A Positive Autoregulatory BDNF Feedback Loop via C/EBPβ Mediates Hippocampal Memory Consolidation
Open accessAbstract
Little is known about the temporal progression and regulation of the mechanisms underlying memory consolidation. Brain-derived-neurotrophic-factor (BDNF) has been shown to mediate the maintenance of memory consolidation, but the mechanisms of this regulation remain unclear. Using inhibitory avoidance (IA) in rats, here we show that a hippocampal BDNF-positive autoregulatory feedback loop via CCAAT-enhancer binding protein β (C/EBPβ) is necessary to mediate memory consolidation. At training, a very rapid, learning-induced requirement of BDNF accompanied by rapid de novo translation controls the induction of a persistent activation of cAMP-response element binding-protein (CREB) and C/EBPβ expression. The latter, in turn, controls an increase in expression of bdnf exon IV transcripts and BDNF protein, both of which are necessary and, together with the initial BDNF requirement, mediate memory consolidation. The autoregulatory loop terminates by 48 h after training with decreased C/EBPβ and pCREB and increased methyl-CpG binding protein-2, histone-deacetylase-2, and switch-independent-3a binding at the bdnf exon IV promoter.
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These BDNF dynamics result from a positive feedback loop in which C/ebp induction leads to Bdnf upregulation, with the resulting increase in BDNF levels further activating the C/EBP signalling pathway.
“These BDNF dynamics result from a positive feedback loop in which C/ebp induction leads to Bdnf upregulation, with the resulting increase in BDNF levels further activating the C/EBP signalling pathway60.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [60]
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 [60]
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- Authors
- Bambah-Mukku, D., Travaglia, A., Chen, D. Y., Pollonini, G., & Alberini, C. M.
- Affiliations
- New York University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-09-10
- Volume
- 34
- Issue
- 37
- Pages
- 12547-12559
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4160783
- OpenAlex
- W2059856205
- Cited by
- 145
- References
- 48
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 14 · 2022: 24 · 2021: 13 · 2020: 15 · 2019: 12 · 2018: 11 · 2017: 14 · 2016: 16 · 2015: 11
- FWCI
- 7.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (MH065635)
- National Institute of Mental Health (R37MH065635, R01MH065635)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- brain-derived neurotrophic factor, C/EBPβ, memory consolidation, hippocampus, passive avoidance, CREB, autoregulatory loop, HDAC2, MeCP2, epigenetic regulation
- MeSH terms
- Animals, Avoidance Learning, Hippocampus, Inhibition, Psychological, Male, Signal Transduction, Brain-Derived Neurotrophic Factor, Rats, Long-Evans, CCAAT-Enhancer-Binding Protein-beta, Feedback, Physiological, Rats, Memory, Long-Term
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