The Cell-adhesion Molecule F3/Contactin Improves Hippocampal Neurogenesis, Synaptic Plasticity and Memory in Adult Mice

Objectives: F3/contactin is a cell-adhesion molecule belonging to the immunoglobulin supergene family, involved in several aspects of neural development, including synapse building, maintaining and function. Here, we address the F3/contactin role in adult hippocampal neurogenesis, synaptic plasticity and memory. Methods: We used transgenic mice undergoing F3/contactin overexpression under control of regulatory sequences from the human TAG-1 (TAX-1) gene (TAG/F3 mice). We performed immunohistochemical, cell proliferation and western blot analyses to study neurogenesis, F3/contactin expression and cAMP-responsive element-binding (CREB) phosphorylation; electrophysiological and behavioral studies allowed us to evaluate hippocampal synaptic plasticity and memory at different ages. Results: Five and twelve month-old transgenic animals show an increase in the hippocampal size, precursor proliferation and NeuN expression, thus suggesting that F3/contactin might promote postnatal hippocampal neurogenesis. Moreover, CA1-long-term potentiation, spatial reference and object recognition memory are improved in 12 month TAG/F3 mice compared to controls. Interestingly, these morphological and functional phenotypes correlate to a higher phosphorylation of the transcription factor and memory molecule CREB. Conclusions: Our data indicate, for the first time, that F3/contactin plays a novel role in late development, where it positively modulates neurogenesis, synaptic plasticity and memory through increased CREB phosphorylation.