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A Role for Extracellular Adenosine in Time-Dependent Reversal of Long-Term Potentiation by Low-Frequency Stimulation at Hippocampal CA1 Synapses
Open accessAbstract
The involvement of adenosine on the development of time-dependent reversal of long-term potentiation (LTP) by low-frequency stimulation (LFS) was investigated at Schaffer collateral–CA1 synapses of rat hippocampal slices. A train of LFS (2 Hz, 10 min, 1200 pulses) had no long-term effects on synaptic transmission but produced lasting depression of previously potentiated responses. This reversal of LTP (depotentiation) was observed when the stimulus was delivered ≤3 min after induction of LTP. However, application at 10 min after induction had no detectable effect on potentiation. This time-dependent reversal of LTP by LFS appeared to be mediated by extracellular adenosine, because it was mimicked by bath-applied adenosine and was specifically inhibited by the selective A 1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (100 n m). The effect of adenosine could be mimicked by 5-HT 1A receptor agonist buspirone, but the LFS-induced depotentiation could not be antagonized by 5-HT 1A receptor antagonist NAN-190. The source of extracellular adenosine in response to LFS appeared to be attributable to the efflux of cAMP. In addition, this LFS-induced depotentiation was blocked by bath application of adenylyl cyclase activator forskolin or injection of a cAMP analog Sp-adenosine cAMP (10 m m) into postsynaptic neurons. Moreover, the selective protein phosphatase 1 and 2A inhibitors okadaic acid and calyculin A prevented the LFS-induced depotentiation. These results thus suggest that increasing extracellular adenosine appears to underlie the LFS-induced depotentiation via acting on the A 1 receptor subtype to interrupt the cAMP-dependent biochemical processes leading to the LTP expression.
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“LTP induced at hippocampal Schaffer collateral synapses can be reversed by low-frequency (1-2 Hz) stimulation mimicking basal conditions as they could occur during SWS, and this depotentiation appears to be essentially mediated through diffuse activation of A1 receptors (576).”
From About Sleep's Role in Memory (2013) · cites this paper as [576]
Experimental — accuracy not yet measuredIn the citing paper
“several types of studies point to the conclusion that the elaborate processes yielding fully developed LTP reach completion within 10–15 min (5, 7, 8);”
From Synaptic evidence for the efficacy of spaced learning (2012) · cites this paper as [8]
In the citing paper
“Low-frequency (5-Hz) stimulation erases LTP1 if applied shortly after TBS but then becomes progressively less effective over the following 30 min (8, 14);”
From Synaptic evidence for the efficacy of spaced learning (2012) · cites this paper as [8]
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Metadata
- Authors
- Huang, C.-C., Liang, Y.-C., & Hsu, K.-S.
- Affiliations
- National Cheng Kung University (TW)
- ORCID
- Hsu, Kuei-Sen
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-11-15
- Volume
- 19
- Issue
- 22
- Pages
- 9728-9738
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782980
- OpenAlex
- W1536302928
- Cited by
- 127
- References
- 49
- Citations by year
- 2025: 2 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 4 · 2016: 7 · 2015: 6 · 2014: 9 · 2013: 6 · 2012: 7
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- extracellular adenosine, long-term potentiation, depotentiation, low-frequency stimulation, adenosine A1 receptor, Schaffer collateral-CA1 synapses, hippocampus, cAMP signaling, protein phosphatase 2A, 5-HT1A receptor, buspirone, synaptic plasticity
- MeSH terms
- Adenosine, Cyclic AMP, Animals, Buspirone, Electric Stimulation, Enzyme Inhibitors, Colforsin, Hippocampus, Male, Synaptic Transmission, Neurons, Piperazines, Receptors, Serotonin, Serotonin Antagonists, Synapses, Theobromine, Thionucleotides, Time Factors, Xanthines, Least-Squares Analysis, Rats, Sprague-Dawley, Serotonin Receptor Agonists, Long-Term Potentiation, Pyramidal Cells, Excitatory Postsynaptic Potentials, Receptors, Serotonin, 5-HT1, Rats, Purinergic P1 Receptor Antagonists, In Vitro Techniques
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