Alpha3-integrins are required for hippocampal long-term potentiation and working memory.
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 beta1-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 alpha3-integrin, one of several binding partners for beta1 subunit. At hippocampal Schaffer collateral-CA1 synapses, deletion of alpha3-integrin resulted in impaired long-term potentiation (LTP). Basal synaptic transmission and paired-pulse facilitation were normal in the absence of alpha3-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 hippocampus-dependent spatial tasks. The impairment in LTP and working memory is similar to that observed in beta1-integrin conditional knockout mice, suggesting that alpha3-integrin is the functional binding partner for beta1 for these processes in the forebrain.
Chan
Chi-Shing
CS
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Levenson
Jonathan M
JM
Mukhopadhyay
Partha S
PS
Zong
Lin
L
Bradley
Allan
A
Sweatt
J David
JD
Davis
Ronald L
RL
D000818:Animals; D004594:Electrophysiology; D017353:Gene Deletion; D006624:Hippocampus / Q000502:physiology* / Q000648:ultrastructure; D066298:In Vitro Techniques; D039422:Integrin alpha3 / Q000235:genetics / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D018782:Maze Learning; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009048:Motor Skills; D016548:Prosencephalon / Q000378:metabolism; D011597:Psychomotor Performance; D013550:Swimming; D013569:Synapses / Q000378:metabolism
D039422:Integrin alpha3