cAMP Response Element-Binding Protein 1 Feedback Loop Is Necessary for Consolidation of Long-Term Synaptic Facilitation in Aplysia
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The transcription factor cAMP response element (CRE)-binding protein (CREB) plays an essential role in the induction of many forms of long-term synaptic plasticity. Levels of CREB1, the Aplysia homolog of CREB, show sustained elevations for several hours after the induction of long-term synaptic facilitation (LTF). Furthermore, CREB1 binds to the promoter of its own gene. These results suggest the existence of a CREB1-positive feedback loop that contributes to the consolidation of LTF. In the present study, we provide a detailed, quantitative characterization of the dynamics of CREB1 mRNA and protein as well as CREB1 phosphorylation after LTF induction. Injections of CRE oligonucleotides prevented the increase in CREB1 in response to 5-HT, corroborating the existence of the CREB1 feedback loop. This loop probably sustains CRE-dependent gene transcription, which remains elevated for at least 12 h after LTF induction. LTF is blocked by injection of CREB1 antibody after the induction phase, suggesting that the CREB1-positive feedback is required for consolidation of LTF.
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Spaced training may be more effective, in part, because it may allow sufficient time for transcription factors such as CREB to be activated, bind to promoters and induce a round of transcription for consolidation of LTP or long-term facilitation.
“Spaced training may be more effective, in part, because it may allow sufficient time for transcription factors such as CREB to be activated, bind to promoters and induce a round of transcription for the consolidation of LTP53 or for long-term facilitation (LTF) of synapses54.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [54]
In Aplysia californica sensory neurons, levels of the transcription activator CREB1 are elevated for at least 24 hours after spaced 5-HT treatments.
“In these sensory neurons, levels of the transcription activator CREB1 are elevated for at least 24 hours after the spaced 5-HT treatments54,55.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [54]
The prolonged elevation of CREB1 levels is due to a positive feedback loop in which CREB1 binds to a CRE regulatory element near creb1 and increases expression of creb1 and other genes upregulated by CREB1.
“This prolonged elevation of CREB1 levels is due to a positive feedback loop in which this protein, by binding to a CRE regulatory element near creb1, increases the expression of creb1 (REFS 54,55) and other genes that are upregulated by CREB1.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [54]
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- Authors
- Liu, R.-Y., Fioravante, D., Shah, S., & Byrne, J. H.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-02-20
- Volume
- 28
- Issue
- 8
- Pages
- 1970-1976
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6671429
- OpenAlex
- W2005304682
- Cited by
- 73
- References
- 24
- Citations by year
- 2025: 2 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 3 · 2012: 6
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NS019895)
- National Institute of Neurological Disorders and Stroke (NS019895, R01NS019895)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- CREB1, CREB, positive feedback loop, Aplysia, serotonin
- MeSH terms
- Animals, Aplysia, Nerve Tissue Proteins, Neurons, Afferent, Synapses, Cyclic AMP Response Element-Binding Protein, Long-Term Potentiation, Coculture Techniques, Feedback, Physiological, Structural Homology, Protein
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