The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Protein Synthesis Is Required for the Enhancement of Long-Term Potentiation and Long-Term Memory by Spaced Training
Abstract
Spaced training is generally more effective than massed training for learning and memory, but the molecular mechanisms underlying this trial spacing effect remain poorly characterized. One potential molecular basis for the trial spacing effect is the differential modulation, by distinct temporal patterns of neuronal activity, of protein synthesis-dependent processes that contribute to the expression of specific forms of synaptic plasticity in the mammalian brain. Long-term potentiation (LTP) is a type of synaptic modification that may be important for certain forms of memory storage in the mammalian brain. To explore the role of protein synthesis in the trial spacing effect, we assessed the protein synthesis dependence of hippocampal LTP induced by 100-Hz tetraburst stimulation delivered to mouse hippocampal slices in either a temporally massed (20-s interburst interval) or spaced (5-min interburst interval) fashion. To extend our studies to the behavioral level, we trained mice in fear conditioning using either a massed or spaced training protocol and examined the sensitivity of long-term memory to protein synthesis inhibition. Larger LTP was induced by spaced stimulation in hippocampal slices. This improvement of synaptic potentiation following temporally spaced synaptic stimulation in slices was attenuated by bath application of an inhibitor of protein synthesis. Further, the maintenance of LTP induced by spaced synaptic stimulation was more sensitive to disruption by anisomycin than the maintenance of LTP elicited following massed stimulation. Temporally spaced behavioral training improved long-term memory for contextual but not for cued fear conditioning, and this enhancement of memory for contextual fear was also protein synthesis dependent. Our data reveal that altering the temporal spacing of synaptic stimulation and behavioral training improved hippocampal LTP and enhanced contextual long-term memory. From a broad perspective, these results suggest that the recruitment of protein synthesis-dependent processes important for long-term memory and for long-lasting forms of LTP can be modulated by the temporal profiles of behavioral training and synaptic stimulation.
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“LTP that persists for several hours or more requires translation and transcription50,51, which is reliant on key transcription factors such as cyclic AMP-responsive element (CRE)-binding protein (CREB)52.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [51]
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Metadata
- Authors
- Scharf, M. T., Woo, N. H., Lattal, K. M., Young, J. Z., Nguyen, P. V., & Abel, T.
- Affiliations
- University of Pennsylvania (US)
- Physiology and
- Department of Biology and
- University of Alberta (CA)
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 2002-06-01
- Volume
- 87
- Issue
- 6
- Pages
- 2770-2777
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W2259231394
- Cited by
- 204
- References
- 39
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 9 · 2017: 6 · 2016: 11 · 2015: 9 · 2014: 11 · 2013: 13 · 2012: 8
- FWCI
- 5.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG18199, R01AG018199)
- National Institute of Mental Health (R01MH060244, MH 60244)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD026979, HD 26979)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- spaced training, massed training, long-term potentiation, protein synthesis, long-term memory, contextual fear conditioning, hippocampus, synaptic plasticity, anisomycin, memory consolidation
- MeSH terms
- Animals, Anisomycin, Conditioning, Psychological, Electric Stimulation, Fear, Female, Hippocampus, Male, Memory, Mice, Inbred C57BL, Organ Culture Techniques, Protein Synthesis Inhibitors, Synapses, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Mice
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