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

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 Itgb11 integrin gene in forebrain excitatory neurons at different developmental stages. Removal of the1 integrins at an embryonic stage resulted in severe cortical lamination defects without affecting the cellular organiza-tion 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, the1-class integrins appear to play distinct roles at different stages of synaptic development, critical for the propermaturation 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 potentiatio