Deficit in Long-Term Synaptic Plasticity Is Rescued by a Computationally Predicted Stimulus Protocol
Open accessAbstract
Mutations in the gene encoding CREB-binding protein (CBP) cause deficits in long-term plasticity, learning, and memory. Here, long-term synaptic facilitation (LTF) at Aplysia sensorimotor synapses in cell culture was used as a model system to investigate methods for overcoming deficits in LTF produced by a CBP knockdown. Injecting CBP–siRNA into individual sensory neurons reduced CBP levels and impaired LTF produced by a standard protocol of five 5-min pulses of serotonin (5-HT) delivered at 20 min interstimulus intervals. A computational model, which simulated molecular processes underlying LTF induction, predicted a rescue protocol of five pulses of 5-HT at non-uniform interstimulus intervals that overcame the consequences of reduced CBP and restored LTF. These results suggest that complementary empirical and computational studies can identify methods for ameliorating impairments of learning attributable to molecular lesions.
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Models have simulated the activity time courses of PKA, CaMKII, other key enzymes and downstream transcription factors during LTP induction.
“Models have also simulated the activity time courses of PKA, calcium/calmodulin-dependent protein kinase II (CaMKII), other key enzymes and downstream transcription factors during LTP induction88–90.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [90]
The recent study used siRNA knockdown of CBP in A. californica sensory neurons to impair LTF.
“The recent study90 used small-interfering RNA (siRNA) knockdown of CBP in A. californica sensory neurons to impair LTF.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [90]
This rescue protocol was empirically validated to restore normal LTF in A. californica.
“This rescue protocol was empirically validated to restore normal LTF in A. californica.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [90]
A 'rescue' protocol with irregularly spaced intervals was predicted to restore peak pC/EBP levels and, correspondingly, LTF.
“A ‘rescue’ protocol with irregularly spaced intervals was predicted to restore peak pC/EBP levels and, correspondingly, LTF.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [90]
Simulations showed a substantial decrease in pC/EBP levels when the level of CBP was reduced by a decrement that corresponded to the siRNA effect.
“Simulations showed a substantial decrease in pC/EBP levels when the level of CBP was reduced by a decrement that corresponded to the siRNA effect.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [90]
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- Authors
- Liu, R.-Y., Zhang, Y., Baxter, D. A., 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
- 2013-04-17
- Volume
- 33
- Issue
- 16
- Pages
- 6944-6949
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3690371
- OpenAlex
- W1977776764
- Cited by
- 29
- References
- 29
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 1 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 2
- FWCI
- 1.96
- 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)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institutes of Health
- Directorate for Biological Sciences
- National Institute of Neurological Disorders and Stroke (NS073974, NS019895, R01NS019895, R01NS073974, 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
- CREB-binding protein, long-term synaptic plasticity, long-term facilitation, serotonin, interstimulus interval, siRNA knockdown, learning and memory impairment, molecular lesions
- MeSH terms
- Analysis of Variance, Animals, Aplysia, Biophysics, Cells, Cultured, Computer Simulation, Electric Stimulation, Models, Neurological, Motor Neurons, Neuronal Plasticity, Predictive Value of Tests, Sensory Receptor Cells, Serotonin, Synapses, Coculture Techniques, Excitatory Postsynaptic Potentials, RNA, Small Interfering, CREB-Binding Protein
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