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The Journal of Neuroscience, October 25, 2006, 26(43):11208-11219; doi:10.1523/JNEUROSCI.3526-06.2006

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Development/Plasticity/Repair
Distinct Roles of the 1-Class Integrins at the Developing and the Mature Hippocampal Excitatory Synapse

Zhen Huang,¹ Kazuhiro Shimazu,³ Newton H. Woo,³ Keling Zang,² Ulrich Müller,⁴ Bai Lu,³ and Louis F. Reichardt^1,2

¹Department of Physiology and ²Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143, ³Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, and ⁴The Scripps Research Institute, Department of Cell Biology, Institute for Childhood and Neglected Disease, La Jolla, California 92037

Correspondence should be addressed to Louis F. Reichardt, Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, 1550 Fourth Street, San Francisco, CA 94143. Email: lfr{at}cgl.ucsf.edu

Integrins are a large family of cell adhesion receptors involved in a variety of cellular functions. To study their roles at central synapses, we used two cre recombinase lines to delete the Itgb1 1 integrin gene in forebrain excitatory neurons at different developmental stages. Removal of the 1 integrins at an embryonic stage resulted in severe cortical lamination defects without affecting the cellular organization of pyramidal neurons in the CA3 and CA1 regions of the hippocampus. Whereas the hippocampal neurons underwent normal dendritic and synaptic differentiation, the adult synapses exhibited deficits in responses to high-frequency stimulation (HFS), as well as in long-term potentiation (LTP). Deletion of 1 integrin at a later postnatal stage also impaired LTP but not synaptic responses to HFS. Thus, the 1-class integrins appear to play distinct roles at different stages of synaptic development, critical for the proper maturation of readily releasable pool of vesicles during early development but essential for LTP throughout adult life.

Key words: 1 integrin; cell adhesion molecule; hippocampus; synaptic maturation; synaptic vesicle pool; long-term potentiation

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Received Oct. 17, 2005; revised Sept. 21, 2006; accepted Sept. 21, 2006.

Correspondence should be addressed to Louis F. Reichardt, Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, 1550 Fourth Street, San Francisco, CA 94143. Email: lfr{at}cgl.ucsf.edu

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