Rescue of Impaired Long-Term Facilitation at Sensorimotor Synapses of Aplysia following siRNA Knockdown of CREB1
Open accessAbstract
Memory impairment is often associated with disrupted regulation of gene induction. For example, deficits in cAMP response element-binding protein (CREB) binding protein (CBP; an essential cofactor for activation of transcription by CREB) impair long-term synaptic plasticity and memory. Previously, we showed that small interfering RNA (siRNA)-induced knockdown of CBP in individual sensory neurons significantly reduced levels of CBP and impaired 5-HT-induced long-term facilitation (LTF) in sensorimotor cocultures from Aplysia. Moreover, computational simulations of the biochemical cascades underlying LTF successfully predicted training protocols that restored LTF following CBP knockdown. We examined whether simulations could also predict a training protocol that restores LTF impaired by siRNA-induced knockdown of the transcription factor CREB1. Simulations based on a previously described model predicted rescue protocols that were specific to CREB1 knockdown. Empirical studies demonstrated that one of these rescue protocols partially restored impaired LTF. In addition, the effectiveness of the rescue protocol was enhanced by pretreatment with rolipram, a selective cAMP phosphodiesterase inhibitor. These results provide further evidence that computational methods can help rescue disruptions in signaling cascades underlying memory formation. Moreover, the study demonstrates that the effectiveness of computationally designed training protocols can be enhanced with complementary pharmacological approaches.
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A similar predicted rescue protocol of irregularly spaced intervals rescued a deficit in LTF that was produced by siRNA knockdown of CREB1.
“A similar predicted rescue protocol of irregularly spaced intervals rescued a deficit in LTF that was produced by siRNA knockdown of CREB1 (REF. 97).”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [97]
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The right time to learn: Mechanisms and optimization of spaced learning
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- Authors
- Zhou, L., Zhang, Y., Liu, R.-Y., Smolen, P., 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
- 2015-01-28
- Volume
- 35
- Issue
- 4
- Pages
- 1617-1626
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4308605
- OpenAlex
- W2047936355
- Cited by
- 14
- References
- 51
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 1 · 2019: 1 · 2017: 2 · 2016: 1
- FWCI
- 0.60
- 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 (R01NS019895, R01NS073974)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- long-term facilitation, CREB1, CREB-binding protein, CBP, Aplysia, siRNA knockdown, memory impairment, serotonin, rolipram, cAMP phosphodiesterase inhibition, synaptic plasticity, memory formation
- MeSH terms
- Animals, Aplysia, Biophysics, Computer Simulation, Electric Stimulation, Models, Neurological, Motor Neurons, Sensory Receptor Cells, Serotonin, Synapses, Time Factors, Long-Term Potentiation, Cyclic AMP-Dependent Protein Kinases, Coculture Techniques, Excitatory Postsynaptic Potentials, RNA, Small Interfering, CREB-Binding Protein
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