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Evidence that integrins contribute to multiple stages in the consolidation of long term potentiation in rat hippocampus.

Abstract：

:Three structurally distinct groups of antagonists were used to test the hypothesis that integrin adhesion receptors play an essential role in consolidating (stabilizing) long term potentiation of the Schaffer collaterals in rat hippocampus. Comparisons were made of percent potentiation at antagonist-treated versus control sites within CA1 stratum radiatum of the same hippocampal slice. Function blocking antibodies against the alpha5 subunit of the fibronectin receptor had no effect on baseline responses or initial potentiation but resulted in a >30% reduction, relative to within-slice control long term potentiation, 45 min later. Larger reductions were recorded in separate experiments continued for 4 h after the induction of potentiation. Alpha(v) and alpha2 subunit antibodies did not reliably affect the stabilization of potentiation. An antagonist peptide with preference for beta1 integrins produced a slowly developing decline of the type seen with alpha5 antibodies. A cyclic peptide antagonist reduced potentiation within 10 min of induction and caused an almost 40% decrease over 45 min. Two disintegrins (snake toxins that potently block integrins) were very effective in preventing the consolidation of long term potentiation: echistatin reduced potentiation by >70%, while triflavin caused approximately 50% decrease. The suppressing effects of echistatin were concentration-dependent, obtained with treatment after induction, and much more rapid than the effects of antibodies. Rapid declines in potentiation were particularly evident when the two disintegrins were applied together. These results indicate that hippocampal fibronectin receptors (alpha5/beta1 integrin) contribute importantly to a slowly developing phase of long term potentiation consolidation. They also suggest that other integrins are critical to aspects of consolidation occurring in the first few minutes after induction.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Chun D,Gall CM,Bi X,Lynch G

doi

10.1016/s0306-4522(01)00173-7

keywords:

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

815-29

issue

4

eissn

0306-4522

issn

1873-7544

pii

S0306452201001737

journal_volume

105

pub_type

杂志文章

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