Long-Term Potentiation: Evidence Against an Increase in Transmitter Release Probability in the CA1 Region of the Hippocampus
Abstract
It is widely accepted that N-methyl-D-aspartate (NMDA)-receptor-dependent long-term potentiation (LTP) in the CA1 region of the hippocampus is triggered postsynaptically, but there is considerable debate as to the site at which the increase in synaptic strength is expressed. The irreversible open-channel blocking action of the NMDA receptor antagonist MK-801 has been used to test whether the probability of transmitter release (Pr) is increased during LTP. Although the rate of decline of the amplitude of the NMDA receptor-mediated excitatory postsynaptic current (EPSC) in the presence of MK-801 strongly depends on Pr, the rate of decline of the EPSC evoked at synapses expressing LTP is identical to that observed at synapses not expressing LTP. These findings are difficult to reconcile with models in which the expression of LTP is due to an increase in Pr.
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The rate of decrease of NMDAR currents during MK-801 application remains unaltered by LTP but is clearly affected by other manipulations that are known to influence the probability of transmitter release.
“Importantly, it was found that the rate of this decrease remains unaltered by LTP but is clearly affected by other manipulations that are known to influence the probability of transmitter release (Manabe and Nicoll 1994).”
From NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). (2012) · cites this paper as Manabe and Nicoll 1994
Cites
Huettner, J. E., & Bean, B. P. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.4.1307 · Cited by 751 · see citing works
McNaughton, B. L. (1982) · The Journal of Physiology · doi:10.1113/jphysiol.1982.sp014110 · Cited by 332 · see citing works
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Long-Term Potentiation--A Decade of Progress?
Malenka, R. C., & Nicoll, A. R. A. (1999) · Science · doi:10.1126/science.285.5435.1870 · Cited by 2,729 · see citing works
Liao, D., Hessler, N. A., & Malinow, R. (1995) · Nature · doi:10.1038/375400a0 · Cited by 1,365 · see citing works
NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD).
Luscher, C., & Malenka, R. C. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005710 · Cited by 1,110 · see citing works
Molecular Mechanisms of Early and Late LTP
Baltaci, S. B., Mogulkoc, R., & Baltaci, A. K. (2019) · Neurochemical Research · doi:10.1007/s11064-018-2695-4 · Cited by 152 · see citing works
Le, A. A., Quintanilla, J., Amani, M., Piomelli, D., Lynch, G., & Gall, C. M. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105565 · Cited by 22 · see citing works
- Authors
- Manabe, T., & Nicoll, R. A.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Science
- Published
- 1994-09-23
- Volume
- 265
- Issue
- 5180
- Pages
- 1888-1892
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2030145065
- Cited by
- 140
- References
- 2
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 2 · 2013: 5 · 2012: 4
- FWCI
- 6.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- long-term potentiation, NMDA receptor, hippocampal CA1, MK-801, excitatory postsynaptic currents, synaptic plasticity
- MeSH terms
- Animals, Guinea Pigs, Hippocampus, Male, Synapses, Receptors, N-Methyl-D-Aspartate, Dizocilpine Maleate, Long-Term Potentiation, Receptors, AMPA, Neurotransmitter Agents, In Vitro Techniques
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