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The Journal of Neuroscience, May 1, 1998, 18(9):3460-3469
Time-Dependent Reversal of Long-Term Potentiation by an Integrin Antagonist
Ursula Stäubli, Daniel Chun, and Gary Lynch2 Center for Neural Science, New York University, New York, New York 10003, and 2 Center for the Neurobiology of Learning and Memory, University of California, Irvine, California 92697
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.
Key words: LTP reversal; adhesion receptors; integrins; NCAMs; consolidation; memory; hippocampus; retrograde amnesia
Copyright © 1998 Society for Neuroscience 0270-6474/98/1893460-10$05.00/0
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