Differences between synaptic plasticity thresholds result in new timing rules for maximizing long-term potentiation
Open accessAbstract
The fundamental observation that the temporal spacing of learning episodes plays a critical role in the efficiency of memory encoding has had little effect on either research on long-term potentiation (LTP) or efforts to develop cognitive enhancers. Here we review recent findings describing a spaced trials phenomenon for LTP that appears to be related to recent evidence that plasticity thresholds differ between synapses in the adult hippocampus. Results of tests with one memory enhancing drug suggest that the compound potently facilitates LTP via effects on 'high threshold' synapses and thus alters the temporally extended timing rules. Possible implications of these results for our understanding of LTP substrates, neurobiological contributors to the distributed practice effect, and the consequences of memory enhancement are discussed. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
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For longer intervals of 60 or 90 minutes, a cumulative increase in LTP was observed over three bursts of stimulation in rat hippocampal slices.
“However, for longer intervals (60 or 90 minutes), a cumulative increase in LTP was observed over three bursts of stimulation.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [48]
Theta-burst stimuli applied at intervals of 10 or 40 minutes did not cumulatively increase LTP in rat hippocampal slices.
“Theta-burst stimuli applied at intervals of 10 or 40 minutes did not cumulatively increase LTP.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [48]
The second theta-burst stimulus yielded polymerization in spines that were not apparently affected by the first stimulus, if the second followed the first by 60 or 90 minutes.
“The second theta-burst stimulus yielded polymerization in spines that were not apparently affected by the first stimulus, if the second followed the first by 60 or 90 minutes.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [48]
For the spaced LTP protocol of Gall, Lynch and colleagues, an interval of 40-60 minutes is needed for successive theta-burst stimuli to further increase LTP.
“For the spaced LTP protocol of Gall, Lynch and colleagues47,48, an interval of 40–60 minutes is needed for successive theta-burst stimuli to further increase LTP.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [48]
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References 91 · Cited by 97
- Authors
- Lynch, G., Kramár, E. A., Babayan, A. H., Rumbaugh, G., & Gall, C. M.
- Affiliations
- University of California, Irvine (US)
- Scripps Research Institute (US)
- Corresponding author
- Gall, Christine M.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 64
- Pages
- 27-36
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC3445784
- OpenAlex
- W2083398179
- Cited by
- 97
- References
- 91
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 20 · 2023: 6 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 1 · 2017: 6 · 2016: 6 · 2015: 4 · 2014: 14 · 2013: 4
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NINDS (NS045260, NS064079)
- NIMH (MH083346)
- ONR MURI (N00014-10-1-0072)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- long-term potentiation, hippocampus, memory enhancement, nootropic drugs, memory encoding
- MeSH terms
- Animals, Cognition, Cognition Disorders, Hippocampus, Humans, Memory, Synaptic Transmission, Neuronal Plasticity, Neurons, Synapses, Long-Term Potentiation, Nootropic Agents, Performance-Enhancing Substances
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