RNF10 as an NMDA receptor-dependent signaling protein necessary for cognitive flexibility

However, the role of synaptonuclear messengers in regulating cognitive behavior has not been fully clarified. Here, we demonstrated that RNF10-mediated synapse-to-nucleus signaling, linking activation of synaptic NMDARs to nuclear gene expression in the dorsal CA1, is necessary for cognitive flexibility.

In vivo RNF10 downregulation, through gene deletion and silencing, induced alterations in dendritic branching, spine morphology, and long-term potentiation, specifically in CA1. At the behavioral level, we observed poor cognitive flexibility, which is reflected in the impaired ability to disengage from previously acquired contextual, visual, and spatial information. Overall, our results identified RNF10 as a key in vivo player necessary for the correct expression of cognitive flexibility.