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The Journal of Neuroscience, January 4, 2006, 26(1):223-232; doi:10.1523/JNEUROSCI.4110-05.2006

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Behavioral/Systems/Cognitive
1-Integrins Are Required for Hippocampal AMPA Receptor-Dependent Synaptic Transmission, Synaptic Plasticity, and Working Memory

Chi-Shing Chan,¹ Edwin J. Weeber,² Lin Zong,¹ Elaine Fuchs,⁴ J. David Sweatt,² and Ronald L. Davis^1,3

Departments of ¹Molecular and Cellular Biology and ²Neuroscience and ³Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas 77030, and ⁴Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021

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 1-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 1-integrins as regulators of synaptic glutamate receptor function and working memory.

Key words: integrins; AMPA receptors; basal synaptic transmission; LTP; working memory; synaptic plasticity

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Received Sep 27, 2005; revised November 10, 2005; accepted November 11, 2005.

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