Molecular mechanisms in perirhinal cortex selectively necessary for discrimination of overlapping memories, but independent of memory persistence

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Successful memory involves not only remembering over time but also keeping memories distinct. The ability to separate similar experiences into distinct memories is a main feature of episodic memory. Discrimination of overlapping representations has been investigated in the dentate gyrus of the hippocampus (DG), but little is known about this process in other regions such as the perirhinal cortex (Prh). We found in male rats that perirhinal brain-derived neurotrophic factor (BDNF) is required for separable storage of overlapping, but not distinct, object representations, which is identical to its role in the DG for spatial representations. Also, activity-regulated cytoskeletal-associated protein (Arc) is required for disambiguation of object memories, as measured by infusion of antisense oligonucleotides. This is the first time Arc has been implicated in the discrimination of objects with overlapping features. Although molecular mechanisms for object memory have been shown previously in Prh, these have been dependent on delay, suggesting a role specifically in memory duration. BDNF and Arc involvement were independent of delay—the same demand for memory persistence was present in all conditions— but only when discrimination of similar objects was required were these mechanisms recruited and necessary. Finally, we show that BDNF and Arc participate in the same pathway during consolidation of overlapping object memories. We provide novel evidence regarding the proteins involved in disambiguation of object memories outside the DG and suggest that, despite the anatomical differences, similar mechanisms underlie this process in the DG and Prh that are engaged depending on the similarity of the stimuli.