scholarly journals Offline knowledge assimilations ensue online obscurity to inspire implicit learning

2021 ◽  
Author(s):  
Mohamed H. Aly ◽  
Kareem Abdou ◽  
Reiko Okubo-Suzuki ◽  
Masanori Nomoto ◽  
Kaoru Inokuchi
Keyword(s):  
Prior Knowledge ◽  
Implicit Learning ◽  
Cognitive Processing ◽  
Memory Consolidation ◽  
Contextual Fear Conditioning ◽  
Anterior Cingulate ◽  
Neural Dynamics ◽  
Contextual Fear ◽  
Neural Underpinnings ◽  
Selective Integration

AbstractPassive priming of prior knowledge to assimilate ongoing experiences underlies advanced cognitive processing. However, the necessary neural dynamics of memory assimilation remains elusive. Uninstructed brain could also show boosted creativity, particularly after idling states, yet it remains unclear whether the idling brain can spontaneously spark relevant knowledge assimilations. We established a paradigm that links/separates context-dependent memories according to geometrical similarities. Mice exploring one of four contexts one day before undergoing contextual fear conditioning in a square context showed a gradual fear transfer to pre-exposed geometrically relevant contexts next day, but not after 15 min. Anterior cingulate cortex neurons representing relevant, rather than distinct, memories were significantly co-reactivated during post-conditioning sleep only, before their selective integration next day during testing. Disrupting sleep co-reactivations prevented assimilation while preserving recent memory consolidation. Thus, assimilating pertinent memories during sleep through co-reactivation of their respective engrams represents the neural underpinnings of sleep-triggered implicit cortical learning.

scholarly journals Hippocampus-retrosplenial cortex interaction is increased during phasic REM and contributes to memory consolidation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel Gomes de Almeida-Filho ◽  
Bruna Del Vechio Koike ◽  
Francesca Billwiller ◽  
Kelly Soares Farias ◽  
Igor Rafael Praxedes de Sales ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Memory Consolidation ◽  
Retrosplenial Cortex ◽  
Contextual Fear Conditioning ◽  
Oscillatory Activity ◽  
Theta Oscillation ◽  
Contextual Fear ◽  
Before And After ◽  
Freely Behaving ◽  
Phasic Rem Sleep

AbstractHippocampal (HPC) theta oscillation during post-training rapid eye movement (REM) sleep supports spatial learning. Theta also modulates neuronal and oscillatory activity in the retrosplenial cortex (RSC) during REM sleep. To investigate the relevance of theta-driven interaction between these two regions to memory consolidation, we computed the Granger causality within theta range on electrophysiological data recorded in freely behaving rats during REM sleep, both before and after contextual fear conditioning. We found a training-induced modulation of causality between HPC and RSC that was correlated with memory retrieval 24 h later. Retrieval was proportional to the change in the relative influence RSC exerted upon HPC theta oscillation. Importantly, causality peaked during theta acceleration, in synchrony with phasic REM sleep. Altogether, these results support a role for phasic REM sleep in hippocampo-cortical memory consolidation and suggest that causality modulation between RSC and HPC during REM sleep plays a functional role in that phenomenon.

scholarly journals Parvalbumin-positive interneurons mediate neocortical-hippocampal interactions that are necessary for memory consolidation

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Frances Xia ◽  
Blake A Richards ◽  
Matthew M Tran ◽  
Sheena A Josselyn ◽  
Kaori Takehara-Nishiuchi ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Fear Conditioning ◽  
Medial Prefrontal Cortex ◽  
Memory Consolidation ◽  
Fear Memory ◽  
Contextual Fear Conditioning ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Spiking Activity

Following learning, increased coupling between spindle oscillations in the medial prefrontal cortex (mPFC) and ripple oscillations in the hippocampus is thought to underlie memory consolidation. However, whether learning-induced increases in ripple-spindle coupling are necessary for successful memory consolidation has not been tested directly. In order to decouple ripple-spindle oscillations, here we chemogenetically inhibited parvalbumin-positive (PV+) interneurons, since their activity is important for regulating the timing of spiking activity during oscillations. We found that contextual fear conditioning increased ripple-spindle coupling in mice. However, inhibition of PV+ cells in either CA1 or mPFC eliminated this learning-induced increase in ripple-spindle coupling without affecting ripple or spindle incidence. Consistent with the hypothesized importance of ripple-spindle coupling in memory consolidation, post-training inhibition of PV+ cells disrupted contextual fear memory consolidation. These results indicate that successful memory consolidation requires coherent hippocampal-neocortical communication mediated by PV+ cells.

scholarly journals Enhanced memory consolidation in mice lacking the circadian modulators Sharp1 and -2 caused by elevated Igf2 signaling in the cortex

2015 ◽  
Vol 112 (27) ◽  
pp. E3582-E3589 ◽  
Author(s):  
Ali Shahmoradi ◽  
Konstantin Radyushkin ◽  
Moritz J. Rossner
Keyword(s):  
Transcription Factors ◽  
Cognitive Processing ◽  
Memory Consolidation ◽  
Molecular Mechanisms ◽  
Negative Impact ◽  
Fear Memory ◽  
Memory Formation ◽  
Anterior Cingulate ◽  
Bhlh Transcription Factors ◽  
Null Mutants

The bHLH transcription factors SHARP1 and SHARP2 are partially redundant modulators of the circadian system. SHARP1/DEC2 has been shown to control sleep length in humans and sleep architecture is also altered in double mutant mice (S1/2−/−). Because of the importance of sleep for memory consolidation, we investigated the role of SHARP1 and SHARP2 in cognitive processing. S1/2−/− mice show enhanced cortex (Cx)-dependent remote fear memory formation as well as improved reversal learning, but do not display alterations in hippocampus (Hi)-dependent recent fear memory formation. SHARP1 and SHARP2 single null mutants do not display any cognitive phenotype supporting functional redundancy of both factors. Molecular and biochemical analyses revealed elevated insulin-related growth factor 2 (IGF2) signaling and increased phosphorylation of MAPK and S6 in the Cx but not the Hi of S1/2−/− mice. No changes were detected in single mutants. Moreover, adeno-associated virus type 2-mediated IGF2 overexpression in the anterior cingulate cortex enhanced remote fear memory formation and the analysis of forebrain-specific double null mutants of the Insulin and IGF1 receptors revealed their essential function for memory formation. Impaired fear memory formation in aged S1/2−/− mice indicates that elevated IGF2 signaling in the long term, however, has a negative impact on cognitive processing. In summary, we conclude that the bHLH transcription factors SHARP1 and SHARP2 are involved in cognitive processing by controlling Igf2 expression and associated signaling cascades. Our analyses provide evidence that the control of sleep and memory consolidation may share common molecular mechanisms.

Synaptic Correlates of Anterograde Amnesia and Intact Retrograde Memory in a Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 17 (3) ◽  
pp. 259-268 ◽  
Author(s):  
Emanuela Rizzello ◽  
Silvia Middei ◽  
Cristina Marchetti
Keyword(s):  
Alzheimer’S Disease ◽  
Patch Clamp ◽  
Mouse Model ◽  
Fear Conditioning ◽  
Contextual Fear Conditioning ◽  
Anterior Cingulate ◽  
Wild Type ◽  
Synaptic Currents ◽  
Contextual Fear ◽  
Tg2576 Mice

Background: Clinical evidence indicates that patients affected by Alzheimer's Disease (AD) fail to form new memories although their memories for old events are intact. This amnesic pattern depends on the selective vulnerability to AD-neurodegeneration of the hippocampus, the brain region that sustains the formation of new memories, while cortical regions that store remote memories are spared. Objective: To identify the cellular mechanisms underlying impaired recent memories and intact remote memories in a mouse model of AD. Method: Glutamatergic synaptic currents were recorded by patch-clamp in acute hippocampal and anterior Cingulate Cortical (aCC) slices of AD-like Tg2576 mice and Wild-type (Wt) littermates subjected to the Contextual Fear Conditioning (CFC) task or in naïve conditions. Results: Glutamatergic synaptic currents were recorded by patch-clamp in acute hippocampal and anterior Cingulate Cortical (aCC) slices of AD-like Tg2576 mice and Wild-type (Wt) littermates subjected to the Contextual Fear Conditioning (CFC) task or in naïve conditions. Conclusion: Our data suggest that in the early AD stages synaptic plasticity of CA1 synapses, crucial to form new memories, is lost, while plasticity of aCC synapses is intact and contributes to the persistence of long-term memories.

scholarly journals Distributed learning episodes create a context fear memory outside the hippocampus that depends on perirhinal and anterior cingulate cortices

2021 ◽  
Vol 28 (11) ◽  
pp. 405-413
Author(s):  
Elizabeth H. Shepherd ◽  
Neil M. Fournier ◽  
Robert J. Sutherland ◽  
Hugo Lehmann
Keyword(s):  
Retrograde Amnesia ◽  
Memory Retrieval ◽  
Distributed Learning ◽  
Perirhinal Cortex ◽  
Contextual Fear Conditioning ◽  
Anterior Cingulate ◽  
Contextual Fear ◽  
Combined Lesions ◽  
Cortical Regions ◽  
Context Memory

Damage to the hippocampus (HPC) typically causes retrograde amnesia for contextual fear conditioning. Repeating the conditioning over several sessions, however, can eliminate the retrograde amnesic effects. This form of reinstatement thus permits modifications to networks that can support context memory retrieval in the absence of the HPC. The present study aims to identify cortical regions that support the nonHPC context memory. Specifically, the contribution of the perirhinal cortex (PRH) and the anterior cingulate cortex (ACC) were examined because of their established importance to context memory. The findings show that context memories established through distributed reinstatement survive damage limited only to the HPC, PRH, or ACC. Combined lesions of the HPC and PRH, as well as the HPC and ACC, caused retrograde amnesia, suggesting that network modifications in the PRH and ACC enable context fear memories to become resistant to HPC damage.

scholarly journals 028 Sleep loss disrupts hippocampal memory consolidation via an acetylcholine- and somatostatin interneuron-mediated inhibitory gate

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A12-A13
Author(s):  
James Delorme ◽  
Lijing Wang ◽  
Femke Kuhn ◽  
Varna Kodoth ◽  
Jingqun Ma ◽  
...  
Keyword(s):  
Memory Consolidation ◽  
Dorsal Hippocampus ◽  
Affinity Purification ◽  
Ribosomal Subunit ◽  
Sleep Loss ◽  
Contextual Fear Conditioning ◽  
Cell Type ◽  
Single Trial ◽  
Contextual Fear ◽  
Cell Type Specific

Abstract Introduction Sleep loss profoundly disrupts consolidation of hippocampus-dependent memory. To better characterize effects of learning and sleep loss on the hippocampal circuit, we quantified activity-dependent phosphorylation of ribosomal subunit S6 (pS6) across the dorsal hippocampus of mice. Methods We first measured pS6 throughout the hippocampus after learning (single trial contextual fear conditioning; CFC), and after subsequent sleep or sleep deprivation (SD). To characterize cell populations with activity affected by SD, we used translating ribosome affinity purification (TRAP)-seq to identify cell type-specific transcripts on pS6 ribosomes after SD vs. sleep. We next used pharmacogenetics to mimic the effects of SD, selectively activating hippocampal Sst+ interneurons or cholinergic inputs to hippocampus from the medial septum (MS) while mice slept in the hours following CFC. We also inhibited these neuronal populations to assess effects on memory consolidation. Results We find that pS6 in enhanced in the dentate gyrus (DG) following single-trial CFC, but is reduced throughout the hippocampus after brief SD – a manipulation which disrupts contextual fear memory (CFM) consolidation. Cell type-specific enrichment analysis (CSEA) of these transcripts revealed that hippocampal somatostatin-expressing (Sst+) interneurons, and cholinergic and orexinergic inputs to hippocampus, are selectively activated after SD. We used TRAP targeted to hippocampal Sst+ interneurons to identify cellular mechanisms mediating SD-driven Sst+ interneuron activation. . We find that activation of Sst+ interneurons is sufficient to disrupt CFM consolidation, by gating activity in surrounding pyramidal neurons, while inhibition of Sst+ interneurons enhances memory consolidation. Similarly, pharmacogenetic activation of cholinergic input to hippocampus from the MS disrupted CFM. Inhibition of MS cholinergic neurons promoted CFM consolidation and disinhibited neurons in the DG, increasing pS6 expression among DG granule cells. Conclusion Our data suggest that state-dependent gating of DG activity during SD is mediated by cholinergic input. Together these data provide evidence for an inhibitory gate on hippocampal information processing, which is activated by sleep loss. Support (if any) R01-NS118440 to SJA from NINDS, DP2-MH104119 to SJA from the NIH Director’s Office, and a Human Frontiers Science Program Young Investigator Award

scholarly journals Learning and Sleep Have Divergent Effects on Cytosolic and Membrane-Associated Ribosomal mRNA Profiles in Hippocampal Neurons

2020 ◽  
Author(s):  
James Delorme ◽  
Lijing Wang ◽  
Varna Kodoth ◽  
Yifan Wang ◽  
Jingqun Ma ◽  
...  
Keyword(s):  
Memory Consolidation ◽  
Hippocampal Neurons ◽  
Affinity Purification ◽  
Ribosomal Subunit ◽  
Sleep Loss ◽  
Contextual Fear Conditioning ◽  
Cellular Mechanisms ◽  
Prior Learning ◽  
Contextual Fear ◽  
Transcript Profiles

AbstractThe hippocampus plays an essential role in consolidating transient experiences into long-lasting memories. Memory consolidation can be facilitated by post-learning sleep, although the underlying cellular mechanisms are undefined. Here, we addressed this question using a mouse model of hippocampally-mediated, sleep-dependent memory consolidation (contextual fear memory; CFM), which is known to be disrupted by post-learning sleep loss. We used translating ribosome affinity purification (TRAP) to quantify ribosome-associated RNAs in different subcellular compartments (cytosol and membrane) and in different hippocampal cell populations (either whole hippocampus, Camk2a+ excitatory neurons, or highly active neurons expressing phosphorylated ribosomal subunit S6 [pS6+]). Using RNA-seq, we examined how these transcript profiles change as a function of sleep vs. sleep deprivation (SD) and as a function of prior learning (contextual fear conditioning; CFC). Surprisingly, we found that while many mRNAs on cytosolic ribosomes were altered by sleep loss, almost none were altered by learning. Of the few changes in cytosolic ribosomal transcript abundance following CFC, almost all were occluded by subsequent SD. This effect was particularly pronounced in pS6+ neurons with the highest level of neuronal activity following CFC, suggesting SD-induced disruption of post-learning transcript changes in putative “engram” neurons. In striking contrast, far fewer transcripts on membranebound (MB) ribosomes were altered by SD, and many more mRNAs (and lncRNAs) were altered on MB ribosomes as a function of prior learning. For hippocampal neurons, cellular pathways most significantly affected by CFC were involved in structural remodeling. Comparisons of post-CFC transcript profiles between freely-sleeping and SD mice implicated changes in cellular metabolism in Camk2a+ neurons, and increased protein synthesis capacity in pS6+ neurons, as biological processes disrupted by post-learning sleep loss.

scholarly journals Hippocampal CCR5/RANTES Elevations in a Rodent Model of Post-Traumatic Stress Disorder: Maraviroc (a CCR5 Antagonist) Increases Corticosterone Levels and Enhances Fear Memory Consolidation

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 212 ◽  
Author(s):  
José Joaquín Merino ◽  
Vilma Muñetón-Gomez ◽  
César Muñetón-Gómez ◽  
María Ángeles Pérez-Izquierdo ◽  
María Loscertales ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Chronic Stress ◽  
Memory Consolidation ◽  
Stress Disorder ◽  
Training Session ◽  
Fear Memory ◽  
Rodent Model ◽  
Contextual Fear Conditioning ◽  
Ccr5 Antagonist ◽  
Contextual Fear

Background: Contextual fear conditioning (CFC) is a rodent model that induces a high and long-lasting level of conditioning associated with traumatic memory formation; this behavioral paradigm resembles many characteristics of posttraumatic stress disorder (PSTD). Chemokines (chemotactic cytokines) play a known role in neuronal migration and neurodegeneration but their role in cognition is not totally elucidated. Aim: We ascertain whether CCR5/RANTES beta chemokines (hippocampus/prefrontal cortex) could play a role in fear memory consolidation (CFC paradigm). We also evaluated whether chronic stress restraint (21 days of restraint, 6-h/day) could regulate levels of these beta chemokines in CFC-trained rats; fear memory retention was determined taking the level of freezing (context and tone) by the animals as an index of fear memory consolidation 24 h after CFC training session; these chemokines (CCR5/RANTES) and IL-6 levels were measured in the hippocampus and prefrontal cortex of chronically stressed rats, 24 h after CFC post-training, and compared with undisturbed CFC-trained rats (Experiment 1). In Experiment 2, rats received 1 mA of footshock during the CFC training session and fear memory consolidation was evaluated at 12 and 24 h after CFC training sessions. We evaluated whether RANTES levels could be differentially regulated at 12 and 24 h after CFC training; in Experiment 3, maraviroc was administered to rats (i.m: 100 mg/Kg, a CCR5 antagonist) before CFC training. These rats were not subjected to chronic stress restraint. We evaluated whether CCR5 blockade before CFC training could increase corticosterone, RANTES, or IL-6 levels and affects fear memory consolidation in the rats 24-h post-testing compared with vehicle CFC-trained rats. Results: Elevations of CCR5/RANTES chemokine levels in the hippocampus could have contributed to fear memory consolidation (24 h post-training) and chronic stress restraint did not affect these chemokines in the hippocampus; there were no significant differences in CCR5/RANTES levels between stressed and control rats in the prefrontal cortex (Experiment 1). In Experiment 2, hippocampal CCR5/RANTES levels increased and enhanced fear memory consolidation was observed 12 and 24 h after CFC training sessions with 1 mA of footshock. Increased corticosterone and CCR5/RANTES levels, as well as a higher freezing percentage to the context, were found at 24 h CFC post-testing in maraviroc-treated rats as compared to vehicle-treated animals (experiment-3). Conversely, IL-6 is not affected by maraviroc treatment in CFC training. Conclusion. Our findings suggest a role for a hippocampal CCR5/RANTES axis in contextual fear memory consolidation; in fact, RANTES levels increased at 12 and 24 h after CFC training. When CCR5 was blocked by maraviroc before CFC training, RANTES (hippocampus), corticosterone levels, and fear memory consolidation were greater than in vehicle CFC-trained rats 24 h after the CFC session.

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