Beta 1-Integrins Are Required for Hippocampal Ampa Receptor-Dependent Synaptic Transmission, Synaptic Plasticity, and Working Memory

Authors

Chi-Shing Chan, Departments of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030
Edwin J. Weeber, Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030
Lin Zong, Departments of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030
Elaine Fuchs, Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021
J David Sweatt, Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030
Ronald L. Davis, Departments of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas 77030

Publication Date

1-4-2006

Journal

The Journal of Neuroscience

DOI

10.1523/JNEUROSCI.4110-05.2006

PMID

16399691

PubMedCentral® Posted Date

January 2006

PubMedCentral® Full Text Version

Post-print

Published Open-Access

no

Keywords

Animals, Antigens, CD29, Hippocampus, Memory, Mice, Mice, Inbred C57BL, Mice, Knockout, Neuronal Plasticity, Receptors, AMPA, Synaptic Transmission

Abstract

Integrins comprise a large family of cell adhesion receptors that mediate diverse biological events through cell-cell and cell-extracellular matrix interactions. Recent studies have shown that several integrins are localized to synapses with suggested roles in synaptic plasticity and memory formation. We generated a postnatal forebrain and excitatory neuron-specific knock-out of beta1-integrin in the mouse. Electrophysiological studies demonstrated that these mutants have impaired synaptic transmission through AMPA receptors and diminished NMDA receptor-dependent long-term potentiation. Despite the impairment in hippocampal synaptic transmission, the mutants displayed normal hippocampal-dependent spatial and contextual memory but were impaired in a hippocampal-dependent, nonmatching-to-place working memory task. These phenotypes parallel those observed in animals carrying knock-outs of the GluR1 (glutamate receptor subunit 1) subunit of the AMPA receptor. These observations suggest a new function of beta1-integrins as regulators of synaptic glutamate receptor function and working memory.

Comments

PMCID: PMC2408376