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

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.

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

10.1101/2020.03.10.985689 ◽

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

eLife ◽

10.7554/elife.57010 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 4

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.

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

10.1101/2020.05.11.088922 ◽

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.

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