Activation of LVGCCs and CB1 receptors required for destabilization of reactivated contextual fear memories
Open accessAbstract
Previous studies have shown that inhibiting protein synthesis shortly after reactivation impairs the subsequent expression of a previously consolidated fear memory. This has suggested that reactivation returns a memory to a labile state and that protein synthesis is required for the subsequent restabilization of memory. While the molecular mechanisms underlying the restabilization of reactivated memories are being uncovered, those underlying the initial destabilization are not known at all. Using a contextual fear conditioning paradigm in mice, here we show that LVGCCs or CB1 receptors in hippocampus are required for the initial destabilization of reactivated memory. Either pharmacological blockade of hippocampal protein synthesis or genetic disruption of CREB-dependent transcription disrupts memory restabilization following reactivation. However, these effects were completely blocked when mice were treated with inhibitors of either LVGCCs or CB1 receptors, indicating that LVGCCs or CB1 receptors are required for the initial destabilization of reactivated memory. In control experiments, we show that blockade of LVGCCs or CB1 receptors does not interfere with the ability of ANI to block protein synthesis, or with the ability of ANI to impair initial consolidation. These experiments begin to reveal mechanisms underlying the destabilization of previously consolidated memories following reactivation and indicate the importance of activation of LVGCCs and CB1 in this process.
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At least in the hippocampus, memory destabilisation depends upon L-type voltage-gated calcium channels, blockade of which prevents the destabilisation of reactivated fear memories.
“At least in the hippocampus, another potential neurochemical mechanism underlying memory destabilisation depends upon L-type voltage-gated calcium channels (LVGCCs), blockade of which prevents the destabilisation of reactivated fear memories (Suzuki et al., 2008; Flavell et al., 2011).”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Suzuki et al., 2008
Administration of LVGCC antagonists nifedipine or nimodipine blocked the destabilisation of the original memory with brief re-exposure.
“and blocked the destabilisation of the original memory with brief re-exposure (Suzuki et al., 2004, 2008).”
From Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between (2020) · cites this paper as Suzuki et al., 2008
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“At least in the hippocampus, another potential neurochemical mechanism underlying memory destabilisation depends upon L-type voltage-gated calcium channels (LVGCCs), blockade of which prevents the destabilisation of reactivated fear memories (Suzuki et al., 2008; Flavell et al., 2011).”
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- Authors
- Suzuki, A., Mukawa, T., Tsukagoshi, A., Frankland, P. W., & Kida, S.
- Affiliations
- Tokyo University of Agriculture (JP)
- University of Toronto (CA)
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2008-05-29
- Volume
- 15
- Issue
- 6
- Pages
- 426-433
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- PMC
- PMC2414253
- OpenAlex
- W2041734103
- Cited by
- 141
- References
- 10
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 8 · 2020: 10 · 2019: 6 · 2018: 6 · 2017: 11 · 2016: 12 · 2015: 8 · 2014: 10 · 2013: 11 · 2012: 9
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Learning & Memory (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (18022038)
- Core Research for Evolutional Science and Technology
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- contextual fear memory, memory reactivation, memory destabilization, L-type calcium channels, CB1 receptor, hippocampus, protein synthesis, anisomycin, CREB-dependent transcription, memory consolidation
- MeSH terms
- Animals, Anisomycin, Conditioning, Classical, Extinction, Psychological, Hippocampus, Immunohistochemistry, Male, Memory, Mice, Inbred C57BL, Protein Synthesis Inhibitors, Cyclic AMP Response Element-Binding Protein, Calcium Channels, L-Type, Receptor, Cannabinoid, CB1, Mice
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