CONICET | Buscador de Institutos y Recursos Humanos

Differentiating between similar memories is a crucial cognitive function that enablescorrect episodic memory formation. The ability to separate the components of mem-ories into distinct representations is thought to rely on a computational processknown as pattern separation, by which differences are amplified to disambiguate sim-ilar events. Although pattern separation has been localized to the dentate gyrus(DG) of the hippocampus and shown to occur in a spatial domain, this cognitive func-tion takes place also during processing of other types of information. In particular,there is some debate on whether the DG participates in pattern separation of non-spatial representations. Considering the classic role of the Prh in the acquisition andstorage of object memories in general and tasks with similar features in particular,this cognitive function could rely more heavily on perirhinal regions when object-related information is processed. Here we show that two plasticity-related proteins,BDNF, and Arc, are required in the DG for nonspatial mnemonic differentiation.Moreover, we found that the crucial role of the DG is transient since activity ofAMPAR is only required in the Prh but not the DG during differentiated object mem-ory retrieval. Additionally, this memory is not modifiable by postacquisition rhBDNFinfusions in the DG that are known to improve memory when given in the Prh. Thishighlights a differential role of Prh and DG during differentiated object memory con-solidation. Additionally, we found that these molecular mechanisms actively interactin the DG and Prh for the formation of distinguishable memories, with infusions ofrhBDNF in the Prh being able to rescue mnemonic deficits caused by reduced Arcexpression in the DG. These results reveal a complex interaction between plasticitymechanisms in the Prh and DG for nonspatial pattern separation and posit the Prh asthe key structure where unique object representations are stored.