Cited by 205Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsCell Adhesion Molecules Research

Time-Dependent Reversal of Long-Term Potentiation by an Integrin Antagonist

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Stäubli, Ursula, Chun, Daniel, Lynch, Gary·1998·The Journal of Neuroscience

Abstract

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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Crossref · 10.1523/jneurosci.18-09-03460.1998

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  1. Russell RW (1959) Brain, memory, learning. Oxford: C larendon.

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Authors
Stäubli, U., Chun, D., & Lynch, G.
Affiliations
University of California, Irvine (US)
Venue
The Journal of Neuroscience
Published
1998-05-01
Volume
18
Issue
9
Pages
3460-3469
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
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
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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