F3/contactin is a cell-adhesion molecule belonging to the immunoglobulin supergene family, involved in several aspects of neural development, which include synapse building, maintaining and function. Because F3/contactin is highly expressed in structures related to learning and memory such as the hippocampus, here we investigate its role in synaptic plasticity and memory. We use transgenic mice undergoing F3/contactin overexpression under control of regulatory sequences from the human TAG-1 (TAX-1) gene (TAG/F3 mice). Although 5-months-old TAG/F3 homozygotes mice show no changes in either behavioral performance or electrophysiological recordings, they display an improvement of spatial reference memory, object recognition memory, and long-term potentiation at CA1 hippocampal region at 12 months of age compared to wild type littermates. Moreover, a higher phosphorylation of the transcription factor and memory molecule CREB parallels the observed cognitive changes. Finally, the increase of NeuN positive cells and hippocampal size support a possible involvement of F3/contactin in hippocampal neurogenesis. Overall, these findings indicate that F3/contactin plays a new interesting role in hippocampal development and functions.