1 day after CPP and CPA training impaired the expression of CPP and CPA 1 day later, and the effect of ZIP on memory lasted at least 2 weeks. Inhibiting PKMζ activity in the infralimbic cortex, but not prelimbic cortex, disrupted the expression of the extinction memory of CPP and CPA. These results indicate that PKMζ in the BLA is required for the maintenance of associative morphine reward memory and morphine withdrawal-associated aversion memory, and PKMζ in the infralimbic cortex is required for the maintenance of extinction memory of morphine reward-related cues and morphine withdrawal-related aversive cues. PMID:21633338

Developmental Abilities to Form Chunks in Immediate Memory and Its Non-Relationship to Span Development.

PubMed

Mathy, Fabien; Fartoukh, Michael; Gauvrit, Nicolas; Guida, Alessandro

2016-01-01

Both adults and children -by the time they are 2-3 years old- have a general ability to recode information to increase memory efficiency. This paper aims to evaluate the ability of untrained children aged 6-10 years old to deploy such a recoding process in immediate memory. A large sample of 374 children were given a task of immediate serial report based on SIMON®, a classic memory game made of four colored buttons (red, green, yellow, blue) requiring players to reproduce a sequence of colors within which repetitions eventually occur. It was hypothesized that a primitive ability across all ages (since theoretically already available in toddlers) to detect redundancies allows the span to increase whenever information can be recoded on the fly. The chunkable condition prompted the formation of chunks based on the perceived structure of color repetition within to-be-recalled sequences of colors. Our result shows a similar linear improvement of memory span with age for both chunkable and non-chunkable conditions. The amount of information retained in immediate memory systematically increased for the groupable sequences across all age groups, independently of the average age-group span that was measured on sequences that contained fewer repetitions. This result shows that chunking gives young children an equal benefit as older children. We discuss the role of recoding in the expansion of capacity in immediate memory and the potential role of data compression in the formation of chunks in long-term memory.

Developmental Abilities to Form Chunks in Immediate Memory and Its Non-Relationship to Span Development

PubMed Central

Mathy, Fabien; Fartoukh, Michael; Gauvrit, Nicolas; Guida, Alessandro

2016-01-01

Both adults and children –by the time they are 2–3 years old– have a general ability to recode information to increase memory efficiency. This paper aims to evaluate the ability of untrained children aged 6–10 years old to deploy such a recoding process in immediate memory. A large sample of 374 children were given a task of immediate serial report based on SIMON®, a classic memory game made of four colored buttons (red, green, yellow, blue) requiring players to reproduce a sequence of colors within which repetitions eventually occur. It was hypothesized that a primitive ability across all ages (since theoretically already available in toddlers) to detect redundancies allows the span to increase whenever information can be recoded on the fly. The chunkable condition prompted the formation of chunks based on the perceived structure of color repetition within to-be-recalled sequences of colors. Our result shows a similar linear improvement of memory span with age for both chunkable and non-chunkable conditions. The amount of information retained in immediate memory systematically increased for the groupable sequences across all age groups, independently of the average age-group span that was measured on sequences that contained fewer repetitions. This result shows that chunking gives young children an equal benefit as older children. We discuss the role of recoding in the expansion of capacity in immediate memory and the potential role of data compression in the formation of chunks in long-term memory. PMID:26941675

Why do we remember? The communicative function of episodic memory.

PubMed

Mahr, Johannes; Csibra, Gergely

2017-01-19

Episodic memory has been analyzed in a number of different ways in both philosophy and psychology, and most controversy has centered on its self-referential, 'autonoetic' character. Here, we offer a comprehensive characterization of episodic memory in representational terms, and propose a novel functional account on this basis. We argue that episodic memory should be understood as a distinctive epistemic attitude taken towards an event simulation. On this view, episodic memory has a metarepresentational format and should not be equated with beliefs about the past. Instead, empirical findings suggest that the contents of human episodic memory are often constructed in the service of the explicit justification of such beliefs. Existing accounts of episodic memory function that have focused on explaining its constructive character through its role in 'future-oriented mental time travel' neither do justice to its capacity to ground veridical beliefs about the past nor to its representational format. We provide an account of the metarepresentational structure of episodic memory in terms of its role in communicative interaction. The generative nature of recollection allows us to represent and communicate the reasons for why we hold certain beliefs about the past. In this process, autonoesis corresponds to the capacity to determine when and how to assert epistemic authority in making claims about the past. A domain where such claims are indispensable are human social engagements. Such engagements commonly require the justification of entitlements and obligations, which is often possible only by explicit reference to specific past events.

The development of episodic memory: items, contexts, and relations.

PubMed

Yim, Hyungwook; Dennis, Simon J; Sloutsky, Vladimir M

2013-11-01

Episodic memory involves the formation of relational structures that bind information about the stimuli people experience to the contexts in which they experience them. The ability to form and retain such structures may be at the core of the development of episodic memory. In the first experiment reported here, 4- and 7-year-olds were presented with paired-associate learning tasks requiring memory structures of different complexity. A multinomial-processing tree model was applied to estimate the use of different structures in the two age groups. The use of two-way list-context-to-target structures and three-way structures was found to increase between the ages of 4 and 7. Experiment 2 demonstrated that the ability to form increasingly complex relational memory structures develops between the ages of 4 and 7 years and that this development extends well into adulthood. These results have important implications for theories of memory development.

Epicatechin, a component of dark chocolate, enhances memory formation if applied during the memory consolidation period.

PubMed

Fernell, Maria; Swinton, Cayley; Lukowiak, Ken

2016-01-01

Epicatechin (Epi), a flavanol found in foods such as dark chocolate has previously been shown to enhance memory formation in our model system, operant conditioning of aerial respiration in Lymnaea. In those experiments snails were trained in Epi. Here we ask whether snails exposed to Epi before training, during the consolidation period immediately following training, or 1 h after training would enhance memory formation. We report here that Epi is only able to enhance memory if snails are placed in Epi-containing pond water immediately after training. That is, Epi enhances memory formation if it is applied during the memory consolidation period as well as if snails are trained in Epi-containing pond water.

Epicatechin, a component of dark chocolate, enhances memory formation if applied during the memory consolidation period

PubMed Central

Fernell, Maria; Swinton, Cayley; Lukowiak, Ken

2016-01-01

ABSTRACT Epicatechin (Epi), a flavanol found in foods such as dark chocolate has previously been shown to enhance memory formation in our model system, operant conditioning of aerial respiration in Lymnaea. In those experiments snails were trained in Epi. Here we ask whether snails exposed to Epi before training, during the consolidation period immediately following training, or 1 h after training would enhance memory formation. We report here that Epi is only able to enhance memory if snails are placed in Epi-containing pond water immediately after training. That is, Epi enhances memory formation if it is applied during the memory consolidation period as well as if snails are trained in Epi-containing pond water. PMID:27574544

FXR1P Limits Long-Term Memory, Long-Lasting Synaptic Potentiation, and de novo GluA2 Translation

PubMed Central

Jones, Emma V.; Altimimi, Haider F.; Farmer, W. Todd; Gandin, Valentina; Hanna, Edith; Zong, Ruiting; Barbon, Alessandro; Nelson, David L.; Topisirovic, Ivan; Rochford, Joseph; Stellwagen, David; Béïque, Jean-Claude; Murai, Keith K.

2014-01-01

SUMMARY Translational control of mRNAs allows for rapid and selective changes in synaptic protein expression, changes that are required for long-lasting plasticity and memory formation in the brain. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein that controls mRNA translation in non-neuronal cells and co-localizes with translational machinery in neurons. However, its neuronal mRNA targets and role in the brain are unknown. Here, we demonstrate that removal of FXR1P from the forebrain of postnatal mice selectively enhances long-term storage of spatial memories, hippocampal late-phase LTP (L-LTP) and de novo GluA2 synthesis. Furthermore, FXR1P binds specifically to the 5’UTR of GluA2 mRNA to repress translation and limit the amount of GluA2 incorporated at potentiated synapses. This study uncovers a new mechanism for regulating long-lasting synaptic plasticity and spatial memory formation and reveals an unexpected divergent role of FXR1P among Fragile X proteins in brain plasticity. PMID:25456134

Temporary formation of highly conducting domain walls for non-destructive read-out of ferroelectric domain-wall resistance switching memories

NASA Astrophysics Data System (ADS)

Jiang, Jun; Bai, Zi Long; Chen, Zhi Hui; He, Long; Zhang, David Wei; Zhang, Qing Hua; Shi, Jin An; Park, Min Hyuk; Scott, James F.; Hwang, Cheol Seong; Jiang, An Quan

2018-01-01

Erasable conductive domain walls in insulating ferroelectric thin films can be used for non-destructive electrical read-out of the polarization states in ferroelectric memories. Still, the domain-wall currents extracted by these devices have not yet reached the intensity and stability required to drive read-out circuits operating at high speeds. This study demonstrated non-destructive read-out of digital data stored using specific domain-wall configurations in epitaxial BiFeO3 thin films formed in mesa-geometry structures. Partially switched domains, which enable the formation of conductive walls during the read operation, spontaneously retract when the read voltage is removed, reducing the accumulation of mobile defects at the domain walls and potentially improving the device stability. Three-terminal memory devices produced 14 nA read currents at an operating voltage of 5 V, and operated up to T = 85 °C. The gap length can also be smaller than the film thickness, allowing the realization of ferroelectric memories with device dimensions far below 100 nm.

Why do we remember? The communicative function of episodic memory

PubMed Central

Mahr, Johannes B.; Csibra, Gergely

2017-01-01

Short Abstract We propose a novel account of episodic memory function based on a conceptual and empirical analysis of its role in belief formation. We provide a critique of the view that episodic memory serves future-directed imagination, and argue that the central features of this capacity can instead be explained by the role it plays in human communication. On this view, episodic memory allows us to communicatively support our interpretations of the past by gauging when we can assert epistemic authority. This capacity is ineliminable in justification of, and negotiations about, social commitments established by past interactions. Long Abstract Episodic memory has been analyzed in a number of different ways in both philosophy and psychology, and most controversy has centered on its self-referential, ‘autonoetic’ character. Here, we offer a comprehensive characterization of episodic memory in representational terms, and propose a novel functional account on this basis. We argue that episodic memory should be understood as a distinctive epistemic attitude taken towards an event simulation. On this view, episodic memory has a metarepresentational format and should not be equated with beliefs about the past. Instead, empirical findings suggest that the contents of human episodic memory are often constructed in the service of the explicit justification of such beliefs. Existing accounts of episodic memory function that have focused on explaining its constructive character through its role in ‘future-oriented mental time travel’ neither do justice to its capacity to ground veridical beliefs about the past nor to its representational format. We provide an account of the metarepresentational structure of episodic memory in terms of its role in communicative interaction. The generative nature of recollection allows us to represent and communicate the reasons for why we hold certain beliefs about the past. In this process, autonoesis corresponds to the capacity to determine when and how to assert epistemic authority in making claims about the past. A domain where such claims are indispensable are human social engagements. Such engagements commonly require the justification of entitlements and obligations, which is often possible only by explicit reference to specific past events. PMID:28100294

Dnmts and Tet target memory-associated genes after appetitive olfactory training in honey bees

PubMed Central

Biergans, Stephanie D.; Giovanni Galizia, C.; Reinhard, Judith; Claudianos, Charles

2015-01-01

DNA methylation and demethylation are epigenetic mechanisms involved in memory formation. In honey bees DNA methyltransferase (Dnmt) function is necessary for long-term memory to be stimulus specific (i.e. to reduce generalization). So far, however, it remains elusive which genes are targeted and what the time-course of DNA methylation is during memory formation. Here, we analyse how DNA methylation affects memory retention, gene expression, and differential methylation in stimulus-specific olfactory long-term memory formation. Out of 30 memory-associated genes investigated here, 9 were upregulated following Dnmt inhibition in trained bees. These included Dnmt3 suggesting a negative feedback loop for DNA methylation. Within these genes also the DNA methylation pattern changed during the first 24 hours after training. Interestingly, this was accompanied by sequential activation of the DNA methylation machinery (i.e. Dnmts and Tet). In sum, memory formation involves a temporally complex epigenetic regulation of memory-associated genes that facilitates stimulus specific long-term memory in the honey bee. PMID:26531238

Opposite effects depending on learning and memory demands in dorsomedial prefrontal cortex lesioned rats performing an olfactory task.

PubMed

Chaillan, F A; Marchetti, E; Delfosse, F; Roman, F S; Soumireu-Mourat, B

1997-01-01

In this study, the functional properties of the dorsomedial prefrontal cortex (dmPFC) of the rat were examined in two olfactory tasks. In a successive cue olfactory discrimination task, dmPFC lesioned animals improved performance across sessions more rapidly than operated control animals. In an olfactory task using fixed interval training, animals with similar lesions were impaired. Both effects, although opposite, can be explained by a temporal processing deficit. The present results seem to indicate that the dmPFC is required for timing, classified as part of non-declarative memory. As reference memory improved in the lesioned animals, the finding is that the dmPFC supports non-declarative memory and thus interacts with declarative memory in the long-term formation of the associations between a particular stimulus (olfactory cue) and particular responses.

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

PubMed

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

2010-08-11

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

Oscillation, Conduction Delays, and Learning Cooperate to Establish Neural Competition in Recurrent Networks

PubMed Central

Kato, Hideyuki; Ikeguchi, Tohru

2016-01-01

Specific memory might be stored in a subnetwork consisting of a small population of neurons. To select neurons involved in memory formation, neural competition might be essential. In this paper, we show that excitable neurons are competitive and organize into two assemblies in a recurrent network with spike timing-dependent synaptic plasticity (STDP) and axonal conduction delays. Neural competition is established by the cooperation of spontaneously induced neural oscillation, axonal conduction delays, and STDP. We also suggest that the competition mechanism in this paper is one of the basic functions required to organize memory-storing subnetworks into fine-scale cortical networks. PMID:26840529

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

PubMed

Potts, Jonathan R; Lewis, Mark A

2016-05-01

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

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

PubMed Central

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 trafficking, enhancement of metabolic activity, and Wnt signaling pathway during the steep phase of memory formation; and (3) cytoskeleton organization proteins. Taken together, this study clearly demonstrates dynamic assembly and disassembly of protein-protein interaction networks depending on the stage of memory formation engrams. PMID:26598641

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

ERIC Educational Resources Information Center

Felsenberg, Johannes; Dombrowski, Vincent; Eisenhardt, Dorothea

2012-01-01

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

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

PubMed

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

2015-08-01

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

Epigenetic regulation of estrogen-dependent memory

PubMed Central

Fortress, Ashley M.; Frick, Karyn M.

2014-01-01

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

Retrieval monitoring and anosognosia in Alzheimer's disease.

PubMed

Gallo, David A; Chen, Jennifer M; Wiseman, Amy L; Schacter, Daniel L; Budson, Andrew E

2007-09-01

This study explored the relationship between episodic memory and anosognosia (a lack of deficit awareness) among patients with mild Alzheimer's disease (AD). Participants studied words and pictures for subsequent memory tests. Healthy older adults made fewer false recognition errors when trying to remember pictures compared with words, suggesting that the perceptual distinctiveness of picture memories enhanced retrieval monitoring (the distinctiveness heuristic). In contrast, although participants with AD could discriminate between studied and nonstudied items, they had difficulty recollecting the specific presentation formats (words or pictures), and they had limited use of the distinctiveness heuristic. Critically, the demands of the memory test modulated the relationship between memory accuracy and anosognosia. Greater anosognosia was associated with impaired memory accuracy when participants with AD tried to remember words but not when they tried to remember pictures. These data further delineate the retrieval monitoring difficulties among individuals with AD and suggest that anosognosia measures are most likely to correlate with memory tests that require the effortful retrieval of nondistinctive information. (PsycINFO Database Record (c) 2007 APA, all rights reserved).

Epigenetic regulation of estrogen-dependent memory.

PubMed

Fortress, Ashley M; Frick, Karyn M

2014-10-01

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

Hippocampal and ventral medial prefrontal activation during retrieval-mediated learning supports novel inference.

PubMed

Zeithamova, Dagmar; Dominick, April L; Preston, Alison R

2012-07-12

Memory enables flexible use of past experience to inform new behaviors. Although leading theories hypothesize that this fundamental flexibility results from the formation of integrated memory networks relating multiple experiences, the neural mechanisms that support memory integration are not well understood. Here, we demonstrate that retrieval-mediated learning, whereby prior event details are reinstated during encoding of related experiences, supports participants' ability to infer relationships between distinct events that share content. Furthermore, we show that activation changes in a functionally coupled hippocampal and ventral medial prefrontal cortical circuit track the formation of integrated memories and successful inferential memory performance. These findings characterize the respective roles of these regions in retrieval-mediated learning processes that support relational memory network formation and inferential memory in the human brain. More broadly, these data reveal fundamental mechanisms through which memory representations are constructed into prospectively useful formats. Copyright © 2012 Elsevier Inc. All rights reserved.

Hippocampal and ventral medial prefrontal activation during retrieval-mediated learning supports novel inference

PubMed Central

Zeithamova, Dagmar; Dominick, April L.; Preston, Alison R.

2012-01-01

SUMMARY Memory enables flexible use of past experience to inform new behaviors. Though leading theories hypothesize that this fundamental flexibility results from the formation of integrated memory networks relating multiple experiences, the neural mechanisms that support memory integration are not well understood. Here, we demonstrate that retrieval-mediated learning, whereby prior event details are reinstated during encoding of related experiences, supports participants’ ability to infer relationships between distinct events that share content. Furthermore, we show that activation changes in a functionally coupled hippocampal and ventral medial prefrontal cortical circuit track the formation of integrated memories and successful inferential memory performance. These findings characterize the respective roles of these regions in retrieval-mediated learning processes that support relational memory network formation and inferential memory in the human brain. More broadly, these data reveal fundamental mechanisms through which memory representations are constructed into prospectively useful formats. PMID:22794270

Opiate-associated contextual memory formation and retrieval are differentially modulated by dopamine D1 and D2 signaling in hippocampal-prefrontal connectivity.

PubMed

Wang, Yunpeng; Zhang, Hongying; Cui, Jingjing; Zhang, Jing; Yin, Fangyuan; Guo, Hao; Lai, Jianghua; Xing, Bo

2018-04-17

Contextual memory driven by abused drugs such as opiates has a central role in maintenance and relapse of drug-taking behaviors. Although dopamine (DA) signaling favors memory storage and retrieval via regulation of hippocampal-prefrontal connectivity, its role in modulating opiate-associated contextual memory is largely unknown. Here, we report roles of DA signaling within the hippocampal-prefrontal circuit for opiate-related memories. Combining-conditioned place preference (CPP) with molecular analyses, we investigated the DA D1 receptor (D1R) and extracellular signal-regulated kinase (ERK)-cAMP-response element binding protein (CREB) signaling, as well as DA D2 receptor (D2R) and protein kinase B (PKB or Akt)/glycogen synthase kinase 3 (GSK3) signaling in the ventral hippocampus (vHip) and medial prefrontal cortex (mPFC) during the formation of opiate-related associative memories. Morphine-CPP acquisition increased the activity of the D1R-ERK-CREB pathway in both the vHip and mPFC. Morphine-CPP reinstatement was associated with the D2R-mediated hyperactive GSK3 via Akt inhibition in the vHip and PFC. Furthermore, integrated D1R-ERK-CREB and D2R-Akt-GSK3 pathways in the vHip-mPFC circuit are required for the acquisition and retrieval of the morphine contextual memory, respectively. Moreover, blockage of D1R or D2R signaling could alleviate normal Hip-dependent spatial memory. These results suggest that D1R and D2R signaling are differentially involved in the acquisition and retrieval of morphine contextual memory, and DA signaling in the vHip-mPFC connection contributes to morphine-associated and normal memory, largely depending on opiate exposure states.

Layered reward signalling through octopamine and dopamine in Drosophila.

PubMed

Burke, Christopher J; Huetteroth, Wolf; Owald, David; Perisse, Emmanuel; Krashes, Michael J; Das, Gaurav; Gohl, Daryl; Silies, Marion; Certel, Sarah; Waddell, Scott

2012-12-20

Dopamine is synonymous with reward and motivation in mammals. However, only recently has dopamine been linked to motivated behaviour and rewarding reinforcement in fruitflies. Instead, octopamine has historically been considered to be the signal for reward in insects. Here we show, using temporal control of neural function in Drosophila, that only short-term appetitive memory is reinforced by octopamine. Moreover, octopamine-dependent memory formation requires signalling through dopamine neurons. Part of the octopamine signal requires the α-adrenergic-like OAMB receptor in an identified subset of mushroom-body-targeted dopamine neurons. Octopamine triggers an increase in intracellular calcium in these dopamine neurons, and their direct activation can substitute for sugar to form appetitive memory, even in flies lacking octopamine. Analysis of the β-adrenergic-like OCTβ2R receptor reveals that octopamine-dependent reinforcement also requires an interaction with dopamine neurons that control appetitive motivation. These data indicate that sweet taste engages a distributed octopamine signal that reinforces memory through discrete subsets of mushroom-body-targeted dopamine neurons. In addition, they reconcile previous findings with octopamine and dopamine and suggest that reinforcement systems in flies are more similar to mammals than previously thought.

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

PubMed Central

2012-01-01

Perception and memory are imperfect reconstructions of reality. These reconstructions are prone to be influenced by several factors, which may result in false memories. A false memory is the recollection of an event, or details of an episode, that did not actually occur. Memory formation comprises at least three different sub-processes: encoding, consolidation and the retrieval of the learned material. All of these sub-processes are vulnerable for specific errors and consequently may result in false memories. Whereas, processes like imagery, self-referential encoding or spreading activation can lead to the formation of false memories at encoding, semantic generalization during sleep and updating processes due to misleading post event information, in particular, are relevant at the consolidation stage. Finally at the retrieval stage, monitoring processes, which are assumed to be essential to reject false memories, are of specific importance. Different neuro-cognitive processes have been linked to the formation of true and false memories. Most consistently the medial temporal lobe and the medial and lateral prefrontal cortex have been reported with regard to the formation of true and false memories. Despite the fact that all phases entailing memory formation, consolidation of stored information and retrieval processes, are relevant for the forming of false memories, most studies focused on either memory encoding or retrieval. Thus, future studies should try to integrate data from all phases to give a more comprehensive view on systematic memory distortions. An initial outline is developed within this review to connect the different memory stages and research strategies. PMID:22827854

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

PubMed

Straube, Benjamin

2012-07-24

Perception and memory are imperfect reconstructions of reality. These reconstructions are prone to be influenced by several factors, which may result in false memories. A false memory is the recollection of an event, or details of an episode, that did not actually occur. Memory formation comprises at least three different sub-processes: encoding, consolidation and the retrieval of the learned material. All of these sub-processes are vulnerable for specific errors and consequently may result in false memories. Whereas, processes like imagery, self-referential encoding or spreading activation can lead to the formation of false memories at encoding, semantic generalization during sleep and updating processes due to misleading post event information, in particular, are relevant at the consolidation stage. Finally at the retrieval stage, monitoring processes, which are assumed to be essential to reject false memories, are of specific importance. Different neuro-cognitive processes have been linked to the formation of true and false memories. Most consistently the medial temporal lobe and the medial and lateral prefrontal cortex have been reported with regard to the formation of true and false memories. Despite the fact that all phases entailing memory formation, consolidation of stored information and retrieval processes, are relevant for the forming of false memories, most studies focused on either memory encoding or retrieval. Thus, future studies should try to integrate data from all phases to give a more comprehensive view on systematic memory distortions. An initial outline is developed within this review to connect the different memory stages and research strategies.

The Role of Ephs and Ephrins in Memory Formation

PubMed Central

Dines, Monica

2016-01-01

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

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

PubMed

Basu, Sreetama; Kustanovich, Irina; Lamprecht, Raphael

2016-01-01

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

Feasibility study of a real-time operating system for a multichannel MPEG-4 encoder

NASA Astrophysics Data System (ADS)

Lehtoranta, Olli; Hamalainen, Timo D.

2005-03-01

Feasibility of DSP/BIOS real-time operating system for a multi-channel MPEG-4 encoder is studied. Performances of two MPEG-4 encoder implementations with and without the operating system are compared in terms of encoding frame rate and memory requirements. The effects of task switching frequency and number of parallel video channels to the encoding frame rate are measured. The research is carried out on a 200 MHz TMS320C6201 fixed point DSP using QCIF (176x144 pixels) video format. Compared to a traditional DSP implementation without an operating system, inclusion of DSP/BIOS reduces total system throughput only by 1 QCIF frames/s. The operating system has 6 KB data memory overhead and program memory requirement of 15.7 KB. Hence, the overhead is considered low enough for resource critical mobile video applications.

Redox driven conductance changes for resistive memory

NASA Astrophysics Data System (ADS)

Shoute, Lian C. T.; Pekas, Nikola; Wu, Yiliang; McCreery, Richard L.

2011-03-01

The relationship between bias-induced redox reactions and resistance switching is considered for memory devices containing TiO2 or a conducting polymer in "molecular heterojunctions" consisting of thin (2-25 nm) films of covalently bonded molecules, polymers, and oxides. Raman spectroscopy was used to monitor changes in the oxidation state of polythiophene in Au/P3HT/SiO2/Au devices, and it was possible to directly determine the formation and stability of the conducting polaron state of P3HT by applied bias pulses [P3HT = poly(3-hexyl thiophene)]. Polaron formation was strongly dependent on junction composition, particularly on the interfaces between the polymer, oxide, and electrodes. In all cases, trace water was required for polaron formation, leading to the proposal that water reduction acts as a redox counter-reaction to polymer oxidation. Polaron stability was longest for the case of a direct contact between Au and SiO2, implying that catalytic water reduction at the Au surface generated hydroxide ions which stabilized the cationic polaron. The spectroscopic information about the dependence of polaron stability on device composition will be useful for designing and monitoring resistive switching memory based on conducting polymers, with or without TiO2 present.

Modulation of neuronal signal transduction and memory formation by synaptic zinc.

PubMed

Sindreu, Carlos; Storm, Daniel R

2011-01-01

The physiological role of synaptic zinc has remained largely enigmatic since its initial detection in hippocampal mossy fibers over 50 years ago. The past few years have witnessed a number of studies highlighting the ability of zinc ions to regulate ion channels and intracellular signaling pathways implicated in neuroplasticity, and others that shed some light on the elusive role of synaptic zinc in learning and memory. Recent behavioral studies using knock-out mice for the synapse-specific zinc transporter ZnT-3 indicate that vesicular zinc is required for the formation of memories dependent on the hippocampus and the amygdala, two brain centers that are prominently innervated by zinc-rich fibers. A common theme emerging from this research is the activity-dependent regulation of the Erk1/2 mitogen-activated-protein kinase pathway by synaptic zinc through diverse mechanisms in neurons. Here we discuss current knowledge on how synaptic zinc may play a role in cognition through its impact on neuronal signaling.

Modulation of Neuronal Signal Transduction and Memory Formation by Synaptic Zinc

PubMed Central

Sindreu, Carlos; Storm, Daniel R.

2011-01-01

The physiological role of synaptic zinc has remained largely enigmatic since its initial detection in hippocampal mossy fibers over 50 years ago. The past few years have witnessed a number of studies highlighting the ability of zinc ions to regulate ion channels and intracellular signaling pathways implicated in neuroplasticity, and others that shed some light on the elusive role of synaptic zinc in learning and memory. Recent behavioral studies using knock-out mice for the synapse-specific zinc transporter ZnT-3 indicate that vesicular zinc is required for the formation of memories dependent on the hippocampus and the amygdala, two brain centers that are prominently innervated by zinc-rich fibers. A common theme emerging from this research is the activity-dependent regulation of the Erk1/2 mitogen-activated-protein kinase pathway by synaptic zinc through diverse mechanisms in neurons. Here we discuss current knowledge on how synaptic zinc may play a role in cognition through its impact on neuronal signaling. PMID:22084630

Cystathionine-β-synthase-derived hydrogen sulfide is required for amygdalar long-term potentiation and cued fear memory in rats.

PubMed

Chen, Hai-Bo; Wu, Wen-Ning; Wang, Wei; Gu, Xun-Hu; Yu, Bin; Wei, Bo; Yang, Yuan-Jian

2017-04-01

Hydrogen sulfide (H 2 S) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that H 2 S regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous H 2 S is required for amygdalar long-term potentiation (LTP) induction and cued fear memory formation remains unclear. Here, we show that cystathionine-β-synthase (CBS), the predominant H 2 S-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of H 2 S in the lateral amygdala (LA) region. Incubating brain slices with CBS inhibitor significantly prevented the induction of NMDA receptors (NMDARs)-dependent LTP in the thalamo-LA pathway, and intra-LA infusion of CBS inhibitor impaired cued fear memory in rats. Notably, treatment with H 2 S donor, but not CBS activator, significantly reversed the impairments of LTP and fear memory caused by CBS inhibition. Mechanismly, inhibition of CBS activity led to a reduction in NMDAR-mediated synaptic response in the thalamo-LA pathway, and treatment with H 2 S donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived H 2 S is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous H 2 S might involve the regulation of NMDAR function. Copyright © 2017 Elsevier Inc. All rights reserved.

Strategic retrieval, confabulations, and delusions: theory and data.

PubMed

Gilboa, Asaf

2010-01-01

Based on Moscovitch and Winocur's "working with memory" framework, confabulation is described as a deficit in strategic retrieval processes. The present paper suggests that only a confluence of deficits on multiple memory-related processes leads to confabulation. These are divided into three categories. Core processes that are unique to confabulation and required for its evolution include: (1) an intuitive, rapid, preconscious "feeling of rightness" monitoring, (2) an elaborate conscious "editor" monitoring, and (3) control processes that mediate the decision whether to act upon a retrieved memory. The second category is deficits on constitutional processes which are required for confabulation to occur but are not unique to it. These include the formation of erroneous memory representation, (temporal) context confusion, and deficits in retrieval cue generation. Finally, associated Features of confabulations determine the content "flavour" and frequency of confabulation but are not required for their evolution. Some associated features are magnification of normal reconstructive memory processes such as reliance on generic/schematic representations, and positivity biases in memory, whereas others are abnormal such as perseveration or source memory deficits. Data on deficits in core processes in confabulation are presented. Next, the apparent correspondences between confabulation and delusion are discussed. Considering confabulation within a strategic memory framework may help elucidate both the commonalities and differences between the two symptoms. Delusions are affected by a convergence of abnormal perception and encoding of information, associated with aberrant cognitive schema structure and disordered belief monitoring. Whereas confabulation is primarily a disorder of retrieval, mnemonic aspects of delusions can be described as primarily a disorder of input and integration of information. It is suggested that delusions might share some of the associated features of confabulation but not its core and constitutional processes. Preliminary data in support of this view are presented.

Decreasing temperature shifts hippocampal function from memory formation to modulation of hibernation bout duration in Syrian hamsters.

PubMed

Arant, Ryan J; Goo, Marisa S; Gill, Phoebe D; Nguyen, Yen; Watson, Katherine D; Hamilton, Jock S; Horowitz, John M; Horwitz, Barbara A

2011-08-01

Previous studies in hibernating species have characterized two forms of neural plasticity in the hippocampus, long-term potentiation (LTP) and its reversal, depotentiation, but not de novo long-term depression (LTD), which is also associated with memory formation. Studies have also shown that histamine injected into the hippocampus prolonged hibernation bout duration. However, spillover into the ventricles may have affected brain stem regions, not the hippocampus. Here, we tested the hypothesis that decreased brain temperature shifts the major function of the hippocampus in the Syrian hamster (Mesocricetus auratus) from one of memory formation (via LTP, depotentiation, and de novo LTD) to increasing hibernation bout duration. We found reduced evoked responses in hippocampal CA1 pyramidal neurons following low-frequency stimulation in young (<30 days old) and adult (>60 days old) hamsters, indicating that de novo LTD was generated in hippocampal slices from both pups and adults at temperatures >20°C. However, at temperatures below 20°C, synchronization of neural assemblies (a requirement for LTD generation) was markedly degraded, implying that de novo LTD cannot be generated in hibernating hamsters. Nonetheless, even at temperatures below 16°C, pyramidal neurons could still generate action potentials that may traverse a neural pathway, suppressing the ascending arousal system (ARS). In addition, histamine increased the excitability of these pyramidal cells. Taken together, these findings are consistent with the hypothesis that hippocampal circuits remain operational at low brain temperatures in Syrian hamsters and suppress the ARS to prolong bout duration, even though memory formation is muted at these low temperatures.

Do you remember where sounds, pictures and words came from? The role of the stimulus format in object location memory.

PubMed

Delogu, Franco; Lilla, Christopher C

2017-11-01

Contrasting results in visual and auditory spatial memory stimulate the debate over the role of sensory modality and attention in identity-to-location binding. We investigated the role of sensory modality in the incidental/deliberate encoding of the location of a sequence of items. In 4 separated blocks, 88 participants memorised sequences of environmental sounds, spoken words, pictures and written words, respectively. After memorisation, participants were asked to recognise old from new items in a new sequence of stimuli. They were also asked to indicate from which side of the screen (visual stimuli) or headphone channel (sounds) the old stimuli were presented in encoding. In the first block, participants were not aware of the spatial requirement while, in blocks 2, 3 and 4 they knew that their memory for item location was going to be tested. Results show significantly lower accuracy of object location memory for the auditory stimuli (environmental sounds and spoken words) than for images (pictures and written words). Awareness of spatial requirement did not influence localisation accuracy. We conclude that: (a) object location memory is more effective for visual objects; (b) object location is implicitly associated with item identity during encoding and (c) visual supremacy in spatial memory does not depend on the automaticity of object location binding.

Future thinking improves prospective memory performance and plan enactment in older adults.

PubMed

Altgassen, Mareike; Rendell, Peter G; Bernhard, Anka; Henry, Julie D; Bailey, Phoebe E; Phillips, Louise H; Kliegel, Matthias

2015-01-01

Efficient intention formation might improve prospective memory by reducing the need for resource-demanding strategic processes during the delayed performance interval. The present study set out to test this assumption and provides the first empirical assessment of whether imagining a future action improves prospective memory performance equivalently at different stages of the adult lifespan. Thus, younger (n = 40) and older (n = 40) adults were asked to complete the Dresden Breakfast Task, which required them to prepare breakfast in accordance with a set of rules and time restrictions. All participants began by generating a plan for later enactment; however, after making this plan, half of the participants were required to imagine themselves completing the task in the future (future thinking condition), while the other half received standard instructions (control condition). As expected, overall younger adults outperformed older adults. Moreover, both older and younger adults benefited equally from future thinking instructions, as reflected in a higher proportion of prospective memory responses and more accurate plan execution. Thus, for both younger and older adults, imagining the specific visual-spatial context in which an intention will later be executed may serve as an easy-to-implement strategy that enhances prospective memory function in everyday life.

Audiovisual integration supports face-name associative memory formation.

PubMed

Lee, Hweeling; Stirnberg, Rüdiger; Stöcker, Tony; Axmacher, Nikolai

2017-10-01

Prior multisensory experience influences how we perceive our environment, and hence how memories are encoded for subsequent retrieval. This study investigated if audiovisual (AV) integration and associative memory formation rely on overlapping or distinct processes. Our functional magnetic resonance imaging results demonstrate that the neural mechanisms underlying AV integration and associative memory overlap substantially. In particular, activity in anterior superior temporal sulcus (STS) is increased during AV integration and also determines the success of novel AV face-name association formation. Dynamic causal modeling results further demonstrate how the anterior STS interacts with the associative memory system to facilitate successful memory formation for AV face-name associations. Specifically, the connection of fusiform gyrus to anterior STS is enhanced while the reverse connection is reduced when participants subsequently remembered both face and name. Collectively, our results demonstrate how multisensory associative memories can be formed for subsequent retrieval.

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

PubMed

Jing, Xu; Sui, Wen-Hai; Wang, Shuai; Xu, Xu-Feng; Yuan, Rong-Rong; Chen, Xiao-Rong; Ma, Hui-Xian; Zhu, Ying-Xiao; Sun, Jin-Kai; Yi, Fan; Chen, Zhe-Yu; Wang, Yue

2017-04-05

Histone acetylation, an epigenetic modification, plays an important role in long-term memory formation. Recently, histone deacetylase (HDAC) inhibitors were demonstrated to promote memory formation, which raises the intriguing possibility that they may be used to rescue memory deficits. However, additional research is necessary to clarify the roles of individual HDACs in memory. In this study, we demonstrated that HDAC7, within the dorsal hippocampus of C57BL6J mice, had a late and persistent decrease after contextual fear conditioning (CFC) training (4-24 h), which was involved in long-term CFC memory formation. We also showed that HDAC7 decreased via ubiquitin-dependent degradation. CBX4 was one of the HDAC7 E3 ligases involved in this process. Nur77, as one of the target genes of HDAC7, increased 6-24 h after CFC training and, accordingly, modulated the formation of CFC memory. Finally, HDAC7 was involved in the formation of other hippocampal-dependent memories, including the Morris water maze and object location test. The current findings facilitate an understanding of the molecular and cellular mechanisms of HDAC7 in the regulation of hippocampal-dependent memory. SIGNIFICANCE STATEMENT The current findings demonstrated the effects of histone deacetylase 7 (HDAC7) on hippocampal-dependent memories. Moreover, we determined the mechanism of decreased HDAC7 in contextual fear conditioning (CFC) through ubiquitin-dependent protein degradation. We also verified that CBX4 was one of the HDAC7 E3 ligases. Finally, we demonstrated that Nur77, as one of the important targets for HDAC7, was involved in CFC memory formation. All of these proteins, including HDAC7, CBX4, and Nur77, could be potential therapeutic targets for preventing memory deficits in aging and neurological diseases. Copyright © 2017 the authors 0270-6474/17/373848-16$15.00/0.

Shaping memory accuracy by left prefrontal transcranial direct current stimulation.

PubMed

Zwissler, Bastian; Sperber, Christoph; Aigeldinger, Sina; Schindler, Sebastian; Kissler, Johanna; Plewnia, Christian

2014-03-12

Human memory is dynamic and flexible but is also susceptible to distortions arising from adaptive as well as pathological processes. Both accurate and false memory formation require executive control that is critically mediated by the left prefrontal cortex (PFC). Transcranial direct current stimulation (tDCS) enables noninvasive modulation of cortical activity and associated behavior. The present study reports that tDCS applied to the left dorsolateral PFC (dlPFC) shaped accuracy of episodic memory via polaritiy-specific modulation of false recognition. When applied during encoding of pictures, anodal tDCS increased whereas cathodal stimulation reduced the number of false alarms to lure pictures in subsequent recognition memory testing. These data suggest that the enhancement of excitability in the dlPFC by anodal tDCS can be associated with blurred detail memory. In contrast, activity-reducing cathodal tDCS apparently acted as a noise filter inhibiting the development of imprecise memory traces and reducing the false memory rate. Consistently, the largest effect was found in the most active condition (i.e., for stimuli cued to be remembered). This first evidence for a polarity-specific, activity-dependent effect of tDCS on false memory opens new vistas for the understanding and potential treatment of disturbed memory control.

The many faces of amnesia.

PubMed

Gold, Paul E

2006-01-01

Results from studies of retrograde amnesia provide much of the evidence for theories of memory consolidation. Retrograde amnesia gradients are often interpreted as revealing the time needed for the formation of long-term memories. The rapid forgetting observed after many amnestic treatments, including protein synthesis inhibitors, and the parallel decay seen in long-term potentiation experiments are presumed to reveal the duration of short-term memory processing. However, there is clear and consistent evidence that the time courses obtained in these amnesia experiments are highly variable within and across experiments and treatments. The evidence is inconsistent with identification of basic temporal properties of memory consolidation. Alternative views include modulation of memory and emphasize the roles that hormones and neurotransmitters have in regulating memory formation. Of related interest, converging lines of evidence suggest that inhibitors of protein synthesis and of other biochemical processes act on modulators of memory formation rather than on mechanisms of memory formation. Based on these findings, memory consolidation and reconsolidation studies might better be identified as memory modulation and "remodulation" studies. Beyond a missing and perhaps unattainable time constant of memory consolidation, some current views of memory consolidation assume that memories, once formed, are generally unmodifiable. It is this perspective that appears to have led to the recent interest in memory reconsolidation. But the view adopted here is that memories are continually malleable, being updated by new experiences and, at the same time, altering the memories of later experiences. Studies of memory remodulation offer promise of understanding the neurobiological bases by which new memories are altered by prior experiences and by which old memories are altered by new experiences.

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

PubMed

Bisaz, Reto; Travaglia, Alessio; Alberini, Cristina M

2014-01-01

The formation of long-term memories is a function necessary for an adaptive survival. In the last two decades, great progress has been made in the understanding of the biological bases of memory formation. The identification of mechanisms necessary for memory consolidation and reconsolidation, the processes by which the posttraining and postretrieval fragile memory traces become stronger and insensitive to disruption, has indicated new approaches for investigating and treating psychopathologies. In this review, we will discuss some key biological mechanisms found to be critical for memory consolidation and strengthening, the role/s and mechanisms of memory reconsolidation, and how the interference with consolidation and/or reconsolidation can modulate the retention and/or storage of memories that are linked to psychopathologies. © 2014 S. Karger AG, Basel.

Genealogical correspondence of a forebrain centre implies an executive brain in the protostome–deuterostome bilaterian ancestor

PubMed Central

2016-01-01

Orthologous genes involved in the formation of proteins associated with memory acquisition are similarly expressed in forebrain centres that exhibit similar cognitive properties. These proteins include cAMP-dependent protein kinase A catalytic subunit (PKA-Cα) and phosphorylated Ca2+/calmodulin-dependent protein kinase II (pCaMKII), both required for long-term memory formation which is enriched in rodent hippocampus and insect mushroom bodies, both implicated in allocentric memory and both possessing corresponding neuronal architectures. Antibodies against these proteins resolve forebrain centres, or their equivalents, having the same ground pattern of neuronal organization in species across five phyla. The ground pattern is defined by olfactory or chemosensory afferents supplying systems of parallel fibres of intrinsic neurons intersected by orthogonal domains of afferent and efferent arborizations with local interneurons providing feedback loops. The totality of shared characters implies a deep origin in the protostome–deuterostome bilaterian ancestor of elements of a learning and memory circuit. Proxies for such an ancestral taxon are simple extant bilaterians, particularly acoels that express PKA-Cα and pCaMKII in discrete anterior domains that can be properly referred to as brains. PMID:26598732

Prion-based memory of heat stress in yeast

PubMed Central

Chernova, Tatiana A.; Wilkinson, Keith D.

2017-01-01

ABSTRACT Amyloids and amyloid-based prions are self-perpetuating protein aggregates which can spread by converting a normal protein of the same sequence into a prion form. They are associated with diseases in humans and mammals, and control heritable traits in yeast and other fungi. Some amyloids are implicated in biologically beneficial processes. As prion formation generates reproducible memory of a conformational change, prions can be considered as molecular memory devices.  We have demonstrated that in yeast, stress-inducible cytoskeleton-associated protein Lsb2 forms a metastable prion in response to high temperature. This prion promotes conversion of other proteins into prions and can persist in a fraction of cells for a significant number of cell generations after stress, thus maintaining the memory of stress in a population of surviving cells. Acquisition of an amino acid substitution required for Lsb2 to form a prion coincides with acquisition of increased thermotolerance in the evolution of Saccharomyces yeast. Thus the ability to form an Lsb2 prion in response to stress coincides with yeast adaptation to growth at higher temperatures. These findings intimately connect prion formation to the cellular response to environmental stresses. PMID:28521568

Prion-based memory of heat stress in yeast.

PubMed

Chernova, Tatiana A; Chernoff, Yury O; Wilkinson, Keith D

2017-05-04

Amyloids and amyloid-based prions are self-perpetuating protein aggregates which can spread by converting a normal protein of the same sequence into a prion form. They are associated with diseases in humans and mammals, and control heritable traits in yeast and other fungi. Some amyloids are implicated in biologically beneficial processes. As prion formation generates reproducible memory of a conformational change, prions can be considered as molecular memory devices.  We have demonstrated that in yeast, stress-inducible cytoskeleton-associated protein Lsb2 forms a metastable prion in response to high temperature. This prion promotes conversion of other proteins into prions and can persist in a fraction of cells for a significant number of cell generations after stress, thus maintaining the memory of stress in a population of surviving cells. Acquisition of an amino acid substitution required for Lsb2 to form a prion coincides with acquisition of increased thermotolerance in the evolution of Saccharomyces yeast. Thus the ability to form an Lsb2 prion in response to stress coincides with yeast adaptation to growth at higher temperatures. These findings intimately connect prion formation to the cellular response to environmental stresses.

Conditional forebrain inactivation of nicastrin causes progressive memory impairment and age-related neurodegeneration.

PubMed

Tabuchi, Katsuhiko; Chen, Guiquan; Südhof, Thomas C; Shen, Jie

2009-06-03

Loss of presenilin function in adult mouse brains causes memory loss and age-related neurodegeneration. Since presenilin possesses gamma-secretase-dependent and -independent activities, it remains unknown which activity is required for presenilin-dependent memory formation and neuronal survival. To address this question, we generated postnatal forebrain-specific nicastrin conditional knock-out (cKO) mice, in which nicastrin, a subunit of gamma-secretase, is inactivated selectively in mature excitatory neurons of the cerebral cortex. nicastrin cKO mice display progressive impairment in learning and memory and exhibit age-dependent cortical neuronal loss, accompanied by astrocytosis, microgliosis, and hyperphosphorylation of the microtubule-associated protein Tau. The neurodegeneration observed in nicastrin cKO mice likely occurs via apoptosis, as evidenced by increased numbers of apoptotic neurons. These findings demonstrate an essential role of nicastrin in the execution of learning and memory and the maintenance of neuronal survival in the brain and suggest that presenilin functions in memory and neuronal survival via its role as a gamma-secretase subunit.

In sync: gamma oscillations and emotional memory

PubMed Central

Headley, Drew B.; Paré, Denis

2013-01-01

Emotional experiences leave vivid memories that can last a lifetime. The emotional facilitation of memory has been attributed to the engagement of diffusely projecting neuromodulatory systems that enhance the consolidation of synaptic plasticity in regions activated by the experience. This process requires the propagation of signals between brain regions, and for those signals to induce long-lasting synaptic plasticity. Both of these demands are met by gamma oscillations, which reflect synchronous population activity on a fast timescale (35–120 Hz). Regions known to participate in the formation of emotional memories, such as the basolateral amygdala, also promote gamma-band activation throughout cortical and subcortical circuits. Recent studies have demonstrated that gamma oscillations are enhanced during emotional situations, coherent between regions engaged by salient stimuli, and predict subsequent memory for cues associated with aversive stimuli. Furthermore, neutral stimuli that come to predict emotional events develop enhanced gamma oscillations, reflecting altered processing in the brain, which may underpin how past emotional experiences color future learning and memory. PMID:24319416

In sync: gamma oscillations and emotional memory.

PubMed

Headley, Drew B; Paré, Denis

2013-11-21

Emotional experiences leave vivid memories that can last a lifetime. The emotional facilitation of memory has been attributed to the engagement of diffusely projecting neuromodulatory systems that enhance the consolidation of synaptic plasticity in regions activated by the experience. This process requires the propagation of signals between brain regions, and for those signals to induce long-lasting synaptic plasticity. Both of these demands are met by gamma oscillations, which reflect synchronous population activity on a fast timescale (35-120 Hz). Regions known to participate in the formation of emotional memories, such as the basolateral amygdala, also promote gamma-band activation throughout cortical and subcortical circuits. Recent studies have demonstrated that gamma oscillations are enhanced during emotional situations, coherent between regions engaged by salient stimuli, and predict subsequent memory for cues associated with aversive stimuli. Furthermore, neutral stimuli that come to predict emotional events develop enhanced gamma oscillations, reflecting altered processing in the brain, which may underpin how past emotional experiences color future learning and memory.

The Role of Ephs and Ephrins in Memory Formation.

PubMed

Dines, Monica; Lamprecht, Raphael

2016-04-01

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

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

PubMed Central

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

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.

PubMed

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.

Sweet Taste and Nutrient Value Subdivide Rewarding Dopaminergic Neurons in Drosophila

PubMed Central

Huetteroth, Wolf; Perisse, Emmanuel; Lin, Suewei; Klappenbach, Martín; Burke, Christopher; Waddell, Scott

2015-01-01

Summary Dopaminergic neurons provide reward learning signals in mammals and insects [1–4]. Recent work in Drosophila has demonstrated that water-reinforcing dopaminergic neurons are different to those for nutritious sugars [5]. Here, we tested whether the sweet taste and nutrient properties of sugar reinforcement further subdivide the fly reward system. We found that dopaminergic neurons expressing the OAMB octopamine receptor [6] specifically convey the short-term reinforcing effects of sweet taste [4]. These dopaminergic neurons project to the β′2 and γ4 regions of the mushroom body lobes. In contrast, nutrient-dependent long-term memory requires different dopaminergic neurons that project to the γ5b regions, and it can be artificially reinforced by those projecting to the β lobe and adjacent α1 region. Surprisingly, whereas artificial implantation and expression of short-term memory occur in satiated flies, formation and expression of artificial long-term memory require flies to be hungry. These studies suggest that short-term and long-term sugar memories have different physiological constraints. They also demonstrate further functional heterogeneity within the rewarding dopaminergic neuron population. PMID:25728694

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

PubMed

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

2005-08-26

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

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

ERIC Educational Resources Information Center

Raj, Vinaya; Bell, Martha Ann

2010-01-01

Episodic memories contain various forms of contextual detail (e.g., perceptual, emotional, cognitive details) that need to become integrated. Each of these contextual features can be used to attribute a memory episode to its source, or origin of information. Memory for source information is one critical component in the formation of episodic…

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

PubMed Central

Scholz, Sebastian; Schneider, Signe Luisa

2017-01-01

Recently, elevated ongoing pre-stimulus beta power (13–17 Hz) at encoding has been associated with subsequent memory formation for visual stimulus material. It is unclear whether this activity is merely specific to visual processing or whether it reflects a state facilitating general memory formation, independent of stimulus modality. To answer that question, the present study investigated the relationship between neural pre-stimulus oscillations and verbal memory formation in different sensory modalities. For that purpose, a within-subject design was employed to explore differences between successful and failed memory formation in the visual and auditory modality. Furthermore, associative memory was addressed by presenting the stimuli in combination with background images. Results revealed that similar EEG activity in the low beta frequency range (13–17 Hz) is associated with subsequent memory success, independent of stimulus modality. Elevated power prior to stimulus onset differentiated successful from failed memory formation. In contrast, differential effects between modalities were found in the theta band (3–7 Hz), with an increased oscillatory activity before the onset of later remembered visually presented words. In addition, pre-stimulus theta power dissociated between successful and failed encoding of associated context, independent of the stimulus modality of the item itself. We therefore suggest that increased ongoing low beta activity reflects a memory promoting state, which is likely to be moderated by modality-independent attentional or inhibitory processes, whereas high ongoing theta power is suggested as an indicator of the enhanced binding of incoming interlinked information. PMID:28192459

Activation of mitogen-activated protein kinase/extracellular signal-regulated kinase in hippocampal circuitry is required for consolidation and reconsolidation of recognition memory.

PubMed

Kelly, Aine; Laroche, Serge; Davis, Sabrina

2003-06-15

Consolidation and reconsolidation of long-term memory have been shown to be dependent on the synthesis of new proteins, but the specific molecular mechanisms underlying these events remain to be elucidated. The mitogen-activated protein kinase (MAPK) pathway can trigger genomic responses in neurons, leading to changes in protein synthesis, and several studies have identified its pivotal role in synaptic plasticity and long-term memory formation. In this study, we analyze the involvement of this pathway in the consolidation and reconsolidation of long-term recognition memory, using an object recognition task. We show that inhibition of the MAPK pathway by intracerebroventricular injection of the MEK [MAPK/extracellular signal-regulated kinase (ERK)] inhibitor UO126 blocks consolidation of object recognition memory but does not affect short-term memory. Brain regions of the entorhinal cortex-hippocampal circuitry were analyzed for ERK activation, and it was shown that consolidation of recognition memory was associated with increased phosphorylation of ERK in the dentate gyrus and entorhinal cortex, although total expression of ERK was unchanged. We also report that inhibition of the MAPK pathway blocks reconsolidation of recognition memory, and this was shown to be dependent on reactivation of the memory trace by brief reexposure to the objects. In addition, reconsolidation of memory was associated with an increase in the phosphorylation of ERK in entorhinal cortex and CA1. In summary, our data show that the MAPK kinase pathway is required for both consolidation and reconsolidation of long-term recognition memory, and that this is associated with hyperphosphorylation of ERK in different subregions of the entorhinal cortex-hippocampal circuitry.

Adults' Memories of Childhood: True and False Reports

ERIC Educational Resources Information Center

Qin, Jianjian; Ogle, Christin M.; Goodman, Gail S.

2008-01-01

In 3 experiments, the authors examined factors that, according to the source-monitoring framework, might influence false memory formation and true/false memory discernment. In Experiment 1, combined effects of warning and visualization on false childhood memory formation were examined, as were individual differences in true and false childhood…

The Learning Hippocampus: Education and Experience-Dependent Plasticity

ERIC Educational Resources Information Center

Wenger, Elisabeth; Lövdén, Martin

2016-01-01

The hippocampal formation of the brain plays a crucial role in declarative learning and memory while at the same time being particularly susceptible to environmental influences. Education requires a well-functioning hippocampus, but may also influence the development of this brain structure. Understanding these bidirectional influences may have…

Epigenetic mechanisms and memory strength: a comparative study.

PubMed

Federman, Noel; Zalcman, Gisela; de la Fuente, Verónica; Fustiñana, Maria Sol; Romano, Arturo

2014-01-01

Memory consolidation requires de novo mRNA and protein synthesis. Transcriptional activation is controlled by transcription factors, their cofactors and repressors. Cofactors and repressors regulate gene expression by interacting with basal transcription machinery, remodeling chromatin structure and/or chemically modifying histones. Acetylation is the most studied epigenetic mechanism of histones modifications related to gene expression. This process is regulated by histone acetylases (HATs) and histone deacetylases (HDACs). More than 5 years ago, we began a line of research about the role of histone acetylation during memory consolidation. Here we review our work, presenting evidence about the critical role of this epigenetic mechanism during consolidation of context-signal memory in the crab Neohelice granulata, as well as during consolidation of novel object recognition memory in the mouse Mus musculus. Our evidence demonstrates that histone acetylation is a key mechanism in memory consolidation, functioning as a distinctive molecular feature of strong memories. Furthermore, we found that the strength of a memory can be characterized by its persistence or its resistance to extinction. Besides, we found that the role of this epigenetic mechanism regulating gene expression only in the formation of strongest memories is evolutionarily conserved. Copyright © 2014 Elsevier Ltd. All rights reserved.

Surface expression of hippocampal NMDA GluN2B receptors regulated by fear conditioning determines its contribution to memory consolidation in adult rats.

PubMed

Sun, Yan-Yan; Cai, Wei; Yu, Jie; Liu, Shu-Su; Zhuo, Min; Li, Bao-Ming; Zhang, Xue-Han

2016-08-04

The number and subtype composition of N-methyl-d-aspartate receptor (NMDAR) at synapses determines their functional properties and role in learning and memory. Genetically increased or decreased amount of GluN2B affects hippocampus-dependent memory in the adult brain. But in some experimental conditions (e.g., memory elicited by a single conditioning trial (1 CS-US)), GluN2B is not a necessary factor, which indicates that the precise role of GluN2B in memory formation requires further exploration. Here, we examined the role of GluN2B in the consolidation of fear memory using two training paradigms. We found that GluN2B was only required for the consolidation of memory elicited by five conditioning trials (5 CS-US), not by 1 CS-US. Strikingly, the expression of membrane GluN2B in CA1was training-strength-dependently increased after conditioning, and that the amount of membrane GluN2B determined its involvement in memory consolidation. Additionally, we demonstrated the increases in the activities of cAMP, ERK, and CREB in the CA1 after conditioning, as well as the enhanced intrinsic excitability and synaptic efficacy in CA1 neurons. Up-regulation of membrane GluN2B contributed to these enhancements. These studies uncover a novel mechanism for the involvement of GluN2B in memory consolidation by its accumulation at the cell surface in response to behavioral training.

Human hippocampus associates information in memory

PubMed Central

Henke, Katharina; Weber, Bruno; Kneifel, Stefan; Wieser, Heinz Gregor; Buck, Alfred

1999-01-01

The hippocampal formation, one of the most complex and vulnerable brain structures, is recognized as a crucial brain area subserving human long-term memory. Yet, its specific functions in memory are controversial. Recent experimental results suggest that the hippocampal contribution to human memory is limited to episodic memory, novelty detection, semantic (deep) processing of information, and spatial memory. We measured the regional cerebral blood flow by positron-emission tomography while healthy volunteers learned pairs of words with different learning strategies. These led to different forms of learning, allowing us to test the degree to which they challenge hippocampal function. Neither novelty detection nor depth of processing activated the hippocampal formation as much as semantically associating the primarily unrelated words in memory. This is compelling evidence for another function of the human hippocampal formation in memory: establishing semantic associations. PMID:10318979

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

PubMed

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

2017-04-12

Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We found that social recognition memory is consolidated through CREB-meditated gene expression in the hippocampus, medial prefrontal cortex, anterior cingulate cortex (ACC), and amygdala. Importantly, network analyses based on c-fos expression suggest that functional connectivity of these four brain regions with other brain regions is increased with time spent in social investigation toward the generation of brain networks to consolidate social recognition memory. Furthermore, our findings suggest that hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. Copyright © 2017 the authors 0270-6474/17/374103-14$15.00/0.

Hippocampal SSTR4 somatostatin receptors control the selection of memory strategies.

PubMed

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

2009-01-01

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

Memory Dynamics in Cross-linked Actin Networks

NASA Astrophysics Data System (ADS)

Scheff, Danielle; Majumdar, Sayantan; Gardel, Margaret

Cells demonstrate the remarkable ability to adapt to mechanical stimuli through rearrangement of the actin cytoskeleton, a cross-linked network of actin filaments. In addition to its importance in cell biology, understanding this mechanical response provides strategies for creation of novel materials. A recent study has demonstrated that applied stress can encode mechanical memory in these networks through changes in network geometry, which gives rise to anisotropic shear response. Under later shear, the network is stiffer in the direction of the previously applied stress. However, the dynamics behind the encoding of this memory are unknown. To address this question, we explore the effect of varying either the rigidity of the cross-linkers or the length of actin filament on the time scales required for both memory encoding and over which it later decays. While previous experiments saw only a long-lived memory, initial results suggest another mechanism where memories relax relatively quickly. Overall, our study is crucial for understanding the process by which an external stress can impact network arrangement and thus the dynamics of memory formation.

A cannabinoid link between mitochondria and memory.

PubMed

Hebert-Chatelain, Etienne; Desprez, Tifany; Serrat, Román; Bellocchio, Luigi; Soria-Gomez, Edgar; Busquets-Garcia, Arnau; Pagano Zottola, Antonio Christian; Delamarre, Anna; Cannich, Astrid; Vincent, Peggy; Varilh, Marjorie; Robin, Laurie M; Terral, Geoffrey; García-Fernández, M Dolores; Colavita, Michelangelo; Mazier, Wilfrid; Drago, Filippo; Puente, Nagore; Reguero, Leire; Elezgarai, Izaskun; Dupuy, Jean-William; Cota, Daniela; Lopez-Rodriguez, Maria-Luz; Barreda-Gómez, Gabriel; Massa, Federico; Grandes, Pedro; Bénard, Giovanni; Marsicano, Giovanni

2016-11-24

Cellular activity in the brain depends on the high energetic support provided by mitochondria, the cell organelles which use energy sources to generate ATP. Acute cannabinoid intoxication induces amnesia in humans and animals, and the activation of type-1 cannabinoid receptors present at brain mitochondria membranes (mtCB 1 ) can directly alter mitochondrial energetic activity. Although the pathological impact of chronic mitochondrial dysfunctions in the brain is well established, the involvement of acute modulation of mitochondrial activity in high brain functions, including learning and memory, is unknown. Here, we show that acute cannabinoid-induced memory impairment in mice requires activation of hippocampal mtCB 1 receptors. Genetic exclusion of CB 1 receptors from hippocampal mitochondria prevents cannabinoid-induced reduction of mitochondrial mobility, synaptic transmission and memory formation. mtCB 1 receptors signal through intra-mitochondrial Gα i protein activation and consequent inhibition of soluble-adenylyl cyclase (sAC). The resulting inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system eventually leads to decreased cellular respiration. Hippocampal inhibition of sAC activity or manipulation of intra-mitochondrial PKA signalling or phosphorylation of the Complex I subunit NDUFS2 inhibit bioenergetic and amnesic effects of cannabinoids. Thus, the G protein-coupled mtCB 1 receptors regulate memory processes via modulation of mitochondrial energy metabolism. By directly linking mitochondrial activity to memory formation, these data reveal that bioenergetic processes are primary acute regulators of cognitive functions.

Level of Processing Modulates the Neural Correlates of Emotional Memory Formation

ERIC Educational Resources Information Center

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

2011-01-01

Emotion is known to influence multiple aspects of memory formation, including the initial encoding of the memory trace and its consolidation over time. However, the neural mechanisms whereby emotion impacts memory encoding remain largely unexplored. The present study used a levels-of-processing manipulation to characterize the impact of emotion on…

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

PubMed Central

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

2014-01-01

Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesised to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluR2 subunit. A myristoylated PKMζ pseudosubstrate peptide (ZIP) blocks PKMζ activity. We examined the actions of ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition memory in rats during early memory formation and memory maintenance. ZIP infusion in either hippocampus or mPFC impaired memory maintenance. However, early memory formation was impaired by ZIP in mPFC but not hippocampus; and blocking GluR2-dependent removal of AMPA receptors did not affect this impairment caused by ZIP in the mPFC. The findings indicate: (i) a difference in the actions of ZIP in hippocampus and medial prefrontal cortex, and (ii) a GluR2-independent target of ZIP (possibly PKCλ) in the mPFC during early memory formation. PMID:24729442

Applying n-bit floating point numbers and integers, and the n-bit filter of HDF5 to reduce file sizes of remote sensing products in memory-sensitive environments

NASA Astrophysics Data System (ADS)

Zinke, Stephan

2017-02-01

Memory sensitive applications for remote sensing data require memory-optimized data types in remote sensing products. Hierarchical Data Format version 5 (HDF5) offers user defined floating point numbers and integers and the n-bit filter to create data types optimized for memory consumption. The European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT) applies a compaction scheme to the disseminated products of the Day and Night Band (DNB) data of Suomi National Polar-orbiting Partnership (S-NPP) satellite's instrument Visible Infrared Imager Radiometer Suite (VIIRS) through the EUMETSAT Advanced Retransmission Service, converting the original 32 bits floating point numbers to user defined floating point numbers in combination with the n-bit filter for the radiance dataset of the product. The radiance dataset requires a floating point representation due to the high dynamic range of the DNB. A compression factor of 1.96 is reached by using an automatically determined exponent size and an 8 bits trailing significand and thus reducing the bandwidth requirements for dissemination. It is shown how the parameters needed for user defined floating point numbers are derived or determined automatically based on the data present in a product.

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

PubMed

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

2011-12-01

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

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

PubMed

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

2015-01-01

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

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

PubMed

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

2013-07-01

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

Dopaminergic influences on formation of a motor memory.

PubMed

Flöel, Agnes; Breitenstein, Caterina; Hummel, Friedhelm; Celnik, Pablo; Gingert, Christian; Sawaki, Lumy; Knecht, Stefan; Cohen, Leonardo G

2005-07-01

The ability of the central nervous system to form motor memories, a process contributing to motor learning and skill acquisition, decreases with age. Dopaminergic activity, one of the mechanisms implicated in memory formation, experiences a similar decline with aging. It is possible that restoring dopaminergic function in elderly adults could lead to improved formation of motor memories with training. We studied the influence of a single oral dose of levodopa (100mg) administered preceding training on the ability to encode an elementary motor memory in the primary motor cortex of elderly and young healthy volunteers in a randomized, double-blind, placebo-controlled design. Attention to the task and motor training kinematics were comparable across age groups and sessions. In young subjects, encoding a motor memory under placebo was more prominent than in older subjects, and the encoding process was accelerated by intake of levodopa. In the elderly group, diminished motor memory encoding under placebo was enhanced by intake of levodopa to levels present in younger subjects. Therefore, upregulation of dopaminergic activity accelerated memory formation in young subjects and restored the ability to form a motor memory in elderly subjects; possible mechanisms underlying the beneficial effects of dopaminergic agents on motor learning in neurorehabilitation.

Memory formation during anaesthesia: plausibility of a neurophysiological basis

PubMed Central

Veselis, R. A.

2015-01-01

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

Intrahippocampal glutamine administration inhibits mTORC1 signaling and impairs long-term memory

PubMed Central

Rozas, Natalia S.; Redell, John B.; Pita-Almenar, Juan D.; Mckenna, James; Moore, Anthony N.; Gambello, Michael J.

2015-01-01

The mechanistic Target of Rapamycin Complex 1 (mTORC1), a key regulator of protein synthesis and cellular growth, is also required for long-term memory formation. Stimulation of mTORC1 signaling is known to be dependent on the availability of energy and growth factors, as well as the presence of amino acids. In vitro studies using serum- and amino acid-starved cells have reported that glutamine addition can either stimulate or repress mTORC1 activity, depending on the particular experimental system that was used. However, these experiments do not directly address the effect of glutamine on mTORC1 activity under physiological conditions in nondeprived cells in vivo. We present experimental results indicating that intrahippocampal administration of glutamine to rats reduces mTORC1 activity. Moreover, post-training administration of glutamine impairs long-term spatial memory formation, while coadministration of glutamine with leucine had no influence on memory. Intracellular recordings in hippocampal slices showed that glutamine did not alter either excitatory or inhibitory synaptic activity, suggesting that the observed memory impairments may not result from conversion of glutamine to either glutamate or GABA. Taken together, these findings indicate that glutamine can decrease mTORC1 activity in the brain and may have implications for treatments of neurological diseases associated with high mTORC1 signaling. PMID:25878136

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

PubMed

Friedrich, Anke; Thomas, Ulf; Müller, Uli

2004-05-05

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

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

PubMed

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

2017-08-01

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

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

PubMed Central

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

2009-01-01

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

Epigenetic mechanisms in fear conditioning: Implications for treating post-traumatic stress disorder

PubMed Central

Kwapis, Janine L.; Wood, Marcelo A.

2014-01-01

Post-traumatic stress disorder (PTSD) and other anxiety disorders stemming from dysregulated fear memory are problematic and costly. Understanding the molecular mechanisms that contribute to the formation and maintenance of these persistent fear associations is critical to developing treatments for PTSD. Epigenetic mechanisms, which control gene expression to produce long-lasting changes in cellular function, may support the formation of fear memory underlying PTSD. Here, we address the role of epigenetic mechanisms in the formation, storage, updating, and extinction of fear memories and discuss methods of targeting these epigenetic mechanisms to reduce the initial formation of fear memory or to enhance its extinction. Epigenetic mechanisms may provide a novel target for pharmaceutical and other treatments to reduce aversive memory contributing to PTSD. PMID:25220045

Dynamic Hippocampal and Prefrontal Contributions to Memory Processes and Representations Blur the Boundaries of Traditional Cognitive Domains

PubMed Central

Schwarb, Hillary; Lucas, Heather D.; Dulas, Michael R.; Cohen, Neal J.

2017-01-01

The hippocampus has long been known to be a critical component of the memory system involved in the formation and use of long-term declarative memory. However, recent findings have revealed that the reach of hippocampal contributions extends to a variety of domains and tasks that require the flexible use of cognitive and social behavior, including domains traditionally linked to prefrontal cortex (PFC), such as decision-making. In addition, the prefrontal cortex (PFC) has gained traction as a necessary part of the memory system. These findings challenge the conventional characterizations of hippocampus and PFC as being circumscribed to traditional cognitive domains. Here, we emphasize that the ability to parsimoniously account for the breadth of hippocampal and PFC contributions to behavior, in terms of memory function and beyond, requires theoretical advances in our understanding of their characteristic processing features and mental representations. Notably, several literatures exist that touch upon this issue, but have remained disjointed because of methodological differences that necessarily limit the scope of inquiry, as well as the somewhat artificial boundaries that have been historically imposed between domains of cognition. In particular, this article focuses on the contribution of relational memory theory as an example of a framework that describes both the representations and processes supported by the hippocampus, and further elucidates the role of the hippocampal–PFC network to a variety of behaviors. PMID:28704928

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

PubMed

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

2018-05-01

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

Intra-Amygdala Injections of CREB Antisense Impair Inhibitory Avoidance Memory: Role of Norepinephrine and Acetylcholine

ERIC Educational Resources Information Center

Canal, Clinton E.; Chang, Qing; Gold, Paul E.

2008-01-01

Infusions of CREB antisense into the amygdala prior to training impair memory for aversive tasks, suggesting that the antisense may interfere with CRE-mediated gene transcription and protein synthesis important for the formation of new memories within the amygdala. However, the amygdala also appears to modulate memory formation in distributed…

Germinal-center development of memory B cells driven by IL-9 from follicular helper T cells.

PubMed

Wang, Yifeng; Shi, Jingwen; Yan, Jiacong; Xiao, Zhengtao; Hou, Xiaoxiao; Lu, Peiwen; Hou, Shiyue; Mao, Tianyang; Liu, Wanli; Ma, Yuanwu; Zhang, Lianfeng; Yang, Xuerui; Qi, Hai

2017-08-01

Germinal centers (GCs) support high-affinity, long-lived humoral immunity. How memory B cells develop in GCs is not clear. Through the use of a cell-cycle-reporting system, we identified GC-derived memory precursor cells (GC-MP cells) that had quit cycling and reached G0 phase while in the GC, exhibited memory-associated phenotypes with signs of affinity maturation and localized toward the GC border. After being transferred into adoptive hosts, GC-MP cells reconstituted a secondary response like genuine memory B cells. GC-MP cells expressed the interleukin 9 (IL-9) receptor and responded to IL-9. Acute treatment with IL-9 or antibody to IL-9 accelerated or retarded the positioning of GC-MP cells toward the GC edge and exit from the GC, and enhanced or inhibited the development of memory B cells, which required B cell-intrinsic responsiveness to IL-9. Follicular helper T cells (T FH cells) produced IL-9, and deletion of IL-9 from T cells or, more specifically, from GC T FH cells led to impaired memory formation of B cells. Therefore, the GC development of memory B cells is promoted by T FH cell-derived IL-9.

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

PubMed

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

2017-11-21

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

CREB Selectively Controls Learning-Induced Structural Remodeling of Neurons

ERIC Educational Resources Information Center

Middei, Silvia; Spalloni, Alida; Longone, Patrizia; Pittenger, Christopher; O'Mara, Shane M.; Marie, Helene; Ammassari-Teule, Martine

2012-01-01

The modulation of synaptic strength associated with learning is post-synaptically regulated by changes in density and shape of dendritic spines. The transcription factor CREB (cAMP response element binding protein) is required for memory formation and in vitro dendritic spine rearrangements, but its role in learning-induced remodeling of neurons…

Properties of Contextual Memory Formed in the Absence of αCaMKII Autophosphorylation

PubMed Central

2011-01-01

The alpha-isoform of calcium/calmodulin-dependent kinase II (αCaMKII) is a major synaptic kinase that undergoes autophosphorylation after NMDA receptor activation, switching the kinase into a calcium-independent activity state. This αCaMKII autophosphorylation is essential for NMDA receptor-dependent long-term potentiation (LTP), induced by a single tetanus, in hippocampal area CA1 and in neocortex. Furthermore, the αCaMKII autophosphorylation is essential for contextual long-term memory (LTM) formation after a single training trial but not after a massed training session. Here, we show that in the absence of αCaMKII autophosphorylation contextual fear conditioning is hippocampus dependent and that multi-tetanus-dependent late-LTP cannot be induced in hippocampal area CA1. Furthermore, we show that in the absence of αCaMKII autophosphorylation contextual LTM persists for 30 days, the latest time point tested. Additionally, contextual, but not cued, LTM formation in the absence of αCaMKII autophosphorylation appears to be impaired in 18 month-old mice. Taken together, our findings suggest that αCaMKII autophosphorylation-independent plasticity in the hippocampus is sufficient for contextual LTM formation and that αCaMKII autophosphorylation may be important for delaying age-related impairments in hippocampal memory formation. Furthermore, they propose that NMDA receptor-dependent LTP in hippocampal area CA1 is essential for contextual LTM formation after a single trial but not after massed training. Finally, our results challenge the proposal that NMDA receptor-dependent LTP in neocortex is required for remote contextual LTM. PMID:21276220

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

PubMed

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

2015-01-01

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

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

NASA Astrophysics Data System (ADS)

Levitan, David; Gal-Ben-Ari, Shunit; Heise, Christopher; Rosenberg, Tali; Elkobi, Alina; Inberg, Sharon; Sala, Carlo; Rosenblum, Kobi

2016-05-01

The current dogma suggests that the formation of long-term memory (LTM) is dependent on protein synthesis but persistence of the memory trace is not. However, many of the studies examining the effect of protein synthesis inhibitors (PSIs) on LTM persistence were performed in the hippocampus, which is known to have a time-dependent role in memory storage, rather than the cortex, which is considered to be the main structure to store long-term memories. Here we studied the effect of PSIs on LTM formation and persistence in male Wistar Hola (n⩾5) rats by infusing the protein synthesis inhibitor, anisomycin (100 μg, 1 μl), into the gustatory cortex (GC) during LTM formation and persistence in conditioned taste aversion (CTA). We found that local anisomycin infusion to the GC before memory acquisition impaired LTM formation (P=8.9E-5), but had no effect on LTM persistence when infused 3 days post acquisition (P=0.94). However, when we extended the time interval between treatment with anisomycin and testing from 3 days to 14 days, LTM persistence was enhanced (P=0.01). The enhancement was on the background of stable and non-declining memory, and was not recapitulated by another amnesic agent, APV (10 μg, 1 μl), an N-methyl-D-aspartate receptor antagonist (P=0.54). In conclusion, CTA LTM remains sensitive to the action of PSIs in the GC even 3 days following memory acquisition. This sensitivity is differentially expressed between the formation and persistence of LTM, suggesting that increased cortical protein synthesis promotes LTM formation, whereas decreased protein synthesis promotes LTM persistence.

Pre-stimulus thalamic theta power predicts human memory formation.

PubMed

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

2016-09-01

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

Histaminergic Mechanisms for Modulation of Memory Systems

PubMed Central

Köhler, Cristiano André; da Silva, Weber Cláudio; Benetti, Fernando; Bonini, Juliana Sartori

2011-01-01

Encoding for several memory types requires neural changes and the activity of distinct regions across the brain. These areas receive broad projections originating in nuclei located in the brainstem which are capable of modulating the activity of a particular area. The histaminergic system is one of the major modulatory systems, and it regulates basic homeostatic and higher functions including arousal, circadian, and feeding rhythms, and cognition. There is now evidence that histamine can modulate learning in different types of behavioral tasks, but the exact course of modulation and its mechanisms are controversial. In the present paper we review the involvement of the histaminergic system and the effects histaminergic receptor agonists/antagonists have on the performance of tasks associated with the main memory types as well as evidence provided by studies with knockout models. Thus, we aim to summarize the possible effects histamine has on modulation of circuits involved in memory formation. PMID:21876818

Memory circuits: CA2.

PubMed

Piskorowski, Rebecca A; Chevaleyre, Vivien

2018-04-26

The hippocampus is a central region in the coding of spatial, temporal and episodic memory. Recent discoveries have revealed surprising and complex roles of the small area CA2 in hippocampal function. Lesion studies have revealed that this region is required for social memory formation. Area CA2 is targeted by extra-hippocampal paraventricular inputs that release vasopressin and can act to enhance social memory performance. In vivo recordings have revealed nonconventional activity by neurons in this region that act to both initiate hippocampal sharp-wave ripple events as well as encode spatial information during immobility. Silencing of CA2 pyramidal neurons has revealed that this area also acts to control hippocampal network excitability during encoding, and this balance of excitation and inhibition is disrupted in disease. This review summarizes recent findings and attempts to integrate these results into pre-existing models. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Mathematical Model for the Hippocampus: Towards the Understanding of Episodic Memory and Imagination

NASA Astrophysics Data System (ADS)

Tsuda, I.; Yamaguti, Y.; Kuroda, S.; Fukushima, Y.; Tsukada, M.

How does the brain encode episode? Based on the fact that the hippocampus is responsible for the formation of episodic memory, we have proposed a mathematical model for the hippocampus. Because episodic memory includes a time series of events, an underlying dynamics for the formation of episodic memory is considered to employ an association of memories. David Marr correctly pointed out in his theory of archecortex for a simple memory that the hippocampal CA3 is responsible for the formation of associative memories. However, a conventional mathematical model of associative memory simply guarantees a single association of memory unless a rule for an order of successive association of memories is given. The recent clinical studies in Maguire's group for the patients with the hippocampal lesion show that the patients cannot make a new story, because of the lack of ability of imagining new things. Both episodic memory and imagining things include various common characteristics: imagery, the sense of now, retrieval of semantic information, and narrative structures. Taking into account these findings, we propose a mathematical model of the hippocampus in order to understand the common mechanism of episodic memory and imagination.

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

ERIC Educational Resources Information Center

Eisenhardt, Dorothea

2014-01-01

The honeybee ("Apis mellifera") has long served as an invertebrate model organism for reward learning and memory research. Its capacity for learning and memory formation is rooted in the ecological need to efficiently collect nectar and pollen during summer to ensure survival of the hive during winter. Foraging bees learn to associate a…

Predicting episodic memory formation for movie events

PubMed Central

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

2016-01-01

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

Predicting episodic memory formation for movie events.

PubMed

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

2016-09-30

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

Memory formation during anaesthesia: plausibility of a neurophysiological basis.

PubMed

Veselis, R A

2015-07-01

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

Structural Components of Synaptic Plasticity and Memory Consolidation

PubMed Central

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

2015-01-01

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

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

PubMed Central

Krupnick, Alexander Sasha; Lin, Xue; Li, Wenjun; Higashikubo, Ryuiji; Zinselmeyer, Bernd H.; Hartzler, Hollyce; Toth, Kelsey; Ritter, Jon H.; Berezin, Mikhail Y.; Wang, Steven T.; Miller, Mark J.; Gelman, Andrew E.; Kreisel, Daniel

2014-01-01

Memory T lymphocytes are commonly viewed as a major barrier for long-term survival of organ allografts and are thought to accelerate rejection responses due to their rapid infiltration into allografts, low threshold for activation, and ability to produce inflammatory mediators. Because memory T cells are usually associated with rejection, preclinical protocols have been developed to target this population in transplant recipients. Here, using a murine model, we found that costimulatory blockade–mediated lung allograft acceptance depended on the rapid infiltration of the graft by central memory CD8+ T cells (CD44hiCD62LhiCCR7+). Chemokine receptor signaling and alloantigen recognition were required for trafficking of these memory T cells to lung allografts. Intravital 2-photon imaging revealed that CCR7 expression on CD8+ T cells was critical for formation of stable synapses with antigen-presenting cells, resulting in IFN-γ production, which induced NO and downregulated alloimmune responses. Thus, we describe a critical role for CD8+ central memory T cells in lung allograft acceptance and highlight the need for tailored approaches for tolerance induction in the lung. PMID:24569377

Cross-modal working memory binding and word recognition skills: how specific is the link?

PubMed

Wang, Shinmin; Allen, Richard J

2018-04-01

Recent research has suggested that the creation of temporary bound representations of information from different sources within working memory uniquely relates to word recognition abilities in school-age children. However, it is unclear to what extent this link is attributable specifically to the binding ability for cross-modal information. This study examined the performance of Grade 3 (8-9 years old) children on binding tasks requiring either temporary association formation of two visual items (i.e., within-modal binding) or pairs of visually presented abstract shapes and auditorily presented nonwords (i.e., cross-modal binding). Children's word recognition skills were related to performance on the cross-modal binding task but not on the within-modal binding task. Further regression models showed that cross-modal binding memory was a significant predictor of word recognition when memory for its constituent elements, general abilities, and crucially, within-modal binding memory were taken into account. These findings may suggest a specific link between the ability to bind information across modalities within working memory and word recognition skills.

Age differences and format effects in working memory.

PubMed

Foos, Paul W; Goolkasian, Paula

2010-07-01

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

Attention improves memory by suppressing spiking-neuron activity in the human anterior temporal lobe.

PubMed

Wittig, John H; Jang, Anthony I; Cocjin, John B; Inati, Sara K; Zaghloul, Kareem A

2018-06-01

We identify a memory-specific attention mechanism in the human anterior temporal lobe, an area implicated in semantic processing and episodic memory formation. Spiking neuron activity is suppressed and becomes more reliable in preparation for verbal memory formation. Intracranial electroencephalography signals implicate this region as a source of executive control for attentional selection. Consistent with this interpretation, its surgical removal causes significant memory impairment for attended words relative to unattended words.

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

ERIC Educational Resources Information Center

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…

Drosophila Learn Opposing Components of a Compound Food Stimulus

PubMed Central

Das, Gaurav; Klappenbach, Martín; Vrontou, Eleftheria; Perisse, Emmanuel; Clark, Christopher M.; Burke, Christopher J.; Waddell, Scott

2014-01-01

Summary Dopaminergic neurons provide value signals in mammals and insects [1–3]. During Drosophila olfactory learning, distinct subsets of dopaminergic neurons appear to assign either positive or negative value to odor representations in mushroom body neurons [4–9]. However, it is not known how flies evaluate substances that have mixed valence. Here we show that flies form short-lived aversive olfactory memories when trained with odors and sugars that are contaminated with the common insect repellent DEET. This DEET-aversive learning required the MB-MP1 dopaminergic neurons that are also required for shock learning [7]. Moreover, differential conditioning with DEET versus shock suggests that formation of these distinct aversive olfactory memories relies on a common negatively reinforcing dopaminergic mechanism. Surprisingly, as time passed after training, the behavior of DEET-sugar-trained flies reversed from conditioned odor avoidance into odor approach. In addition, flies that were compromised for reward learning exhibited a more robust and longer-lived aversive-DEET memory. These data demonstrate that flies independently process the DEET and sugar components to form parallel aversive and appetitive olfactory memories, with distinct kinetics, that compete to guide learned behavior. PMID:25042590

Real-Time Data Processing in the muon system of the D0 detector.

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

Neeti Parashar et al.

2001-07-03

This paper presents a real-time application of the 16-bit fixed point Digital Signal Processors (DSPs), in the Muon System of the D0 detector located at the Fermilab Tevatron, presently the world's highest-energy hadron collider. As part of the Upgrade for a run beginning in the year 2000, the system is required to process data at an input event rate of 10 KHz without incurring significant deadtime in readout. The ADSP21csp01 processor has high I/O bandwidth, single cycle instruction execution and fast task switching support to provide efficient multisignal processing. The processor's internal memory consists of 4K words of Program Memorymore » and 4K words of Data Memory. In addition there is an external memory of 32K words for general event buffering and 16K words of Dual port Memory for input data queuing. This DSP fulfills the requirement of the Muon subdetector systems for data readout. All error handling, buffering, formatting and transferring of the data to the various trigger levels of the data acquisition system is done in software. The algorithms developed for the system complete these tasks in about 20 {micro}s per event.« less

The role of the ubiquitin proteasome system in the memory process.

PubMed

Lip, Philomena Z Y; Demasi, Marilene; Bonatto, Diego

2017-01-01

Quite intuitive is the notion that memory formation and consolidation is orchestrated by protein synthesis because of the synaptic plasticity necessary for those processes. Nevertheless, recent advances have begun accumulating evidences of a high requirement for protein degradation on the molecular mechanisms of the memory process in the mammalian brain. Because degradation determines protein half-life, degradation has been increasingly recognized as an important intracellular regulatory mechanism. The proteasome is the main player in the degradation of intracellular proteins. Proteasomal substrates are mainly degraded after a post-translational modification by a poly-ubiquitin chain. Latter process, namely poly-ubiquitination, is highly regulated at the step of the ubiquitin molecule transferring to the protein substrate mediated by a set of proteins whose genes represent almost 2% of the human genome. Understanding the role of polyubiquitin-mediated protein degradation has challenging researchers in many fields of investigation as a new source of targets for therapeutic intervention, e.g. E3 ligases that transfer ubiquitin moieties to the substrate. The goal of present work was to uncover mechanisms underlying memory processes regarding the role of the ubiquitin-proteasome system (UPS). For that purpose, preceded of a short review on UPS and memory processes a top-down systems biology approach was applied to establish central proteins involved in memory formation and consolidation highlighting their cross-talking with the UPS. According to that approach, the pattern of expression of several elements of the UPS were found overexpressed in regions of the brain involved in processing cortical inputs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protein synthesis in the basolateral amygdala complex is required for consolidation of a first-order fear memory, but not for consolidation of a higher-order fear memory.

PubMed

Leidl, Dana M; Lay, Belinda P P; Chakouch, Cassandra; Westbrook, R Frederick; Holmes, Nathan M

2018-04-12

The present series of experiments pursued our recent findings that consolidation of a second-order fear memory requires neuronal activity, but not de novo protein synthesis, in the basolateral amygdala complex (BLA). It used a modified second-order conditioning protocol in which rats were exposed to S1-shock pairings in stage 1 and pairings of the serial S2-S1 compound and shock in stage 2. Experiment 1 showed that responding (freezing) to S2 in this protocol is conditional on its compounding with S1 in stage 2 (Experiment 1), and therefore, the result of associative formation. The remaining experiments then showed that the protein synthesis requirement for consolidation of new learning about S2 varied with the training afforded S1. When S1 was trained in stage 1 and present in stage 2, consolidation of the new S2 fear memory was unaffected by pre- or post-stage 2 infusions of the protein synthesis inhibitor, cycloheximide, into the BLA (Experiments 2 and 5). This result was observed independently of the number of S1-shock pairings in stage 1 (even a single pairing produced the result), and alongside demonstrations that cycloheximide infusions disrupt consolidation of a first-order fear memory (Experiments 2 and 5). However, when S1 was not conditioned in stage 1 (Experiment 3) or was omitted from conditioning in stage 2 (Experiment 4), consolidation of the new S2 fear memory was disrupted by post-stage 2 cycloheximide infusions into the BLA. These results were taken to imply that the consolidation of a higher-order fear memory exploits molecular events associated with consolidation of a reactivated first-order fear memory; hence it occurs independently of de novo protein synthesis in the BLA. Alternatively, the nature of the association formed in higher-order conditioning may be such as to not require de novo protein synthesis for its consolidation. Copyright © 2018 Elsevier Inc. All rights reserved.

Transcriptional profiling reveals regulated genes in the hippocampus during memory formation

NASA Technical Reports Server (NTRS)

Donahue, Christine P.; Jensen, Roderick V.; Ochiishi, Tomoyo; Eisenstein, Ingrid; Zhao, Mingrui; Shors, Tracey; Kosik, Kenneth S.

2002-01-01

Transcriptional profiling (TP) offers a powerful approach to identify genes activated during memory formation and, by inference, the molecular pathways involved. Trace eyeblink conditioning is well suited for the study of regional gene expression because it requires the hippocampus, whereas the highly parallel task, delay conditioning, does not. First, we determined when gene expression was most regulated during trace conditioning. Rats were exposed to 200 trials per day of paired and unpaired stimuli each day for 4 days. Changes in gene expression were most apparent 24 h after exposure to 200 trials. Therefore, we profiled gene expression in the hippocampus 24 h after 200 trials of trace eyeblink conditioning, on multiple arrays using additional animals. Of 1,186 genes on the filter array, seven genes met the statistical criteria and were also validated by real-time polymerase chain reaction. These genes were growth hormone (GH), c-kit receptor tyrosine kinase (c-kit), glutamate receptor, metabotropic 5 (mGluR5), nerve growth factor-beta (NGF-beta), Jun oncogene (c-Jun), transmembrane receptor Unc5H1 (UNC5H1), and transmembrane receptor Unc5H2 (UNC5H2). All these genes, except for GH, were downregulated in response to trace conditioning. GH was upregulated; therefore, we also validated the downregulation of the GH inhibitor, somatostatin (SST), even though it just failed to meet criteria on the arrays. By during situ hybridization, GH was expressed throughout the cell layers of the hippocampus in response to trace conditioning. None of the genes regulated in trace eyeblink conditioning were similarly affected by delay conditioning, a task that does not require the hippocampus. These findings demonstrate that transcriptional profiling can exhibit a repertoire of genes sensitive to the formation of hippocampal-dependent associative memories.

Event segmentation improves event memory up to one month later.

PubMed

Flores, Shaney; Bailey, Heather R; Eisenberg, Michelle L; Zacks, Jeffrey M

2017-08-01

When people observe everyday activity, they spontaneously parse it into discrete meaningful events. Individuals who segment activity in a more normative fashion show better subsequent memory for the events. If segmenting events effectively leads to better memory, does asking people to attend to segmentation improve subsequent memory? To answer this question, participants viewed movies of naturalistic activity with instructions to remember the activity for a later test, and in some conditions additionally pressed a button to segment the movies into meaningful events or performed a control condition that required button-pressing but not attending to segmentation. In 5 experiments, memory for the movies was assessed at intervals ranging from immediately following viewing to 1 month later. Performing the event segmentation task led to superior memory at delays ranging from 10 min to 1 month. Further, individual differences in segmentation ability predicted individual differences in memory performance for up to a month following encoding. This study provides the first evidence that manipulating event segmentation affects memory over long delays and that individual differences in event segmentation are related to differences in memory over long delays. These effects suggest that attending to how an activity breaks down into meaningful events contributes to memory formation. Instructing people to more effectively segment events may serve as a potential intervention to alleviate everyday memory complaints in aging and clinical populations. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Environmental enrichment reverses histone methylation changes in the aged hippocampus and restores age-related memory deficits.

PubMed

Morse, Sarah J; Butler, Anderson A; Davis, Robin L; Soller, Ian J; Lubin, Farah D

2015-04-01

A decline in long-term memory (LTM) formation is a common feature of the normal aging process, which corresponds with abnormal expression of memory-related genes in the aged hippocampus. Epigenetic modulation of chromatin structure is required for proper transcriptional control of genes, such as the brain-derived neurotrophic factor (Bdnf) and Zif268 in the hippocampus during the consolidation of new memories. Recently, the view has emerged that aberrant transcriptional regulation of memory-related genes may be reflective of an altered epigenetic landscape within the aged hippocampus, resulting in memory deficits with aging. Here, we found that baseline resting levels for tri-methylation of histone H3 at lysine 4 (H3K4me3) and acetylation of histone H3 at lysine 9 and 14 (H3K9,K14ac) were altered in the aged hippocampus as compared to levels in the hippocampus of young adult rats. Interestingly, object learning failed to increase activity-dependent H3K4me3 and di-methylation of histone H3 at lysine 9 (H3K9me2) levels in the hippocampus of aged adults as compared to young adults. Treatment with the LSD-1 histone demethylase inhibitor, t-PCP, increased baseline resting H3K4me3 and H3K9,K14ac levels in the young adult hippocampus, while young adult rats exhibited similar memory deficits as observed in aged rats. After environmental enrichment (EE), we found that object learning induced increases in H3K4me3 levels around the Bdnf, but not the Zif268, gene region in the aged hippocampus and rescued memory deficits in aged adults. Collectively, these results suggest that histone lysine methylation levels are abnormally regulated in the aged hippocampus and identify histone lysine methylation as a transcriptional mechanism by which EE may serve to restore memory formation with aging.

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

PubMed

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

2018-06-06

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

The integrated role of ACh, ERK and mTOR in the mechanisms of hippocampal inhibitory avoidance memory.

PubMed

Giovannini, Maria Grazia; Lana, Daniele; Pepeu, Giancarlo

2015-03-01

The purpose of this review is to summarize the present knowledge on the interplay among the cholinergic system, Extracellular signal-Regulated Kinase (ERK) and Mammalian Target of Rapamycin (mTOR) pathways in the development of short and long term memories during the acquisition and recall of the step-down inhibitory avoidance in the hippocampus. The step-down inhibitory avoidance is a form of associative learning that is acquired in a relatively simple one-trial test through several sensorial inputs. Inhibitory avoidance depends on the integrated activity of hippocampal CA1 and other brain areas. Recall can be performed at different times after acquisition, thus allowing for the study of both short and long term memory. Among the many neurotransmitter systems involved, the cholinergic neurons that originate in the basal forebrain and project to the hippocampus are of crucial importance in inhibitory avoidance processes. Acetylcholine released from cholinergic fibers during acquisition and/or recall of behavioural tasks activates muscarinic and nicotinic acetylcholine receptors and brings about a long-lasting potentiation of the postsynaptic membrane followed by downstream activation of intracellular pathway (ERK, among others) that create conditions favourable for neuronal plasticity. ERK appears to be salient not only in long term memory, but also in the molecular mechanisms underlying short term memory formation in the hippocampus. Since ERK can function as a biochemical coincidence detector in response to extracellular signals in neurons, the activation of ERK-dependent downstream effectors is determined, in part, by the duration of ERK phosphorylation itself. Long term memories require protein synthesis, that in the synapto-dendritic compartment represents a direct mechanism that can produce rapid changes in protein content in response to synaptic activity. mTOR in the brain regulates protein translation in response to neuronal activity, thereby modulating synaptic plasticity and long term memory formation. Some studies demonstrate a complex interplay among the cholinergic system, ERK and mTOR. It has been shown that co-activation of muscarinic acetylcholine receptors and β-adrenergic receptors facilitates the conversion of short term to long term synaptic plasticity through an ERK- and mTOR-dependent mechanism which requires translation initiation. It seems therefore that the complex interplay among the cholinergic system, ERK and mTOR is crucial in the development of new inhibitory avoidance memories in the hippocampus. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-01-01

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

Structural synaptic plasticity in the hippocampus induced by spatial experience and its implications in information processing.

PubMed

Carasatorre, M; Ramírez-Amaya, V; Díaz Cintra, S

2016-10-01

Long-lasting memory formation requires that groups of neurons processing new information develop the ability to reproduce the patterns of neural activity acquired by experience. Changes in synaptic efficiency let neurons organise to form ensembles that repeat certain activity patterns again and again. Among other changes in synaptic plasticity, structural modifications tend to be long-lasting which suggests that they underlie long-term memory. There is a large body of evidence supporting that experience promotes changes in the synaptic structure, particularly in the hippocampus. Structural changes to the hippocampus may be functionally implicated in stabilising acquired memories and encoding new information. Copyright © 2012 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Spatial-sequential and spatial-simultaneous working memory in individuals with Williams syndrome.

PubMed

Lanfranchi, Silvia; De Mori, Letizia; Mammarella, Irene C; Carretti, Barbara; Vianello, Renzo

2015-05-01

The aim of the present study was to compare visuospatial working memory performance in 18 individuals with Williams syndrome (WS) and 18 typically developing (TD) children matched for nonverbal mental age. Two aspects were considered: task presentation format (i.e., spatial-sequential or spatial-simultaneous), and level of attentional control (i.e., passive or active tasks). Our results showed that individuals with WS performed less well than TD children in passive spatial-simultaneous tasks, but not in passive spatial-sequential tasks. The former's performance was also worse in both active tasks. These findings suggest an impairment in the spatial-simultaneous working memory of individuals with WS, together with a more generalized difficulty in tasks requiring information storage and concurrent processing, as seen in other etiologies of intellectual disability.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-09-19

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

Continuing the search for the engram: examining the mechanism of fear memories.

PubMed

Josselyn, Sheena A

2010-07-01

The goal of my research is to gain insight using rodent models into the fundamental molecular, cellular and systems that make up the base of memory formation. My work focuses on fear memories. Aberrant fear and/or anxiety may be at the heart of many psychiatric disorders. In this article, I review the results of my research group; these results show that particular neurons in the lateral amygdala, a brain region important for fear, are specifically involved in particular fear memories. We started by showing that the transcription factor CREB (cAMP/Ca(2+) response element binding protein) plays a key role in the formation of fear memories. Next, we used viral vectors to overexpress CREB in a subset of lateral amygdala neurons. This not only facilitated fear memory formation but also "drove" the memory into the neurons with relatively increased CREB function. Finally, we showed that selective ablation of the neurons overexpressing CREB in the lateral amygdala selectively erased the fear memory. These findings are the first to show disruption of a specific memory by disrupting select neurons within a distributed network.

Neural and Cellular Mechanisms of Fear and Extinction Memory Formation

PubMed Central

Orsini, Caitlin A.; Maren, Stephen

2012-01-01

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

Remote Memory and Cortical Synaptic Plasticity Require Neuronal CCCTC-Binding Factor (CTCF).

PubMed

Kim, Somi; Yu, Nam-Kyung; Shim, Kyu-Won; Kim, Ji-Il; Kim, Hyopil; Han, Dae Hee; Choi, Ja Eun; Lee, Seung-Woo; Choi, Dong Il; Kim, Myung Won; Lee, Dong-Sung; Lee, Kyungmin; Galjart, Niels; Lee, Yong-Seok; Lee, Jae-Hyung; Kaang, Bong-Kiun

2018-05-30

The molecular mechanism of long-term memory has been extensively studied in the context of the hippocampus-dependent recent memory examined within several days. However, months-old remote memory maintained in the cortex for long-term has not been investigated much at the molecular level yet. Various epigenetic mechanisms are known to be important for long-term memory, but how the 3D chromatin architecture and its regulator molecules contribute to neuronal plasticity and systems consolidation is still largely unknown. CCCTC-binding factor (CTCF) is an 11-zinc finger protein well known for its role as a genome architecture molecule. Male conditional knock-out mice in which CTCF is lost in excitatory neurons during adulthood showed normal recent memory in the contextual fear conditioning and spatial water maze tasks. However, they showed remarkable impairments in remote memory in both tasks. Underlying the remote memory-specific phenotypes, we observed that female CTCF conditional knock-out mice exhibit disrupted cortical LTP, but not hippocampal LTP. Similarly, we observed that CTCF deletion in inhibitory neurons caused partial impairment of remote memory. Through RNA sequencing, we observed that CTCF knockdown in cortical neuron culture caused altered expression of genes that are highly involved in cell adhesion, synaptic plasticity, and memory. These results suggest that remote memory storage in the cortex requires CTCF-mediated gene regulation in neurons, whereas recent memory formation in the hippocampus does not. SIGNIFICANCE STATEMENT CCCTC-binding factor (CTCF) is a well-known 3D genome architectural protein that regulates gene expression. Here, we use two different CTCF conditional knock-out mouse lines and reveal, for the first time, that CTCF is critically involved in the regulation of remote memory. We also show that CTCF is necessary for appropriate expression of genes, many of which we found to be involved in the learning- and memory-related processes. Our study provides behavioral and physiological evidence for the involvement of CTCF-mediated gene regulation in the remote long-term memory and elucidates our understanding of systems consolidation mechanisms. Copyright © 2018 the authors 0270-6474/18/385042-11$15.00/0.

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

PubMed

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

2017-07-01

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

WARP3D-Release 10.8: Dynamic Nonlinear Analysis of Solids using a Preconditioned Conjugate Gradient Software Architecture

NASA Technical Reports Server (NTRS)

Koppenhoefer, Kyle C.; Gullerud, Arne S.; Ruggieri, Claudio; Dodds, Robert H., Jr.; Healy, Brian E.

1998-01-01

This report describes theoretical background material and commands necessary to use the WARP3D finite element code. WARP3D is under continuing development as a research code for the solution of very large-scale, 3-D solid models subjected to static and dynamic loads. Specific features in the code oriented toward the investigation of ductile fracture in metals include a robust finite strain formulation, a general J-integral computation facility (with inertia, face loading), an element extinction facility to model crack growth, nonlinear material models including viscoplastic effects, and the Gurson-Tver-gaard dilatant plasticity model for void growth. The nonlinear, dynamic equilibrium equations are solved using an incremental-iterative, implicit formulation with full Newton iterations to eliminate residual nodal forces. The history integration of the nonlinear equations of motion is accomplished with Newmarks Beta method. A central feature of WARP3D involves the use of a linear-preconditioned conjugate gradient (LPCG) solver implemented in an element-by-element format to replace a conventional direct linear equation solver. This software architecture dramatically reduces both the memory requirements and CPU time for very large, nonlinear solid models since formation of the assembled (dynamic) stiffness matrix is avoided. Analyses thus exhibit the numerical stability for large time (load) steps provided by the implicit formulation coupled with the low memory requirements characteristic of an explicit code. In addition to the much lower memory requirements of the LPCG solver, the CPU time required for solution of the linear equations during each Newton iteration is generally one-half or less of the CPU time required for a traditional direct solver. All other computational aspects of the code (element stiffnesses, element strains, stress updating, element internal forces) are implemented in the element-by- element, blocked architecture. This greatly improves vectorization of the code on uni-processor hardware and enables straightforward parallel-vector processing of element blocks on multi-processor hardware.

TrkB blockade in the hippocampus after training or retrieval impairs memory: protection from consolidation impairment by histone deacetylase inhibition.

PubMed

Blank, Martina; Petry, Fernanda S; Lichtenfels, Martina; Valiati, Fernanda E; Dornelles, Arethuza S; Roesler, Rafael

2016-03-01

Relatively little is known about the requirement of signaling initiated by brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), in the early phases of memory consolidation, as well as about its possible functional interactions with epigenetic mechanisms. Here we show that blocking TrkB in the dorsal hippocampus after learning or retrieval impairs retention of memory for inhibitory avoidance (IA). More importantly, the impairing effect of TrkB antagonism on consolidation was completely prevented by the histone deacetylase (HDAC) inhibitor sodium butyrate (NaB). Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or NaB before training, followed by an infusion of either vehicle (VEH) or the selective TrkB antagonist ANA-12 immediately after training. In a second experiment, the infusions were administered before and after retrieval. ANA-12 after either training or retrieval produced a significant impairment in a subsequent memory retention test. Pretraining administration of NaB prevented the effect of ANA-12, although NaB given before retrieval did not alter the impairment resulting from TrkB blockade. The results indicate that inhibition of BDNF/TrkB in the hippocampus can hinder consolidation and reconsolidation of IA memory. However, TrkB activity is not required for consolidation in the presence of NaB, suggesting that a dysfunction in BDNF/TrkB signaling can be fully compensated by HDAC inhibition to allow hippocampal memory formation.

Application-Controlled Demand Paging for Out-of-Core Visualization

NASA Technical Reports Server (NTRS)

Cox, Michael; Ellsworth, David; Kutler, Paul (Technical Monitor)

1997-01-01

In the area of scientific visualization, input data sets are often very large. In visualization of Computational Fluid Dynamics (CFD) in particular, input data sets today can surpass 100 Gbytes, and are expected to scale with the ability of supercomputers to generate them. Some visualization tools already partition large data sets into segments, and load appropriate segments as they are needed. However, this does not remove the problem for two reasons: 1) there are data sets for which even the individual segments are too large for the largest graphics workstations, 2) many practitioners do not have access to workstations with the memory capacity required to load even a segment, especially since the state-of-the-art visualization tools tend to be developed by researchers with much more powerful machines. When the size of the data that must be accessed is larger than the size of memory, some form of virtual memory is simply required. This may be by segmentation, paging, or by paged segments. In this paper we demonstrate that complete reliance on operating system virtual memory for out-of-core visualization leads to poor performance. We then describe a paged segment system that we have implemented, and explore the principles of memory management that can be employed by the application for out-of-core visualization. We show that application control over some of these can significantly improve performance. We show that sparse traversal can be exploited by loading only those data actually required. We show also that application control over data loading can be exploited by 1) loading data from alternative storage format (in particular 3-dimensional data stored in sub-cubes), 2) controlling the page size. Both of these techniques effectively reduce the total memory required by visualization at run-time. We also describe experiments we have done on remote out-of-core visualization (when pages are read by demand from remote disk) whose results are promising.

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

PubMed Central

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

2016-01-01

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

Method matters: Systematic effects of testing procedure on visual working memory sensitivity

PubMed Central

Makovski, Tal; Watson, Leah M.; Koutstaal, Wilma; Jiang, Yuhong V.

2010-01-01

Visual working memory (WM) is traditionally considered a robust form of visual representation that survives changes in object motion, observer's position, and other visual transients. This study presents data that are inconsistent with the traditional view. We show that memory sensitivity is dramatically influenced by small variations in the testing procedure, supporting the idea that representations in visual WM are susceptible to interference from testing. In this study, participants were shown an array of colors to remember. After a short retention interval, memory for one of the items was tested with either a same-different task or a 2-alternative-forced-choice (2AFC) task. Memory sensitivity was much lower in the 2AFC task than in the same-different task. This difference was found regardless of encoding similarity or whether visual WM required a fine memory resolution or a coarse resolution. The 2AFC disadvantage was reduced when participants were informed shortly before testing which item would be probed. The 2AFC disadvantage diminished in perceptual tasks and was not found in tasks probing visual long-term memory. These results support memory models that acknowledge the labile nature of visual WM, and have implications for the format of visual WM and its assessment. PMID:20854011

IOS: PDP 11/45 formatted input/output task stacker and processer. [In MACRO-II

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

Koschik, J.

1974-07-08

IOS allows the programer to perform formated Input/Output at assembly language level to/from any peripheral device. It runs under DOS versions V8-O8 or V9-19, reading and writing DOS-compatible files. Additionally, IOS will run, with total transparency, in an environment with memory management enabled. Minimum hardware required is a 16K PDP 11/45, Keyboard Device, DISK (DK,DF, or DC), and Line Frequency Clock. The source language is MACRO-11 (3.3K Decimal Words).

Rewriting My Autobiography: The Legal and Ethical Implications of Memory-Dampening Agents

ERIC Educational Resources Information Center

Aoki, Cynthia R. A.

2008-01-01

The formation and recall of memories are fundamental aspects of life and help preserve the complex collection of experiences that provide us with a sense of identity and autonomy. Scientists have recently started to investigate pharmacological agents that inhibit or "dampen" the strength of memory formation and recall. The development of…

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

PubMed

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 memory consolidation during long-term memory formation. Our results thus provide an idea about how nucleosome remodeling can be regulated during long-term memory formation and contributes to the permanent storage of associative fear memory in the lateral amygdala, which is relevant to fear and anxiety-related mental disorders. Copyright © 2017 the authors 0270-6474/17/373686-12$15.00/0.

Factors affecting reorganisation of memory encoding networks in temporal lobe epilepsy

PubMed Central

Sidhu, M.K.; Stretton, J.; Winston, G.P.; Symms, M.; Thompson, P.J.; Koepp, M.J.; Duncan, J.S.

2015-01-01

Summary Aims In temporal lobe epilepsy (TLE) due to hippocampal sclerosis reorganisation in the memory encoding network has been consistently described. Distinct areas of reorganisation have been shown to be efficient when associated with successful subsequent memory formation or inefficient when not associated with successful subsequent memory. We investigated the effect of clinical parameters that modulate memory functions: age at onset of epilepsy, epilepsy duration and seizure frequency in a large cohort of patients. Methods We studied 53 patients with unilateral TLE and hippocampal sclerosis (29 left). All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words. A continuous regression analysis was used to investigate the effects of age at onset of epilepsy, epilepsy duration and seizure frequency on the activation patterns in the memory encoding network. Results Earlier age at onset of epilepsy was associated with left posterior hippocampus activations that were involved in successful subsequent memory formation in left hippocampal sclerosis patients. No association of age at onset of epilepsy was seen with face encoding in right hippocampal sclerosis patients. In both left hippocampal sclerosis patients during word encoding and right hippocampal sclerosis patients during face encoding, shorter duration of epilepsy and lower seizure frequency were associated with medial temporal lobe activations that were involved in successful memory formation. Longer epilepsy duration and higher seizure frequency were associated with contralateral extra-temporal activations that were not associated with successful memory formation. Conclusion Age at onset of epilepsy influenced verbal memory encoding in patients with TLE due to hippocampal sclerosis in the speech-dominant hemisphere. Shorter duration of epilepsy and lower seizure frequency were associated with less disruption of the efficient memory encoding network whilst longer duration and higher seizure frequency were associated with greater, inefficient, extra-temporal reorganisation. PMID:25616449

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

PubMed

Vogel, Susanne; Schwabe, Lars

2016-09-01

Although stress is well known to modulate human memory, precisely how memory formation is altered by a stressful encounter remains unclear. Stress effects on cognition are mainly mediated by the rapidly acting sympathetic nervous system, resulting in the release of catecholamines, and the slower acting hypothalamus-pituitary-adrenal axis secreting cortisol, which induces its effects on cognition through fast, non-genomic actions and delayed, genomic actions. Importantly, these different waves of the physiological stress response are thought to dynamically alter neural processing in brain regions important for memory such as the amygdala and the hippocampus. However, the precise time course of stress effects on memory formation is still unclear. To track the development of stress effects on memory over time, we tested individuals who underwent a stressful experience or a control procedure before a 2-h walk through a zoo, while an automatic camera continuously photographed the events they encoded. In a recognition memory test one week later, participants were presented with target photographs of their own zoo tour and lure photographs from an alternate tour. Stressed participants showed better memory for the experimental treatment than control participants, and this memory enhancement for the stressful encounter itself was directly linked to the sympathetic stress response. Moreover, stress enhanced memory for events encoded 41-65min after stressor onset, which was associated with the cortisol stress response, most likely arising from non-genomic cortisol actions. However, memory for events encoded long after the stressor, when genomic cortisol actions had most likely developed, remained unchanged. Our findings provide novel insights into how stress effects on memory formation develop over time, depending on the activity of major physiological stress response systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Histone Deacetylase HDAC4 Regulates Long-Term Memory in Drosophila

PubMed Central

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

2013-01-01

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

Synchrony and desynchrony in circadian clocks: impacts on learning and memory

PubMed Central

Krishnan, Harini C.

2015-01-01

Circadian clocks evolved under conditions of environmental variation, primarily alternating light dark cycles, to enable organisms to anticipate daily environmental events and coordinate metabolic, physiological, and behavioral activities. However, modern lifestyle and advances in technology have increased the percentage of individuals working in phases misaligned with natural circadian activity rhythms. Endogenous circadian oscillators modulate alertness, the acquisition of learning, memory formation, and the recall of memory with examples of circadian modulation of memory observed across phyla from invertebrates to humans. Cognitive performance and memory are significantly diminished when occurring out of phase with natural circadian rhythms. Disruptions in circadian regulation can lead to impairment in the formation of memories and manifestation of other cognitive deficits. This review explores the types of interactions through which the circadian clock modulates cognition, highlights recent progress in identifying mechanistic interactions between the circadian system and the processes involved in memory formation, and outlines methods used to remediate circadian perturbations and reinforce circadian adaptation. PMID:26286653

Memory for Lectures: How Lecture Format Impacts the Learning Experience

PubMed Central

Varao-Sousa, Trish L.; Kingstone, Alan

2015-01-01

The present study investigated what impact the presentation style of a classroom lecture has on memory, mind wandering, and the subjective factors of interest and motivation. We examined if having a professor lecturing live versus on video alters the learning experience of the students in the classroom. During the lectures, students were asked to report mind wandering and later complete a memory test. The lecture format was manipulated such that all the students received two lectures, one live and one a pre-recorded video. Results indicate that lecture format affected memory performance but not mind wandering, with enhanced memory in the live lectures. Additionally, students reported greater interest and motivation in the live lectures. Given that a single change to the classroom environment, professor presence, impacted memory performance, as well as motivation and interest, the present results have several key implications for technology-based integrations into higher education classrooms. PMID:26561235

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

PubMed

Varao-Sousa, Trish L; Kingstone, Alan

2015-01-01

The present study investigated what impact the presentation style of a classroom lecture has on memory, mind wandering, and the subjective factors of interest and motivation. We examined if having a professor lecturing live versus on video alters the learning experience of the students in the classroom. During the lectures, students were asked to report mind wandering and later complete a memory test. The lecture format was manipulated such that all the students received two lectures, one live and one a pre-recorded video. Results indicate that lecture format affected memory performance but not mind wandering, with enhanced memory in the live lectures. Additionally, students reported greater interest and motivation in the live lectures. Given that a single change to the classroom environment, professor presence, impacted memory performance, as well as motivation and interest, the present results have several key implications for technology-based integrations into higher education classrooms.

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

PubMed Central

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

2016-01-01

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

Effects of post-encoding stress on performance in the DRM false memory paradigm

PubMed Central

Pardilla-Delgado, Enmanuelle; Alger, Sara E.; Cunningham, Tony J.; Kinealy, Brian

2016-01-01

Numerous studies have investigated how stress impacts veridical memory, but how stress influences false memory formation remains poorly understood. In order to target memory consolidation specifically, a psychosocial stress (TSST) or control manipulation was administered following encoding of 15 neutral, semantically related word lists (DRM false memory task) and memory was tested 24 h later. Stress decreased recognition of studied words, while increasing false recognition of semantically related lure words. Moreover, while control subjects remembered true and false words equivalently, stressed subjects remembered more false than true words. These results suggest that stress supports gist memory formation in the DRM task, perhaps by hindering detail-specific processing in the hippocampus. PMID:26670187

Spermidine boosts autophagy to protect from synapse aging.

PubMed

Bhukel, Anuradha; Madeo, Frank; Sigrist, Stephan J

2017-02-01

All animals form memories to adapt their behavior in a context-dependent manner. With increasing age, however, forming new memories becomes less efficient. While synaptic plasticity promotes memory formation, the etiology of age-induced memory formation remained enigmatic. Previous work showed that simple feeding of polyamine spermidine protects from age-induced memory impairment in Drosophila. Most recent work now shows that spermidine operates directly at synapses, allowing for an autophagy-dependent homeostatic regulation of presynaptic specializations. How exactly autophagic regulations intersect with synaptic plasticity should be an interesting subject for future research.

Estradiol replacement enhances fear memory formation, impairs extinction and reduces COMT expression levels in the hippocampus of ovariectomized female mice.

PubMed

McDermott, Carmel M; Liu, Dan; Ade, Catherine; Schrader, Laura A

2015-02-01

Females experience depression, posttraumatic stress disorder (PTSD), and anxiety disorders at approximately twice the rate of males, but the mechanisms underlying this difference remain undefined. The effect of sex hormones on neural substrates presents a possible mechanism. We investigated the effect of ovariectomy at two ages, before puberty and in adulthood, and 17β-estradiol (E2) replacement administered chronically in drinking water on anxiety level, fear memory formation, and extinction. Based on previous studies, we hypothesized that estradiol replacement would impair fear memory formation and enhance extinction rate. Females, age 4 weeks and 10 weeks, were divided randomly into 4 groups; sham surgery, OVX, OVX+low E2 (200nM), and OVX+high E2 (1000nM). Chronic treatment with high levels of E2 significantly increased anxiety levels measured in the elevated plus maze. In both age groups, high levels of E2 significantly increased contextual fear memory but had no effect on cued fear memory. In addition, high E2 decreased the rate of extinction in both ages. Finally, catechol-O-methyltransferase (COMT) is important for regulation of catecholamine levels, which play a role in fear memory formation and extinction. COMT expression in the hippocampus was significantly reduced by high E2 replacement, implying increased catecholamine levels in the hippocampus of high E2 mice. These results suggest that estradiol enhanced fear memory formation, and inhibited fear memory extinction, possibly stabilizing the fear memory in female mice. This study has implications for a neurobiological mechanism for PTSD and anxiety disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

RNA sequencing from neural ensembles activated during fear conditioning in the mouse temporal association cortex

PubMed Central

Cho, Jin-Hyung; Huang, Ben S.; Gray, Jesse M.

2016-01-01

The stable formation of remote fear memories is thought to require neuronal gene induction in cortical ensembles that are activated during learning. However, the set of genes expressed specifically in these activated ensembles is not known; knowledge of such transcriptional profiles may offer insights into the molecular program underlying stable memory formation. Here we use RNA-Seq to identify genes whose expression is enriched in activated cortical ensembles labeled during associative fear learning. We first establish that mouse temporal association cortex (TeA) is required for remote recall of auditory fear memories. We then perform RNA-Seq in TeA neurons that are labeled by the activity reporter Arc-dVenus during learning. We identify 944 genes with enriched expression in Arc-dVenus+ neurons. These genes include markers of L2/3, L5b, and L6 excitatory neurons but not glial or inhibitory markers, confirming Arc-dVenus to be an excitatory neuron-specific but non-layer-specific activity reporter. Cross comparisons to other transcriptional profiles show that 125 of the enriched genes are also activity-regulated in vitro or induced by visual stimulus in the visual cortex, suggesting that they may be induced generally in the cortex in an experience-dependent fashion. Prominent among the enriched genes are those encoding potassium channels that down-regulate neuronal activity, suggesting the possibility that part of the molecular program induced by fear conditioning may initiate homeostatic plasticity. PMID:27557751

The Formation and Stability of Recognition Memory: What Happens Upon Recall?

PubMed Central

Davis, Sabrina; Renaudineau, Sophie; Poirier, Roseline; Poucet, Bruno; Save, Etienne; Laroche, Serge

2010-01-01

The idea that an already consolidated memory can become destabilized after recall and requires a process of reconsolidation to maintain it for subsequent use has gained much credence over the past decade. Experimental studies in rodents have shown pharmacological, genetic, or injurious manipulation at the time of memory reactivation can disrupt the already consolidated memory. Despite the force of experimental data showing this phenomenon, a number of questions have remained unanswered and no consensus has emerged as to the conditions under which a memory can be disrupted following reactivation. To date most rodent studies of reconsolidation are based on negatively reinforced memories, in particular fear-associated memories, while the storage and stability of forms of memory that do not rely on explicit reinforcement have been less often studied. In this review, we focus on recognition memory, a paradigm widely used in humans to probe declarative memory. We briefly outline recent advances in our understanding of the processes and brain circuits involved in recognition memory and review the evidence that recognition memory can undergo reconsolidation upon reactivation. We also review recent findings suggesting that some molecular mechanisms underlying consolidation of recognition memory are similarly recruited after recall to ensure memory stability, while others are more specifically engaged in consolidation or reconsolidation. Finally, we provide novel data on the role of Rsk2, a mental retardation gene, and of the transcription factor zif268/egr1 in reconsolidation of object-location memory, and offer suggestions as to how assessing the activation of certain molecular mechanisms following recall in recognition memory may help understand the relative importance of different aspects of remodeling or updating long-lasting memories. PMID:21120149

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

PubMed

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

2016-08-15

Exposure to negative environmental events triggers defensive behavior and leads to the formation of aversive associative memory. Cellular and molecular changes in the central nervous system underlie this memory formation, as well as the associated behavioral changes. In general, memory process is established in distinct phases such as acquisition, consolidation, evocation, persistence, and extinction of the acquired information. After exposure to a particular event, early changes in involved neural circuits support the memory consolidation, which corresponds to the short-term memory. Re-exposure to previously memorized events evokes the original memory, a process that is considered essential for the reactivation and consequent persistence of memory, ensuring that long-term memory is established. Different environmental stimuli may modulate the memory formation process, as well as their distinct phases. Among the different environmental stimuli able of modulating memory formation is the physical exercise which is a potent modulator of neuronal activity. There are many studies showing that physical exercise modulates learning and memory processes, mainly in the consolidation phase of the explicit memory. However, there are few reports in the literature regarding the role of physical exercise in implicit aversive associative memory, especially at the persistence phase. Thus, the present study aimed to investigate the relationship between swimming exercise and the consolidation and persistence of contextual and auditory-cued fear memory. Male Wistar rats were submitted to sessions of swimming exercise five times a week, over six weeks. After that, the rats were submitted to classical aversive conditioning training by a pairing tone/foot shock paradigm. Finally, rats were evaluated for consolidation and persistence of fear memory to both auditory and contextual cues. Our results demonstrate that classical aversive conditioning with tone/foot shock pairing induced consolidation as well as persistence of conditioned fear memory. In addition, rats submitted to swimming exercise over six weeks showed an improved performance in the test of auditory-cued fear memory persistence, but not in the test of contextual fear memory persistence. Moreover, no significant effect from swimming exercise was observed on consolidation of both contextual and auditory fear memory. So, our study, revealing the effect of the swimming exercise on different stages of implicit memory of tone/foot shock conditioning, contributes to and complements the current knowledge about the environmental modulation of memory process. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2018-03-19

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

Serine 133 Phosphorylation Is Not Required for Hippocampal CREB-Mediated Transcription and Behavior

ERIC Educational Resources Information Center

Brian, Lisa A.; Lee, Bridgin G.; Lelay, John; Kaestner, Klaus H.; Blendy, Julie A.

2015-01-01

The cAMP response element (CRE)-binding protein, CREB, is a transcription factor whose activity in the brain is critical for long-term memory formation. Phosphorylation of Ser133 in the kinase-inducible domain (KID), that in turn leads to the recruitment of the transcriptional coactivator CREB-binding protein (CBP), is thought to mediate the…

Object properties and cognitive load in the formation of associative memory during precision lifting.

PubMed

Li, Yong; Randerath, Jennifer; Bauer, Hans; Marquardt, Christian; Goldenberg, Georg; Hermsdörfer, Joachim

2009-01-03

When we manipulate familiar objects in our daily life, our grip force anticipates the physical demands right from the moment of contact with the object, indicating the existence of a memory for relevant object properties. This study explores the formation and consolidation of the memory processes that associate either familiar (size) or arbitrary object features (color) with object weight. In the general task, participants repetitively lifted two differently weighted objects (580 and 280 g) in a pseudo-random order. Forty young healthy adults participated in this study and were randomly distributed into four groups: Color Cue Single task (CCS, blue and red, 9.8(3)cm(3)), Color Cue Dual task (CCD), No Cue (NC) and Size Cue (SC, 9.8(3) and 6(3)cm(3)) group. All groups performed a repetitive precision grasp-lift task and were retested with the same protocol after a 5-min pause. The CCD group was also required to simultaneously perform a memory task during each lift of differently weighted objects coded by color. The results show that groups lifting objects with arbitrary or familiar features successfully formed the association between object weight and manipulated object features and incorporated this into grip force programming, as observed in the different scaling of grip force and grip force rate for different object weights. An arbitrary feature, i.e., color, can be sufficiently associated with object weight, however with less strength than the familiar feature of size. The simultaneous memory task impaired anticipatory force scaling during repetitive object lifting but did not jeopardize the learning process and the consolidation of the associative memory.

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

ERIC Educational Resources Information Center

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

2018-01-01

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

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

ERIC Educational Resources Information Center

Schott, Bjorn H.; Sellner, Daniela B.; Lauer, Corinna-J.; Habib, Reza; Frey, Julietta U.; Guderian, Sebastian; Heinze, Hans-Jochen; Duzel, Emrah

2004-01-01

Recent evidence suggests a close functional relationship between memory formation in the hippocampus and dopaminergic neuromodulation originating in the ventral tegmental area and medial substantia nigra of the midbrain. Here we report midbrain activation in two functional MRI studies of visual memory in healthy young adults. In the first study,…

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

ERIC Educational Resources Information Center

Hosono, Shouhei; Matsumoto, Yukihisa; Mizunami, Makoto

2016-01-01

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

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

PubMed

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

2016-03-01

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

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

PubMed Central

Miller, Adam M. P.; Vedder, Lindsey C.; Law, L. Matthew; Smith, David M.

2014-01-01

Spatial navigation requires memory representations of landmarks and other navigation cues. The retrosplenial cortex (RSC) is anatomically positioned between limbic areas important for memory formation, such as the hippocampus (HPC) and the anterior thalamus, and cortical regions along the dorsal stream known to contribute importantly to long-term spatial representation, such as the posterior parietal cortex. Damage to the RSC severely impairs allocentric representations of the environment, including the ability to derive navigational information from landmarks. The specific deficits seen in tests of human and rodent navigation suggest that the RSC supports allocentric representation by processing the stable features of the environment and the spatial relationships among them. In addition to spatial cognition, the RSC plays a key role in contextual and episodic memory. The RSC also contributes importantly to the acquisition and consolidation of long-term spatial and contextual memory through its interactions with the HPC. Within this framework, the RSC plays a dual role as part of the feedforward network providing sensory and mnemonic input to the HPC and as a target of the hippocampal-dependent systems consolidation of long-term memory. PMID:25140141

Understanding the function of visual short-term memory: transsaccadic memory, object correspondence, and gaze correction.

PubMed

Hollingworth, Andrew; Richard, Ashleigh M; Luck, Steven J

2008-02-01

Visual short-term memory (VSTM) has received intensive study over the past decade, with research focused on VSTM capacity and representational format. Yet, the function of VSTM in human cognition is not well understood. Here, the authors demonstrate that VSTM plays an important role in the control of saccadic eye movements. Intelligent human behavior depends on directing the eyes to goal-relevant objects in the world, yet saccades are very often inaccurate and require correction. The authors hypothesized that VSTM is used to remember the features of the current saccade target so that it can be rapidly reacquired after an errant saccade, a task faced by the visual system thousands of times each day. In 4 experiments, memory-based gaze correction was accurate, fast, automatic, and largely unconscious. In addition, a concurrent VSTM load interfered with memory-based gaze correction, but a verbal short-term memory load did not. These findings demonstrate that VSTM plays a direct role in a fundamentally important aspect of visually guided behavior, and they suggest the existence of previously unknown links between VSTM representations and the occulomotor system. PsycINFO Database Record (c) 2008 APA, all rights reserved.

Motor Skills Enhance Procedural Memory Formation and Protect against Age-Related Decline

PubMed Central

Müller, Nils C. J.; Genzel, Lisa; Konrad, Boris N.; Pawlowski, Marcel; Neville, David; Fernández, Guillén; Steiger, Axel

2016-01-01

The ability to consolidate procedural memories declines with increasing age. Prior knowledge enhances learning and memory consolidation of novel but related information in various domains. Here, we present evidence that prior motor experience–in our case piano skills–increases procedural learning and has a protective effect against age-related decline for the consolidation of novel but related manual movements. In our main experiment, we tested 128 participants with a sequential finger-tapping motor task during two sessions 24 hours apart. We observed enhanced online learning speed and offline memory consolidation for piano players. Enhanced memory consolidation was driven by a strong effect in older participants, whereas younger participants did not benefit significantly from prior piano experience. In a follow up independent control experiment, this compensatory effect of piano experience was not visible after a brief offline period of 30 minutes, hence requiring an extended consolidation window potentially involving sleep. Through a further control experiment, we rejected the possibility that the decreased effect in younger participants was caused by training saturation. We discuss our results in the context of the neurobiological schema approach and suggest that prior experience has the potential to rescue memory consolidation from age-related cognitive decline. PMID:27333186

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

PubMed

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

2018-05-11

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

How mood challenges emotional memory formation: an fMRI investigation.

PubMed

Fitzgerald, Daniel A; Arnold, Jennifer F; Becker, Eni S; Speckens, Anne E M; Rinck, Mike; Rijpkema, Mark; Fernández, Guillén; Tendolkar, Indira

2011-06-01

Experimental mood manipulations and functional magnetic resonance imaging (fMRI) provide a unique opportunity for examining the neural correlates of mood-congruent memory formation. While prior studies in mood-disorder patients point to the medial temporal lobe in the genesis of mood-congruent memory (MCM) bias, the interaction between mood and emotional memory formation has not been investigated in healthy participants. In particular it remains unclear how regulatory structures in the pre-frontal cortex may be involved in mediating this phenomenon. In this study, event-related fMRI was performed on 20 healthy participants using a full-factorial, within-subjects repeated-measures design to examine how happy and sad moods impact memory for valenced stimuli (positive, negative and neutral words). Main effects of mood, stimulus valence and memory were examined as was activity related to successful memory formation during congruent and in-congruent moods. Behavioral results confirm an MCM bias while imaging results show amygdala and hippocampal engagement in a global mood and successful recall, respectively. MCM formation was characterized by increased activity during mood-congruent encoding of negative words in the orbito-frontal cortex (OFC) and for mood-incongruent processing of negative words in medial- and inferior-frontal gyri (MFG/IFG). These findings indicate that different pre-frontal regions facilitate mood-congruent and incongruent encoding of successfully recalled negative words at the time of learning, with OFC enhancing congruency and the left IFG and MFG helping overcome semantic incongruities between mood and stimulus valence. Copyright © 2011 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-04-14

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

Decreased susceptibility to false memories from misinformation in hormonal contraception users.

PubMed

Petersen, Nicole; Patihis, Lawrence; Nielsen, Shawn E

2015-01-01

Sex hormones are increasingly implicated in memory formation. Recent literature has documented a relationship between hormones and emotional memory and sex differences, which are likely related to hormones, have long been demonstrated in a variety of mnemonic domains, including false memories. Hormonal contraception (HC), which alters sex hormones, has been associated with a bias towards gist memory and away from detailed memory in women who use it during an emotional memory task. Here, we investigated whether HC was associated with changes in susceptibility to false memories, which may be related to the formation of gist memories. We tested false memory susceptibility using two well-validated false memory paradigms: the Deese-Roediger-McDermott (DRM) task, and a story-based misinformation task. We found that hormonal contraceptive users were less susceptible to false memories compared to non-users in the misinformation task, and no differences were seen between groups on the DRM task. We hypothesise that the differences in false memories from the misinformation task may be related to hormonal contraceptive users' memory bias away from details, towards gist memory.

Search strategy selection in the Morris water maze indicates allocentric map formation during learning that underpins spatial memory formation.

PubMed

Rogers, Jake; Churilov, Leonid; Hannan, Anthony J; Renoir, Thibault

2017-03-01

Using a Matlab classification algorithm, we demonstrate that a highly salient distal cue array is required for significantly increased likelihoods of spatial search strategy selection during Morris water maze spatial learning. We hypothesized that increased spatial search strategy selection during spatial learning would be the key measure demonstrating the formation of an allocentric map to the escape location. Spatial memory, as indicated by quadrant preference for the area of the pool formally containing the hidden platform, was assessed as the main measure that this allocentric map had formed during spatial learning. Our C57BL/6J wild-type (WT) mice exhibit quadrant preference in the highly salient cue paradigm but not the low, corresponding with a 120% increase in the odds of a spatial search strategy selection during learning. In contrast, quadrant preference remains absent in serotonin 1A receptor (5-HT 1A R) knockout (KO) mice, who exhibit impaired search strategy selection during spatial learning. Additionally, we also aimed to assess the impact of the quality of the distal cue array on the spatial learning curves of both latency to platform and path length using mixed-effect regression models and found no significant associations or interactions. In contrast, we demonstrated that the spatial learning curve for search strategy selection was absent during training in the low saliency paradigm. Therefore, we propose that allocentric search strategy selection during spatial learning is the learning parameter in mice that robustly indicates the formation of a cognitive map for the escape goal location. These results also suggest that both latency to platform and path length spatial learning curves do not discriminate between allocentric and egocentric spatial learning and do not reliably predict spatial memory formation. We also show that spatial memory, as indicated by the absolute time in the quadrant formerly containing the hidden platform alone (without reference to the other areas of the pool), was not sensitive to cue saliency or impaired in 5-HT 1A R KO mice. Importantly, in the absence of a search strategy analysis, this suggests that to establish that the Morris water maze has worked (i.e. control mice have formed an allocentric map to the escape goal location), a measure of quadrant preference needs to be reported to establish spatial memory formation. This has implications for studies that claim hippocampal functioning is impaired using latency to platform or path length differences within the existing Morris water maze literature. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-05-01

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

Theta synchronization networks emerge during human object-place memory encoding.

PubMed

Sato, Naoyuki; Yamaguchi, Yoko

2007-03-26

Recent rodent hippocampus studies have suggested that theta rhythm-dependent neural dynamics ('theta phase precession') is essential for an on-line memory formation. A computational study indicated that the phase precession enables a human object-place association memory with voluntary eye movements, although it is still an open question whether the human brain uses the dynamics. Here we elucidated subsequent memory-correlated activities in human scalp electroencephalography in an object-place association memory designed according the former computational study. Our results successfully demonstrated that subsequent memory recall is characterized by an increase in theta power and coherence, and further, that multiple theta synchronization networks emerge. These findings suggest the human theta dynamics in common with rodents in episodic memory formation.

Nogo-A regulates spatial learning as well as memory formation and modulates structural plasticity in the adult mouse hippocampus.

PubMed

Zagrebelsky, Marta; Lonnemann, Niklas; Fricke, Steffen; Kellner, Yves; Preuß, Eike; Michaelsen-Preusse, Kristin; Korte, Martin

2017-02-01

Behavioral learning has been shown to involve changes in the function and structure of synaptic connections of the central nervous system (CNS). On the other hand, the neuronal circuitry in the mature brain is characterized by a high degree of stability possibly providing a correlate for long-term storage of information. This observation indicates the requirement for a set of molecules inhibiting plasticity and promoting stability thereby providing temporal and spatial specificity to plastic processes. Indeed, signaling of Nogo-A via its receptors has been shown to play a crucial role in restricting activity-dependent functional and structural plasticity in the adult CNS. However, whether Nogo-A controls learning and memory formation and what are the cellular and molecular mechanisms underlying this function is still unclear. Here we show that Nogo-A signaling controls spatial learning and reference memory formation upon training in the Morris water maze and negatively modulates structural changes at spines in the mouse hippocampus. Learning processes and the correlated structural plasticity have been shown to involve changes in excitatory as well as in inhibitory neuronal connections. We show here that Nogo-A is highly expressed not only in excitatory, but also in inhibitory, Parvalbumin positive neurons in the adult hippocampus. By this means our current and previous data indicate that Nogo-A loss-of-function positively influences spatial learning by priming the neuronal structure to a higher plasticity level. Taken together our results link the role of Nogo-A in negatively regulating plastic processes to a physiological function in controlling learning and memory processes in the mature hippocampus and open the interesting possibility that it might mainly act by controlling the function of the hippocampal inhibitory circuitry. Copyright © 2016 Elsevier Inc. All rights reserved.

Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine.

PubMed

Boury-Jamot, B; Carrard, A; Martin, J L; Halfon, O; Magistretti, P J; Boutrel, B

2016-08-01

A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte-neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine.

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

PubMed

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 molecular mechanisms underlie either short term memory, long term memory, or both. Furthermore, our discovery that administration of rapamycin increased the activation of mTORC2 in microglial cells supports a reappraisal of the beneficial/adverse effects of rapamycin administration. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2016-01-01

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 30 min 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 molecular mechanisms underlie either short term memory, long term memory, or both. Furthermore, our discovery that administration of rapamycin increased the activation of mTORC2 in microglial cells supports a reappraisal of the beneficial/adverse effects of rapamycin administration. PMID:27838442

Reduction and elimination of format effects on recall.

PubMed

Goolkasian, Paula; Foos, Paul W; Krusemark, Daniel C

2008-01-01

Two experiments investigated whether the recall advantage of pictures and spoken words over printed words in working memory (Foos & Goolkasian, 2005; Goolkasian & Foos, 2002) could be reduced by manipulating letter case and sequential versus simultaneous presentation. Participants were required to remember 3 or 6 items presented in varied presentation formats while verifying the accuracy of a sentence. Presenting words in alternating uppercase and lowercase improved recall, and presenting words simultaneously rather than successively removed the effect of presentation format. The findings suggest that when forcing participants to pay attention to printed words you can make them more memorable and thereby diminish or remove any disadvantage in the recall of printed words in comparison with pictures and spoken words.

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

ERIC Educational Resources Information Center

Ghetti, Simona

2008-01-01

C. J. Brainerd, V. F. Reyna, and S. J. Ceci (2008) reviewed compelling evidence of developmental reversals in false-memory formation (i.e., younger children exhibit lower false-memory rates than do older children and adults) and proposed that this phenomenon depends on the development of gist processing (i.e., the ability to identify and process…

Involvement of the Anterior Cingulate Cortex in Formation, Consolidation, and Reconsolidation of Recent and Remote Contextual Fear Memory

ERIC Educational Resources Information Center

Einarsson, Einar O.; Nader, Karim

2012-01-01

It has been suggested that memories become more stable and less susceptible to the disruption of reconsolidation over weeks after learning. Here, we test this by targeting the anterior cingulate cortex (ACC) and test its involvement in the formation, consolidation, and reconsolidation of recent and remote contextual fear memory. We found that…

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

PubMed Central

2014-01-01

The honeybee (Apis mellifera) has long served as an invertebrate model organism for reward learning and memory research. Its capacity for learning and memory formation is rooted in the ecological need to efficiently collect nectar and pollen during summer to ensure survival of the hive during winter. Foraging bees learn to associate a flower's characteristic features with a reward in a way that resembles olfactory appetitive classical conditioning, a learning paradigm that is used to study mechanisms underlying learning and memory formation in the honeybee. Due to a plethora of studies on appetitive classical conditioning and phenomena related to it, the honeybee is one of the best characterized invertebrate model organisms from a learning psychological point of view. Moreover, classical conditioning and associated behavioral phenomena are surprisingly similar in honeybees and vertebrates, suggesting a convergence of underlying neuronal processes, including the molecular mechanisms that contribute to them. Here I review current thinking on the molecular mechanisms underlying long-term memory (LTM) formation in honeybees following classical conditioning and extinction, demonstrating that an in-depth analysis of the molecular mechanisms of classical conditioning in honeybees might add to our understanding of associative learning in honeybees and vertebrates. PMID:25225299

Subjective memory complaints are associated with brain activation supporting successful memory encoding.

PubMed

Hayes, Jessica M; Tang, Lingfei; Viviano, Raymond P; van Rooden, Sanneke; Ofen, Noa; Damoiseaux, Jessica S

2017-12-01

Subjective memory complaints, the perceived decline in cognitive abilities in the absence of clinical deficits, may precede Alzheimer's disease. Individuals with subjective memory complaints show differential brain activation during memory encoding; however, whether such differences contribute to successful memory formation remains unclear. Here, we investigated how subsequent memory effects, activation which is greater for hits than misses during an encoding task, differed between healthy older adults aged 50 to 85 years with (n = 23) and without (n = 41) memory complaints. Older adults with memory complaints, compared to those without, showed lower subsequent memory effects in the occipital lobe, superior parietal lobe, and posterior cingulate cortex. In addition, older adults with more memory complaints showed a more negative subsequent memory effects in areas of the default mode network, including the posterior cingulate cortex, precuneus, and ventromedial prefrontal cortex. Our findings suggest that for successful memory formation, older adults with subjective memory complaints rely on distinct neural mechanisms which may reflect an overall decreased task-directed attention. Copyright © 2017 Elsevier Inc. All rights reserved.

Methionine increases BDNF DNA methylation and improves memory in epilepsy.

PubMed

Parrish, R Ryley; Buckingham, Susan C; Mascia, Katherine L; Johnson, Jarvis J; Matyjasik, Michal M; Lockhart, Roxanne M; Lubin, Farah D

2015-04-01

Temporal lobe epilepsy (TLE) patients exhibit signs of memory impairments even when seizures are pharmacologically controlled. Surprisingly, the underlying molecular mechanisms involved in TLE-associated memory impairments remain elusive. Memory consolidation requires epigenetic transcriptional regulation of genes in the hippocampus; therefore, we aimed to determine how epigenetic DNA methylation mechanisms affect learning-induced transcription of memory-permissive genes in the epileptic hippocampus. Using the kainate rodent model of TLE and focusing on the brain-derived neurotrophic factor (Bdnf) gene as a candidate of DNA methylation-mediated transcription, we analyzed DNA methylation levels in epileptic rats following learning. After detection of aberrant DNA methylation at the Bdnf gene, we investigated functional effects of altered DNA methylation on hippocampus-dependent memory formation in our TLE rodent model. We found that behaviorally driven BdnfDNA methylation was associated with hippocampus-dependent memory deficits. Bisulfite sequencing revealed that decreased BdnfDNA methylation levels strongly correlated with abnormally high levels of BdnfmRNA in the epileptic hippocampus during memory consolidation. Methyl supplementation via methionine (Met) increased BdnfDNA methylation and reduced BdnfmRNA levels in the epileptic hippocampus during memory consolidation. Met administration reduced interictal spike activity, increased theta rhythm power, and reversed memory deficits in epileptic animals. The rescue effect of Met treatment on learning-induced BdnfDNA methylation, Bdnf gene expression, and hippocampus-dependent memory, were attenuated by DNA methyltransferase blockade. Our findings suggest that manipulation of DNA methylation in the epileptic hippocampus should be considered as a viable treatment option to ameliorate memory impairments associated with TLE.

Roles of α- and β-estrogen receptors in mouse social recognition memory: effects of gender and the estrous cycle.

PubMed

Sánchez-Andrade, G; Kendrick, K M

2011-01-01

Establishing clear effects of gender and natural hormonal changes during female ovarian cycles on cognitive function has often proved difficult. Here we have investigated such effects on the formation and long-term (24 h) maintenance of social recognition memory in mice together with the respective involvement of α- and β-estrogen receptors using α- and β-estrogen receptor knockout mice and wildtype controls. Results in wildtype animals showed that while females successfully formed a memory in the context of a habituation/dishabituation paradigm at all stages of their ovarian cycle, only when learning occurred during proestrus (when estrogen levels are highest) was it retained after 24 h. In α-receptor knockout mice (which showed no ovarian cycles) both formation and maintenance of this social recognition memory were impaired, whereas β-receptor knockouts showed no significant deficits and exhibited the same proestrus-dependent retention of memory at 24 h. To investigate possible sex differences, male α- and β-estrogen receptor knockout mice were also tested and showed similar effects to females excepting that α-receptor knockouts had normal memory formation and only exhibited a 24 h retention deficit. This indicates a greater dependence in females on α-receptor expression for memory formation in this task. Since non-specific motivational and attentional aspects of the task were unaffected, our findings suggest a general α-receptor dependent facilitation of memory formation by estrogen as well as an enhanced long-term retention during proestrus. Results are discussed in terms of the differential roles of the two estrogen receptors, the neural substrates involved and putative interactions with oxytocin. Copyright © 2010 Elsevier Inc. All rights reserved.

Memory disorders in probable Alzheimer's disease: the role of hippocampal atrophy as shown with MRI.

PubMed Central

Deweer, B; Lehéricy, S; Pillon, B; Baulac, M; Chiras, J; Marsault, C; Agid, Y; Dubois, B

1995-01-01

Magnetic resonance based volumetric measures of hippocampal formation, amygdala (A), caudate nucleus (CN), normalised for total intracranial volume (TIV), were analysed in relation to measures of cognitive deterioration and specific features of memory functions in 18 patients with probable Alzheimer's disease. Neuropsychological examination included the mini mental state examination (MMSE), the Mattis dementia rating scale (DRS), tests of executive functions, assessment of language abilities and praxis, the Wechsler memory scale (WMS), the California verbal learning test (CVLT) and the Grober and Buschke test. The volume of the hippocampal formation (HF/TIV) was correlated with specific memory variables: memory quotient and paired associates of the WMS; intrusions and discriminability at recognition for the Grober and Buschke test. By contrast, except for intrusions, no correlations were found between memory variables and the volume of amygdala (A/TIV). No correlations were found between the volume of caudate nuclei (CN/TIV) and any neuropsychological score. The volume of the hippocampal formation was therefore selectively related to quantitative and qualitative aspects of memory performance in patients with probable Alzheimer's disease. Images PMID:7745409

Circadian modulation of short-term memory in Drosophila.

PubMed

Lyons, Lisa C; Roman, Gregg

2009-01-01

Endogenous biological clocks are widespread regulators of behavior and physiology, allowing for a more efficient allocation of efforts and resources over the course of a day. The extent that different processes are regulated by circadian oscillators, however, is not fully understood. We investigated the role of the circadian clock on short-term associative memory formation using a negatively reinforced olfactory-learning paradigm in Drosophila melanogaster. We found that memory formation was regulated in a circadian manner. The peak performance in short-term memory (STM) occurred during the early subjective night with a twofold performance amplitude after a single pairing of conditioned and unconditioned stimuli. This rhythm in memory is eliminated in both timeless and period mutants and is absent during constant light conditions. Circadian gating of sensory perception does not appear to underlie the rhythm in short-term memory as evidenced by the nonrhythmic shock avoidance and olfactory avoidance behaviors. Moreover, central brain oscillators appear to be responsible for the modulation as cryptochrome mutants, in which the antennal circadian oscillators are nonfunctional, demonstrate robust circadian rhythms in short-term memory. Together these data suggest that central, rather than peripheral, circadian oscillators modulate the formation of short-term associative memory and not the perception of the stimuli.

Memory vs memory-like: The different facets of CD8+ T-cell memory in HCV infection.

PubMed

Hofmann, Maike; Wieland, Dominik; Pircher, Hanspeter; Thimme, Robert

2018-05-01

Memory CD8 + T cells are essential in orchestrating protection from re-infection. Hallmarks of virus-specific memory CD8 + T cells are the capacity to mount recall responses with rapid induction of effector cell function and antigen-independent survival. Growing evidence reveals that even chronic infection does not preclude virus-specific CD8 + T-cell memory formation. However, whether this kind of CD8 + T-cell memory that is established during chronic infection is indeed functional and provides protection from re-infection is still unclear. Human chronic hepatitis C virus infection represents a unique model system to study virus-specific CD8 + T-cell memory formation during and after cessation of persisting antigen stimulation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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

2013-07-01

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

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

PubMed

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

2005-12-01

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

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

PubMed Central

Iino, Shiori; Kubo, Takeo

2018-01-01

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

Level of processing modulates the neural correlates of emotional memory formation

PubMed Central

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

2010-01-01

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

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

PubMed

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

2011-04-01

Emotion is known to influence multiple aspects of memory formation, including the initial encoding of the memory trace and its consolidation over time. However, the neural mechanisms whereby emotion impacts memory encoding remain largely unexplored. The present study used a levels-of-processing manipulation to characterize the impact of emotion on encoding with and without the influence of elaborative processes. Participants viewed emotionally negative, neutral, and positive scenes under two conditions: a shallow condition focused on the perceptual features of the scenes and a deep condition that queried their semantic meaning. Recognition memory was tested 2 days later. Results showed that emotional memory enhancements were greatest in the shallow condition. fMRI analyses revealed that the right amygdala predicted subsequent emotional memory in the shallow more than deep condition, whereas the right ventrolateral PFC demonstrated the reverse pattern. Furthermore, the association of these regions with the hippocampus was modulated by valence: the amygdala-hippocampal link was strongest for negative stimuli, whereas the prefrontal-hippocampal link was strongest for positive stimuli. Taken together, these results suggest two distinct activation patterns underlying emotional memory formation: an amygdala component that promotes memory during shallow encoding, especially for negative information, and a prefrontal component that provides extra benefits during deep encoding, especially for positive information.

Protein degradation by ubiquitin–proteasome system in formation and labilization of contextual conditioning memory

PubMed Central

Sol Fustiñana, María; de la Fuente, Verónica; Federman, Noel; Freudenthal, Ramiro

2014-01-01

The ubiquitin–proteasome system (UPS) of protein degradation has been evaluated in different forms of neural plasticity and memory. The role of UPS in such processes is controversial. Several results support the idea that the activation of this system in memory consolidation is necessary to overcome negative constrains for plasticity. In this case, the inhibition of the UPS during consolidation impairs memory. Similar results were reported for memory reconsolidation. However, in other cases, the inhibition of UPS had no effect on memory consolidation and reconsolidation but impedes the amnesic action of protein synthesis inhibition after retrieval. The last finding suggests a specific action of the UPS inhibitor on memory labilization. However, another interpretation is possible in terms of the synthesis/degradation balance of positive and negative elements in neural plasticity, as was found in the case of long-term potentiation. To evaluate these alternative interpretations, other reconsolidation-interfering drugs than translation inhibitors should be tested. Here we analyzed initially the UPS inhibitor effect in contextual conditioning in crabs. We found that UPS inhibition during consolidation impaired long-term memory. In contrast, UPS inhibition did not affect memory reconsolidation after contextual retrieval but, in fact, impeded memory labilization, blocking the action of drugs that does not affect directly the protein synthesis. To extend these finding to vertebrates, we performed similar experiments in contextual fear memory in mice. We found that the UPS inhibitor in hippocampus affected memory consolidation and blocked memory labilization after retrieval. These findings exclude alternative interpretations to the requirement of UPS in memory labilization and give evidence of this mechanism in both vertebrates and invertebrates. PMID:25135196

Effects of post-encoding stress on performance in the DRM false memory paradigm.

PubMed

Pardilla-Delgado, Enmanuelle; Alger, Sara E; Cunningham, Tony J; Kinealy, Brian; Payne, Jessica D

2016-01-01

Numerous studies have investigated how stress impacts veridical memory, but how stress influences false memory formation remains poorly understood. In order to target memory consolidation specifically, a psychosocial stress (TSST) or control manipulation was administered following encoding of 15 neutral, semantically related word lists (DRM false memory task) and memory was tested 24 h later. Stress decreased recognition of studied words, while increasing false recognition of semantically related lure words. Moreover, while control subjects remembered true and false words equivalently, stressed subjects remembered more false than true words. These results suggest that stress supports gist memory formation in the DRM task, perhaps by hindering detail-specific processing in the hippocampus. © 2015 Pardilla-Delgado et al.; Published by Cold Spring Harbor Laboratory Press.

Inhibition of histone deacetylase 3 via RGFP966 facilitates cortical plasticity underlying unusually accurate auditory associative cue memory for excitatory and inhibitory cue-reward associations.

PubMed

Shang, Andrea; Bylipudi, Sooraz; Bieszczad, Kasia M

2018-05-31

Epigenetic mechanisms are key for regulating long-term memory (LTM) and are known to exert control on memory formation in multiple systems of the adult brain, including the sensory cortex. One epigenetic mechanism is chromatin modification by histone acetylation. Blocking the action of histone de-acetylases (HDACs) that normally negatively regulate LTM by repressing transcription has been shown to enable memory formation. Indeed, HDAC inhibition appears to facilitate memory by altering the dynamics of gene expression events important for memory consolidation. However, less understood are the ways in which molecular-level consolidation processes alter subsequent memory to enhance storage or facilitate retrieval. Here we used a sensory perspective to investigate whether the characteristics of memory formed with HDAC inhibitors are different from naturally-formed memory. One possibility is that HDAC inhibition enables memory to form with greater sensory detail than normal. Because the auditory system undergoes learning-induced remodeling that provides substrates for sound-specific LTM, we aimed to identify behavioral effects of HDAC inhibition on memory for specific sound features using a standard model of auditory associative cue-reward learning, memory, and cortical plasticity. We found that three systemic post-training treatments of an HDAC3-inhibitor (RGPF966, Abcam Inc.) in rats in the early phase of training facilitated auditory discriminative learning, changed auditory cortical tuning, and increased the specificity for acoustic frequency formed in memory of both excitatory (S+) and inhibitory (S-) associations for at least 2 weeks. The findings support that epigenetic mechanisms act on neural and behavioral sensory acuity to increase the precision of associative cue memory, which can be revealed by studying the sensory characteristics of long-term associative memory formation with HDAC inhibitors. Published by Elsevier B.V.

Tracking the Fear Memory Engram: Discrete Populations of Neurons within Amygdala, Hypothalamus, and Lateral Septum Are Specifically Activated by Auditory Fear Conditioning

ERIC Educational Resources Information Center

Butler, Christopher W.; Wilson, Yvette M.; Gunnersen, Jenny M.; Murphy, Mark

2015-01-01

Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used "fos-tau-lacZ" ("FTL") transgenic mice to identify…

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

PubMed

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

2002-01-01

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

Context and Auditory Fear are Differentially Regulated by HDAC3 Activity in the Lateral and Basal Subnuclei of the Amygdala

PubMed Central

Kwapis, Janine L; Alaghband, Yasaman; López, Alberto J; White, André O; Campbell, Rianne R; Dang, Richard T; Rhee, Diane; Tran, Ashley V; Carl, Allison E; Matheos, Dina P; Wood, Marcelo A

2017-01-01

Histone acetylation is a fundamental epigenetic mechanism that is dynamically regulated during memory formation. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) compete to modulate histone acetylation, allowing for rapid changes in acetylation in response to a learning event. HDACs are known to be powerful negative regulators of memory formation, but it is not clear whether this function depends on HDAC enzymatic activity per se. Here, we tested whether the enzymatic activity of an individual Class I HDAC, HDAC3, has a role in fear memory formation in subregions of the hippocampus and amygdala. We found that fear conditioning drove expression of the immediate early genes cFos and Nr4a2 in the hippocampus, which coincided with reduced HDAC3 occupancy at these promoters. Using a dominant-negative, deacetylase-dead point mutant virus (AAV-HDAC3(Y298H)-v5), we found that selectively blocking HDAC3 deacetylase activity in either the dorsal hippocampus or basal nucleus of the amygdala enhanced context fear without affecting tone fear. Blocking HDAC3 activity in the lateral nucleus of the amygdala, on the other hand, enhanced tone, but not context fear memory. These results show for the first time that the enzymatic activity of HDAC3 functions to negatively regulate fear memory formation. Further, HDAC3 activity regulates different aspects of fear memory in the basal and lateral subregions of the amygdala. Thus, the deacetylase activity of HDAC3 is a powerful negative regulator of fear memory formation in multiple subregions of the fear circuit. PMID:27924874

Stably maintained dendritic spines are associated with lifelong memories

PubMed Central

Yang, Guang; Pan, Feng; Gan, Wen-Biao

2016-01-01

Changes in synaptic connections are considered essential for learning and memory formation1–6. However, it is unknown how neural circuits undergo continuous synaptic changes during learning while maintaining lifelong memories. Here we show, by following postsynaptic dendritic spines over time in the mouse cortex7–8, that learning and novel sensory experience lead to spine formation and elimination by a protracted process. The extent of spine remodelling correlates with behavioural improvement after learning, suggesting a crucial role of synaptic structural plasticity in memory formation and storage. Importantly, a small fraction of new spines induced by novel experience, together with most spines formed early during development and surviving experience-dependent elimination, are preserved throughout the entire life of an animal. These studies indicate that learning and daily sensory experience leave minute but permanent marks on cortical connections and suggest that lifelong memories are stored in largely stably connected synaptic networks. PMID:19946265

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

PubMed

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

2014-01-01

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

Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation.

PubMed

Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano; Alviña, Karina; Zhang, Yuxiang; Dushko, Margaret; Ku, Taeyun; Zemoura, Khaled; Rich, David; Garcia-Dominguez, Dario; Hung, Matthew; Yelhekar, Tushar D; Sørensen, Andreas Toft; Xu, Weifeng; Chung, Kwanghun; Castillo, Pablo E; Lin, Yingxi

2018-03-07

Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report that the activity-dependent transcription factor Npas4 selectively regulates the structure and strength of MF-CA3 synapses by restricting the number of their functional synaptic contacts without affecting the other synaptic inputs onto CA3 pyramidal neurons. Using an activity-dependent reporter, we identified CA3 pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

Xiu, Daiming; Geiger, Maximilian J; Klaver, Peter

2015-01-01

This study investigated the role of bottom-up and top-down neural mechanisms in the processing of emotional face expression during memory formation. Functional brain imaging data was acquired during incidental learning of positive ("happy"), neutral and negative ("angry" or "fearful") faces. Dynamic Causal Modeling (DCM) was applied on the functional magnetic resonance imaging (fMRI) data to characterize effective connectivity within a brain network involving face perception (inferior occipital gyrus and fusiform gyrus) and successful memory formation related areas (hippocampus, superior parietal lobule, amygdala, and orbitofrontal cortex). The bottom-up models assumed processing of emotional face expression along feed forward pathways to the orbitofrontal cortex. The top-down models assumed that the orbitofrontal cortex processed emotional valence and mediated connections to the hippocampus. A subsequent recognition memory test showed an effect of negative emotion on the response bias, but not on memory performance. Our DCM findings showed that the bottom-up model family of effective connectivity best explained the data across all subjects and specified that emotion affected most bottom-up connections to the orbitofrontal cortex, especially from the occipital visual cortex and superior parietal lobule. Of those pathways to the orbitofrontal cortex the connection from the inferior occipital gyrus correlated with memory performance independently of valence. We suggest that bottom-up neural mechanisms support effects of emotional face expression and memory formation in a parallel and partially overlapping fashion.

Different types of working memory binding in epilepsy patients with unilateral anterior temporal lobectomy.

PubMed

van Geldorp, Bonnie; Bouman, Zita; Hendriks, Marc P H; Kessels, Roy P C

2014-03-01

The medial temporal lobe is an important structure for long-term memory formation, but its role in working memory is less clear. Recent studies have shown hippocampal involvement during working memory tasks requiring binding of information. It is yet unclear whether this is limited to tasks containing spatial features. The present study contrasted three binding conditions and one single-item condition in patients with unilateral anterior temporal lobectomy. A group of 43 patients with temporal lobectomy (23 left; 20 right) and 20 matched controls were examined with a working memory task assessing spatial relational binding (object-location), non-spatial relational binding (object-object), conjunctive binding (object-colour) and working memory for single items. We varied the delay period (3 or 6s), as there is evidence showing that delay length may modulate working memory performance. The results indicate that performance was worse for patients than for controls in both relational binding conditions, whereas patients were unimpaired in conjunctive binding. Single-item memory was found to be marginally impaired, due to a deficit on long-delay trials only. In conclusion, working memory binding deficits are found in patients with unilateral anterior temporal lobectomy. The role of the medial temporal lobe in working memory is not limited to tasks containing spatial features. Rather, it seems to be involved in relational binding, but not in conjunctive binding. The medial temporal lobe gets involved when working memory capacity does not suffice, for example when relations have to be maintained or when the delay period is long. Copyright © 2014 Elsevier Inc. All rights reserved.

Statistical Computations Underlying the Dynamics of Memory Updating

PubMed Central

Gershman, Samuel J.; Radulescu, Angela; Norman, Kenneth A.; Niv, Yael

2014-01-01

Psychophysical and neurophysiological studies have suggested that memory is not simply a carbon copy of our experience: Memories are modified or new memories are formed depending on the dynamic structure of our experience, and specifically, on how gradually or abruptly the world changes. We present a statistical theory of memory formation in a dynamic environment, based on a nonparametric generalization of the switching Kalman filter. We show that this theory can qualitatively account for several psychophysical and neural phenomena, and present results of a new visual memory experiment aimed at testing the theory directly. Our experimental findings suggest that humans can use temporal discontinuities in the structure of the environment to determine when to form new memory traces. The statistical perspective we offer provides a coherent account of the conditions under which new experience is integrated into an old memory versus forming a new memory, and shows that memory formation depends on inferences about the underlying structure of our experience. PMID:25375816

Recordkeeping alters economic history by promoting reciprocity

PubMed Central

Basu, Sudipta; Dickhaut, John; Hecht, Gary; Towry, Kristy; Waymire, Gregory

2009-01-01

We experimentally demonstrate a causal link between recordkeeping and reciprocal exchange. Recordkeeping improves memory of past interactions in a complex exchange environment, which promotes reputation formation and decision coordination. Economies with recordkeeping exhibit a beneficially altered economic history where the risks of exchanging with strangers are substantially lessened. Our findings are consistent with prior assertions that complex and extensive reciprocity requires sophisticated memory to store information on past transactions. We offer insights on this research by scientifically demonstrating that reciprocity can be facilitated by information storage external to the brain. This is consistent with the archaeological record, which suggests that prehistoric transaction records and the invention of writing for recordkeeping were linked to increased complexity in human interaction. PMID:19147843

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

ERIC Educational Resources Information Center

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…

Forming-free resistive switching characteristics of Ag/CeO2/Pt devices with a large memory window

NASA Astrophysics Data System (ADS)

Zheng, Hong; Kim, Hyung Jun; Yang, Paul; Park, Jong-Sung; Kim, Dong Wook; Lee, Hyun Ho; Kang, Chi Jung; Yoon, Tae-Sik

2017-05-01

Ag/CeO2(∼45 nm)/Pt devices exhibited forming-free bipolar resistive switching with a large memory window (low-resistance-state (LRS)/high-resistance-state (HRS) ratio >106) at a low switching voltage (<±1 ∼ 2 V) in voltage sweep condition. Also, they retained a large memory window (>104) at a pulse operation (±5 V, 50 μs). The high oxygen ionic conductivity of the CeO2 layer as well as the migration of silver facilitated the formation of filament for the transition to LRS at a low voltage without a high voltage forming operation. Also, a certain amount of defects in the CeO2 layer was required for stable HRS with space-charge-limited-conduction, which was confirmed comparing the devices with non-annealed and annealed CeO2 layers.

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

PubMed

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

2018-05-01

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

Neural correlates of social odor recognition and the representation of individual distinctive social odors within entorhinal cortex and ventral subiculum.

PubMed

Petrulis, A; Alvarez, P; Eichenbaum, H

2005-01-01

Recognition of individual conspecifics is important for social behavior and requires the formation of memories for individually distinctive social signals. Individual recognition is often mediated by olfactory cues in mammals, especially nocturnal rodents such as golden hamsters. In hamsters, this form of recognition requires main olfactory system input to the lateral entorhinal cortex (LEnt). Here, we tested whether neurons in LEnt and the nearby ventral subiculum (VS) would show cellular correlates of this natural form of recognition memory. Two hundred ninety single neurons were recorded from both superficial (SE) and deep layers of LEnt (DE) and VS while male hamsters investigated volatile odorants from female vaginal secretions. Many neurons encoded differences between female's odors with many discriminating between odors from different individual females but not between different odor samples from the same female. Other neurons discriminated between odor samples from one female and generalized across collections from other females. LEnt and VS neurons showed enhanced or suppressed cellular activity during investigation of previously presented odors and in response to novel odors. A majority of SE neurons decreased firing to odor repetition and increased activity to novel odors. In contrast, DE neurons often showed suppressed activity in response to novel odors. Thus, neurons in LEnt and VS of male hamsters encode information that is critical for the identification and recognition of individual females by odor cues. This study reveals cellular mechanisms in LEnt and VS that may mediate a natural form of recognition memory in hamsters. These neuronal responses were similar to those observed in rats and monkeys during performance in standard recognition memory tasks. Consequently, the present data extend our understanding of the cellular basis for recognition memory and suggest that individual recognition requires similar neural mechanisms as those employed in laboratory tests of recognition memory.

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

PubMed

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

2016-01-01

Lymphopenia promotes naïve T-cell homeostatic proliferation and adoptive effector T-cell survival and memory formation. IL-7 plays a critical role in homeostatic proliferation, survival and memory formation of naïve T-cells in lymphopenia, and its underlying molecular mechanism has also been well studied. However, the mechanism for adoptively transferred effector T-cell survival and memory formation is not fully understood. Here, we transferred in vitro-activated transgenic OT-I CD8(+) effector T-cells into irradiation (600 rads)-induced lymphopenic C57BL/6, IL-7 knockout (KO) and IL-15 KO mice, and investigated the survival and memory formation of transferred T-cells in lymphopenia. We demonstrate that transferred T-cells prolong their survival and enhance their memory in lymphopenic mice, in a manner that depends on IL-15 signaling, but not IL-7. We determine that in vitro stimulation of naïve or effector T-cells with IL-7 and IL-15 reduces IL-7Rα, and increases and/or maintains IL-15Rβ expression, respectively. Consistent with these findings, the expression of IL-7Rα and IL-15Rβ is down- and up-regulated, respectively, in vivo on transferred T-cells in an early phase post T-cell transfer in lymphopenia. We further show that in vitro IL-15 restimulation-induced memory T-cells (compared to IL-2 restimulation-induced effector T-cells) and in vivo transferred T-cells in irradiated IL-15-sufficient C57BL/6 mice (compared to IL-15-deficient IL-15 KO mice) have increased mitochondrial content, but less NADH and lower mitochondrial potential (ΔΨm), and demonstrate greater phosphorylation of signal transducers and activators of transcription-5 (STAT5) and Unc-51-like kinase-1 (ULK1), and higher expression of B-cell leukemia/lymphoma-2 (Bcl2) and memory-, autophagy- and mitochondrial biogenesis-related molecules. Irradiation-induced lymphopenia promotes effector T-cell survival via IL-15 signaling the STAT5/Bcl2 pathway, enhances T-cell memory formation via IL-15 activation of the forkhead-box family of transcription factor (FOXO)/eomesodermin (Eomes) memory and ULK1/autophagy-related gene-7 (ATG7) autophagy pathways, and via IL-15 activation of the mitochondrial remodeling. Our data thus identify some important targets to consider when designing potent adoptive T-cell immunotherapies of cancer.

Habitat stability, predation risk and 'memory syndromes'.

PubMed

Dalesman, S; Rendle, A; Dall, S R X

2015-05-27

Habitat stability and predation pressure are thought to be major drivers in the evolutionary maintenance of behavioural syndromes, with trait covariance only occurring within specific habitats. However, animals also exhibit behavioural plasticity, often through memory formation. Memory formation across traits may be linked, with covariance in memory traits (memory syndromes) selected under particular environmental conditions. This study tests whether the pond snail, Lymnaea stagnalis, demonstrates consistency among memory traits ('memory syndrome') related to threat avoidance and foraging. We used eight populations originating from three different habitat types: i) laboratory populations (stable habitat, predator-free); ii) river populations (fairly stable habitat, fish predation); and iii) ditch populations (unstable habitat, invertebrate predation). At a population level, there was a negative relationship between memories related to threat avoidance and food selectivity, but no consistency within habitat type. At an individual level, covariance between memory traits was dependent on habitat. Laboratory populations showed no covariance among memory traits, whereas river populations showed a positive correlation between food memories, and ditch populations demonstrated a negative relationship between threat memory and food memories. Therefore, selection pressures among habitats appear to act independently on memory trait covariation at an individual level and the average response within a population.

Age Differences in the Contribution of Recollection and Familiarity to False-Memory Formation: A New Paradigm to Examine Developmental Reversals

ERIC Educational Resources Information Center

Lyons, Kristen E.; Ghetti, Simona; Cornoldi, Cesare

2010-01-01

Using a new method for studying the development of false-memory formation, we examined developmental differences in the rates at which 6-, 7-, 9-, 10-, and 18-year-olds made two types of memory errors: backward causal-inference errors (i.e. falsely remembering having viewed the non-viewed cause of a previously viewed effect), and gap-filling…

DNA Methylation Adjusts the Specificity of Memories Depending on the Learning Context and Promotes Relearning in Honeybees

PubMed Central

Biergans, Stephanie D.; Claudianos, Charles; Reinhard, Judith; Galizia, C. G.

2016-01-01

The activity of the epigenetic writers DNA methyltransferases (Dnmts) after olfactory reward conditioning is important for both stimulus-specific long-term memory (LTM) formation and extinction. It, however, remains unknown which components of memory formation Dnmts regulate (e.g., associative vs. non-associative) and in what context (e.g., varying training conditions). Here, we address these aspects in order to clarify the role of Dnmt-mediated DNA methylation in memory formation. We used a pharmacological Dnmt inhibitor and classical appetitive conditioning in the honeybee Apis mellifera, a well characterized model for classical conditioning. We quantified the effect of DNA methylation on naïve odor and sugar responses, and on responses following olfactory reward conditioning. We show that (1) Dnmts do not influence naïve odor or sugar responses, (2) Dnmts do not affect the learning of new stimuli, but (3) Dnmts influence odor-coding, i.e., ‘correct’ (stimulus-specific) LTM formation. Particularly, Dnmts reduce memory specificity when experience is low (one-trial training), and increase memory specificity when experience is high (multiple-trial training), generating an ecologically more useful response to learning. (4) In reversal learning conditions, Dnmts are involved in regulating both excitatory (re-acquisition) and inhibitory (forgetting) processes. PMID:27672359

DNA Methylation Adjusts the Specificity of Memories Depending on the Learning Context and Promotes Relearning in Honeybees.

PubMed

Biergans, Stephanie D; Claudianos, Charles; Reinhard, Judith; Galizia, C G

2016-01-01

The activity of the epigenetic writers DNA methyltransferases (Dnmts) after olfactory reward conditioning is important for both stimulus-specific long-term memory (LTM) formation and extinction. It, however, remains unknown which components of memory formation Dnmts regulate (e.g., associative vs. non-associative) and in what context (e.g., varying training conditions). Here, we address these aspects in order to clarify the role of Dnmt-mediated DNA methylation in memory formation. We used a pharmacological Dnmt inhibitor and classical appetitive conditioning in the honeybee Apis mellifera, a well characterized model for classical conditioning. We quantified the effect of DNA methylation on naïve odor and sugar responses, and on responses following olfactory reward conditioning. We show that (1) Dnmts do not influence naïve odor or sugar responses, (2) Dnmts do not affect the learning of new stimuli, but (3) Dnmts influence odor-coding, i.e., 'correct' (stimulus-specific) LTM formation. Particularly, Dnmts reduce memory specificity when experience is low (one-trial training), and increase memory specificity when experience is high (multiple-trial training), generating an ecologically more useful response to learning. (4) In reversal learning conditions, Dnmts are involved in regulating both excitatory (re-acquisition) and inhibitory (forgetting) processes.

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

PubMed Central

Sunada, Hiroshi; Lukowiak, Ken; Sakakibara, Manabu

2013-01-01

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

Gene repressive mechanisms in the mouse brain involved in memory formation

PubMed Central

Yu, Nam-Kyung; Kaang, Bong-Kiun

2016-01-01

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

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

PubMed

Yu, Nam-Kyung; Kaang, Bong-Kiun

2016-04-01

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

Proteolytic Degradation of SCOP in the Hippocampus Contributes to Activation of MAP Kinase and Memory

PubMed Central

Shimizu, Kimiko; Phan, Trongha; Mansuy, Isabelle; Storm, Daniel R.

2007-01-01

Summary Because activation of Erk1/2 MAP kinase (MAPK) is critical for hippocampus-dependent memory, there is considerable interest in mechanisms for regulation of MAPK during memory formation. Here we report that MAPK and CREB-mediated transcription are negatively regulated by SCOP (SCN Circadian Oscillatory Protein) and that SCOP is proteolyzed by calpain when hippocampal neurons are stimulated by BDNF, KCl depolarization, or NMDA. Moreover, training for novel object memory decreases SCOP in the hippocampus. To determine if hippocampus-dependent memory is influenced by SCOP in vivo, we generated a transgenic mouse strain for the inducible overexpression of SCOP in the forebrain. Overexpression of SCOP completely blocked memory for novel objects. We conclude that degradation of SCOP by calpain contributes to activation of MAPK during memory formation. PMID:17382888

Opiate exposure state controls dopamine D3 receptor and cdk5/calcineurin signaling in the basolateral amygdala during reward and withdrawal aversion memory formation.

PubMed

Rosen, Laura G; Rushlow, Walter J; Laviolette, Steven R

2017-10-03

The dopamine (DA) D3 receptor (D3R) is highly expressed in the basolateral nucleus of the amygdala (BLA), a neural region critical for processing opiate-related reward and withdrawal aversion-related memories. Functionally, D3R transmission is linked to downstream Cdk5 and calcineurin signaling, both of which regulate D3R activity states and play critical roles in memory-related synaptic plasticity. Previous evidence links D3R transmission to opiate-related memory processing, however little is known regarding how chronic opiate exposure may alter D3R-dependent memory mechanisms. Using conditioned place preference (CPP) and withdrawal aversion (conditioned place aversion; CPA) procedures in rats, combined with molecular analyses of BLA protein expression, we examined the effects of chronic opiate exposure on the functional role of intra-BLA D3R transmission during the acquisition of opiate reward or withdrawal aversion memories. Remarkably, we report that the state of opiate exposure during behavioural conditioning (opiate-naïve/non-dependent vs. chronically exposed and in withdrawal) controlled the functional role of intra-BLA D3R transmission during the acquisition of both opiate reward memories and withdrawal-aversion associative memories. Thus, whereas intra-BLA D3R blockade had no effect on opiate reward memory formation in the non-dependent state, blockade of intra-BLA D3R transmission prevented the formation of opiate reward and withdrawal aversion memory in the chronically exposed state. This switch in the functional role of D3R transmission corresponded to significant increases in Cdk5 phosphorylation and total expression levels of calcineurin, and a corresponding decrease in intra-BLA D3R expression. Inhibition of either intra-BLA Cdk5 or calcineurin reversed these effects, switching intra-BLA associative memory formation back to a D3R-independent mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term avoidance memory formation is associated with a transient increase in mushroom body synaptic complexes in leaf-cutting ants

PubMed Central

Falibene, Agustina; Roces, Flavio; Rössler, Wolfgang

2015-01-01

Long-term behavioral changes related to learning and experience have been shown to be associated with structural remodeling in the brain. Leaf-cutting ants learn to avoid previously preferred plants after they have proved harmful for their symbiotic fungus, a process that involves long-term olfactory memory. We studied the dynamics of brain microarchitectural changes after long-term olfactory memory formation following avoidance learning in Acromyrmex ambiguus. After performing experiments to control for possible neuronal changes related to age and body size, we quantified synaptic complexes (microglomeruli, MG) in olfactory regions of the mushroom bodies (MBs) at different times after learning. Long-term avoidance memory formation was associated with a transient change in MG densities. Two days after learning, MG density was higher than before learning. At days 4 and 15 after learning—when ants still showed plant avoidance—MG densities had decreased to the initial state. The structural reorganization of MG triggered by long-term avoidance memory formation clearly differed from changes promoted by pure exposure to and collection of novel plants with distinct odors. Sensory exposure by the simultaneous collection of several, instead of one, non-harmful plant species resulted in a decrease in MG densities in the olfactory lip. We hypothesize that while sensory exposure leads to MG pruning in the MB olfactory lip, the formation of long-term avoidance memory involves an initial growth of new MG followed by subsequent pruning. PMID:25904854

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

PubMed

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

2008-01-31

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

Dynorphins regulate the strength of social memory.

PubMed

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

2014-02-01

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

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

PubMed

Chekaf, Mustapha; Cowan, Nelson; Mathy, Fabien

2016-10-01

This paper attempts to evaluate the capacity of immediate memory to cope with new situations in relation to the compressibility of information likely to allow the formation of chunks. We constructed a task in which untrained participants had to immediately recall sequences of stimuli with possible associations between them. Compressibility of information was used to measure the chunkability of each sequence on a single trial. Compressibility refers to the recoding of information in a more compact representation. Although compressibility has almost exclusively been used to study long-term memory, our theory suggests that a compression process relying on redundancies within the structure of the list materials can occur very rapidly in immediate memory. The results indicated a span of about three items when the list had no structure, but increased linearly as structure was added. The amount of information retained in immediate memory was maximal for the most compressible sequences, particularly when information was ordered in a way that facilitated the compression process. We discuss the role of immediate memory in the rapid formation of chunks made up of new associations that did not already exist in long-term memory, and we conclude that immediate memory is the starting place for the reorganization of information. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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.

Dopamine D1 receptor activation leads to object recognition memory in a coral reef fish.

PubMed

Hamilton, Trevor J; Tresguerres, Martin; Kline, David I

2017-07-01

Object recognition memory is the ability to identify previously seen objects and is an adaptive mechanism that increases survival for many species throughout the animal kingdom. Previously believed to be possessed by only the highest order mammals, it is now becoming clear that fish are also capable of this type of memory formation. Similar to the mammalian hippocampus, the dorsolateral pallium regulates distinct memory processes and is modulated by neurotransmitters such as dopamine. Caribbean bicolour damselfish ( Stegastes partitus ) live in complex environments dominated by coral reef structures and thus likely possess many types of complex memory abilities including object recognition. This study used a novel object recognition test in which fish were first presented two identical objects, then after a retention interval of 10 min with no objects, the fish were presented with a novel object and one of the objects they had previously encountered in the first trial. We demonstrate that the dopamine D 1 -receptor agonist (SKF 38393) induces the formation of object recognition memories in these fish. Thus, our results suggest that dopamine-receptor mediated enhancement of spatial memory formation in fish represents an evolutionarily conserved mechanism in vertebrates. © 2017 The Author(s).

From sensorimotor learning to memory cells in prefrontal and temporal association cortex: a neurocomputational study of disembodiment.

PubMed

Pulvermüller, Friedemann; Garagnani, Max

2014-08-01

Memory cells, the ultimate neurobiological substrates of working memory, remain active for several seconds and are most commonly found in prefrontal cortex and higher multisensory areas. However, if correlated activity in "embodied" sensorimotor systems underlies the formation of memory traces, why should memory cells emerge in areas distant from their antecedent activations in sensorimotor areas, thus leading to "disembodiment" (movement away from sensorimotor systems) of memory mechanisms? We modelled the formation of memory circuits in six-area neurocomputational architectures, implementing motor and sensory primary, secondary and higher association areas in frontotemporal cortices along with known between-area neuroanatomical connections. Sensorimotor learning driven by Hebbian neuroplasticity led to formation of cell assemblies distributed across the different areas of the network. These action-perception circuits (APCs) ignited fully when stimulated, thus providing a neural basis for long-term memory (LTM) of sensorimotor information linked by learning. Subsequent to ignition, activity vanished rapidly from APC neurons in sensorimotor areas but persisted in those in multimodal prefrontal and temporal areas. Such persistent activity provides a mechanism for working memory for actions, perceptions and symbols, including short-term phonological and semantic storage. Cell assembly ignition and "disembodied" working memory retreat of activity to multimodal areas are documented in the neurocomputational models' activity dynamics, at the level of single cells, circuits, and cortical areas. Memory disembodiment is explained neuromechanistically by APC formation and structural neuroanatomical features of the model networks, especially the central role of multimodal prefrontal and temporal cortices in bridging between sensory and motor areas. These simulations answer the "where" question of cortical working memory in terms of distributed APCs and their inner structure, which is, in part, determined by neuroanatomical structure. As the neurocomputational model provides a mechanistic explanation of how memory-related "disembodied" neuronal activity emerges in "embodied" APCs, it may be key to solving aspects of the embodiment debate and eventually to a better understanding of cognitive brain functions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Affect influences feature binding in memory: Trading between richness and strength of memory representations.

PubMed

Spachtholz, Philipp; Kuhbandner, Christof; Pekrun, Reinhard

2016-10-01

Research has shown that long-term memory representations of objects are formed as a natural product of perception even without any intentional memorization. It is not known, however, how rich these representations are in terms of the number of bound object features. In particular, because feature binding rests on resource-limited processes, there may be a context-dependent trade-off between the quantity of stored features and their memory strength. The authors examined whether affective state may bring about such a trade-off. Participants incidentally encoded pictures of real-world objects while experiencing positive or negative affect, and the authors later measured memory for 2 features. Results showed that participants traded between richness and strength of memory representations as a function of affect, with positive affect tuning memory formation toward richness and negative affect tuning memory formation toward strength. These findings demonstrate that memory binding is a flexible process that is modulated by affective state. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Lateral entorhinal cortex is necessary for associative but not nonassociative recognition memory

PubMed Central

Wilson, David IG; Watanabe, Sakurako; Milner, Helen; Ainge, James A

2013-01-01

The lateral entorhinal cortex (LEC) provides one of the two major input pathways to the hippocampus and has been suggested to process the nonspatial contextual details of episodic memory. Combined with spatial information from the medial entorhinal cortex it is hypothesised that this contextual information is used to form an integrated spatially selective, context-specific response in the hippocampus that underlies episodic memory. Recently, we reported that the LEC is required for recognition of objects that have been experienced in a specific context (Wilson et al. (2013) Hippocampus 23:352-366). Here, we sought to extend this work to assess the role of the LEC in recognition of all associative combinations of objects, places and contexts within an episode. Unlike controls, rats with excitotoxic lesions of the LEC showed no evidence of recognizing familiar combinations of object in place, place in context, or object in place and context. However, LEC lesioned rats showed normal recognition of objects and places independently from each other (nonassociative recognition). Together with our previous findings, these data suggest that the LEC is critical for associative recognition memory and may bind together information relating to objects, places, and contexts needed for episodic memory formation. PMID:23836525

A neural mechanism for background information-gated learning based on axonal-dendritic overlaps.

PubMed

Mainetti, Matteo; Ascoli, Giorgio A

2015-03-01

Experiencing certain events triggers the acquisition of new memories. Although necessary, however, actual experience is not sufficient for memory formation. One-trial learning is also gated by knowledge of appropriate background information to make sense of the experienced occurrence. Strong neurobiological evidence suggests that long-term memory storage involves formation of new synapses. On the short time scale, this form of structural plasticity requires that the axon of the pre-synaptic neuron be physically proximal to the dendrite of the post-synaptic neuron. We surmise that such "axonal-dendritic overlap" (ADO) constitutes the neural correlate of background information-gated (BIG) learning. The hypothesis is based on a fundamental neuroanatomical constraint: an axon must pass close to the dendrites that are near other neurons it contacts. The topographic organization of the mammalian cortex ensures that nearby neurons encode related information. Using neural network simulations, we demonstrate that ADO is a suitable mechanism for BIG learning. We model knowledge as associations between terms, concepts or indivisible units of thought via directed graphs. The simplest instantiation encodes each concept by single neurons. Results are then generalized to cell assemblies. The proposed mechanism results in learning real associations better than spurious co-occurrences, providing definitive cognitive advantages.

A Neural Mechanism for Background Information-Gated Learning Based on Axonal-Dendritic Overlaps

PubMed Central

Mainetti, Matteo; Ascoli, Giorgio A.

2015-01-01

Experiencing certain events triggers the acquisition of new memories. Although necessary, however, actual experience is not sufficient for memory formation. One-trial learning is also gated by knowledge of appropriate background information to make sense of the experienced occurrence. Strong neurobiological evidence suggests that long-term memory storage involves formation of new synapses. On the short time scale, this form of structural plasticity requires that the axon of the pre-synaptic neuron be physically proximal to the dendrite of the post-synaptic neuron. We surmise that such “axonal-dendritic overlap” (ADO) constitutes the neural correlate of background information-gated (BIG) learning. The hypothesis is based on a fundamental neuroanatomical constraint: an axon must pass close to the dendrites that are near other neurons it contacts. The topographic organization of the mammalian cortex ensures that nearby neurons encode related information. Using neural network simulations, we demonstrate that ADO is a suitable mechanism for BIG learning. We model knowledge as associations between terms, concepts or indivisible units of thought via directed graphs. The simplest instantiation encodes each concept by single neurons. Results are then generalized to cell assemblies. The proposed mechanism results in learning real associations better than spurious co-occurrences, providing definitive cognitive advantages. PMID:25767887

Preventing the Return of Fear Using Reconsolidation Update Mechanisms Depends on the Met-Allele of the Brain Derived Neurotrophic Factor Val66Met Polymorphism.

PubMed

Asthana, Manish Kumar; Brunhuber, Bettina; Mühlberger, Andreas; Reif, Andreas; Schneider, Simone; Herrmann, Martin J

2016-06-01

Memory reconsolidation is the direct effect of memory reactivation followed by stabilization of newly synthesized proteins. It has been well proven that neural encoding of both newly and reactivated memories requires synaptic plasticity. Brain derived neurotrophic factor (BDNF) has been extensively investigated regarding its role in the formation of synaptic plasticity and in the alteration of fear memories. However, its role in fear reconsolidation is still unclear; hence, the current study has been designed to investigate the role of the BDNF val66met polymorphism (rs6265) in fear memory reconsolidation in humans. An auditory fear-conditioning paradigm was conducted, which comprised of three stages (acquisition, reactivation, and spontaneous recovery). One day after fear acquisition, the experimental group underwent reactivation of fear memory followed by the extinction training (reminder group), whereas the control group (non-reminder group) underwent only extinction training. On day 3, both groups were subjected to spontaneous recovery of earlier learned fearful memories. The treat-elicited defensive response due to conditioned threat was measured by assessing the skin conductance response to the conditioned stimulus. All participants were genotyped for rs6265. The results indicate a diminishing effect of reminder on the persistence of fear memory only in the Met-allele carriers, suggesting a moderating effect of the BDNF polymorphism in fear memory reconsolidation. Our findings suggest a new role for BDNF gene variation in fear memory reconsolidation in humans. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Heat stress enhances LTM formation in Lymnaea: role of HSPs and DNA methylation.

PubMed

Sunada, Hiroshi; Riaz, Hamza; de Freitas, Emily; Lukowiak, Kai; Swinton, Cayley; Swinton, Erin; Protheroe, Amy; Shymansky, Tamila; Komatsuzaki, Yoshimasa; Lukowiak, Ken

2016-05-01

Environmentally relevant stressors alter the memory-forming process in Lymnaea following operant conditioning of aerial respiration. One such stressor is heat. Previously, we found that following a 1 h heat shock, long-term memory (LTM) formation was enhanced. We also had shown that the heat stressor activates at least two heat shock proteins (HSPs): HSP40 and HSP70. Here, we tested two hypotheses: (1) the production of HSPs is necessary for enhanced LTM formation; and (2) blocking DNA methylation prevents the heat stressor-induced enhancement of LTM formation. We show here that the enhancing effect of the heat stressor on LTM formation occurs even if snails experienced the stressor 3 days previously. We further show that a flavonoid, quercetin, which inhibits HSP activation, blocks the enhancing effect of the heat stressor on LTM formation. Finally, we show that injection of a DNA methylation blocker, 5-AZA, before snails experience the heat stressor prevents enhancement of memory formation. © 2016. Published by The Company of Biologists Ltd.

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

NASA Astrophysics Data System (ADS)

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

2011-11-01

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

Regulation of Memory Formation by the Transcription Factor XBP1.

PubMed

Martínez, Gabriela; Vidal, René L; Mardones, Pablo; Serrano, Felipe G; Ardiles, Alvaro O; Wirth, Craig; Valdés, Pamela; Thielen, Peter; Schneider, Bernard L; Kerr, Bredford; Valdés, Jose L; Palacios, Adrian G; Inestrosa, Nibaldo C; Glimcher, Laurie H; Hetz, Claudio

2016-02-16

Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer's disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR), mediating adaptation to endoplasmic reticulum (ER) stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP), whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF), a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Influence of memory effect on the state-of-charge estimation of large-format Li-ion batteries based on LiFePO4 cathode

NASA Astrophysics Data System (ADS)

Shi, Wei; Wang, Jiulin; Zheng, Jianming; Jiang, Jiuchun; Viswanathan, Vilayanur; Zhang, Ji-Guang

2016-04-01

In this work, we systematically investigated the influence of the memory effect of LiFePO4 cathodes in large-format full batteries. The electrochemical performance of the electrodes used in these batteries was also investigated separately in half-cells to reveal their intrinsic properties. We noticed that the memory effect of LiFePO4/graphite cells depends not only on the maximum state of charge reached during the memory writing process, but is also affected by the depth of discharge reached during the memory writing process. In addition, the voltage deviation in a LiFePO4/graphite full battery is more complex than in a LiFePO4/Li half-cell, especially for a large-format battery, which exhibits a significant current variation in the region near its terminals. Therefore, the memory effect should be taken into account in advanced battery management systems to further extend the long-term cycling stabilities of Li-ion batteries using LiFePO4 cathodes.

Increased plasma d-lactic acid associated with impaired memory in rats.

PubMed

Hanstock, T L; Mallet, P E; Clayton, E H

2010-12-02

d-Lactic acidosis is associated with memory impairment in humans. Recent research indicates that d-lactic acid may inhibit the supply of energy from astrocytes to neurons involved with memory formation. However, little is known about the effects of increased hind-gut fermentation due to changes in diet on circulating lactic acid concentrations and memory. Thirty-six male Wistar rats were fed three dietary treatments: a commercial rat and mouse chow, a soluble carbohydrate based diet or a fermentable carbohydrate based diet. The parameters estimating memory were examined by employing the object recognition test. Physical parameters of fermentation including hind-gut and plasma lactic acid concentrations were examined after sacrifice, either 3 or 21h after feeding. Increased fermentation in the hind-gut of rats, indicated by lower caecum pH, was associated with increased plasma l-lactic acid (r=-0.41, p=0.020) and d-lactic acid (r=-0.33, p=0.087). Memory, being able to discriminate between a familiar and a novel object during the object recognition test, was reduced with increasing plasma d-lactic acid (r=-0.51, p=0.021). Memory impairment was associated with alterations in plasma d-lactic acid following the fermentation of carbohydrate in the hind-gut. Further work is still required to determine whether these effects are mediated centrally or via direct connections through the enteric nervous system. Copyright © 2010 Elsevier Inc. All rights reserved.

Canadian Association of Neurosciences Review: learning at a snail's pace.

PubMed

Parvez, Kashif; Rosenegger, David; Martens, Kara; Orr, Michael; Lukowiak, Ken

2006-11-01

While learning and memory are related, they are distinct processes each with different forms of expression and underlying molecular mechanisms. An invertebrate model system, Lymnaea stagnalis, is used to study memory formation of a non-declarative memory. We have done so because: (1) We have discovered the neural circuit that mediates an interesting and tractable behaviour; (2) This behaviour can be operantly conditioned and intermediate-term and long-term memory can be demonstrated; and (3) It is possible to demonstrate that a single neuron in the model system is a necessary site of memory formation. This article reviews how Lymnaea has been used in the study of behavioural and molecular mechanisms underlying consolidation, reconsolidation, extinction and forgetting.

Memory systems, processes, and tasks: taxonomic clarification via factor analysis.

PubMed

Bruss, Peter J; Mitchell, David B

2009-01-01

The nature of various memory systems was examined using factor analysis. We reanalyzed data from 11 memory tasks previously reported in Mitchell and Bruss (2003). Four well-defined factors emerged, closely resembling episodic and semantic memory and conceptual and perceptual implicit memory, in line with both memory systems and transfer-appropriate processing accounts. To explore taxonomic issues, we ran separate analyses on the implicit tasks. Using a cross-format manipulation (pictures vs. words), we identified 3 prototypical tasks. Word fragment completion and picture fragment identification tasks were "factor pure," tapping perceptual processes uniquely. Category exemplar generation revealed its conceptual nature, yielding both cross-format priming and a picture superiority effect. In contrast, word stem completion and picture naming were more complex, revealing attributes of both processes.

Synaptic clustering within dendrites: an emerging theory of memory formation

PubMed Central

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

2015-01-01

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

Hierarchical Traces for Reduced NSM Memory Requirements

NASA Astrophysics Data System (ADS)

Dahl, Torbjørn S.

This paper presents work on using hierarchical long term memory to reduce the memory requirements of nearest sequence memory (NSM) learning, a previously published, instance-based reinforcement learning algorithm. A hierarchical memory representation reduces the memory requirements by allowing traces to share common sub-sequences. We present moderated mechanisms for estimating discounted future rewards and for dealing with hidden state using hierarchical memory. We also present an experimental analysis of how the sub-sequence length affects the memory compression achieved and show that the reduced memory requirements do not effect the speed of learning. Finally, we analyse and discuss the persistence of the sub-sequences independent of specific trace instances.

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

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

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

2015-08-21

This work explores resistive switching mechanisms in non-volatile organic memory devices based on tris(8-hydroxyquinolie)aluminum (Alq{sub 3}). Advanced characterization tools are applied to investigate metal diffusion in ITO/Alq{sub 3}/Ag memory device stacks leading to conductive filament formation. The morphology of Alq{sub 3}/Ag layers as a function of the metal evaporation conditions is studied by X-ray reflectivity, while depth profile analysis with X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry is applied to characterize operational memory elements displaying reliable bistable current-voltage characteristics. 3D images of the distribution of silver inside the organic layer clearly point towards the existence of conductive filamentsmore » and allow for the identification of the initial filament formation and inactivation mechanisms during switching of the device. Initial filament formation is suggested to be driven by field assisted diffusion of silver from abundant structures formed during the top electrode evaporation, whereas thermochemical effects lead to local filament inactivation.« less

From network heterogeneities to familiarity detection and hippocampal memory management

PubMed Central

Wang, Jane X.; Poe, Gina; Zochowski, Michal

2009-01-01

Hippocampal-neocortical interactions are key to the rapid formation of novel associative memories in the hippocampus and consolidation to long term storage sites in the neocortex. We investigated the role of network correlates during information processing in hippocampal-cortical networks. We found that changes in the intrinsic network dynamics due to the formation of structural network heterogeneities alone act as a dynamical and regulatory mechanism for stimulus novelty and familiarity detection, thereby controlling memory management in the context of memory consolidation. This network dynamic, coupled with an anatomically established feedback between the hippocampus and the neocortex, recovered heretofore unexplained properties of neural activity patterns during memory management tasks which we observed during sleep in multiunit recordings from behaving animals. Our simple dynamical mechanism shows an experimentally matched progressive shift of memory activation from the hippocampus to the neocortex and thus provides the means to achieve an autonomous off-line progression of memory consolidation. PMID:18999453

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding.

PubMed

Du, Huiyun; Deng, Wei; Aimone, James B; Ge, Minyan; Parylak, Sarah; Walch, Keenan; Zhang, Wei; Cook, Jonathan; Song, Huina; Wang, Liping; Gage, Fred H; Mu, Yangling

2016-09-13

Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2-expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioral experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Overall, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience.

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

PubMed Central

Du, Huiyun; Deng, Wei; Aimone, James B.; Ge, Minyan; Parylak, Sarah; Walch, Keenan; Zhang, Wei; Cook, Jonathan; Song, Huina; Wang, Liping; Gage, Fred H.; Mu, Yangling

2016-01-01

Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2–expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioral experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Overall, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience. PMID:27573822

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

PubMed Central

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

Negative Affect Impairs Associative Memory but Not Item Memory

ERIC Educational Resources Information Center

Bisby, James A.; Burgess, Neil

2014-01-01

The formation of associations between items and their context has been proposed to rely on mechanisms distinct from those supporting memory for a single item. Although emotional experiences can profoundly affect memory, our understanding of how it interacts with different aspects of memory remains unclear. We performed three experiments to examine…

Improvement of Allocentric Spatial Memory Resolution in Children from 2 to 4 Years of Age

ERIC Educational Resources Information Center

Lambert, Farfalla Ribordy; Lavenex, Pierre; Lavenex, Pamela Banta

2015-01-01

Allocentric spatial memory, the memory for locations coded in relation to objects comprising our environment, is a fundamental component of episodic memory and is dependent on the integrity of the hippocampal formation in adulthood. Previous research from different laboratories reported that basic allocentric spatial memory abilities are reliably…

A Mismatch-Based Model for Memory Reconsolidation and Extinction in Attractor Networks

PubMed Central

Amaral, Olavo B.

2011-01-01

The processes of memory reconsolidation and extinction have received increasing attention in recent experimental research, as their potential clinical applications begin to be uncovered. A number of studies suggest that amnestic drugs injected after reexposure to a learning context can disrupt either of the two processes, depending on the behavioral protocol employed. Hypothesizing that reconsolidation represents updating of a memory trace in the hippocampus, while extinction represents formation of a new trace, we have built a neural network model in which either simple retrieval, reconsolidation or extinction of a stored attractor can occur upon contextual reexposure, depending on the similarity between the representations of the original learning and reexposure sessions. This is achieved by assuming that independent mechanisms mediate Hebbian-like synaptic strengthening and mismatch-driven labilization of synaptic changes, with protein synthesis inhibition preferentially affecting the former. Our framework provides a unified mechanistic explanation for experimental data showing (a) the effect of reexposure duration on the occurrence of reconsolidation or extinction and (b) the requirement of memory updating during reexposure to drive reconsolidation. PMID:21826231

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

PubMed

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

2016-12-01

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

TBI-Induced Formation of Toxic Tau and Its Biochemical Similarities to Tau in AD Brains

DTIC Science & Technology

2016-10-01

onto wild-type mice markedly reduces 1) memory including contextual fear memory and spatial memory, and 2) long-term potentiation, a type of...TERMS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s disease 16. SECURITY CLASSIFICATION OF: 17...mechanism leading to TBI and AD. 2 KEYWORDS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s

Distinct neuroanatomical bases of episodic and semantic memory performance in Alzheimer's disease.

PubMed

Hirni, Daniela I; Kivisaari, Sasa L; Monsch, Andreas U; Taylor, Kirsten I

2013-04-01

Alzheimer's disease (AD) neurofibrillary pathology begins in the medial perirhinal cortex (mPRC) before spreading to the entorhinal cortex (ERC) and hippocampus (HP) in anterior medial temporal lobe (aMTL). While the role of the ERC/HP complex in episodic memory formation is well-established, recent research suggests that the PRC is required to form semantic memories of individual objects. We aimed to test whether commonly used clinical measures of episodic and semantic memory are distinctly associated with ERC/HP and mPRC integrity, respectively, in healthy mature individuals and very early AD patients. One hundred thirty normal controls, 32 amnestic mild cognitive impairment patients, some of whom are in the earliest (i.e., preclinical) stages of AD, and ten early-stage AD patients received neuropsychological testing and high-resolution anatomic and diffusion MRI. Voxel-based regression analyses tested for regions where episodic memory (delayed recall scores on the California Verbal Learning and Rey Osterrieth Complex Figure Tests) and semantic memory (Boston Naming Test, category fluency) performance correlated with gray matter (GM) regions of interest and whole-brain fractional anisotropy (FA) voxel values. When controlling for the opposing memory performance, poorer episodic memory performance was associated with reduced bilateral ERC/HP GM volume and related white matter integrity, but not with mPRC GM volume. Poor semantic memory performance was associated with both reduced left mPRC and ERC/HP GM volume, as well as reduced FA values in white matter tracts leading to the PRC. These results indicate a partial division of labor within the aMTL and suggest that mPRC damage in very early AD may be detectable with common clinical tests of semantic memory if episodic memory performance is controlled. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed

Bieszczad, Kasia M; Bechay, Kiro; Rusche, James R; Jacques, Vincent; Kudugunti, Shashi; Miao, Wenyan; Weinberger, Norman M; McGaugh, James L; Wood, Marcelo A

2015-09-23

Research over the past decade indicates a novel role for epigenetic mechanisms in memory formation. Of particular interest is chromatin modification by histone deacetylases (HDACs), which, in general, negatively regulate transcription. HDAC deletion or inhibition facilitates transcription during memory consolidation and enhances long-lasting forms of synaptic plasticity and long-term memory. A key open question remains: How does blocking HDAC activity lead to memory enhancements? To address this question, we tested whether a normal function of HDACs is to gate information processing during memory formation. We used a class I HDAC inhibitor, RGFP966 (C21H19FN4O), to test the role of HDAC inhibition for information processing in an auditory memory model of learning-induced cortical plasticity. HDAC inhibition may act beyond memory enhancement per se to instead regulate information in ways that lead to encoding more vivid sensory details into memory. Indeed, we found that RGFP966 controls memory induction for acoustic details of sound-to-reward learning. Rats treated with RGFP966 while learning to associate sound with reward had stronger memory and additional information encoded into memory for highly specific features of sounds associated with reward. Moreover, behavioral effects occurred with unusually specific plasticity in primary auditory cortex (A1). Class I HDAC inhibition appears to engage A1 plasticity that enables additional acoustic features to become encoded in memory. Thus, epigenetic mechanisms act to regulate sensory cortical plasticity, which offers an information processing mechanism for gating what and how much is encoded to produce exceptionally persistent and vivid memories. Significance statement: Here we provide evidence of an epigenetic mechanism for information processing. The study reveals that a class I HDAC inhibitor (Malvaez et al., 2013; Rumbaugh et al., 2015; RGFP966, chemical formula C21H19FN4O) alters the formation of auditory memory by enabling more acoustic information to become encoded into memory. Moreover, RGFP966 appears to affect cortical plasticity: the primary auditory cortex reorganized in a manner that was unusually "tuned-in" to the specific sound cues and acoustic features that were related to reward and subsequently remembered. We propose that HDACs control "informational capture" at a systems level for what and how much information is encoded by gating sensory cortical plasticity that underlies the sensory richness of newly formed memories. Copyright © 2015 the authors 0270-6474/15/3513125-09$15.00/0.

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

PubMed Central

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

2015-01-01

Research over the past decade indicates a novel role for epigenetic mechanisms in memory formation. Of particular interest is chromatin modification by histone deacetylases (HDACs), which, in general, negatively regulate transcription. HDAC deletion or inhibition facilitates transcription during memory consolidation and enhances long-lasting forms of synaptic plasticity and long-term memory. A key open question remains: How does blocking HDAC activity lead to memory enhancements? To address this question, we tested whether a normal function of HDACs is to gate information processing during memory formation. We used a class I HDAC inhibitor, RGFP966 (C21H19FN4O), to test the role of HDAC inhibition for information processing in an auditory memory model of learning-induced cortical plasticity. HDAC inhibition may act beyond memory enhancement per se to instead regulate information in ways that lead to encoding more vivid sensory details into memory. Indeed, we found that RGFP966 controls memory induction for acoustic details of sound-to-reward learning. Rats treated with RGFP966 while learning to associate sound with reward had stronger memory and additional information encoded into memory for highly specific features of sounds associated with reward. Moreover, behavioral effects occurred with unusually specific plasticity in primary auditory cortex (A1). Class I HDAC inhibition appears to engage A1 plasticity that enables additional acoustic features to become encoded in memory. Thus, epigenetic mechanisms act to regulate sensory cortical plasticity, which offers an information processing mechanism for gating what and how much is encoded to produce exceptionally persistent and vivid memories. SIGNIFICANCE STATEMENT Here we provide evidence of an epigenetic mechanism for information processing. The study reveals that a class I HDAC inhibitor (Malvaez et al., 2013; Rumbaugh et al., 2015; RGFP966, chemical formula C21H19FN4O) alters the formation of auditory memory by enabling more acoustic information to become encoded into memory. Moreover, RGFP966 appears to affect cortical plasticity: the primary auditory cortex reorganized in a manner that was unusually “tuned-in” to the specific sound cues and acoustic features that were related to reward and subsequently remembered. We propose that HDACs control “informational capture” at a systems level for what and how much information is encoded by gating sensory cortical plasticity that underlies the sensory richness of newly formed memories. PMID:26400942

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

PubMed

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

2016-12-01

The identification of neural substrates underlying the long lasting debilitating impact of drug cues is critical for developing novel therapeutic tools. Metabolic coupling has long been considered a key mechanism through which astrocytes and neurons actively interact in response of neuronal activity, but recent findings suggested that disrupting metabolic coupling may represent an innovative approach to prevent memory formation, in particular drug-related memories. Here, we review converging evidence illustrating how memory and addiction share neural circuitry and molecular mechanisms implicating lactate-mediated metabolic coupling between astrocytes and neurons. With several aspects of addiction depending on mnemonic processes elicited by drug experience, disrupting lactate transport involved in the formation of a pathological learning, linking the incentive, and motivational effects of drugs with drug-conditioned stimuli represent a promising approach to encourage abstinence. © 2016 WILEY Periodicals, Inc.

Neuromodulation: acetylcholine and memory consolidation.

PubMed

Hasselmo

1999-09-01

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

Memory and cognitive control circuits in mathematical cognition and learning.

PubMed

Menon, V

2016-01-01

Numerical cognition relies on interactions within and between multiple functional brain systems, including those subserving quantity processing, working memory, declarative memory, and cognitive control. This chapter describes recent advances in our understanding of memory and control circuits in mathematical cognition and learning. The working memory system involves multiple parietal-frontal circuits which create short-term representations that allow manipulation of discrete quantities over several seconds. In contrast, hippocampal-frontal circuits underlying the declarative memory system play an important role in formation of associative memories and binding of new and old information, leading to the formation of long-term memories that allow generalization beyond individual problem attributes. The flow of information across these systems is regulated by flexible cognitive control systems which facilitate the integration and manipulation of quantity and mnemonic information. The implications of recent research for formulating a more comprehensive systems neuroscience view of the neural basis of mathematical learning and knowledge acquisition in both children and adults are discussed. © 2016 Elsevier B.V. All rights reserved.

Calpain modulates fear memory consolidation, retrieval and reconsolidation in the hippocampus.

PubMed

Popik, Bruno; Crestani, Ana Paula; Silva, Mateus Oliveira; Quillfeldt, Jorge Alberto; de Oliveira Alvares, Lucas

2018-05-01

It has been proposed that long-lasting changes in dendritic spines provide a physical correlate for memory formation and maintenance. Spine size and shape are highly plastic, controlled by actin polymerization/depolymerization cycles. This actin dynamics are regulated by proteins such as calpain, a calcium-dependent cysteine protease that cleaves the structural cytoskeleton proteins and other targets involved in synaptic plasticity. Here, we tested whether the pharmacological inhibition of calpain in the dorsal hippocampus affects memory consolidation, retrieval and reconsolidation in rats trained in contextual fear conditioning. We first found that post-training infusion of the calpain inhibitor PD150606 impaired long-term memory consolidation, but not short-term memory. Next, we showed that pre-test infusion of the calpain inhibitor hindered memory retrieval. Finally, blocking calpain activity after memory reactivation disrupted reconsolidation. Taken together, our results show that calpain play an essential role in the hippocampus by enabling memory formation, expression and reconsolidation. Copyright © 2018 Elsevier Inc. All rights reserved.

Both mineralocorticoid and glucocorticoid receptors regulate emotional memory in mice.

PubMed

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

2010-11-01

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

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

PubMed Central

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

2016-01-01

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

Memory and cognitive control circuits in mathematical cognition and learning

PubMed Central

Menon, V.

2018-01-01

Numerical cognition relies on interactions within and between multiple functional brain systems, including those subserving quantity processing, working memory, declarative memory, and cognitive control. This chapter describes recent advances in our understanding of memory and control circuits in mathematical cognition and learning. The working memory system involves multiple parietal–frontal circuits which create short-term representations that allow manipulation of discrete quantities over several seconds. In contrast, hippocampal–frontal circuits underlying the declarative memory system play an important role in formation of associative memories and binding of new and old information, leading to the formation of long-term memories that allow generalization beyond individual problem attributes. The flow of information across these systems is regulated by flexible cognitive control systems which facilitate the integration and manipulation of quantity and mnemonic information. The implications of recent research for formulating a more comprehensive systems neuroscience view of the neural basis of mathematical learning and knowledge acquisition in both children and adults are discussed. PMID:27339012

Arc in synaptic plasticity: from gene to behavior

PubMed Central

Korb, Erica; Finkbeiner, Steven

2011-01-01

The activity-regulated cytoskeletal (Arc) gene encodes a protein that is critical for memory consolidation. Arc is one of the most tightly regulated molecules known: neuronal activity controls Arc mRNA induction, trafficking, and accumulation, and Arc protein production, localization and stability. Arc regulates synaptic strength through multiple mechanisms and is involved in essentially every known form of synaptic plasticity. It also mediates memory formation and is implicated in multiple neurological diseases. In this review, we will discuss how Arc is regulated and used as a tool to study neuronal activity. We will also attempt to clarify how its molecular functions correspond to its requirement for various forms of plasticity, discuss Arc’s role in behavior and disease, and highlight critical unresolved questions. PMID:21963089

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

PubMed

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

2014-02-01

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

Dopamine modulation of GABAergic function enables network stability and input selectivity for sustaining working memory in a computational model of the prefrontal cortex.

PubMed

Lew, Sergio E; Tseng, Kuei Y

2014-12-01

Dopamine modulation of GABAergic transmission in the prefrontal cortex (PFC) is thought to be critical for sustaining cognitive processes such as working memory and decision-making. Here, we developed a neurocomputational model of the PFC that includes physiological features of the facilitatory action of dopamine on fast-spiking interneurons to assess how a GABAergic dysregulation impacts on the prefrontal network stability and working memory. We found that a particular non-linear relationship between dopamine transmission and GABA function is required to enable input selectivity in the PFC for the formation and retention of working memory. Either degradation of the dopamine signal or the GABAergic function is sufficient to elicit hyperexcitability in pyramidal neurons and working memory impairments. The simulations also revealed an inverted U-shape relationship between working memory and dopamine, a function that is maintained even at high levels of GABA degradation. In fact, the working memory deficits resulting from reduced GABAergic transmission can be rescued by increasing dopamine tone and vice versa. We also examined the role of this dopamine-GABA interaction for the termination of working memory and found that the extent of GABAergic excitation needed to reset the PFC network begins to occur when the activity of fast-spiking interneurons surpasses 40 Hz. Together, these results indicate that the capability of the PFC to sustain working memory and network stability depends on a robust interplay of compensatory mechanisms between dopamine tone and the activity of local GABAergic interneurons.

Encoding, consolidation, and retrieval of contextual memory: differential involvement of dorsal CA3 and CA1 hippocampal subregions.

PubMed

Daumas, Stéphanie; Halley, Hélène; Francés, Bernard; Lassalle, Jean-Michel

2005-01-01

Studies on human and animals shed light on the unique hippocampus contributions to relational memory. However, the particular role of each hippocampal subregion in memory processing is still not clear. Hippocampal computational models and theories have emphasized a unique function in memory for each hippocampal subregion, with the CA3 area acting as an autoassociative memory network and the CA1 area as a critical output structure. In order to understand the respective roles of the CA3- and CA1-hippocampal areas in the formation of contextual memory, we studied the effects of the reversible inactivation by lidocaine of the CA3 or CA1 areas of the dorsal hippocampus on acquisition, consolidation, and retrieval of a contextual fear conditioning. Whereas infusions of lidocaine never impaired elementary tone conditioning, their effects on contextual conditioning provided interesting clues about the role of these two hippocampal regions. They demonstrated first that the CA3 area is necessary for the rapid elaboration of a unified representation of the context. Secondly, they suggested that the CA1 area is rather involved in the consolidation process of contextual memory. Third, they showed that CA1 or CA3 inactivation during retention test has no effect on contextual fear retrieval when a recognition memory procedure is used. In conclusion, our findings point as evidence that CA1 and CA3 subregions of the dorsal hippocampus play important and different roles in the acquisition and consolidation of contextual fear memory, whereas they are not required for context recognition.

Modelling the formation of working memory with networks of integrate-and-fire neurons connected by plastic synapses.

PubMed

Del Giudice, Paolo; Fusi, Stefano; Mattia, Maurizio

2003-01-01

In this paper we review a series of works concerning models of spiking neurons interacting via spike-driven, plastic, Hebbian synapses, meant to implement stimulus driven, unsupervised formation of working memory (WM) states. Starting from a summary of the experimental evidence emerging from delayed matching to sample (DMS) experiments, we briefly review the attractor picture proposed to underlie WM states. We then describe a general framework for a theoretical approach to learning with synapses subject to realistic constraints and outline some general requirements to be met by a mechanism of Hebbian synaptic structuring. We argue that a stochastic selection of the synapses to be updated allows for optimal memory storage, even if the number of stable synaptic states is reduced to the extreme (bistable synapses). A description follows of models of spike-driven synapses that implement the stochastic selection by exploiting the high irregularity in the pre- and post-synaptic activity. Reasons are listed why dynamic learning, that is the process by which the synaptic structure develops under the only guidance of neural activities, driven in turn by stimuli, is hard to accomplish. We provide a 'feasibility proof' of dynamic formation of WM states in this context the beneficial role of short-term depression (STD) is illustrated. by showing how an initially unstructured network autonomously develops a synaptic structure supporting simultaneously stable spontaneous and WM states in this context the beneficial role of short-term depression (STD) is illustrated. After summarizing heuristic indications emerging from the study performed, we conclude by briefly discussing open problems and critical issues still to be clarified.

Reversal of age-related learning deficiency by the vertebrate PACAP and IGF-1 in a novel invertebrate model of aging: the pond snail (Lymnaea stagnalis).

PubMed

Pirger, Zsolt; Naskar, Souvik; László, Zita; Kemenes, György; Reglődi, Dóra; Kemenes, Ildikó

2014-11-01

With the increase of life span, nonpathological age-related memory decline is affecting an increasing number of people. However, there is evidence that age-associated memory impairment only suspends, rather than irreversibly extinguishes, the intrinsic capacity of the aging nervous system for plasticity (1). Here, using a molluscan model system, we show that the age-related decline in memory performance can be reversed by administration of the pituitary adenylate cyclase activating polypeptide (PACAP). Our earlier findings showed that a homolog of the vertebrate PACAP38 and its receptors exist in the pond snail (Lymnaea stagnalis) brain (2), and it is both necessary and instructive for memory formation after reward conditioning in young animals (3). Here we show that exogenous PACAP38 boosts memory formation in aged Lymnaea, where endogenous PACAP38 levels are low in the brain. Treatment with insulin-like growth factor-1, which in vertebrates was shown to transactivate PACAP type I (PAC1) receptors (4) also boosts memory formation in aged pond snails. Due to the evolutionarily conserved nature of these polypeptides and their established role in memory and synaptic plasticity, there is a very high probability that they could also act as "memory rejuvenating" agents in humans. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.

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

PubMed Central

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

2003-01-01

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

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

PubMed

Reber, Thomas P; Henke, Katharina

2011-01-01

Our daily experiences are incidentally and rapidly encoded as episodic memories. Episodic memories consist of numerous associations (e.g., who gave what to whom where and when) that can be expressed flexibly in new situations. Key features of episodic memory are speed of encoding, its associative nature, and its representational flexibility. Another defining feature of human episodic memory has been consciousness of encoding/retrieval. Here, we show that humans can rapidly form associations between subliminal words and minutes later retrieve these associations even if retrieval words were conceptually related to, but different from encoding words. Because encoding words were presented subliminally, associative encoding, and retrieval were unconscious. Unconscious association formation and retrieval were dependent on a preceding understanding of task principles. We conclude that key computations underlying episodic memory - rapid encoding and flexible expression of associations - can operate outside consciousness.

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

PubMed Central

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

2017-01-01

Galectin-3, a member of the galectin protein family, has been found to regulate cell proliferation, inhibit apoptosis and promote inflammatory responses. Galectin-3 is also expressed in the adult rat hippocampus, but its role in learning and memory function is not known. Here, we found that contextual fear-conditioning training, spatial training or injection of NMDA into the rat CA1 area each dramatically decreased the level of endogenous galectin-3 expression. Overexpression of galectin-3 impaired fear memory, whereas galectin-3 knockout (KO) enhanced fear retention, spatial memory and hippocampal long-term potentiation. Galectin-3 was further found to associate with integrin α3, an association that was decreased after fear-conditioning training. Transfection of the rat CA1 area with small interfering RNA against galectin-3 facilitated fear memory and increased phosphorylated focal adhesion kinase (FAK) levels, effects that were blocked by co-transfection of the FAK phosphorylation-defective mutant Flag-FAKY397F. Notably, levels of serine-phosphorylated galectin-3 were decreased by fear conditioning training. In addition, blockade of galectin-3 phosphorylation at Ser-6 facilitated fear memory, whereas constitutive activation of galectin-3 at Ser-6 impaired fear memory. Interestingly galectin-1 plays a role in fear-memory formation similar to that of galectin-3. Collectively, our data provide the first demonstration that galectin-3 is a novel negative regulator of memory formation that exerts its effects through both extracellular and intracellular mechanisms. PMID:28744198

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

PubMed

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

2017-11-28

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

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

PubMed

Wang, Bo; Sun, Bukuan

2017-03-01

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

Genetic Dissociation of Acquisition and Memory Strength in the Heat-Box Spatial Learning Paradigm in "Drosophila"

ERIC Educational Resources Information Center

Diegelmann, Soeren; Zars, Melissa; Zars, Troy

2006-01-01

Memories can have different strengths, largely dependent on the intensity of reinforcers encountered. The relationship between reinforcement and memory strength is evident in asymptotic memory curves, with the level of the asymptote related to the intensity of the reinforcer. Although this is likely a fundamental property of memory formation,…

The 'missing man' formation concluded the memorial for the STS 51-L crew

NASA Technical Reports Server (NTRS)

1986-01-01

The 'missing man' formation concluded the memorial services at JSC for the STS 51-L crew. Four NASA T-38 jet aircraft were used for the symbolic flight. A small portion of the crowd is visible in the bottom portion of the frame.

Epigenetic Regulation of Memory Formation and Maintenance

ERIC Educational Resources Information Center

Zovkic, Iva B.; Guzman-Karlsson, Mikael C.; Sweatt, J. David

2013-01-01

Understanding the cellular and molecular mechanisms underlying the formation and maintenance of memories is a central goal of the neuroscience community. It is well regarded that an organism's ability to lastingly adapt its behavior in response to a transient environmental stimulus relies on the central nervous system's capability for structural…

Constitutive Activation of the G-Protein Subunit G[alpha]s within Forebrain Neurons Causes PKA-Dependent Alterations in Fear Conditioning and Cortical "Arc" mRNA Expression

ERIC Educational Resources Information Center

Kelly, Michele P.; Cheung, York-Fong; Favilla, Christopher; Siegel, Steven J.; Kanes, Stephen J.; Houslay, Miles D.; Abel, Ted

2008-01-01

Memory formation requires cAMP signaling; thus, this cascade has been of great interest in the search for cognitive enhancers. Given that medications are administered long-term, we determined the effects of chronically increasing cAMP synthesis in the brain by expressing a constitutively active isoform of the G-protein subunit G[alpha]s…

Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release

PubMed Central

Gupta, Varun K.; Pech, Ulrike; Fulterer, Andreas; Ender, Anatoli; Mauermann, Stephan F.; Andlauer, Till F. M.; Beuschel, Christine; Thriene, Kerstin; Quentin, Christine; Schwärzel, Martin; Mielke, Thorsten; Madeo, Frank; Dengjel, Joern; Fiala, André; Sigrist, Stephan J.

2016-01-01

Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ), increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP) impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse. PMID:27684064

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

PubMed

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

2018-05-07

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

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

PubMed

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

2018-01-01

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

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

PubMed Central

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

2018-01-01

Volitional exploration and learning are key to adaptive behavior, yet their characterization remains a complex problem for cognitive science. Exploration has been posited as a mechanism by which motivation promotes memory, but this relationship is not well-understood, in part because novel stimuli that motivate exploration also reliably elicit changes in neuromodulatory brain systems that directly alter memory formation, via effects on neural plasticity. To deconfound interrelationships between motivation, exploration, and memory formation we manipulated motivational state prior to entering a spatial context, measured exploratory responses to the context and novel stimuli within it, and then examined motivation and exploration as predictors of memory outcomes. To elicit spontaneous exploration, we used the physical space of an art exhibit with affectively rich content; we expected motivated exploration and memory to reflect multiple factors, including not only motivational valence, but also individual differences. Motivation was manipulated via an introductory statement framing exhibit themes in terms of Promotion- or Prevention-oriented goals. Participants explored the exhibit while being tracked by video. They returned 24 hours later for recall and spatial memory tests, followed by measures of motivation, personality, and relevant attitude variables. Promotion and Prevention condition participants did not differ in terms of group-level exploration time or memory metrics, suggesting similar motivation to explore under both framing contexts. However, exploratory behavior and memory outcomes were significantly more closely related under Promotion than Prevention, indicating that Prevention framing disrupted expected depth-of-encoding effects. Additionally, while trait measures predicted exploration similarly across framing conditions, traits interacted with motivational framing context and facial affect to predict memory outcomes. This novel characterization of motivated learning implies that dissociable behavioral and biological mechanisms, here varying as a function of valence, contribute to memory outcomes in complex, real-life environments. PMID:29558526

The Role of Actin Cytoskeleton in Dendritic Spines in the Maintenance of Long-Term Memory.

PubMed

Basu, Sreetama; Lamprecht, Raphael

2018-01-01

Evidence indicates that long-term memory formation involves alterations in synaptic efficacy produced by modifications in neural transmission and morphology. However, it is not clear how such alterations induced by learning, that encode memory, are maintained over long period of time to preserve long-term memory. This is especially intriguing as the half-life of most of the proteins that underlie such changes is usually in the range of hours to days and these proteins may change their location over time. In this review we describe studies that indicate the involvement of dendritic spines in memory formation and its maintenance. These studies show that learning leads to changes in the number and morphology of spines. Disruption in spines morphology or manipulations that lead to alteration in their number after consolidation are associated with impairment in memory maintenance. We further ask how changes in dendritic spines morphology, induced by learning and reputed to encode memory, are maintained to preserve long-term memory. We propose a mechanism, based on studies described in the review, whereby the actin cytoskeleton and its regulatory proteins involved in the initial alteration in spine morphology induced by learning are also essential for spine structural stabilization that maintains long-term memory. In this model glutamate receptors and other synaptic receptors activation during learning leads to the creation of new actin cytoskeletal scaffold leading to changes in spines morphology and memory formation. This new actin cytoskeletal scaffold is preserved beyond actin and its regulatory proteins turnover and dynamics by active stabilization of the level and activity of actin regulatory proteins within these memory spines.

Stimulation of the noradrenergic system during memory formation impairs extinction learning but not the disruption of reconsolidation.

PubMed

Soeter, Marieke; Kindt, Merel

2012-04-01

The noradrenergic system plays a critical role in the 'consolidation' of emotional memory. If we are to target 'reconsolidation' in patients with anxiety disorders, the noradrenergic strengthening of fear memory should not impair the disruption of reconsolidation. In Experiment I, we addressed this issue using a differential fear conditioning procedure allowing selective reactivation of one of two fear associations. First, we strengthened fear memory by administering an α(2)-adrenergic receptor antagonist (ie, yohimbine HCl; double-blind placebo-controlled study) 30 min before acquisition (time for peak value yohimbine HCl <1 h). Next, the reconsolidation of one of the fear associations was manipulated by administering a β-adrenergic receptor antagonist (ie, propranolol HCl) 90 min before its selective reactivation (time for peak value propranolol HCl <2 h). In Experiment II, we administered propranolol HCl after reactivation of the memory to rule out a possible effect of the pharmacological manipulation on the memory retrieval itself. The excessive release of noradrenaline during memory formation not only delayed the process of extinction 48 h later, but also triggered broader fear generalization. Yet, the β-adrenergic receptor blocker during reconsolidation selectively 'neutralized' the fear-arousing aspects of the noradrenergic-strengthened memory and undermined the generalization of fear. We observed a similar reduction in fear responding when propranolol HCl was administered after reactivation of the memory. The present findings demonstrate the involvement of noradrenergic modulation in the formation as well as generalization of human fear memory. Given that the noradrenergic strengthening of fear memory impaired extinction learning but not the disruption of reconsolidation, our findings may have implications for the treatment of anxiety disorders.

Perioperative nurse training in cardiothoracic surgical robotics.

PubMed

Connor, M A; Reinbolt, J A; Handley, P J

2001-12-01

The exponential growth of OR technology during the past 10 years has placed increased demands on perioperative nurses. Proficiency is required not only in patient care but also in the understanding, operating, and troubleshooting of video systems, computers, and cutting edge medical devices. The formation of a surgical team dedicated to robotically assisted cardiac surgery requires careful selection, education, and hands-on practice. This article details the six-week training process undertaken at Sarasota Memorial Hospital, Sarasota, Fla, which enabled staff members to deliver excellent patient care with a high degree of confidence in themselves and the robotic technology.

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

PubMed Central

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

2010-01-01

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

Retinoid hyposignaling contributes to aging-related decline in hippocampal function in short-term/working memory organization and long-term declarative memory encoding in mice.

PubMed

Mingaud, Frédérique; Mormede, Cécile; Etchamendy, Nicole; Mons, Nicole; Niedergang, Betty; Wietrzych, Marta; Pallet, Véronique; Jaffard, Robert; Krezel, Wojciech; Higueret, Paul; Marighetto, Aline

2008-01-02

An increasing body of evidence indicates that the vitamin A metabolite retinoic acid (RA) plays a role in adult brain plasticity by activating gene transcription through nuclear receptors. Our previous studies in mice have shown that a moderate downregulation of retinoid-mediated transcription contributed to aging-related deficits in hippocampal long-term potentiation and long-term declarative memory (LTDM). Here, knock-out, pharmacological, and nutritional approaches were used in a series of radial-arm maze experiments with mice to further assess the hypothesis that retinoid-mediated nuclear events are causally involved in preferential degradation of hippocampal function in aging. Molecular and behavioral findings confirmed our hypothesis. First, a lifelong vitamin A supplementation, like short-term RA administration, was shown to counteract the aging-related hippocampal (but not striatal) hypoexpression of a plasticity-related retinoid target-gene, GAP43 (reverse transcription-PCR analyses, experiment 1), as well as short-term/working memory (STWM) deterioration seen particularly in organization demanding trials (STWM task, experiment 2). Second, using a two-stage paradigm of LTDM, we demonstrated that the vitamin A supplementation normalized memory encoding-induced recruitment of (hippocampo-prefrontal) declarative memory circuits, without affecting (striatal) procedural memory system activity in aged mice (Fos neuroimaging, experiment 3A) and alleviated their LTDM impairment (experiment 3B). Finally, we showed that (knock-out, experiment 4) RA receptor beta and retinoid X receptor gamma, known to be involved in STWM (Wietrzych et al., 2005), are also required for LTDM. Hence, aging-related retinoid signaling hypoexpression disrupts hippocampal cellular properties critically required for STWM organization and LTDM formation, and nutritional vitamin A supplementation represents a preventive strategy. These findings are discussed within current neurobiological perspectives questioning the historical consensus on STWM and LTDM system partition.

Evaluation of the Implications of Nanoscale Architectures on Contextual Knowledge Discovery and Memory: Self-Assembled Architectures and Memory

DTIC Science & Technology

2008-05-01

patterns. Our strategy to nucleate Ag nanoparticles has been to use a templating protein (e.g., streptavidin) that has been chemically pre- charged with...assembly is used to direct the formation of switching devices and wires to create logic circuitry, memory, and I/O interfaces . We can control the reaction...determines the formation of structures (through complementarity ). Sequence design is important because it determines many aspects of the target DNA

Staging memory for massively parallel processor

NASA Technical Reports Server (NTRS)

Batcher, Kenneth E. (Inventor)

1988-01-01

The invention herein relates to a computer organization capable of rapidly processing extremely large volumes of data. A staging memory is provided having a main stager portion consisting of a large number of memory banks which are accessed in parallel to receive, store, and transfer data words simultaneous with each other. Substager portions interconnect with the main stager portion to match input and output data formats with the data format of the main stager portion. An address generator is coded for accessing the data banks for receiving or transferring the appropriate words. Input and output permutation networks arrange the lineal order of data into and out of the memory banks.

Extracellular matrix controls neuronal features that mediate the persistence of fear.

PubMed

Pignataro, Annabella; Pagano, Roberto; Guarneri, Giorgia; Middei, Silvia; Ammassari-Teule, Martine

2017-12-01

Degradation of the chondroitin sulfate proteoglycans of the extracellular matrix (ECM) by injections of the bacterial enzyme chondroitinase ABC (ChABC) in the basolateral amygdala (BLA) does not impair fear memory formation but accelerates its extinction and disrupts its reactivation. These observations suggest that the treatment might selectively interfere with the post-extinction features of neurons that mediate the reinstatement of fear. Here, we report that ChABC mice show regular fear memory and memory-driven c-fos activation and dendritic spine formation in the BLA. These mice then rapidly extinguish their fear response and exhibit a post-extinction concurrent reduction in c-fos activation and large dendritic spines that extends to the anterior cingulate cortex 7 days later. At this remote time point, fear renewal and fear retrieval are impaired. These findings show that a non-cellular component of the brain tissue controls post-extinction levels of neuronal activity and spine enlargement in the regions sequentially remodelled during the formation of recent and remote fear memory. By preventing BLA and aCC neurons to retain neuronal features that serve to reactivate an extinguished fear memory, ECM digestion might offer a therapeutic strategy for durable attenuation of traumatic memories.

On brain lesions, the milkman and Sigmunda.

PubMed

Izquierdo, I; Medina, J H

1998-10-01

Lesion studies have been of historical importance in establishing the brain systems involved in memory processes. Many of those studies, however, have been overinterpreted in terms of the actual role of each system and of connections between systems. The more recent molecular pharmacological approach has produced major advances in these two areas. The main biochemical steps of memory formation in the CAI region of the hippocampus have been established by localized microinfusions of drugs acting on specific enzymes of receptors, by subcellular measurements of the activity or function of those enzymes and receptors at definite times, and by transgenic deletions or changes of those proteins. The biochemical steps of long-term memory formation in CAI have been found to be quite similar to those of long-term potentiation in the same region, and of other forms of plasticity. Connections between the hippocampus and the entorhinal and parietal cortices in the formation and modulation of short- and long-term memory have also been elucidated using these techniques. Lesion studies, coupled with imaging studies, still have a role to play; with regard to human memory, this role is in many ways unique. But these methods by themselves are not informative as to the mechanisms of memory processing, storage or modulation.

An intervention study on the effect of matcha tea, in drink and snack bar formats, on mood and cognitive performance.

PubMed

Dietz, Christina; Dekker, Matthijs; Piqueras-Fiszman, Betina

2017-09-01

Matcha tea is gaining popularity throughout the world in recent years and is frequently referred to as a mood-and-brain food. Previous research has demonstrated that three constituents present in matcha tea, l-theanine, epigallocatechin gallate (EGCG), and caffeine, affect mood and cognitive performance. However, to date there are no studies assessing the effect of matcha tea itself. The present study investigates these effects by means of a human intervention study administering matcha tea and a matcha containing product. Using a randomized, placebo-controlled, single-blind study, 23 consumers participated in four test sessions. In each session, participants consumed one of the four test products: matcha tea, matcha tea bar (each containing 4g matcha tea powder), placebo tea, or placebo bar. The assessment was performed at baseline and 60min post-treatment. The participants performed a set of cognitive tests assessing attention, information processing, working memory, and episodic memory. The mood state was measured by means of a Profile of Mood States (POMS). After consuming the matcha products compared to placebo versions, there were mainly significant improvements in tasks measuring basic attention abilities and psychomotor speed in response to stimuli over a defined period of time. In contrast to expectations, the effect was barely present in the other cognitive tasks. The POMS results revealed no significant changes in mood. The influence of the food matrix was demonstrated by the fact that on most cognitive performance measures the drink format outperformed the bar format, particularly in tasks measuring speed of spatial working memory and delayed picture recognition. This study suggests that matcha tea consumed in a realistic dose can induce slight effects on speed of attention and episodic secondary memory to a low degree. Further studies are required to elucidate the influences of the food matrix. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of Post-Encoding Stress on Performance in the DRM False Memory Paradigm

ERIC Educational Resources Information Center

Pardilla-Delgado, Enmanuelle; Alger, Sara E.; Cunningham, Tony J.; Kinealy, Brian; Payne, Jessica D.

2016-01-01

Numerous studies have investigated how stress impacts veridical memory, but how stress influences false memory formation remains poorly understood. In order to target memory consolidation specifically, a psychosocial stress (TSST) or control manipulation was administered following encoding of 15 neutral, semantically related word lists (DRM false…

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

PubMed

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

2018-06-18

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

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

PubMed Central

Nunes, Ludmila D.; Garcia-Marques, Leonel; Ferreira, Mário B.; Ramos, Tânia

2017-01-01

An extension of the DRM paradigm was used to study the impact of central traits (Asch, 1946) in impression formation. Traits corresponding to the four clusters of the implicit theory of personality—intellectual, positive and negative; and social, positive and negative (Rosenberg et al., 1968)—were used to develop lists containing several traits of one cluster and one central trait prototypical of the opposite cluster. Participants engaging in impression formation relative to participants engaging in memorization not only produced higher levels of false memories corresponding to the same cluster of the list traits but, under response time pressure at retrieval, also produced more false memories of the cluster corresponding to the central trait. We argue that the importance of central traits stems from their ability to activate their corresponding semantic space within a specialized associative memory structure underlying the implicit theory of personality. PMID:28878708

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

PubMed

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

2006-06-01

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

A mega-analysis of memory reports from eight peer-reviewed false memory implantation studies.

PubMed

Scoboria, Alan; Wade, Kimberley A; Lindsay, D Stephen; Azad, Tanjeem; Strange, Deryn; Ost, James; Hyman, Ira E

2017-02-01

Understanding that suggestive practices can promote false beliefs and false memories for childhood events is important in many settings (e.g., psychotherapeutic, medical, and legal). The generalisability of findings from memory implantation studies has been questioned due to variability in estimates across studies. Such variability is partly due to false memories having been operationalised differently across studies and to differences in memory induction techniques. We explored ways of defining false memory based on memory science and developed a reliable coding system that we applied to reports from eight published implantation studies (N = 423). Independent raters coded transcripts using seven criteria: accepting the suggestion, elaboration beyond the suggestion, imagery, coherence, emotion, memory statements, and not rejecting the suggestion. Using this scheme, 30.4% of cases were classified as false memories and another 23% were classified as having accepted the event to some degree. When the suggestion included self-relevant information, an imagination procedure, and was not accompanied by a photo depicting the event, the memory formation rate was 46.1%. Our research demonstrates a useful procedure for systematically combining data that are not amenable to meta-analysis, and provides the most valid estimate of false memory formation and associated moderating factors within the implantation literature to date.

A Key Role for Nectin-1 in the Ventral Hippocampus in Contextual Fear Memory

PubMed Central

Grosse, Jocelyn; Krummenacher, Claude; Sandi, Carmen

2013-01-01

Nectins are cell adhesion molecules that are widely expressed in the brain. Nectin expression shows a dynamic spatiotemporal regulation, playing a role in neural migratory processes during development. Nectin-1 and nectin-3 and their heterophilic trans-interactions are important for the proper formation of synapses. In the hippocampus, nectin-1 and nectin-3 localize at puncta adherentia junctions and may play a role in synaptic plasticity, a mechanism essential for memory and learning. We evaluated the potential involvement of nectin-1 and nectin-3 in memory consolidation using an emotional learning paradigm. Rats trained for contextual fear conditioning showed transient nectin-1—but not nectin-3—protein upregulation in synapse-enriched hippocampal fractions at about 2 h posttraining. The upregulation of nectin-1 was found exclusively in the ventral hippocampus and was apparent in the synaptoneurosomal fraction. This upregulation was induced by contextual fear conditioning but not by exposure to context or shock alone. When an antibody against nectin-1, R165, was infused in the ventral-hippocampus immediately after training, contextual fear memory was impaired. However, treatment with the antibody in the dorsal hippocampus had no effect in contextual fear memory formation. Similarly, treatment with the antibody in the ventral hippocampus did not interfere with acoustic memory formation. Further control experiments indicated that the effects of ventral hippocampal infusion of the nectin-1 antibody in contextual fear memory cannot be ascribed to memory non-specific effects such as changes in anxiety-like behavior or locomotor behavior. Therefore, we conclude that nectin-1 recruitment to the perisynaptic environment in the ventral hippocampus plays an important role in the formation of contextual fear memories. Our results suggest that these mechanisms could be involved in the connection of emotional and contextual information processed in the amygdala and dorsal hippocampus, respectively, thus opening new venues for the development of treatments to psychopathological alterations linked to impaired contextualization of emotions. PMID:23418609

Critical Role of Nitric Oxide-cGMP Cascade in the Formation of cAMP-Dependent Long-Term Memory

ERIC Educational Resources Information Center

Aonuma, Hitoshi; Mizunami, Makoto; Matsumoto, Yukihisa; Unoki, Sae

2006-01-01

Cyclic AMP pathway plays an essential role in formation of long-term memory (LTM). In some species, the nitric oxide (NO)-cyclic GMP pathway has been found to act in parallel and complementary to the cAMP pathway for LTM formation. Here we describe a new role of the NO-cGMP pathway, namely, stimulation of the cAMP pathway to induce LTM. We have…

A Place at the Table: LTD as a Mediator of Memory Genesis.

PubMed

Connor, Steven A; Wang, Yu Tian

2016-08-01

Resolving how our brains encode information requires an understanding of the cellular processes taking place during memory formation. Since the 1970s, considerable effort has focused on determining the properties and mechanisms underlying long-term potentiation (LTP) at glutamatergic synapses and how these processes influence initiation of new memories. However, accumulating evidence suggests that long-term depression (LTD) of synaptic strength, particularly at glutamatergic synapses, is a bona fide learning and memory mechanism in the mammalian brain. The known range of mechanisms capable of inducing LTD has been extended to those including NMDAR-independent forms, neuromodulator-dependent LTD, synaptic depression following stress, and non-synaptically induced forms. The examples of LTD observed at the hippocampal CA1 synapse to date demonstrate features consistent with LTP, including homo- and heterosynaptic expression, extended duration beyond induction (several hours to weeks), and association with encoding of distinct types of memories. Canonical mechanisms through which synapses undergo LTD include activation of phosphatases, initiation of protein synthesis, and dynamic regulation of presynaptic glutamate release and/or postsynaptic glutamate receptor endocytosis. Here, we will discuss the pre- and postsynaptic changes underlying LTD, recent advances in the identification and characterization of novel mechanisms underlying LTD, and how engagement of these processes constitutes a cellular analog for the genesis of specific types of memories. © The Author(s) 2015.

The impact of modality and working memory capacity on achievement in a multimedia environment

NASA Astrophysics Data System (ADS)

Stromfors, Charlotte M.

This study explored the impact of working memory capacity and student learning in a dual modality, multimedia environment titled Visualizing Topography. This computer-based instructional program focused on the basic skills in reading and interpreting topographic maps. Two versions of the program presented the same instructional content but varied the modality of verbal information: the audio-visual condition coordinated topographic maps and narration; the visual-visual condition provided the same topographic maps with readable text. An analysis of covariance procedure was conducted to evaluate the effects due to the two conditions in relation to working memory capacity, controlling for individual differences in spatial visualization and prior knowledge. The scores on the Figural Intersection Test were used to separate subjects into three levels in terms of their measured working memory capacity: low, medium, and high. Subjects accessed Visualizing Topography by way of the Internet and proceeded independently through the program. The program architecture was linear in format. Subjects had a minimum amount of flexibility within each of five segments, but not between segments. One hundred and fifty-one subjects were randomly assigned to either the audio-visual or the visual-visual condition. The average time spent in the program was thirty-one minutes. The results of the ANCOVA revealed a small to moderate modality effect favoring an audio-visual condition. The results also showed that subjects with low and medium working capacity benefited more from the audio-visual condition than the visual-visual condition, while subjects with a high working memory capacity did not benefit from either condition. Although splitting the data reduced group sizes, ANCOVA results by gender suggested that the audio-visual condition favored females with low working memory capacities. The results have implications for designers of educational software, the teachers who select software, and the students themselves. Splitting information into two, non-redundant sources, one audio and one visual, may effectively extend working memory capacity. This is especially significant for the student population encountering difficult science concepts that require the formation and manipulation of mental representations. It is recommended that multimedia environments be designed or selected with attention to modality conditions that facilitate student learning.

ASIC-dependent LTP at multiple glutamatergic synapses in amygdala network is required for fear memory

PubMed Central

Chiang, Po-Han; Chien, Ta-Chun; Chen, Chih-Cheng; Yanagawa, Yuchio; Lien, Cheng-Chang

2015-01-01

Genetic variants in the human ortholog of acid-sensing ion channel-1a subunit (ASIC1a) gene are associated with panic disorder and amygdala dysfunction. Both fear learning and activity-induced long-term potentiation (LTP) of cortico-basolateral amygdala (BLA) synapses are impaired in ASIC1a-null mice, suggesting a critical role of ASICs in fear memory formation. In this study, we found that ASICs were differentially expressed within the amygdala neuronal population, and the extent of LTP at various glutamatergic synapses correlated with the level of ASIC expression in postsynaptic neurons. Importantly, selective deletion of ASIC1a in GABAergic cells, including amygdala output neurons, eliminated LTP in these cells and reduced fear learning to the same extent as that found when ASIC1a was selectively abolished in BLA glutamatergic neurons. Thus, fear learning requires ASIC-dependent LTP at multiple amygdala synapses, including both cortico-BLA input synapses and intra-amygdala synapses on output neurons. PMID:25988357

Rapid Formation and Flexible Expression of Memories of Subliminal Word Pairs

PubMed Central

Reber, Thomas P.; Henke, Katharina

2011-01-01

Our daily experiences are incidentally and rapidly encoded as episodic memories. Episodic memories consist of numerous associations (e.g., who gave what to whom where and when) that can be expressed flexibly in new situations. Key features of episodic memory are speed of encoding, its associative nature, and its representational flexibility. Another defining feature of human episodic memory has been consciousness of encoding/retrieval. Here, we show that humans can rapidly form associations between subliminal words and minutes later retrieve these associations even if retrieval words were conceptually related to, but different from encoding words. Because encoding words were presented subliminally, associative encoding, and retrieval were unconscious. Unconscious association formation and retrieval were dependent on a preceding understanding of task principles. We conclude that key computations underlying episodic memory – rapid encoding and flexible expression of associations – can operate outside consciousness. PMID:22125545

Mapping virtual addresses to different physical addresses for value disambiguation for thread memory access requests

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

Gala, Alan; Ohmacht, Martin

A multiprocessor system includes nodes. Each node includes a data path that includes a core, a TLB, and a first level cache implementing disambiguation. The system also includes at least one second level cache and a main memory. For thread memory access requests, the core uses an address associated with an instruction format of the core. The first level cache uses an address format related to the size of the main memory plus an offset corresponding to hardware thread meta data. The second level cache uses a physical main memory address plus software thread meta data to store the memorymore » access request. The second level cache accesses the main memory using the physical address with neither the offset nor the thread meta data after resolving speculation. In short, this system includes mapping of a virtual address to a different physical addresses for value disambiguation for different threads.« less

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

PubMed Central

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

2013-01-01

Memory storage in the brain relies on mechanisms acting on time scales from minutes, for long-term synaptic potentiation, to days, for memory consolidation. During such processes, neural circuits distinguish synapses relevant for forming a long-term storage, which are consolidated, from synapses of short-term storage, which fade. How time scale integration and synaptic differentiation is simultaneously achieved remains unclear. Here we show that synaptic scaling – a slow process usually associated with the maintenance of activity homeostasis – combined with synaptic plasticity may simultaneously achieve both, thereby providing a natural separation of short- from long-term storage. The interaction between plasticity and scaling provides also an explanation for an established paradox where memory consolidation critically depends on the exact order of learning and recall. These results indicate that scaling may be fundamental for stabilizing memories, providing a dynamic link between early and late memory formation processes. PMID:24204240

The Role and Mechanisms of Action of Glucocorticoid Involvement in Memory Storage

PubMed Central

Sandi, Carmen

1998-01-01

Adrenal steroid hormones modulate learning and memory processes by interacting with specific glucocorticoid receptors at different brain areas. In this article, certain components of the physiological response to stress elicited by learning situations are proposed to form an integral aspect of the neurobiological mechanism underlying memory formation. By reviewing the work carried out in different learning models in chicks (passive avoidance learning) and rats (spatial orientation in the Morris water maze and contextual fear conditioning), a role for brain corticosterone action through the glucocorticoid receptor type on the mechanisms of memory consolidation is hypothesized. Evidence is also presented to relate post-training corticosterone levels to the strength of memory storage. Finally, the possible molecular mechanisms that might mediate the influences of glucocorticoids in synaptic plasticity subserving long-term memory formation are considered, mainly by focusing on studies implicating a steroid action through (i) glutamatergic transmission and (ii) cell adhesion molecules. PMID:9920681

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

PubMed

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

2013-10-01

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

Interregional synaptic maps among engram cells underlie memory formation.

PubMed

Choi, Jun-Hyeok; Sim, Su-Eon; Kim, Ji-Il; Choi, Dong Il; Oh, Jihae; Ye, Sanghyun; Lee, Jaehyun; Kim, TaeHyun; Ko, Hyoung-Gon; Lim, Chae-Seok; Kaang, Bong-Kiun

2018-04-27

Memory resides in engram cells distributed across the brain. However, the site-specific substrate within these engram cells remains theoretical, even though it is generally accepted that synaptic plasticity encodes memories. We developed the dual-eGRASP (green fluorescent protein reconstitution across synaptic partners) technique to examine synapses between engram cells to identify the specific neuronal site for memory storage. We found an increased number and size of spines on CA1 engram cells receiving input from CA3 engram cells. In contextual fear conditioning, this enhanced connectivity between engram cells encoded memory strength. CA3 engram to CA1 engram projections strongly occluded long-term potentiation. These results indicate that enhanced structural and functional connectivity between engram cells across two directly connected brain regions forms the synaptic correlate for memory formation. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The Influence of Textbook Format on Postsecondary Proficient and Remedial Readers: Designing Information Using Visual Language

ERIC Educational Resources Information Center

Tetlan, W. Lou

2009-01-01

This study examined whether the design of textbook material affects comprehension and memory of textbook material under certain cognitive conditions for proficient and remedial readers. Using quantitative and qualitative research methods, format was found to significantly affect comprehension and memory. Proficient Male scored significantly…

Transcranial focal electrical stimulation via tripolar concentric ring electrodes does not modify the short- and long-term memory formation in rats evaluated in the novel object recognition test

PubMed Central

Rogel-Salazar, G; Luna-Munguía, H; Stevens, KE; Besio, WG

2013-01-01

Noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCREs) has been under development by Besio as an alternative/complementary therapy for seizure control. TFS has shown efficacy attenuating penicillin, pilocarpine, and pentylenetetrazole– induced acute seizures in rat models. This study evaluated the effects of TFS via TCREs on the memory formation of healthy rats as a safety test of TFS. The short and long-term memory formation was tested after the application of TFS using the novel object recognition (NOR) test. Independent groups were used: naïve, control (without TFS), and TFS (treated). Naïve, control, and stimulated groups spent more time investigating the new object than the familiar one during the test phase. TFS via TCREs given once does not modify the short- and long-term memory formation in rats in the NOR test. Results provide an important step towards a better understanding for the safe usage of TFS via TCREs. PMID:23419871

CREB and the discovery of cognitive enhancers.

PubMed

Scott, Roderick; Bourtchuladze, Rusiko; Gossweiler, Scott; Dubnau, Josh; Tully, Tim

2002-01-01

In the past few years, a series of molecular-genetic, biochemical, cellular and behavioral studies in fruit flies, sea slugs and mice have confirmed a long-standing notion that long-term memory formation depends on the synthesis of new proteins. Experiments focused on the cAMP-responsive transcription factor, CREB, have established that neural activity-induced regulation of gene transcription promotes a synaptic growth process that strengthens the connections among active neurons. This process constitutes a physical basis for the engram--and CREB is a "molecular switch" to produce the engram. Helicon Therapeutics has been formed to identify drug compounds that enhance memory formation via augmentation of CREB biochemistry. Candidate compounds have been identified from a high throughput cell-based screen and are being evaluated in animal models of memory formation. A gene discovery program also seeks to identify new genes, which function downstream of CREB during memory formation, as a source for new drug discoveries in the future. Together, these drug and gene discovery efforts promise new class of pharmaceutical therapies for the treatment of various forms of cognitive dysfunction.

Autosophy: an alternative vision for satellite communication, compression, and archiving

NASA Astrophysics Data System (ADS)

Holtz, Klaus; Holtz, Eric; Kalienky, Diana

2006-08-01

Satellite communication and archiving systems are now designed according to an outdated Shannon information theory where all data is transmitted in meaningless bit streams. Video bit rates, for example, are determined by screen size, color resolution, and scanning rates. The video "content" is irrelevant so that totally random images require the same bit rates as blank images. An alternative system design, based on the newer Autosophy information theory, is now evolving, which transmits data "contend" or "meaning" in a universally compatible 64bit format. This would allow mixing all multimedia transmissions in the Internet's packet stream. The new systems design uses self-assembling data structures, which grow like data crystals or data trees in electronic memories, for both communication and archiving. The advantages for satellite communication and archiving may include: very high lossless image and video compression, unbreakable encryption, resistance to transmission errors, universally compatible data formats, self-organizing error-proof mass memories, immunity to the Internet's Quality of Service problems, and error-proof secure communication protocols. Legacy data transmission formats can be converted by simple software patches or integrated chipsets to be forwarded through any media - satellites, radio, Internet, cable - without needing to be reformatted. This may result in orders of magnitude improvements for all communication and archiving systems.

Propofol and memory: a study using a process dissociation procedure and functional magnetic resonance imaging.

PubMed

Quan, X; Yi, J; Ye, T H; Tian, S Y; Zou, L; Yu, X R; Huang, Y G

2013-04-01

Thirty volunteers randomly received either mild or deep propofol sedation, to assess its effect on explicit and implicit memory. Blood oxygen level-dependent functional magnetic resonance during sedation examined brain activation by auditory word stimulus and a process dissociation procedure was performed 4 h after scanning. Explicit memory formation did not occur in either group. Implicit memories were formed during mild but not deep sedation (p = 0.04). Mild propofol sedation inhibited superior temporal gyrus activation (Z value 4.37, voxel 167). Deep propofol sedation inhibited superior temporal gyrus (Z value 4.25, voxel 351), middle temporal gyrus (Z value 4.39, voxel 351) and inferior parietal lobule (Z value 5.06, voxel 239) activation. Propofol only abolishes implicit memory during deep sedation. The superior temporal gyrus is associated with explicit memory processing, while the formation of both implicit and explicit memories is associated with superior and middle temporal gyri and inferior parietal lobule activation. Anaesthesia © 2013 The Association of Anaesthetists of Great Britain and Ireland.

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

DOE PAGES

Du, Huiyun; Deng, Wei; Aimone, James B.; ...

2016-09-13

Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2–expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioralmore » experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Altogether, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience.« less

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

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

Du, Huiyun; Deng, Wei; Aimone, James B.

Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2–expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioralmore » experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Altogether, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience.« less

Design and evaluation of an architecture for a digital signal processor for instrumentation applications

NASA Astrophysics Data System (ADS)

Fellman, Ronald D.; Kaneshiro, Ronald T.; Konstantinides, Konstantinos

1990-03-01

The authors present the design and evaluation of an architecture for a monolithic, programmable, floating-point digital signal processor (DSP) for instrumentation applications. An investigation of the most commonly used algorithms in instrumentation led to a design that satisfies the requirements for high computational and I/O (input/output) throughput. In the arithmetic unit, a 16- x 16-bit multiplier and a 32-bit accumulator provide the capability for single-cycle multiply/accumulate operations, and three format adjusters automatically adjust the data format for increased accuracy and dynamic range. An on-chip I/O unit is capable of handling data block transfers through a direct memory access port and real-time data streams through a pair of parallel I/O ports. I/O operations and program execution are performed in parallel. In addition, the processor includes two data memories with independent addressing units, a microsequencer with instruction RAM, and multiplexers for internal data redirection. The authors also present the structure and implementation of a design environment suitable for the algorithmic, behavioral, and timing simulation of a complete DSP system. Various benchmarking results are reported.

Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits.

PubMed

Kohara, Keigo; Pignatelli, Michele; Rivest, Alexander J; Jung, Hae-Yoon; Kitamura, Takashi; Suh, Junghyup; Frank, Dominic; Kajikawa, Koichiro; Mise, Nathan; Obata, Yuichi; Wickersham, Ian R; Tonegawa, Susumu

2014-02-01

The formation and recall of episodic memory requires precise information processing by the entorhinal-hippocampal network. For several decades, the trisynaptic circuit entorhinal cortex layer II (ECII)→dentate gyrus→CA3→CA1 and the monosynaptic circuit ECIII→CA1 have been considered the primary substrates of the network responsible for learning and memory. Circuits linked to another hippocampal region, CA2, have only recently come to light. Using highly cell type-specific transgenic mouse lines, optogenetics and patch-clamp recordings, we found that dentate gyrus cells, long believed to not project to CA2, send functional monosynaptic inputs to CA2 pyramidal cells through abundant longitudinal projections. CA2 innervated CA1 to complete an alternate trisynaptic circuit, but, unlike CA3, projected preferentially to the deep, rather than to the superficial, sublayer of CA1. Furthermore, contrary to existing knowledge, ECIII did not project to CA2. Our results allow a deeper understanding of the biology of learning and memory.

A connectome of a learning and memory center in the adult Drosophila brain

PubMed Central

Takemura, Shin-ya; Aso, Yoshinori; Hige, Toshihide; Wong, Allan; Lu, Zhiyuan; Xu, C Shan; Rivlin, Patricia K; Hess, Harald; Zhao, Ting; Parag, Toufiq; Berg, Stuart; Huang, Gary; Katz, William; Olbris, Donald J; Plaza, Stephen; Umayam, Lowell; Aniceto, Roxanne; Chang, Lei-Ann; Lauchie, Shirley; Ogundeyi, Omotara; Ordish, Christopher; Shinomiya, Aya; Sigmund, Christopher; Takemura, Satoko; Tran, Julie; Turner, Glenn C; Rubin, Gerald M; Scheffer, Louis K

2017-01-01

Understanding memory formation, storage and retrieval requires knowledge of the underlying neuronal circuits. In Drosophila, the mushroom body (MB) is the major site of associative learning. We reconstructed the morphologies and synaptic connections of all 983 neurons within the three functional units, or compartments, that compose the adult MB’s α lobe, using a dataset of isotropic 8 nm voxels collected by focused ion-beam milling scanning electron microscopy. We found that Kenyon cells (KCs), whose sparse activity encodes sensory information, each make multiple en passant synapses to MB output neurons (MBONs) in each compartment. Some MBONs have inputs from all KCs, while others differentially sample sensory modalities. Only 6% of KC>MBON synapses receive a direct synapse from a dopaminergic neuron (DAN). We identified two unanticipated classes of synapses, KC>DAN and DAN>MBON. DAN activation produces a slow depolarization of the MBON in these DAN>MBON synapses and can weaken memory recall. DOI: http://dx.doi.org/10.7554/eLife.26975.001 PMID:28718765

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

PubMed

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

2011-03-01

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

Wada testing reveals frontal lateralization for the memorization of words and faces.

PubMed

Kelley, W M; Ojemann, J G; Wetzel, R D; Derdeyn, C P; Moran, C J; Cross, D T; Dowling, J L; Miller, J W; Petersen, S E

2002-01-01

Neuroimaging studies have suggested that specific regions of the frontal and medial temporal cortex are engaged during memory formation. Further, there is specialization across these regions such that verbal materials appear to preferentially engage the left regions while nonverbal materials primarily engage the right regions. An open question, however, has been to what extent frontal regions contribute to successful memory formation. The present study investigates this question using a reversible lesion technique known as the Wada test. Patients memorized words and unfamiliar faces while portions of their left and right hemispheres were temporarily anesthetized with sodium amytal. Subsequent memory tests revealed that faces were remembered better than words following left-hemisphere anesthesia, whereas words were remembered better than faces following right-hemisphere anesthesia. Importantly, inspection of the circulation affected by the amytal further suggests that these memory impairments did not result from direct anesthetization of the medial temporal regions. Taken in the context of the imaging findings, these results suggest that frontal regions may also contribute to memory formation in normal performance.

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

PubMed Central

Hales, J. B.

2011-01-01

The process of associating items encountered over time and across variable time delays is fundamental for creating memories in daily life, such as for stories and episodes. Forming associative memory for temporally discontiguous items involves medial temporal lobe structures and additional neocortical processing regions, including prefrontal cortex, parietal lobe, and lateral occipital regions. However, most prior memory studies, using concurrently presented stimuli, have failed to examine the temporal aspect of successful associative memory formation to identify when activity in these brain regions is predictive of associative memory formation. In the current study, functional MRI data were acquired while subjects were shown pairs of sequentially presented visual images with a fixed interitem delay within pairs. This design allowed the entire time course of the trial to be analyzed, starting from onset of the first item, across the 5.5-s delay period, and through offset of the second item. Subjects then completed a postscan recognition test for the items and associations they encoded during the scan and their confidence for each. After controlling for item-memory strength, we isolated brain regions selectively involved in associative encoding. Consistent with prior findings, increased regional activity predicting subsequent associative memory success was found in anterior medial temporal lobe regions of left perirhinal and entorhinal cortices and in left prefrontal cortex and lateral occipital regions. The temporal separation within each pair, however, allowed extension of these findings by isolating the timing of regional involvement, showing that increased response in these regions occurs during binding but not during maintenance. PMID:21248058

Examining object recognition and object-in-Place memory in plateau zokors, Eospalax baileyi.

PubMed

Hegab, Ibrahim M; Tan, Yuchen; Wang, Chan; Yao, Baohui; Wang, Haifang; Ji, Weihong; Su, Junhu

2018-01-01

Recognition memory is important for the survival and fitness of subterranean rodents due to the barren underground conditions that require avoiding the burden of higher energy costs or possible conflict with conspecifics. Our study aims to examine the object and object/place recognition memories in plateau zokors (Eospalax baileyi) and test whether their underground life exerts sex-specific differences in memory functions using Novel Object Recognition (NOR) and Object-in-Place (OiP) paradigms. Animals were tested in the NOR with short (10min) and long-term (24h) inter-trial intervals (ITI) and in the OiP for a 30-min ITI between the familiarization and testing sessions. Plateau zokors showed a strong preference for novel objects manifested by a longer exploration time for the novel object after 10min ITI but failed to remember the familiar object when tested after 24h, suggesting a lack of long-term memory. In the OiP test, zokors effectively formed an association between the objects and the place where they were formerly encountered, resulting in a higher duration of exploration to the switched objects. However, both sexes showed equivalent results in exploration time during the NOR and OiP tests, which eliminates the possibility of discovering sex-specific variations in memory performance. Taken together, our study illustrates robust novelty preference and an effective short-term recognition memory without marked sex-specific differences, which might elucidate the dynamics of recognition memory formation and retrieval in plateau zokors. Copyright © 2017 Elsevier B.V. All rights reserved.

Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction.

PubMed

Markram, Kamila; Lopez Fernandez, Miguel Angel; Abrous, Djoher Nora; Sandi, Carmen

2007-05-01

There is much interest to understand the mechanisms leading to the establishment, maintenance, and extinction of fear memories. The amygdala has been critically involved in the processing of fear memories and a number of molecular changes have been implicated in this brain region in relation to fear learning. Although neural cell adhesion molecules (NCAMs) have been hypothesized to play a role, information available about their contribution to fear memories is scarce. We investigate here whether polysialylated NCAM (PSA-NCAM) contributes to auditory fear conditioning in the amygdala. First, PSA-NCAM expression was evaluated in different amygdala nuclei after auditory fear conditioning at two different shock intensities. Results showed that PSA-NCAM expression was increased 24 h post-training only in animals subjected to the highest shock intensity (1mA). Second, PSA-NCAM was cleaved in the basolateral amygdaloid complex through micro-infusions of the enzyme endoneuraminidase N, and the consequences of such treatment were investigated on the acquisition, consolidation, remote memory expression, and extinction of conditioned fear memories. Intra-amygdaloid cleavage of PSA-NCAM did not affect acquisition, consolidation or expression of remote fear memories. However, intra-amygdaloid PSA-NCAM cleavage enhanced fear extinction processes. These results suggest that upregulation of PSA-NCAM is a correlate of fear conditioning that is not necessary for the establishment of fear memory in the amygdala, but participates in mechanisms precluding fear extinction. These findings point out PSA-NCAM as a potential target for the treatment of psychopathologies that involve impairment in fear extinction.

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

PubMed

Orban de Xivry, Jean-Jacques; Lefèvre, Philippe

2015-04-01

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

Characteristics of Reduced Graphene Oxide Quantum Dots for a Flexible Memory Thin Film Transistor.

PubMed

Kim, Yo-Han; Lee, Eun Yeol; Lee, Hyun Ho; Seo, Tae Seok

2017-05-17

Reduced graphene oxide quantum dot (rGOQD) devices in formats of capacitor and thin film transistor (TFT) were demonstrated and examined as the first trial to achieve nonambipolar channel property. In addition, through a gold nanoparticle (Au NP) layer embedded between the rGOQD active channel and dielectric layer, memory capacitor and TFT performances were realized by capacitance-voltage (C-V) hysteresis and gate program, erase, and reprogram biases. First, capacitor structure of the rGOQD memory device was constructed to examine memory charging effect featured in hysteretic C-V behavior with a 30 nm dielectric layer of cross-linked poly(vinyl alcohol). For the intervening Au NP charging layer, self-assembled monolayer (SAM) formation of the Au NP was executed to utilize electrostatic interaction by a dip-coating process under ambient environments with a conformal fabrication uniformity. Second, the rGOQD memory TFT device was also constructed in the same format of the Au NPs SAMs on a flexible substrate. Characteristics of the rGOQD TFT output showed novel saturation curves unlike typical graphene-based TFTs. However, The rGOQD TFT device reveals relatively low on/off ratio of 10 1 and mobility of 5.005 cm 2 /V·s. For the memory capacitor, the flat-band voltage shift (ΔV FB ) was measured as 3.74 V for ±10 V sweep, and for the memory TFT, the threshold voltage shift (ΔV th ) by the Au NP charging was detected as 7.84 V. In summary, it was concluded that the rGOQD memory device could accomplish an ideal graphene-based memory performance, which could have provided a wide memory window and saturated output characteristics.

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

PubMed Central

Lefèvre, Philippe

2015-01-01

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

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

ERIC Educational Resources Information Center

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

2011-01-01

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

Muscarinic Acetylcholine Receptors Act in Synergy to Facilitate Learning and Memory

ERIC Educational Resources Information Center

Leaderbrand, Katherine; Chen, Helen J.; Corcoran, Kevin A.; Guedea, Anita L.; Jovasevic, Vladimir; Wess, Jurgen; Radulovic, Jelena

2016-01-01

Understanding how episodic memories are formed and retrieved is necessary if we are to treat disorders in which they malfunction. Muscarinic acetylcholine receptors (mAChR) in the hippocampus and cortex underlie memory formation, but there is conflicting evidence regarding their role in memory retrieval. Additionally, there is no consensus on…

Williams Syndrome and Memory: A Neuroanatomic and Cognitive Approach

ERIC Educational Resources Information Center

Sampaio, Adriana; Sousa, Nuno; Fernandez, Montse; Vasconcelos, Cristiana; Shenton, Martha E.; Goncalves, Oscar F.

2010-01-01

Williams Syndrome (WS) is described as displaying a dissociation within memory systems. As the integrity of hippocampal formation (HF) is determinant for memory performance, we examined HF volumes and its association with memory measures in a group of WS and in a typically development group. A significantly reduced intracranial content was found…

Adults' memories of childhood: true and false reports.

PubMed

Qin, Jianjian; Ogle, Christin M; Goodman, Gail S

2008-12-01

In 3 experiments, the authors examined factors that, according to the source-monitoring framework, might influence false memory formation and true/false memory discernment. In Experiment 1, combined effects of warning and visualization on false childhood memory formation were examined, as were individual differences in true and false childhood memories. Combining warnings and visualization led to the lowest false memory and highest true memory. Several individual difference factors (e.g., parental fearful attachment style) predicted false recall. In addition, true and false childhood memories differed (e.g., in amount of information). Experiment 2 examined relations between Deese/Roediger-McDermott task performance and false childhood memories. Deese/Roediger-McDermott performance (e.g., intrusion of unrelated words in free recall) was associated with false childhood memory, suggesting liberal response criteria in source decisions as a common underlying mechanism. Experiment 3 investigated adults' abilities to discern true and false childhood memory reports (e.g., by detecting differences in amount of information as identified in Experiment 1). Adults who were particularly successful in discerning such reports indicated reliance on event plausibility. Overall, the source-monitoring framework provided a viable explanatory framework. Implications for theory and clinical and forensic interviews are discussed. PsycINFO Database Record (c) 2008 APA, all rights reserved.

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

PubMed

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

2010-03-01

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

Theta Phase Synchronization Is the Glue that Binds Human Associative Memory.

PubMed

Clouter, Andrew; Shapiro, Kimron L; Hanslmayr, Simon

2017-10-23

Episodic memories are information-rich, often multisensory events that rely on binding different elements [1]. The elements that will constitute a memory episode are processed in specialized but distinct brain modules. The binding of these elements is most likely mediated by fast-acting long-term potentiation (LTP), which relies on the precise timing of neural activity [2]. Theta oscillations in the hippocampus orchestrate such timing as demonstrated by animal studies in vitro [3, 4] and in vivo [5, 6], suggesting a causal role of theta activity for the formation of complex memory episodes, but direct evidence from humans is missing. Here, we show that human episodic memory formation depends on phase synchrony between different sensory cortices at the theta frequency. By modulating the luminance of visual stimuli and the amplitude of auditory stimuli, we directly manipulated the degree of phase synchrony between visual and auditory cortices. Memory for sound-movie associations was significantly better when the stimuli were presented in phase compared to out of phase. This effect was specific to theta (4 Hz) and did not occur in slower (1.7 Hz) or faster (10.5 Hz) frequencies. These findings provide the first direct evidence that episodic memory formation in humans relies on a theta-specific synchronization mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Long-term memory, neurogenesis and novelty signal].

PubMed

Sokolova, E N; Nezlina, N I

2003-01-01

In accordance with the advanced hypothesis the long-term memory is a collection of "gnostic units" selectively tuned to experienced events. The long-term memory is continuously supplemented by new neurons differentiated from stem cells during neurogenesis (particularly, in adults). The transformation of neuronal progenitors into event-selective gnostic units is accomplished with participation of hippocampal "novelty neurons" emphasizing information inputs to be stored in the long-term memory. The formation of the gnostic units is preceded by informational processes occurring in the ventral ("what?") and dorsal ("where?") systems. The formation of a new gnostic unit selectively tuned to a particular event is a result of combination of feature-detector excitation and novelty signal generated by hippocampal novelty neurons.

EBLAST: an efficient high-compression image transformation 3. application to Internet image and video transmission

NASA Astrophysics Data System (ADS)

Schmalz, Mark S.; Ritter, Gerhard X.; Caimi, Frank M.

2001-12-01

A wide variety of digital image compression transforms developed for still imaging and broadcast video transmission are unsuitable for Internet video applications due to insufficient compression ratio, poor reconstruction fidelity, or excessive computational requirements. Examples include hierarchical transforms that require all, or large portion of, a source image to reside in memory at one time, transforms that induce significant locking effect at operationally salient compression ratios, and algorithms that require large amounts of floating-point computation. The latter constraint holds especially for video compression by small mobile imaging devices for transmission to, and compression on, platforms such as palmtop computers or personal digital assistants (PDAs). As Internet video requirements for frame rate and resolution increase to produce more detailed, less discontinuous motion sequences, a new class of compression transforms will be needed, especially for small memory models and displays such as those found on PDAs. In this, the third series of papers, we discuss the EBLAST compression transform and its application to Internet communication. Leading transforms for compression of Internet video and still imagery are reviewed and analyzed, including GIF, JPEG, AWIC (wavelet-based), wavelet packets, and SPIHT, whose performance is compared with EBLAST. Performance analysis criteria include time and space complexity and quality of the decompressed image. The latter is determined by rate-distortion data obtained from a database of realistic test images. Discussion also includes issues such as robustness of the compressed format to channel noise. EBLAST has been shown to perform superiorly to JPEG and, unlike current wavelet compression transforms, supports fast implementation on embedded processors with small memory models.

Cognitive and neuropsychological underpinnings of relational and conjunctive working memory binding across age.

PubMed

van Geldorp, Bonnie; Parra, Mario A; Kessels, Roy P C

2015-01-01

The ability to form associations (i.e., binding) is critical for memory formation. Recent studies suggest that aging specifically affects relational binding (associating separate features) but not conjunctive binding (integrating features within an object). Possibly, this dissociation may be driven by the spatial nature of the studies so far. Alternatively, relational binding may simply require more attentional resources. We assessed relational and conjunctive binding in three age groups and we included an interfering task (i.e., an articulatory suppression task). Binding was examined in a working memory (WM) task using non-spatial features: shape and colour. Thirty-one young adults (mean age = 22.35), 30 middle-aged adults (mean age = 54.80) and 30 older adults (mean age = 70.27) performed the task. Results show an effect of type of binding and an effect of age but no interaction between type of binding and age. The interaction between type of binding and interference was significant. These results indicate that aging affects relational binding and conjunctive binding similarly. However, relational binding is more susceptible to interference than conjunctive binding, which suggests that relational binding may require more attentional resources. We suggest that a general decline in WM resources associated with frontal dysfunction underlies age-related deficits in WM binding.

Technology for organization of the onboard system for processing and storage of ERS data for ultrasmall spacecraft

NASA Astrophysics Data System (ADS)

Strotov, Valery V.; Taganov, Alexander I.; Konkin, Yuriy V.; Kolesenkov, Aleksandr N.

2017-10-01

Task of processing and analysis of obtained Earth remote sensing data on ultra-small spacecraft board is actual taking into consideration significant expenditures of energy for data transfer and low productivity of computers. Thereby, there is an issue of effective and reliable storage of the general information flow obtained from onboard systems of information collection, including Earth remote sensing data, into a specialized data base. The paper has considered peculiarities of database management system operation with the multilevel memory structure. For storage of data in data base the format has been developed that describes a data base physical structure which contains required parameters for information loading. Such structure allows reducing a memory size occupied by data base because it is not necessary to store values of keys separately. The paper has shown architecture of the relational database management system oriented into embedment into the onboard ultra-small spacecraft software. Data base for storage of different information, including Earth remote sensing data, can be developed by means of such database management system for its following processing. Suggested database management system architecture has low requirements to power of the computer systems and memory resources on the ultra-small spacecraft board. Data integrity is ensured under input and change of the structured information.

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

PubMed

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) mecamylamine plus scopolamine treatment did not impair long term memory formation; (6) in vitro treatment with carbachol activated mTOR and p70S6K and this effect was blocked by scopolamine and mecamylamine. Taken together our data reinforce the idea that distinct molecular mechanisms are at the basis of the two different forms of memory and are in accordance with data presented by other groups that there exist molecular mechanisms that underlie short term memory, others that underlie long term memories, but some mechanisms are involved in both. Copyright © 2013 Elsevier Inc. All rights reserved.

Coherent concepts are computed in the anterior temporal lobes.

PubMed

Lambon Ralph, Matthew A; Sage, Karen; Jones, Roy W; Mayberry, Emily J

2010-02-09

In his Philosophical Investigations, Wittgenstein famously noted that the formation of semantic representations requires more than a simple combination of verbal and nonverbal features to generate conceptually based similarities and differences. Classical and contemporary neuroscience has tended to focus upon how different neocortical regions contribute to conceptualization through the summation of modality-specific information. The additional yet critical step of computing coherent concepts has received little attention. Some computational models of semantic memory are able to generate such concepts by the addition of modality-invariant information coded in a multidimensional semantic space. By studying patients with semantic dementia, we demonstrate that this aspect of semantic memory becomes compromised following atrophy of the anterior temporal lobes and, as a result, the patients become increasingly influenced by superficial rather than conceptual similarities.

Spacecraft optical disk recorder memory buffer control

NASA Technical Reports Server (NTRS)

Hodson, Robert F.

1993-01-01

This paper discusses the research completed under the NASA-ASEE summer faculty fellowship program. The project involves development of an Application Specific Integrated Circuit (ASIC) to be used as a Memory Buffer Controller (MBC) in the Spacecraft Optical Disk System (SODR). The SODR system has demanding capacity and data rate specifications requiring specialized electronics to meet processing demands. The system is being designed to support Gigabit transfer rates with Terabit storage capability. The complete SODR system is designed to exceed the capability of all existing mass storage systems today. The ASIC development for SODR consist of developing a 144 pin CMOS device to perform format conversion and data buffering. The final simulations of the MBC were completed during this summer's NASA-ASEE fellowship along with design preparations for fabrication to be performed by an ASIC manufacturer.

Epigenetic regulation and chromatin remodeling in learning and memory.

PubMed

Kim, Somi; Kaang, Bong-Kiun

2017-01-13

Understanding the underlying mechanisms of memory formation and maintenance has been a major goal in the field of neuroscience. Memory formation and maintenance are tightly controlled complex processes. Among the various processes occurring at different levels, gene expression regulation is especially crucial for proper memory processing, as some genes need to be activated while some genes must be suppressed. Epigenetic regulation of the genome involves processes such as DNA methylation and histone post-translational modifications. These processes edit genomic properties or the interactions between the genome and histone cores. They then induce structural changes in the chromatin and lead to transcriptional changes of different genes. Recent studies have focused on the concept of chromatin remodeling, which consists of 3D structural changes in chromatin in relation to gene regulation, and is an important process in learning and memory. In this review, we will introduce three major epigenetic processes involved in memory regulation: DNA methylation, histone methylation and histone acetylation. We will also discuss general mechanisms of long-term memory storage and relate the epigenetic control of learning and memory to chromatin remodeling. Finally, we will discuss how epigenetic mechanisms can contribute to the pathologies of neurological disorders and cause memory-related symptoms.

Using visual lateralization to model learning and memory in zebrafish larvae

PubMed Central

Andersson, Madelene Åberg; Ek, Fredrik; Olsson, Roger

2015-01-01

Impaired learning and memory are common symptoms of neurodegenerative and neuropsychiatric diseases. Present, there are several behavioural test employed to assess cognitive functions in animal models, including the frequently used novel object recognition (NOR) test. However, although atypical functional brain lateralization has been associated with neuropsychiatric conditions, spanning from schizophrenia to autism, few animal models are available to study this phenomenon in learning and memory deficits. Here we present a visual lateralization NOR model (VLNOR) in zebrafish larvae as an assay that combines brain lateralization and NOR. In zebrafish larvae, learning and memory are generally assessed by habituation, sensitization, or conditioning paradigms, which are all representatives of nondeclarative memory. The VLNOR is the first model for zebrafish larvae that studies a memory similar to the declarative memory described for mammals. We demonstrate that VLNOR can be used to study memory formation, storage, and recall of novel objects, both short and long term, in 10-day-old zebrafish. Furthermore we show that the VLNOR model can be used to study chemical modulation of memory formation and maintenance using dizocilpine (MK-801), a frequently used non-competitive antagonist of the NMDA receptor, used to test putative antipsychotics in animal models. PMID:25727677

Inhibition of Different Histone Acetyltransferases (HATs) Uncovers Transcription-Dependent and -Independent Acetylation-Mediated Mechanisms in Memory Formation

ERIC Educational Resources Information Center

Merschbaecher, Katja; Hatko, Lucyna; Folz, Jennifer; Mueller, Uli

2016-01-01

Acetylation of histones changes the efficiency of the transcription processes and thus contributes to the formation of long-term memory (LTM). In our comparative study, we used two inhibitors to characterize the contribution of different histone acetyl transferases (HATs) to appetitive associative learning in the honeybee. For one we applied…

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

ERIC Educational Resources Information Center

Kim, Alice S. N.; Vallesi, Antonino; Picton, Terence W.; Tulving, Endel

2009-01-01

The present study focused on the processes underlying cognitive association formation by investigating subsequent memory effects. Event-related potentials were recorded as participants studied pairs of words, presented one word at a time, for later recall. The findings showed that a frontal-positive late wave (LW), which occurred 1-1.6 s after the…

The Ubiquitin-Specific Protease 14 (USP14) Is a Critical Regulator of Long-Term Memory Formation

ERIC Educational Resources Information Center

Jarome, Timothy J.; Kwapis, Janine L.; Hallengren, Jada J.; Wilson, Scott M.; Helmstetter, Fred J.

2014-01-01

Numerous studies have suggested a role for ubiquitin-proteasome-mediated protein degradation in learning-dependent synaptic plasticity; however, very little is known about how protein degradation is regulated at the level of the proteasome during memory formation. The ubiquitin-specific protease 14 (USP14) is a proteasomal deubiquitinating enzyme…

Neurons in the Primate Medial Basal Forebrain Signal Combined Information about Reward Uncertainty, Value, and Punishment Anticipation

PubMed Central

Leopold, David A.; Hikosaka, Okihide

2015-01-01

It has been suggested that the basal forebrain (BF) exerts strong influences on the formation of memory and behavior. However, what information is used for the memory-behavior formation is unclear. We found that a population of neurons in the medial BF (medial septum and diagonal band of Broca) of macaque monkeys encodes a unique combination of information: reward uncertainty, expected reward value, anticipation of punishment, and unexpected reward and punishment. The results were obtained while the monkeys were expecting (often with uncertainty) a rewarding or punishing outcome during a Pavlovian procedure, or unexpectedly received an outcome outside the procedure. In vivo anterograde tracing using manganese-enhanced MRI suggested that the major recipient of these signals is the intermediate hippocampal formation. Based on these findings, we hypothesize that the medial BF identifies various contexts and outcomes that are critical for memory processing in the hippocampal formation. PMID:25972172

Presentation format effects in a levels-of-processing task.

PubMed

Foos, Paul W; Goolkasian, Paula

2008-01-01

Three experiments were conducted to examine better performance in long-term memory when stimulus items are pictures or spoken words compared to printed words. Hypotheses regarding the allocation of attention to printed words, the semantic link between pictures and processing, and a rich long-term representation for pictures were tested. Using levels-of-processing tasks eliminated format effects when no memory test was expected and processing was deep (El), and when study and test formats did not match (E3). Pictures produced superior performance when a memory test was expected (El & 2) and when study and test formats were the same (E3). Results of all experiments support the attenuation of attention model and that picture superiority is due to a more direct access to semantic processing and a richer visual code. General principles to guide the processing of stimulus information are discussed.

The perirhinal cortex of the rat is necessary for spatial memory retention long after but not soon after learning.

PubMed

Ramos, Juan M J; Vaquero, Joaquín M M

2005-09-15

Many observations in humans and experimental animals support the view that the hippocampus is critical immediately after learning in order for long-term memory formation to take place. However, exactly when the medial temporal cortices adjacent to the hippocampus are necessary for this process to occur normally is not yet well known. Using a spatial task, we studied whether the perirhinal cortex of rats is necessary to establish representations in long-term memory. Results showed that, in a spatial task sensitive to hippocampal lesions, control and perirhinal lesioned rats can both learn at the same rate (Experiment 1). Interestingly, a differential involvement of the perirhinal cortex in memory retention was observed as time passes after learning. Thus, 24 days following the end of learning, lesioned and control rats remembered the task perfectly as measured by a retraining test. In contrast, 74 days after the learning the perirhinal animals showed a profound impairment in the retention of the spatial information (Experiment 2). Taken together, these results suggest that the perirhinal region is critical for the formation of long-term spatial memory. However, its contribution to memory formation and retention is time-dependent, it being necessary only long after learning takes place and not during the phase immediately following acquisition.

Prefrontal θ-Burst Stimulation Disrupts the Organizing Influence of Active Short-Term Retrieval on Episodic Memory.

PubMed

Marin, Bianca M; VanHaerents, Stephen A; Voss, Joel L; Bridge, Donna J

2018-01-01

Dorsolateral prefrontal cortex (DLPFC) is thought to organize items in working memory and this organizational role may also influence long-term memory. To causally test this hypothesized role of DLPFC in long-term memory formation, we used θ-burst noninvasive stimulation (TBS) to modulate DLPFC involvement in a memory task that assessed the influence of active short-term retrieval on later memory. Human subjects viewed three objects on a grid and then either actively retrieved or passively restudied one object's location after a brief delay. Long-term memory for the other objects was assessed after a delay to evaluate the beneficial role of active short-term retrieval on subsequent memory for the entire set of object locations. We found that DLPFC TBS had no significant effects on short-term memory. In contrast, DLPFC TBS impaired long-term memory selectively in the active-retrieval condition but not in the passive-restudy condition. These findings are consistent with the hypothesized contribution of DLPFC to the organizational processes operative during active short-term retrieval that influence long-term memory, although other regions that were not stimulated could provide similar contributions. Notably, active-retrieval and passive-restudy conditions were intermixed, and therefore nonspecific influences of stimulation were well controlled. These results suggest that DLPFC is causally involved in organizing event information during active retrieval to support coherent long-term memory formation.

Prefrontal θ-Burst Stimulation Disrupts the Organizing Influence of Active Short-Term Retrieval on Episodic Memory

PubMed Central

2018-01-01

Abstract Dorsolateral prefrontal cortex (DLPFC) is thought to organize items in working memory and this organizational role may also influence long-term memory. To causally test this hypothesized role of DLPFC in long-term memory formation, we used θ-burst noninvasive stimulation (TBS) to modulate DLPFC involvement in a memory task that assessed the influence of active short-term retrieval on later memory. Human subjects viewed three objects on a grid and then either actively retrieved or passively restudied one object’s location after a brief delay. Long-term memory for the other objects was assessed after a delay to evaluate the beneficial role of active short-term retrieval on subsequent memory for the entire set of object locations. We found that DLPFC TBS had no significant effects on short-term memory. In contrast, DLPFC TBS impaired long-term memory selectively in the active-retrieval condition but not in the passive-restudy condition. These findings are consistent with the hypothesized contribution of DLPFC to the organizational processes operative during active short-term retrieval that influence long-term memory, although other regions that were not stimulated could provide similar contributions. Notably, active-retrieval and passive-restudy conditions were intermixed, and therefore nonspecific influences of stimulation were well controlled. These results suggest that DLPFC is causally involved in organizing event information during active retrieval to support coherent long-term memory formation. PMID:29445769

De Novo mRNA Synthesis Is Required for Both Consolidation and Reconsolidation of Fear Memories in the Amygdala

ERIC Educational Resources Information Center

Duvarci, Sevil; Nader, Karim; LeDoux, Joseph E.

2008-01-01

Memory consolidation is the process by which newly learned information is stabilized into long-term memory (LTM). Considerable evidence indicates that retrieval of a consolidated memory returns it to a labile state that requires it to be restabilized. Consolidation of new fear memories has been shown to require de novo RNA and protein synthesis in…

The effect of Twitter exposure on false memory formation.

PubMed

Fenn, Kimberly M; Griffin, Nicholas R; Uitvlugt, Mitchell G; Ravizza, Susan M

2014-12-01

Social media sites such as Facebook and Twitter have increased drastically in popularity. However, information on these sites is not verified and may contain inaccuracies. It is well-established that false information encountered after an event can lead to memory distortion. Therefore, social media may be particularly harmful for autobiographical memory. Here, we tested the effect of Twitter on false memory. We presented participants with a series of images that depicted a story and then presented false information about the images in a scrolling feed that bore either a low or high resemblance to a Twitter feed. Confidence for correct information was similar across the groups, but confidence for suggested information was significantly lower when false information was presented in a Twitter format. We propose that individuals take into account the medium of the message when integrating information into memory.

Azurin/CdSe-ZnS-Based Bio-Nano Hybrid Structure for Nanoscale Resistive Memory Device.

PubMed

Yagati, Ajay Kumar; Lee, Taek; Choi, Jeong-Woo

2017-07-15

In the present study, we propose a method for bio-nano hybrid formation by coupling a redox metalloprotein, Azurin, with CdSe-ZnS quantum dot for the development of a nanoscale resistive memory device. The covalent interaction between the two nanomaterials enables a strong and effective binding to form an azurin/CdSe-ZnS hybrid, and also enabled better controllability to couple with electrodes to examine the memory function properties. Morphological and optical properties were performed to confirm both hybrid formations and also their individual components. Current-Voltage (I-V) measurements on the hybrid nanostructures exhibited bistable current levels towards the memory function device, that and those characteristics were unnoticeable on individual nanomaterials. The hybrids showed good retention characteristics with high stability and durability, which is a promising feature for future nanoscale memory devices.

Multifunctional shape-memory polymers.

PubMed

Behl, Marc; Razzaq, Muhammad Yasar; Lendlein, Andreas

2010-08-17

The thermally-induced shape-memory effect (SME) is the capability of a material to change its shape in a predefined way in response to heat. In shape-memory polymers (SMP) this shape change is the entropy-driven recovery of a mechanical deformation, which was obtained before by application of external stress and was temporarily fixed by formation of physical crosslinks. The high technological significance of SMP becomes apparent in many established products (e.g., packaging materials, assembling devices, textiles, and membranes) and the broad SMP development activities in the field of biomedical as well as aerospace applications (e.g., medical devices or morphing structures for aerospace vehicles). Inspired by the complex and diverse requirements of these applications fundamental research is aiming at multifunctional SMP, in which SME is combined with additional functions and is proceeding rapidly. In this review different concepts for the creation of multifunctionality are derived from the various polymer network architectures of thermally-induced SMP. Multimaterial systems, such as nanocomposites, are described as well as one-component polymer systems, in which independent functions are integrated. Future challenges will be to transfer the concept of multifunctionality to other emerging shape-memory technologies like light-sensitive SMP, reversible shape changing effects or triple-shape polymers.

Ultralow Power Consumption Flexible Biomemristors.

PubMed

Kim, Min-Kyu; Lee, Jang-Sik

2018-03-28

Low power consumption is the important requirement in memory devices for saving energy. In particular, improved energy efficiency is essential in implantable electronic devices for operation under a limited power supply. Here, we demonstrate the use of κ-carrageenan (κ-car) as the resistive switching layer to achieve memory that has low power consumption. A carboxymethyl (CM) group is introduced to the κ-car to increase its ionic conductivity. Ag was doped in CM:κ-car to improve the resistive switching properties of the devices. Memory devices based on Ag-doped CM:κ-car showed electroforming-free resistive switching. This device exhibited low reset voltage (∼0.05 V), fast switching speed (50 ns), and high on/off ratio (>10 3 ) under low compliance current (10 -5 A). Its power consumption (∼0.35 μW) is much lower than those of the previously reported biomemristors. The resistive switching may be a result of an electrochemical redox process and Ag filament formation in the CM:κ-car under an electric field. This biopolymer memory can also be fabricated on flexible substrate. This study verifies the feasibility of using biopolymers for applications to future implantable and biocompatible nanoelectronics.

Putting the Pieces Together: The Role of Dorsolateral Prefrontal Cortex in Relational Memory Encoding

ERIC Educational Resources Information Center

Blumenfeld, Robert S.; Parks, Colleen M.; Yonelinas, Andrew P.; Ranganath, Charan

2011-01-01

Results from fMRI have strongly supported the idea that the ventrolateral PFC (VLPFC) contributes to successful memory formation, but the role the dorsolateral PFC (DLPFC) in memory encoding is more controversial. Some findings suggest that the DLPFC is recruited when one is processing relationships between items in working memory, and this…

Histone Deacetylase Inhibition Facilitates Massed Pattern-Induced Synaptic Plasticity and Memory

ERIC Educational Resources Information Center

Pandey, Kiran; Sharma, Kaushik P.; Sharma, Shiv K.

2015-01-01

Massed training is less effective for long-term memory formation than the spaced training. The role of acetylation in synaptic plasticity and memory is now well established. However, the role of this important protein modification in synaptic plasticity induced by massed pattern of stimulation or memory induced by massed training is not well…

Working Memory and Learning: A Practical Guide for Teachers

ERIC Educational Resources Information Center

Gathercole, Susan E.; Alloway, Tracy Packiam

2008-01-01

A good working memory is crucial to becoming a successful leaner, yet there is very little material available in an easy-to-use format that explains the concept and offers practitioners ways to support children with poor working memory in the classroom. This book provides a coherent overview of the role played by working memory in learning during…

Dorsal Hippocampal CREB Is Both Necessary and Sufficient for Spatial Memory

ERIC Educational Resources Information Center

Sekeres, Melanie J.; Neve, Rachael L.; Frankland, Paul W.; Josselyn, Sheena A.

2010-01-01

Although the transcription factor CREB has been widely implicated in memory, whether it is sufficient to produce spatial memory under conditions that do not normally support memory formation in mammals is unknown. We found that locally and acutely increasing CREB levels in the dorsal hippocampus using viral vectors is sufficient to induce robust…

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

PubMed

Meneses, Alfredo

2002-05-01

Recent studies using invertebrate and mammal species have revealed that, endogenous serotonin (5-hydroxytryptamine, 5-HT) modulates cognitive processes, particularly learning and memory, though, at present, it is unclear the manner, where, and how long 5-HT systems are involved. Hence in this work, an attempt was made to study the effects of 5-HT endogenous on memory formation, using a 5-HT uptake facilitator (tianeptine) and, selective 5-HT(1-7) receptor antagonists to determine whether 5-HT uptake sites and which 5-HT receptors are involved, respectively. Results showed that post-training tianeptine injection enhanced memory consolidation in an autoshaping Pavlovian/instrumental learning task, which has been useful to detect changes on memory formation elicited by drugs or aging. On interaction experiments, ketanserin (5-HT(1D/2A/2C) antagonist) slightly enhanced tianeptine effects, while WAY 100635 (5-HT(1A) antagonist), SB-224289 (5-HT(1B) inverse agonist), SB-200646 (5-HT(2B/2C) antagonist), ondansetron (5-HT(3) antagonist), GR 127487 (5-HT(4) antagonist), Ro 04-6790 (5-HT(6) antagonist), DR 4004 (5-HT(7) antagonist), or fluoxetine (an inhibitor of 5-HT reuptake) blocked the facilitatory tianeptine effect. Notably, together tianeptine and Ro 04-6790 impaired learning consolidation. Moreover, 5-HT depletion completely reversed the tianeptine effect. Tianeptine also normalized an impaired memory elicited by scopolamine (an antimuscarinic) or dizocilpine (non-competitive glutamatergic antagonist), while partially reversed that induced by TFMPP (5-HT(1B/1D/2A-2C/7) agonist/antagonist). Finally, tianeptine-fluoxetine coadministration had no effect on learning consolidation; nevertheless, administration of an acetylcholinesterase inhibitor, phenserine, potentiated subeffective tianeptine or fluoxetine doses. Collectively, these data confirmed that endogenously 5-HT modulates, via uptake sites and 5-HT(1-7) receptors, memory consolidation, and are consistent with the emerging notion that 5-HT plays a key role on memory formation.

Technical support for digital systems technology development. Task order 1: ISP contention analysis and control

NASA Technical Reports Server (NTRS)

Stehle, Roy H.; Ogier, Richard G.

1993-01-01

Alternatives for realizing a packet-based network switch for use on a frequency division multiple access/time division multiplexed (FDMA/TDM) geostationary communication satellite were investigated. Each of the eight downlink beams supports eight directed dwells. The design needed to accommodate multicast packets with very low probability of loss due to contention. Three switch architectures were designed and analyzed. An output-queued, shared bus system yielded a functionally simple system, utilizing a first-in, first-out (FIFO) memory per downlink dwell, but at the expense of a large total memory requirement. A shared memory architecture offered the most efficiency in memory requirements, requiring about half the memory of the shared bus design. The processing requirement for the shared-memory system adds system complexity that may offset the benefits of the smaller memory. An alternative design using a shared memory buffer per downlink beam decreases circuit complexity through a distributed design, and requires at most 1000 packets of memory more than the completely shared memory design. Modifications to the basic packet switch designs were proposed to accommodate circuit-switched traffic, which must be served on a periodic basis with minimal delay. Methods for dynamically controlling the downlink dwell lengths were developed and analyzed. These methods adapt quickly to changing traffic demands, and do not add significant complexity or cost to the satellite and ground station designs. Methods for reducing the memory requirement by not requiring the satellite to store full packets were also proposed and analyzed. In addition, optimal packet and dwell lengths were computed as functions of memory size for the three switch architectures.

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

PubMed

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

2007-11-01

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

Changes in spatial memory mediated by experimental variation in food supply do not affect hippocampal anatomy in mountain chickadees (Poecile gambeli).

PubMed

Pravosudov, V V; Lavenex, P; Clayton, N S

2002-05-01

Earlier reports suggested that seasonal variation in food-caching behavior (caching intensity and cache retrieval accuracy) might correlate with morphological changes in the hippocampal formation, a brain structure thought to play a role in remembering cache locations. We demonstrated that changes in cache retrieval accuracy can also be triggered by experimental variation in food supply: captive mountain chickadees (Poecile gambeli) maintained on limited and unpredictable food supply were more accurate at recovering their caches and performed better on spatial memory tests than birds maintained on ad libitum food. In this study, we investigated whether these two treatment groups also differed in the volume and neuron number of the hippocampal formation. If variation in memory for food caches correlates with hippocampal size, then our birds with enhanced cache recovery and spatial memory performance should have larger hippocampal volumes and total neuron numbers. Contrary to this prediction we found no significant differences in volume or total neuron number of the hippocampal formation between the two treatment groups. Our results therefore indicate that changes in food-caching behavior and spatial memory performance, as mediated by experimental variations in food supply, are not necessarily accompanied by morphological changes in volume or neuron number of the hippocampal formation in fully developed, experienced food-caching birds. Copyright 2002 Wiley Periodicals, Inc.

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

PubMed

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

2016-04-13

The persistently active protein kinase Mζ (PKMζ) has been found to be involved in the formation and maintenance of long-term memory. Most of the studies investigating PKMζ, however, have used either putatively unselective inhibitors or conventional knock-out animal models in which compensatory mechanisms may occur. Here, we overexpressed an active form of PKMζ in rat hippocampus, a structure highly involved in memory formation, and embedded in several neural networks. We investigated PKMζ's influence on synaptic plasticity using electrophysiological recordings of basal transmission, paired pulse facilitation, and LTP and combined this with behavioral cognitive experiments addressing formation and retention of both contextual memory during aversive conditioning and spatial memory during spontaneous exploration. We demonstrate that hippocampal slices overexpressing PKMζ show enhanced basal transmission, suggesting a potential role of PKMζ in postsynaptic AMPAR trafficking. Moreover, the PKMζ-overexpressing slices augmented LTP and this effect was not abolished by protein-synthesis blockers, indicating that PKMζ induces enhanced LTP formation in a protein-synthesis-independent manner. In addition, we found selectively enhanced long-term memory for contextual but not cued fear memory, underlining the theory of the hippocampus' involvement in the contextual aspect of aversive reinforced tasks. Memory for spatial orientation during spontaneous exploration remained unaltered, suggesting that PKMζ may not affect the neural circuits underlying spontaneous tasks that are different from aversive tasks. In this study, using an overexpression strategy as opposed to an inhibitor-based approach, we demonstrate an important modulatory role of PKMζ in synaptic plasticity and selective memory processing. Most of the literature investigating protein kinase Mζ (PKMζ) used inhibitors with selectivity that has been called into question or conventional knock-out animal models in which compensatory mechanisms may occur. To avoid these issues, some studies have been done using viral overexpression of PKMζ in different brain structures to show cognitive enhancement. However, electrophysiological experiments were exclusively done in knock-out models or inhibitory studies to show depletion of LTP. There was no study showing the effect of PKMζ overexpression in the hippocampus on behavior and LTP experiments. To our knowledge, this is the first study to combine these aspects with the result of enhanced memory for contextual fear memory and to show enhanced LTP in hippocampal slices overexpressing PKMζ. Copyright © 2016 Schuette et al.

Hippocampal Sleep Features: Relations to Human Memory Function

PubMed Central

Ferrara, Michele; Moroni, Fabio; De Gennaro, Luigi; Nobili, Lino

2012-01-01

The recent spread of intracranial electroencephalographic (EEG) recording techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific patterns of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, non-REM sleep) in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples) that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate sleep function. PMID:22529835

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

PubMed

Aberg, Kristoffer C; Müller, Julia; Schwartz, Sophie

2017-01-01

Anticipation and delivery of rewards improves memory formation, but little effort has been made to disentangle their respective contributions to memory enhancement. Moreover, it has been suggested that the effects of reward on memory are mediated by dopaminergic influences on hippocampal plasticity. Yet, evidence linking memory improvements to actual reward computations reflected in the activity of the dopaminergic system, i.e., prediction errors and expected values, is scarce and inconclusive. For example, different previous studies reported that the magnitude of prediction errors during a reinforcement learning task was a positive, negative, or non-significant predictor of successfully encoding simultaneously presented images. Individual sensitivities to reward and punishment have been found to influence the activation of the dopaminergic reward system and could therefore help explain these seemingly discrepant results. Here, we used a novel associative memory task combined with computational modeling and showed independent effects of reward-delivery and reward-anticipation on memory. Strikingly, the computational approach revealed positive influences from both reward delivery, as mediated by prediction error magnitude, and reward anticipation, as mediated by magnitude of expected value, even in the absence of behavioral effects when analyzed using standard methods, i.e., by collapsing memory performance across trials within conditions. We additionally measured trait estimates of reward and punishment sensitivity and found that individuals with increased reward (vs. punishment) sensitivity had better memory for associations encoded during positive (vs. negative) prediction errors when tested after 20 min, but a negative trend when tested after 24 h. In conclusion, modeling trial-by-trial fluctuations in the magnitude of reward, as we did here for prediction errors and expected value computations, provides a comprehensive and biologically plausible description of the dynamic interplay between reward, dopamine, and associative memory formation. Our results also underline the importance of considering individual traits when assessing reward-related influences on memory.

The Influence of Metacognitive Skills on Learners' Memory of Information in a Hypermedia Environment

ERIC Educational Resources Information Center

Schwartz, Neil H.; Andersen, Christopher; Hong, Namsoo; Howard, Bruce; McGee, Steven

2004-01-01

Twenty-eight students (aged 9 to 17) freely explored a science Web site structured either in an outline (linear) format or "puzzle" (non-linear) format for 2.5 hours. Subjects then engaged in tasks involving locational memory and informational recall. The results indicate that presence of metacognitive skills was a necessary but not sufficient…

Transcranial focal electrical stimulation via tripolar concentric ring electrodes does not modify the short- and long-term memory formation in rats evaluated in the novel object recognition test.

PubMed

Rogel-Salazar, G; Luna-Munguía, H; Stevens, K E; Besio, W G

2013-04-01

Noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCREs) has been under development as an alternative/complementary therapy for seizure control. Transcranial focal electrical stimulation has shown efficacy in attenuating penicillin-, pilocarpine-, and pentylenetetrazole-induced acute seizures in rat models. This study evaluated the effects of TFS via TCREs on the memory formation of healthy rats as a safety test of TFS. Short- and long-term memory formation was tested after the application of TFS using the novel object recognition (NOR) test. The following independent groups were used: naïve, control (without TFS), and TFS (treated). The naïve, control, and stimulated groups spent more time investigating the new object than the familiar one during the test phase. Transcranial focal electrical stimulation via TCREs given once does not modify the short- and long-term memory formation in rats in the NOR test. Results provide an important step towards a better understanding for the safe usage of TFS via TCREs. Copyright © 2013 Elsevier Inc. All rights reserved.

Green tea and cocoa enhance cognition in Lymnaea

PubMed Central

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

2018-01-01

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

CaM Kinases: From Memories to Addiction.

PubMed

Müller, Christian P; Quednow, Boris B; Lourdusamy, Anbarasu; Kornhuber, Johannes; Schumann, Gunter; Giese, K Peter

2016-02-01

Drug addiction is a major psychiatric disorder with a neurobiological basis that is still insufficiently understood. Initially, non-addicted, controlled drug consumption and drug instrumentalization are established. They comprise highly systematic behaviours acquired by learning and the establishment of drug memories. Ca(2+)/calmodulin-dependent protein kinases (CaMKs) are important Ca(2+) sensors translating glutamatergic activation into synaptic plasticity during learning and memory formation. Here we review the role of CaMKs in the establishment of drug-related behaviours in animal models and in humans. Converging evidence now shows that CaMKs are a crucial mechanism of how addictive drugs induce synaptic plasticity and establish various types of drug memories. Thereby, CaMKs are not only molecular relays for glutamatergic activity but they also directly control dopaminergic and serotonergic activity in the mesolimbic reward system. They can now be considered as major molecular pathways translating normal memory formation into establishment of drug memories and possibly transition to drug addiction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inhibiting DNA methylation alters olfactory extinction but not acquisition learning in Apis cerana and Apis mellifera.

PubMed

Gong, Zhiwen; Wang, Chao; Nieh, James C; Tan, Ken

2016-07-01

DNA methylation plays a key role in invertebrate acquisition and extinction memory. Honey bees have excellent olfactory learning, but the role of DNA methylation in memory formation has, to date, only been studied in Apis mellifera. We inhibited DNA methylation by inhibiting DNA methyltransferase (DNMT) with zebularine (zeb) and studied the resulting effects upon olfactory acquisition and extinction memory in two honey bee species, Apis cerana and A. mellifera. We used the proboscis extension reflex (PER) assay to measure memory. We provide the first demonstration that DNA methylation is also important in the olfactory extinction learning of A. cerana. DNMT did not reduce acquisition learning in either species. However, zeb bidirectionally and differentially altered extinction learning in both species. In particular, zeb provided 1h before acquisition learning improved extinction memory retention in A. mellifera, but reduced extinction memory retention in A. cerana. The reasons for these differences are unclear, but provide a basis for future studies to explore species-specific differences in the effects of methylation on memory formation. Copyright © 2016 Elsevier Ltd. All rights reserved.