CONTACTIN-2: A NOVEL PLAYER IN SYNAPTIC PLASTICITY

Contactin-2 (CNTN2/TAG-1), a member of the immunoglobulin superfamily of neuronal adhesion molecules, is implicated in neurite outgrowth, guidance, fasciculation, and the organization of subdomains around the nodes of Ranvier in myelinated axons. Results from animal models targeting CNTNs and their co-receptors (CNTNAPs) demonstrate their involvement in neurodevelopmental and other central nervous system pathologies. CNTN2 in particular is correlated with multiple sclerosis and idiopathic generalized epilepsy (IGE). Given the yet unexplored function of CNTN2 in synapses and accumulating evidence implicating cell adhesion molecules in activity-dependent synaptic modifications associated with LTP or LTD, we investigated the significance of its expression by analyzing the synaptic phenotype of CNTN2-deficient mice using a plethora of in vitro and in vivo techniques, electrophysiology, behavior, and high-throughput analysis. Our unpublished data show CNTN2 in synaptoneurosomes and establish its expression in both inhibitory and excitatory synapses in vitro in both presynaptic and postsynaptic compartments. Additionally, they highlight its significance in the maintenance of synaptic plasticity, as evidenced by severe deficits in the long-term potentiation (LTP) profile of the mouse hippocampus of CNTN2-deficient mice. Other accompanying significant defects are observed in mature spine density, while behavioral defects assessment of the mutant mice point to defects in fear memory and cognition. These functional results are further supported by high-throughput proteomic analysis, which present candidate pathways that are currently under validation. In conclusion, our work points to the important role of a novel, yet unexplored player in synaptic plasticity mechanisms.