scholarly journals Post-reactivation mifepristone impairs generalisation of strongly-conditioned contextual fear memories

2020 ◽  
Author(s):  
Charlotte R. Flavell ◽  
Rebecca M. Gascoyne ◽  
Jonathan L. C. Lee
Keyword(s):  
Systemic Treatment ◽  
Combined Treatment ◽  
Fear Memory ◽  
Male Rats ◽  
Memory Reconsolidation ◽  
Memory Strength ◽  
Contextual Fear ◽  
Fear Expression

AbstractThe efficacy of pharmacological disruption of fear memory reconsolidation depends on several factors, including memory strength and age. We built on previous observations that systemic treatment with the nootropic nefiracetam potentiates cued fear memory destabilization to facilitate mifepristone-induced reconsolidation impairment. Here, we applied nefiratecam and mifepristone to strongly-conditioned, 1-week old contextual fear memories in male rats. Unexpectedly, the combined treatment did not result in impairment of contextual fear expression. However, mifepristone did reduce freezing to a novel context. These observations suggest that strong and established contextual fear memories do undergo destabilization without the need for pharmacological facilitation, and that impairments in strong context fear memory reconsolidation can manifest as a reduction in generalization.

scholarly journals Role of Amygdala-Infralimbic Cortex Circuitry in Glucocorticoid-Induced Facilitation of Auditory Fear Memory Extinction

2021 ◽  
pp. 1-22
Author(s):  
Masoomeh Dadkhah ◽  
◽  
Abbas Ali Vafaei ◽  
Ali Rashidy-Pour ◽  
Parnia Trahomi ◽  
...  
Keyword(s):  
Critical Role ◽  
Fear Memory ◽  
Fear Extinction ◽  
Freezing Behavior ◽  
Extinction Training ◽  
Male Rats ◽  
Memory Extinction ◽  
The Right ◽  
Fear Expression

Purpose: The basolateral amygdala (BLA) and infralimbic area (IL) of medial prefrontal cortex (mPFC) are two inter-connected brain structures that mediate both fear memory expression and extinction. Besides the well-known role of the BLA in the acquisition and expression of fear memory, projections from IL to BLA inhibit fear expression and have a critical role in fear extinction. However, the details of IL-BLA interaction remain unclear. Here, we aimed to investigate the role of functional reciprocal interactions between BLA and IL in mediating fear memory extinction. Methods: Using lidocaine (LID), male rats underwent unilateral or bilateral inactivation of the BLA and then unilateral intra-IL infusion of CORT, prior to extinction training of auditory fear conditioning paradigm. Freezing behavior was reported as an index for the measurement of conditioned fear. Infusions were performed before the extinction training, allowing to examine the effects on fear expression and also further extinction memory. Experiments 1-3 investigated the effects of left or right infusion of CORT into IL, and LID unilaterally into BLA on fear memory extinction. Results: Results showed that intra-IL infusion of CORT in the right hemisphere reduced freezing behavior when administrated before the extinction training. Auditory fear memory extinction was impaired by asymmetric inactivation of BLA and CORT infusion in the right IL; however, the same effect was not observed with symmetric inactivation of BLA. Conclusion: It is concluded that that the IL-BLA neural circuit may provide additional evidence to contribution of this circuit in auditory fear extinction. This study demonstrate dissociable roles for right or left BLA in subserving the auditory fear extinction. Our finding also raise the possibility that left BLA-IL circuitry may contribute in mediating auditory fear memory extinction via underlying mechanisms, however further research is required.

Lack of neurotensin type 1 receptor facilitates contextual fear memory depending on the memory strength

2010 ◽  
Vol 96 (3) ◽  
pp. 363-369 ◽  
Author(s):  
Daisuke Yamada ◽  
Etsuko Wada ◽  
Taiju Amano ◽  
Keiji Wada ◽  
Masayuki Sekiguchi
Keyword(s):  
Fear Memory ◽  
Memory Strength ◽  
Contextual Fear ◽  
Contextual Fear Memory

scholarly journals Activation of nociceptin/orphanin FQ receptors inhibits contextual fear memory reconsolidation

2017 ◽  
Vol 125 ◽  
pp. 39-49 ◽  
Author(s):  
Khaoula Rekik ◽  
Raquel Faria Da Silva ◽  
Morgane Colom ◽  
Salvatore Pacifico ◽  
Nurulain T. Zaveri ◽  
...  
Keyword(s):  
Fear Memory ◽  
Memory Reconsolidation ◽  
Orphanin Fq ◽  
Contextual Fear ◽  
Contextual Fear Memory

scholarly journals The lateral neocortex is critical for contextual fear memory reconsolidation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Verónica de la Fuente ◽  
Candela Medina ◽  
Germán Falasco ◽  
Leandro Urrutia ◽  
Alexxai V. Kravitz ◽  
...  
Keyword(s):  
Fear Memory ◽  
Memory Reconsolidation ◽  
Contextual Fear ◽  
Contextual Fear Memory

Nicotine enhances contextual fear memory reconsolidation in rats

2011 ◽  
Vol 487 (3) ◽  
pp. 368-371 ◽  
Author(s):  
Shaowen Tian ◽  
Fulian Huang ◽  
Peng Li ◽  
Zhenbang Li ◽  
Shouhong Zhou ◽  
...  
Keyword(s):  
Fear Memory ◽  
Memory Reconsolidation ◽  
Contextual Fear ◽  
Contextual Fear Memory

scholarly journals Dopaminergic signalling is necessary, but not sufficient for cued fear memory destabilisation

2019 ◽  
Author(s):  
Charlotte R. Flavell ◽  
Jonathan L. C. Lee
Keyword(s):  
Therapeutic Strategy ◽  
Combined Treatment ◽  
Fear Memory ◽  
Receptor Activation ◽  
D1 Receptor ◽  
Extinction Learning ◽  
Enhancing Effect ◽  
Memory Reactivation ◽  
Therapeutic Benefits ◽  
Fear Expression

AbstractPharmacological targeting of memory reconsolidation is a promising therapeutic strategy for the treatment of fear memory-related disorders. However, the success of reconsolidation-based approaches depends upon the effective destabilisation of the fear memory by memory reactivation. Here, we show that the nootropic nefiracetam stimulates tone fear memory destabilisation to facilitate reconsolidation disruption by the glucocorticoid receptor antagonist mifepristone. Moreover, the enhancing effect of nefiracetam was dependent upon dopamine D1 receptor activation, although direct D1 receptor agonism was not sufficient to facilitate destabilisation. Finally, while the combined treatment with nefiracetam and mifepristone did not confer fear-reducing effects under conditions of extinction learning, there was some evidence that mifepristone reduces fear expression irrespective of memory reactivation parameters. Therefore, the use of combination pharmacological treatment to stimulate memory destabilisation and impair reconsolidation has potential therapeutic benefits, without risking a maladaptive increase of fear.

scholarly journals Contextual Fear Memory Formation and Destabilization Induce Hippocampal RyR2 Calcium Channel Upregulation

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Jamileth More ◽  
María Mercedes Casas ◽  
Gina Sánchez ◽  
Cecilia Hidalgo ◽  
Paola Haeger
Keyword(s):  
Spatial Memory ◽  
Fear Memory ◽  
Contextual Fear Conditioning ◽  
Male Rats ◽  
Endoplasmic Reticulum Membrane ◽  
Memory Retention ◽  
Contextual Fear ◽  
Memory Processes ◽  
Contextual Fear Memory ◽  
Protein Levels

Hippocampus-dependent spatial and aversive memory processes entail Ca2+ signals generated by ryanodine receptor (RyR) Ca2+ channels residing in the endoplasmic reticulum membrane. Rodents exposed to different spatial memory tasks exhibit significant hippocampal RyR upregulation. Contextual fear conditioning generates robust hippocampal memories through an associative learning process, but the effects of contextual fear memory acquisition, consolidation, or extinction on hippocampal RyR protein levels remain unreported. Accordingly, here we investigated if exposure of male rats to contextual fear protocols, or subsequent exposure to memory destabilization protocols, modified the hippocampal content of type-2 RyR (RyR2) channels, the predominant hippocampal RyR isoforms that hold key roles in synaptic plasticity and spatial memory processes. We found that contextual memory retention caused a transient increase in hippocampal RyR2 protein levels, determined 5 h after exposure to the conditioning protocol; this increase vanished 29 h after training. Context reexposure 24 h after training, for 3, 15, or 30 min without the aversive stimulus, decreased fear memory and increased RyR2 protein levels, determined 5 h after reexposure. We propose that both fear consolidation and extinction memories induce RyR2 protein upregulation in order to generate the intracellular Ca2+ signals required for these distinct memory processes.

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.

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