scholarly journals Noradrenergic projections from the locus coeruleus to the amygdala constrain auditory fear memory reconsolidation

2020 ◽  
Author(s):  
Josue Haubrich ◽  
Matteo Bernabo ◽  
Karim Nader
Keyword(s):  
Boundary Condition ◽  
Boundary Conditions ◽  
Locus Coeruleus ◽  
Molecular Mechanisms ◽  
Fear Memory ◽  
Memory Formation ◽  
Memory Reconsolidation ◽  
Memory Encoding ◽  
Memory Strength ◽  
The Brain

ABSTRACTMemory reconsolidation is a fundamental plasticity process in the brain that allows established memories to be changed or erased. However, certain boundary conditions limit the parameters under which memories can be made plastic. Strong memories do not destabilize, for instance, although why they are resilient is mostly unknown. Here, we extend the understanding of the mechanisms implicated in reconsolidation-resistant memories by investigating the hypothesis that specific modulatory signals shape memory formation into a state that lacks lability. We find that the activation of the noradrenaline-locus coeruleus system (NOR-LC) during strong fear memory encoding increases molecular mechanisms of stability at the expense of lability in the amygdala. Preventing the NOR-LC from modulating strong fear encoding results in the formation of memories that can undergo reconsolidation within the amygdala and thus are vulnerable to post-reactivation interference. Thus, the memory strength boundary condition on reconsolidation is set at the time of encoding by the action of the NOR-LC.

scholarly journals Noradrenergic projections from the locus coeruleus to the amygdala constrain fear memory reconsolidation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Josué Haubrich ◽  
Matteo Bernabo ◽  
Karim Nader
Keyword(s):  
Boundary Condition ◽  
Boundary Conditions ◽  
Locus Coeruleus ◽  
Molecular Mechanisms ◽  
Fear Memory ◽  
Memory Formation ◽  
Memory Reconsolidation ◽  
Memory Encoding ◽  
Memory Strength ◽  
The Brain

Memory reconsolidation is a fundamental plasticity process in the brain that allows established memories to be changed or erased. However, certain boundary conditions limit the parameters under which memories can be made plastic. Strong memories do not destabilize, for instance, although why they are resilient is mostly unknown. Here, we investigated the hypothesis that specific modulatory signals shape memory formation into a state that is reconsolidation-resistant. We find that the activation of the noradrenaline-locus coeruleus system (NOR-LC) during strong fear memory encoding increases molecular mechanisms of stability at the expense of lability in the amygdala of rats. Preventing the NOR-LC from modulating strong fear encoding results in the formation of memories that can undergo reconsolidation within the amygdala and thus are vulnerable to post-reactivation interference. Thus, the memory strength boundary condition on reconsolidation is set at the time of encoding by the action of the NOR-LC.

scholarly journals Using Extinction-Renewal to Circumvent the Memory Strength Boundary Condition in Fear Memory Reconsolidation

2021 ◽  
Vol 11 (8) ◽  
pp. 1023
Author(s):  
Tiffany L. Campbell ◽  
Daniel E. Kochli ◽  
Mitch A. McDaniel ◽  
Mallory K. Myers ◽  
Mallory E. Dunn ◽  
...  
Keyword(s):  
Boundary Condition ◽  
Fear Memory ◽  
Memory Reconsolidation ◽  
Tone Presentation ◽  
Memory Strength ◽  
Training Context ◽  
Single Tone ◽  
Emotional Memories ◽  
Memory Rats

Reconsolidation is a process by which memories are destabilized, updated, and then restabilized. Strong memories are resistant to undergoing reconsolidation. Here, we addressed whether an overtrained fear memory could be made susceptible to reconsolidation by first extinguishing, and then renewing, the memory. Rats were trained with ten tone-footshock pairings, followed by eight days of tone extinction in the training context. The next day, rats were placed into a second context and memory for the tone was renewed/reactivated with a single tone presentation. Immediately following reactivation, rats received an injection of midazolam or vehicle. Rats were then tested for freezing to the tone in a third context. Midazolam had no effect in rats that did not undergo tone extinction, but significantly attenuated freezing to the tone in extinguished rats. Thus, rats that received tone extinction underwent tone memory reconsolidation following its renewal. In a second experiment, we administered the reactivation session and midazolam injections prior to extinction. Midazolam had no effect and rats extinguished at a rate similar to controls. These data suggest that strong emotional memories are capable of updating following weakening of memory expression through extinction.

scholarly journals The genomic underpinnings of oscillatory biomarkers supporting successful memory encoding in humans

2019 ◽  
Author(s):  
Stefano Berto ◽  
Miles Fontenot ◽  
Sarah Seger ◽  
Fatma Ayhan ◽  
Emre Caglayan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Memory Performance ◽  
Temporal Cortex ◽  
Memory Task ◽  
Memory Formation ◽  
Inhibitory Neurons ◽  
Patient Specific ◽  
Memory Encoding ◽  
Brain Oscillations ◽  
Resected Tissue

AbstractIn humans, brain oscillations are thought to support critical features of memory formation such as coordination of activity across regions, consolidation, and temporal ordering of events. However, understanding the molecular mechanisms underlining this activity in humans remains a major challenge. Here, we measured memory-sensitive oscillations using direct intracranial electroencephalography recordings from the temporal cortex of patients performing an episodic memory task. By then employing transcriptomics on the resected tissue from the same patients, we linked gene expression with brain oscillations, identifying genes correlated with oscillatory signatures of memory formation across six frequency bands. A co-expression analysis isolated biomarker-specific modules associated with neuropsychiatric disorders as well as ion channel activity. Using single-nuclei transcriptomic data from this resected tissue, we further revealed that biomarker-specific modules are enriched for both excitatory and inhibitory neurons. This unprecedented dataset of patient-specific brain oscillations coupled to genomics unlocks new insights into the genetic mechanisms that support memory encoding. By linking brain expression of these genes to oscillatory patterns, our data help overcome limitations of phenotypic methods to uncover genetic links to memory performance.

scholarly journals Pupillometry as a Glimpse into the Neurochemical Basis of Human Memory Encoding

2015 ◽  
Vol 27 (4) ◽  
pp. 765-774 ◽  
Author(s):  
Russell Cohen Hoffing ◽  
Aaron R. Seitz
Keyword(s):  
Locus Coeruleus ◽  
Pupil Size ◽  
Ethical Issues ◽  
Human Memory ◽  
Memory Encoding ◽  
Learning Paradigm ◽  
Surrogate Measure ◽  
Second Procedure ◽  
Task Irrelevant ◽  
The Brain

Neurochemical systems are well studied in animal learning; however, ethical issues limit methodologies to explore these systems in humans. Pupillometry provides a glimpse into the brain's neurochemical systems, where pupil dynamics in monkeys have been linked with locus coeruleus (LC) activity, which releases norepinephrine (NE) throughout the brain. Here, we use pupil dynamics as a surrogate measure of neurochemical activity to explore the hypothesis that NE is involved in modulating memory encoding. We examine this using a task-irrelevant learning paradigm in which learning is boosted for stimuli temporally paired with task targets. We show that participants better recognize images that are paired with task targets than distractors and, in correspondence, that pupil size changes more for target-paired than distractor-paired images. To further investigate the hypothesis that NE nonspecifically guides learning for stimuli that are present with its release, a second procedure was used that employed an unexpected sound to activate the LC–NE system and induce pupil-size changes; results indicated a corresponding increase in memorization of images paired with the unexpected sounds. Together, these results suggest a relationship between the LC–NE system, pupil-size changes, and human memory encoding.

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.

scholarly journals The Mechanisms and Boundary Conditions of Drug Memory Reconsolidation

2021 ◽  
Vol 15 ◽  
Author(s):  
Liangpei Chen ◽  
He Yan ◽  
Yufang Wang ◽  
Ziping He ◽  
Qihao Leng ◽  
...  
Keyword(s):  
Boundary Conditions ◽  
Relapse Prevention ◽  
Therapeutic Potential ◽  
Brain Structures ◽  
Vital Role ◽  
Memory Reconsolidation ◽  
Molecular Processes ◽  
Memory Engram ◽  
The Brain ◽  
Drug Relapse

Drug addiction can be seen as a disorder of maladaptive learning characterized by relapse. Therefore, disrupting drug-related memories could be an approach to improving therapies for addiction. Pioneering studies over the last two decades have revealed that consolidated memories are not static, but can be reconsolidated after retrieval, thereby providing candidate pathways for the treatment of addiction. The limbic–corticostriatal system is known to play a vital role in encoding the drug memory engram. Specific structures within this system contribute differently to the process of memory reconsolidation, making it a potential target for preventing relapse. In addition, as molecular processes are also active during memory reconsolidation, amnestic agents can be used to attenuate drug memory. In this review, we focus primarily on the brain structures involved in storing the drug memory engram, as well as the molecular processes involved in drug memory reconsolidation. Notably, we describe reports regarding boundary conditions constraining the therapeutic potential of memory reconsolidation. Furthermore, we discuss the principles that could be employed to modify stored memories. Finally, we emphasize the challenge of reconsolidation-based strategies, but end with an optimistic view on the development of reconsolidation theory for drug relapse prevention.

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