The Requirement for Enhanced CREB1 Expression in Consolidation of Long-Term Synaptic Facilitation and Long-Term Excitability in Sensory Neurons of Aplysia
Open accessAbstract
Accumulating evidence suggests that the transcriptional activator cAMP response element-binding protein 1 (CREB1) is important for serotonin (5-HT)-induced long-term facilitation (LTF) of the sensorimotor synapse in Aplysia. Moreover,creb1 is among the genes activated by CREB1, suggesting a role for this protein beyond the induction phase of LTF. The time course of the requirement for CREB1 synthesis in the consolidation of long-term facilitation was examined using RNA interference techniques in sensorimotor cocultures. Injection of CREB1 small-interfering RNA (siRNA) immediately or 10 h after 5-HT treatment blocked LTF when measured at 24 and 48 h after treatment. In contrast, CREB1 siRNA did not block LTF when injected 16 h after 5-HT treatment. These results demonstrate that creb1 expression must be sustained for a relatively long time to support the consolidation of LTF. In addition, LTF is also accompanied by a long-term increase in the excitability (LTE) of sensory neurons (SNs). Because LTE was observed in the isolated SN after 5-HT treatment, this long-term change was intrinsic to that element of the circuit. LTE was blocked when CREB1 siRNA was injected into isolated SNs immediately after 5-HT treatment. These data suggest that 5-HT-induced CREB1 synthesis is required for consolidation of both LTF and LTE.
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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 [55]
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 [55]
Slow dynamics of additional biochemical cascades contribute to LTM, such as changes in the synthesis of transcription factors CREB1 and CREB2.
“For example, the slow dynamics of additional biochemical cascades contribute to LTM (e.g., changes in the synthesis of transcription factors such as CREB1 and CREB22,32).”
From Computational design of enhanced learning protocols (2012) · cites this paper as [2]
Increased levels of CREB1 phosphorylation are associated with the induction and consolidation of LTF at sensorimotor synapses.
“For example, increased levels of CREB1 phosphorylation are associated with the induction and consolidation of LTF at sensorimotor synapses2,25,28.”
From Computational design of enhanced learning protocols (2012) · cites this paper as [2]
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- Authors
- Liu, R.-Y., Cleary, L. J., & Byrne, J. H.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-05-04
- Volume
- 31
- Issue
- 18
- Pages
- 6871-6879
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3092379
- OpenAlex
- W2081408258
- Cited by
- 60
- References
- 42
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 2 · 2015: 6 · 2014: 11 · 2013: 5 · 2012: 1
- FWCI
- 2.65
- 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
- National Institute of Neurological Disorders and Stroke (NS019895, R01NS019895, R37NS019895)
- 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, long-term facilitation, sensory neurons, Aplysia, serotonin, transcriptional regulation, siRNA knockdown, neuronal excitability
- MeSH terms
- Animals, Aplysia, Cells, Cultured, Electrophysiology, Sensory Receptor Cells, Synapses, Cyclic AMP Response Element-Binding Protein, Long-Term Potentiation, Coculture Techniques, Excitatory Postsynaptic Potentials, RNA, Small Interfering
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