Long-term potentiation of exogenous glutamate responses at single dendritic spines
Open accessAbstract
Long-term increases in the strength of excitatory transmission at Schaffer collateral-CA1 cell synapses of the hippocampus require the insertion of new α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) into the synapse, but the kinetics of this process are not well established. Using microphotolysis of caged glutamate to activate receptors at single dendritic spines in hippocampal CA1 cells, we report the long-lasting potentiation of AMPAR-mediated currents with only a single pairing of photoreleased glutamate and brief postsynaptic depolarization. This potentiation was N -methyl- d -aspartate receptor (NMDAR)-dependent and was reversed with low-frequency photostimulation in an NMDAR-dependent manner, suggesting that it is mediated by the same mechanism(s) as conventional synaptic long-term potentiation. Potentiation of photolytic responses developed rapidly in a stepwise manner after a brief and variable delay (<60 s) at spines, but could not be induced at extrasynaptic sites on the dendritic shaft. Potentiation was accompanied by a concomitant decrease in postsynaptic, polyamine-dependent paired-pulse facilitation of the photolytic currents, indicating that a change in the subunit composition of the AMPARs underlying the response contributed to the potentiation. These changes are consistent with an increase in the proportion of GluR2-containing AMPARs in the spine head. These results demonstrate that activation of postsynaptic glutamate receptors by glutamate is not only necessary, but sufficient, for the induction of NMDAR-dependent long-term potentiation and reveal additional aspects of its expression.
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NMDA-Rs regulate the functional state and number of AMPA-Rs by phosphorylation or by changing trafficking of AMPA-R subunits.
“they regulate the functional state and number of AMPA-Rs – by phosphorylation or by changing the trafficking of AMPA-R subunits to and from the cell membrane (Passafaro et al., 2001; Montgomery and Madison, 2004; Bagal et al., 2005).”
From The Computational Anatomy of Psychosis (2013) · cites this paper as Bagal et al., 2005
The Abstract reports NMDAR-dependent potentiation accompanied by a change in AMPAR subunit composition. The Discussion suggests insertion of new GluR1-GluR2 AMPARs into the spine membrane, supporting the trafficking aspect. Our copy does not establish regulation by phosphorylation or describe trafficking both to and from the membrane. (LLM, conf=0.87)
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- Authors
- Bagal, A. A., Kao, J. P. Y., Tang, C.-M., & Thompson, S. M.
- Affiliations
- University of Maryland, Baltimore (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-09-26
- Volume
- 102
- Issue
- 40
- Pages
- 14434-14439
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1242281
- OpenAlex
- W2053287773
- Cited by
- 169
- References
- 43
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 1 · 2014: 10 · 2013: 4 · 2012: 9
- FWCI
- 9.07
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (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, dendritic spines, AMPA receptors, NMDA receptor, Schaffer collateral-CA1 synapses, hippocampus, GluR2 subunit, paired-pulse facilitation, polyamines, synaptic plasticity, excitatory synaptic transmission
- MeSH terms
- Animals, Cells, Cultured, Electrophysiology, Hippocampus, Photolysis, Synapses, Receptors, N-Methyl-D-Aspartate, Receptors, Glutamate, Long-Term Potentiation, Glutamic Acid, Dendritic Spines, Rats
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