CONICET | Buscador de Institutos y Recursos Humanos

Successful memory involves not only remembering information over time but also keeping memories distinct and less confusable. The abilityto separate the components of memories into distinct memory representations relies on pattern separation, a computational process bywhich differences are amplified to disambiguate similar events. Despite the importance of this mnemonic function, the molecular mechanismsand signals necessary for the behavioral manifestations of this process remain unknown. Although pattern separation has been localizedto the dentate gyrus (DG) of the hippocampus and shown to occur in a spatial domain, this cognitive function is thought to take place alsoduring processing of other types of information. The perirhinal cortex (PRH) is involved in the acquisition and storage of object memories,and it was shown to be crucial for the resolution of tasks with ambiguous features. However, there is some debate on whether the DG participatesin pattern separation of non spatial representations. Here we show that two plasticity-related proteins, BDNF and Arc, are required forpattern separation of object memories in the PRH and that Arc is also required in the DG for this process. In addition, while exogenous BDNFwas able to enhance pattern separation when injected into PRH, it was not effective when infused within the DG. Finally, BDNF injected intoPRH was able to rescue the memory deficit produce by blockade of Arc in the DG. These results reveal a complex interaction between plasticitymechanisms in the PRH and the DG for non spatial pattern separation and posit the Prh as the key structure where unique object representationsare stored.