Journal
JOURNAL OF NEUROSCIENCE
Volume 26, Issue 1, Pages 223-232Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4110-05.2006
Keywords
integrins; AMPA receptors; basal synaptic transmission; LTP; working memory; synaptic plasticity
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Funding
- NIAMS NIH HHS [R01 AR027883-28] Funding Source: Medline
- NICHD NIH HHS [HD24064, P30 HD024064] Funding Source: Medline
- NIMH NIH HHS [R01 MH060420, MH60420] Funding Source: Medline
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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 beta 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 beta 1-integrins as regulators of synaptic glutamate receptor function and working memory.
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