Persistence of Long-Term Memory Storage Requires a Late Protein Synthesis- and BDNF- Dependent Phase in the Hippocampus
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Persistence is the most characteristic attribute of long-term memory (LTM). To understand LTM, we must understand how memory traces persist over time despite the short-lived nature and rapid turnover of their molecular substrates. It is widely accepted that LTM formation is dependent upon hippocampal de novo protein synthesis and Brain-Derived Neurotrophic Factor (BDNF) signaling during or early after acquisition. Here we show that 12 hr after acquisition of a one-trial associative learning task, there is a novel protein synthesis and BDNF-dependent phase in the rat hippocampus that is critical for the persistence of LTM storage. Our findings indicate that a delayed stabilization phase is specifically required for maintenance, but not formation, of the memory trace. We propose that memory formation and memory persistence share some of the same molecular mechanisms and that recurrent rounds of consolidation-like events take place in the hippocampus for maintenance of the memory trace.
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Following inhibitory avoidance training in rats, late peaks in BDNF expression and C/EBP expression occur at about 12 hours post-training, and inhibiting BDNF action at this time blocks memory maintenance.
“Following inhibitory avoidance training in rats, late peaks in brain-derived neurotrophic factor (BDNF) expression and in C/EBP expression occur at ~12 hours post-training, and inhibiting BDNF action at this time blocks memory maintenance59.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [59]
In the hippocampus, CREB and C/EBP can remain active for many hours after learning.
“Recent data also illustrate that, in the hippocampus, CREB and CCAAT enhancer-binding protein (C/EBP), another transcription factor that is important for LTP, can remain active for many hours after learning.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [59]
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A Positive Autoregulatory BDNF Feedback Loop via C/EBPβ Mediates Hippocampal Memory Consolidation
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BDNF in the dentate gyrus is required for consolidation of “pattern-separated” memories.
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- Authors
- Bekinschtein, P., Cammarota, M., Igaz, L. M., Bevilaqua, L. R. M., Izquierdo, I., & Medina, J. H.
- Affiliations
- Universidad de Buenos Aires (AR)
- Pontifícia Universidade Católica do Rio Grande do Sul (BR)
- Corresponding author
- Medina, Jorge H.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 53
- Issue
- 2
- Pages
- 261-277
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2029712849
- Cited by
- 633
- References
- 126
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 24 · 2023: 29 · 2022: 25 · 2021: 32 · 2020: 25 · 2019: 37 · 2018: 34 · 2017: 33 · 2016: 41 · 2015: 46 · 2014: 47 · 2013: 60 · 2012: 38
- FWCI
- 18.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- long-term memory, memory persistence, hippocampus, de novo protein synthesis, BDNF signaling, memory consolidation, associative learning, memory maintenance
- MeSH terms
- Animals, Avoidance Learning, Conditioning, Psychological, Fear, Learning, Male, Memory, Nerve Tissue Proteins, Swimming, Time Factors, Rats, Wistar, Maze Learning, Brain-Derived Neurotrophic Factor, Rats
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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