The cannabinoid system in the retrosplenial cortex modulates fear memory consolidation, reconsolidation, and extinction

Sachser, Ricardo Marcelo; Crestani, Ana Paula; Quillfeldt, Jorge Alberto; Souza, Tadéu Mello e; Alvares, Lucas de Oliveira

doi:10.1101/lm.039891.115

Cited by 26 publications

(15 citation statements)

References 55 publications

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“…An activation of CB1 receptors with the cannabinoid agonist in the BLA induced a dose‐dependent enhancement of inhibitory avoidance memory; however, co‐infusion of the β‐adrenoceptor antagonist propranolol prevented this memory enhancement. Such an enhancement of memory consolidation by cannabinoid activation is consistent with the findings of other studies and also occurs in other brain regions . These findings thus indicate that noradrenergic signalling is required for endocannabinoids to induce memory consolidation enhancement.…”

Section: Endocannabinoid Mediation Of the Effects Of Gcs On Memorysupporting

confidence: 91%

Stress and Memory: A Selective Review on Recent Developments in the Understanding of Stress Hormone Effects on Memory and Their Clinical Relevance

Wolf

Atsak

Quervain

et al. 2016

J Neuroendocrinology

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Stress causes a neuroendocrine response cascade, leading to the release of catecholamines and glucocorticoids (GCs). GCs influence learning and memory by acting on mineralocorticoid (MR) and glucocorticoid (GR) receptors. Typically, GCs enhance the consolidation of memory processing at the same time as impairing the retrieval of memory of emotionally arousing experiences. The present selective review addresses four recent developments in this area. First, the role of the endocannabinoid system in mediating the rapid, nongenomic effects of GCs on memory is illustrated in rodents. Subsequently, studies on the impact of the selective stimulation of MRs on different memory processes in humans are summarised. Next, a series of human experiments on the impact of stress or GC treatment on fear extinction and fear reconsolidation is presented. Finally, the clinical relevance of the effects of exogenous GC administration is highlighted by the description of patients with anxiety disorders who demonstrate an enhancement of extinction-based therapies by GC treatment. The review highlights the substantial progress made in our mechanistic understanding of the memory-modulating properties of GCs, as well as their clinical potential.

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Section: Endocannabinoid Mediation Of the Effects Of Gcs On Memorysupporting

confidence: 91%

Stress and Memory: A Selective Review on Recent Developments in the Understanding of Stress Hormone Effects on Memory and Their Clinical Relevance

Wolf

Atsak

Quervain

et al. 2016

J Neuroendocrinology

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“…a). All things considered, it seems reconsolidation is the mechanism underlying remote memory rescue, which is also consistent with the effectiveness of the short reexposure time of 4 min (Bustos et al, ; de Oliveira Alvares et al, ; Sachser et al, ). Finally, we gave a further step and have shown the involvement of RE as a necessary relay between cortical and subcortical areas operating during reconsolidation (Fig.…”

Section: Discussionsupporting

confidence: 71%

“…b), subjects were reexposed to the context 2 days after training without the US (footshocks) during 240 s, allowing both (a) to measure recent (48 h) long‐term memory recall and (b) to induce memory reactivation, whose effect was later accessed in a remote test session (38 days later). In our lab, reexposure to the context without the US for 3–5 min used to be enough to induce memory reactivation/reconsolidation (de Oliveira et al, , 2013; Sierra et al, ; Sachser et al, ).…”

Section: Methodsmentioning

confidence: 99%

Reconsolidation‐induced rescue of a remote fear memory blocked by an early cortical inhibition: Involvement of the anterior cingulate cortex and the mediation by the thalamic nucleus reuniens

et al. 2017

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Systems consolidation is a time-dependent reorganization process involving neocortical and hippocampal networks underlying memory storage and retrieval. The involvement of the hippocampus during acquisition is well described; however we know much less about the concomitant contribution of cortical activity levels to the formation of stable remote memories. Here, after a reversible pharmacological inhibition of the anterior cingulate cortex (ACC) during the acquisition of a contextual fear conditioning, retrieval of both recent and remote memories were impaired, an effect that was reverted by a single memory reactivation session 48 h after training, through a destabilization-dependent mechanism interpreted as reconsolidation, that restored the normal course of systems consolidation in order to rescue a remote memory. Next we have shown that the integrity of both the anterior cingulate cortex and the thalamic nucleus reuniens (RE) were required for this reactivation-induced memory rescue. Because lidocaine infused into the RE inhibited LTP induction in the CA1-anterior cingulate cortex pathways, it seems that RE is a necessary component of the circuit underlying systems consolidation, mediating communication between dorsal hippocampus and cortical areas. To our notice, this is the first demonstration of the rescue of remote memories disrupted by ACC inhibition during acquisition, via a reconsolidation-driven mechanism. We have also shown the importance of RE to ensure the interconnection among brain areas that collectively seem to control the natural course of systems consolidation and allow the persistence of relevant emotional engrams. © 2017 Wiley Periodicals, Inc.

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“…While time to single exposure in the training context seem to be critical to induce reconsolidation or extinction 65 , repetitive contextual exposition promotes fear extinction 66 . We have previously shown that 3-to-5 min exposure to the context induces memory reactivation/reconsolidation 2 , 36 , 37 , 67 . Accordingly, this allows us to hypothesize that caffeine administration using single memory reactivation may attenuate fear memories via reconsolidation-driven mechanism.…”

Section: Discussionmentioning

confidence: 99%

Periodical reactivation under the effect of caffeine attenuates fear memory expression in rats

Pedraza

Sierra

Lotz

et al. 2018

Sci Rep

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In the last decade, several studies have shown that fear memories can be attenuated by interfering with reconsolidation. However, most of the pharmacological agents used in preclinical studies cannot be administered to humans. Caffeine is one of the world’s most popular psychoactive drugs and its effects on cognitive and mood states are well documented. Nevertheless, the influence of caffeine administration on fear memory processing is not as clear. We employed contextual fear conditioning in rats and acute caffeine administration under a standard memory reconsolidation protocol or periodical memory reactivation. Additionally, potential rewarding/aversion and anxiety effects induced by caffeine were evaluated by conditioning place preference or open field, respectively. Caffeine administration was able to attenuate weak fear memories in a standard memory reconsolidation protocol; however, periodical memory reactivation under caffeine effect was necessary to attenuate strong and remote memories. Moreover, caffeine promoted conditioned place preference and anxiolytic-like behavior, suggesting that caffeine weakens the initial learning during reactivation through counterconditioning mechanisms. Thus, our study shows that rewarding and anxiolytic effects of caffeine during fear reactivation can change the emotional valence of fear memory. It brings a new promising pharmacological approach based on drugs widely used such as caffeine to treat fear-related disorders.

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The cannabinoid system in the retrosplenial cortex modulates fear memory consolidation, reconsolidation, and extinction

Cited by 26 publications

References 55 publications

Stress and Memory: A Selective Review on Recent Developments in the Understanding of Stress Hormone Effects on Memory and Their Clinical Relevance

Stress and Memory: A Selective Review on Recent Developments in the Understanding of Stress Hormone Effects on Memory and Their Clinical Relevance

Reconsolidation‐induced rescue of a remote fear memory blocked by an early cortical inhibition: Involvement of the anterior cingulate cortex and the mediation by the thalamic nucleus reuniens

Periodical reactivation under the effect of caffeine attenuates fear memory expression in rats

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