Musgrove, M. R. B.; Leighton, L. J.; Liau, W.-S.; Walsh, A. D.; Marshall, P. R.; Heyworth, S. M.; Bademosi, A. T. D.; Hertrich, N.; Zhao, Q.; Madugalle, S. U.; Periyakaruppiah, A.; Li, X.; Davies, J. W. A.; Ren, H.; Gong, H.; Meunier, F.; Mikhaylova, M.; Bredy, T.

Vaults are large ribonucleoprotein complexes of unknown function in neurons. Here, we report that the Vault-associated noncoding RNA, Vaultrc5, is highly enriched at the synapse and is required for activity-dependent Vault trafficking in neurons. We have discovered that Vaults are comprised of unique populations of coding and non-coding RNA, and that this cargo varies dynamically between subcellular compartments. In addition, Vaultrc5 knockdown at the synapse shifts the RNA cargo toward transcripts associated with immune surveillance, and Vaultrc5 knockdown, in vivo, leads to impaired fear learning. These findings suggest that the Vaultrc5 is critically involved in coordinating the experience-dependent trafficking of Vaults and related RNA cargo, which represents a novel feature of neuronal plasticity underlying learning and memory.