Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec;33(12):1267-1276.
doi: 10.1002/hipo.23579. Epub 2023 Oct 5.

Molecular mechanisms underpinning deconditioning-update in fear memory

Bruno Popik  1 , Jordana Griebler Luft  1 , Kétlyn Talise Knak Guerra  2 , Lucas de Oliveira Alvares  1
Affiliations

Molecular mechanisms underpinning deconditioning-update in fear memory

Bruno Popik et al. Hippocampus. 2023 Dec.

Abstract

Traumatic experiences are closely associated with some psychiatric conditions such as post-traumatic stress disorder. Deconditioning-update promotes robust and long-lasting attenuation of aversive memories. The deconditioning protocol consists of applying weak/neutral footshocks during reactivations, so that the original tone-shock association is replaced by an innocuous stimulus that does not produce significant fear response. Here, we present the molecular bases that can support this mechanism. To this end, we used pharmacological tools to inhibit the activity of ionotropic glutamate receptors (NMDA-GluN2B and CP-AMPA), the activity of proteases (calpains), and the receptors that control intracellular calcium storage (IP3 receptors), as well as the endocannabinoid system (CB1). Our results indicate that blocking these molecular targets prevents fear memory update by deconditioning. Therefore, this study uncovered the molecular substrate of deconditioning-update strategy, and, broadly, shed new light on the traumatic memory destabilization mechanisms that might be used to break the boundaries regarding reconsolidation-based approaches to deal with maladaptive memories.

Keywords: endocannabinoid system; glutamatergic system; intracellular calcium; protease; update.

PubMed Disclaimer

References

REFERENCES

    1. Acutain, M. F., Griebler Luft, J., Vazquez, C. A., Popik, B., Cercato, M. C., Epstein, A., Salvetti, A., Jerusalinsky, D. A., de Oliveira Alvares, L., & Baez, M. V. (2021). Reduced expression of hippocampal GluN2A-NMDAR increases seizure susceptibility and causes deficits in contextual memory. Frontiers in Neuroscience, 15, 1-15. https://doi.org/10.3389/fnins.2021.644100
    1. Aisenberg, N., Serova, L., Sabblan, E., & Akirav, I. (2017). The effects of enhancing endocannabinoid signaling and blocking corticotrophin releasing factor receptor in the amygdala and hippocampus on the consolidation of a stressful event. European Neuropsychopharmacology, 27(9), 913-927. https://doi.org/10.1016/j.euroneuro.2017.06.006
    1. Ben Mamou, C., Gamache, K., & Nader, K. (2006). NMDA receptors are critical for unleashing consolidated auditory fear memories. Nature Neuroscience, 9(10), 1237-1239. https://doi.org/10.1038/nn1778
    1. Bonanno, G. R., Met Hoxha, E., Robinson, P. K., Ferrara, N. C., & Trask, S. (2023). Fear reduced through unconditional stimulus deflation is behaviorally distinct from extinction and differentially engages the amygdala. Biological Psychiatry Global Open Science, 13, 216-223. https://doi.org/10.1016/j.bpsgos.2023.01.001
    1. Briz, V., & Baudry, M. (2017). Calpains: Master regulators of synaptic plasticity. The Neuroscientist, 23(3), 221-231. https://doi.org/10.1177/1073858416649178

Publication types

MeSH terms

LinkOut - more resources