Alpha3-integrins are required for hippocampal long-term potentiation and working memory.

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.