F3, also known as Contactin, is a neuronal cell adhesion molecule belonging to the immunoglobulin superfamily [1]. It plays crucial roles in axogenesis, myelination, synaptic plasticity, and memory. It exerts heterophilic binding activities, interacting with molecules like the L1 family of Ig-CAMs, extracellular matrix components, and RPTPbeta/phosphacan, influencing axonal growth, fasciculation, and the organization of axonal subdomains at the node of Ranvier [1].

F3-deficient mice display severe ataxia correlated with defects in axonal and dendritic projections in the cerebellum, as well as nerve influx conduction defects due to disrupted axo-glial contacts at paranodes [1]. In adult and aged mice, overexpression of F3/Contactin in a transgenic model affects long-term potentiation (LTP), spatial and object recognition memory, and phosphorylation of the transcription factor cAMP-Responsive-Element Binding protein (CREB) [2]. In the context of depression, chronic stress (such as chronic restraint stress and chronic social defeat stress) significantly decreases F3/Contactin expression in the hippocampus of mice. Over-expression of hippocampal F3/Contactin prevents chronic stress-induced depressive-like behaviors, while knockdown abolishes the protective effects of the antidepressant vortioxetine [3].

In conclusion, F3 is essential for neuronal development, synaptic function, and memory. The study of F3 using mouse models, especially those with gene manipulation, has revealed its significance in neurological functions and in conditions like ataxia and depression, providing insights into potential therapeutic targets for related diseases.