The role of Ca2+ entry via synaptically activated NMDA receptors in the induction of long-term potentiation
Abstract
Influx of Ca2+ through the NMDA subtype of glutamate receptor is widely accepted as a trigger for many forms of neural plasticity. However, direct support for this model has been elusive, since indirect activation of dendritic voltage-sensitive Ca2+ channels is difficult to exclude. We have optically measured synaptically induced changes in cytoplasmic free Ca2+ concentration in pyramidal cell dendrites in hippocampal slices. Steady postsynaptic depolarization to the synaptic reversal potential eliminated the effect of voltage-sensitive Ca2+ channels. Under these conditions, synaptically induced Ca2+ transients were observed, which were blocked by the NMDA receptor antagonist APV. In addition, the magnitude of LTP was diminished when induced with the postsynaptic membrane held at progressively more positive potentials. LTP could be completely suppressed at potentials near +100 mV. These results provide important experimental support for a role for Ca2+ influx through NMDA receptors in synaptic plasticity.
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After the pairing protocol, robust LTP was recorded in pathway 1 (0 mV), but no LTP was recorded in pathway 2 (+70 mV).
“robust LTP was recorded in pathway 1 (0 mV), but no LTP was recorded in pathway 2 (+70 mV).”
From Synaptic memory and CaMKII (2023) · cites this paper as [178]
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Llinás, R. R. (1988) · Science · doi:10.1126/science.3059497 · Cited by 2,285 · 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
O'Reilly, R. C. (1996) · Neural Computation · doi:10.1162/neco.1996.8.5.895 · Cited by 352 · see citing works
Pettit, D. L., Perlman, S., & Malinow, R. (1994) · Science · doi:10.1126/science.7997883 · Cited by 329 · see citing works
Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
Self-citationBrown, G. P., Blitzer, R. D., Connor, J. H., Wong, T., Shenolikar, S., Iyengar, R., & Landau, E. M. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-21-07880.2000 · Cited by 98 · see citing works
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- Authors
- Perkel, D. J., Petrozzino, J. J., Nicoll, R. A., & Connor, J. A.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1993-11
- Volume
- 11
- Issue
- 5
- Pages
- 817-823
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2065965042
- Cited by
- 138
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2021: 1 · 2018: 2 · 2017: 2 · 2016: 5 · 2014: 2 · 2013: 1
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuron (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
- NMDA receptor, calcium influx, long-term potentiation, synaptic plasticity, dendritic calcium transients, voltage-gated calcium channels, postsynaptic depolarization, hippocampal pyramidal neurons, cytosolic free calcium, APV
- MeSH terms
- Animals, Calcium, Electric Stimulation, Guinea Pigs, Hippocampus, Neurons, Osmolar Concentration, Synapses, 2-Amino-5-phosphonovalerate, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, In Vitro Techniques
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