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Time-Dependent Reversal of Long-Term Potentiation by an Integrin Antagonist
Open accessAbstract
The integrin antagonist Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) was applied by local ejection to one of two recording sites in hippocampal slices at various times before and after long-term potentiation (LTP) was induced at both sites with theta burst stimulation. Applications 10 min before, immediately after, and 10 min after induction caused LTP at the experimental site to decay steadily relative to that at the within-slice control site. However, application at 25 min or more after induction had no detectable effect on potentiation. Similar results were obtained when the integrin antagonist was perfused into the slice rather than applied locally. The time period after induction during which GRGDSP interfered with LTP consolidation corresponds to that during which LTP is susceptible to reversal by low-frequency afferent stimulation and newly formed memories are vulnerable to various disruptive treatments. Comparable experiments using a peptide that blocks an extracellular binding site of neural cell adhesion molecules (NCAMs) did not yield time-dependent reversal of LTP; i.e., an antagonist that interacts with the fourth immunoglobulin-like domain reduced LTP when applied before induction but not afterward. Moreover, LTP formation occurred normally in the presence of an antibody against the fibronectin repeat domain of NCAM. These results suggest that integrin activation and signaling occurring over several minutes after LTP induction are necessary for stabilizing synaptic potentiation and by inference may be required for the conversion of new memories into a not readily disrupted state.
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“The RGD sequence is a short amino acid motif essential for cell adhesion. It is found in various cell adhesion molecules, and its importance in recognizing and binding to integrins and the role in plasticity and LTP have been widely documented (Bahr et al. 1997; Stäubli et al. 1998; Watson et al. 2007).”
From The Serine/Threonine Kinase NDR2 Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Stäubli et al. 1998
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Metadata
- Authors
- Stäubli, U., Chun, D., & Lynch, G.
- Affiliations
- University of California, Irvine (US)
- ORCID
- Lynch, Gary
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1998-05-01
- Volume
- 18
- Issue
- 9
- Pages
- 3460-3469
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6792671
- OpenAlex
- W1555498151
- Cited by
- 205
- References
- 57
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 8 · 2013: 6 · 2012: 6
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Whitehall Foundation
- Air Force Office of Scientific Research (F49620)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- long-term potentiation, integrin antagonism, GRGDSP peptide, hippocampus, theta burst stimulation, CD56, synaptic potentiation, memory consolidation, integrin signaling
- MeSH terms
- Amino Acid Sequence, Animals, Binding, Competitive, Electric Stimulation, Molecular Sequence Data, Oligopeptides, Time Factors, Integrins, Rats, Sprague-Dawley, Long-Term Potentiation, Neural Cell Adhesion Molecules, Excitatory Postsynaptic Potentials, Rats, In Vitro Techniques
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