α3-Integrins are required for hippocampal long-term potentiation and working memory
- Chi-Shing Chan1,
- Jonathan M. Levenson2,3,6,
- Partha S. Mukhopadhyay3,
- Lin Zong1,
- Allan Bradley4,7,
- J. David Sweatt2,8, and
- Ronald L. Davis1,5,9
- 1 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA;
- 2 Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA;
- 3 Department of Pharmacology and The Waisman Center, University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin 53706, USA;
- 4 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA;
- 5 Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas 77030, USA
Abstract
Integrins comprise a large family of heterodimeric, transmembrane cell adhesion receptors that mediate diverse neuronal functions in the developing and adult CNS. Recent pharmacological and genetic studies have suggested that β1-integrins are critical in synaptic plasticity and memory formation. To further define the role of integrins in these processes, we generated a postnatal forebrain and excitatory neuron-specific knockout of α3-integrin, one of several binding partners for β1 subunit. At hippocampal Schaffer collateral-CA1 synapses, deletion of α3-integrin resulted in impaired long-term potentiation (LTP). Basal synaptic transmission and paired-pulse facilitation were normal in the absence of α3-integrin. Behavioral studies demonstrated that the mutant mice were selectively defective in a hippocampus-dependent, nonmatch-to-place working memory task, but were normal in other hippocampusdependent spatial tasks. The impairment in LTP and working memory is similar to that observed in β1-integrin conditional knockout mice, suggesting that α3-integrin is the functional binding partner for β1 for these processes in the forebrain.
Footnotes
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↵6 Present addresses: Galenea Corp., Cambridge, MA 02139, USA;
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↵7 Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK;
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↵8 Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35282-9191, USA.
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↵9 Corresponding author.
↵9 E-mail rdavis{at}bcm.tmc.edu; fax (713) 798-8005.
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Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.648607
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- Received May 25, 2007.
- Accepted July 30, 2007.
- Copyright © 2007, Cold Spring Harbor Laboratory Press