Double dissociation between the involvement of Gadd45α and Gadd45β/γ in the perirhinal cortex and hippocampus of male rats for object memory

The GADD45 family of proteins (GADD45α, GADD45β, GADD45γ) has been implicated in DNA demethylation and long-term memory formation. Recently, conflicting findings have emerged surrounding the involvement of Gadd45α in various object recognition tasks. These discrepancies could be due to differences in Gadd45α KO mouse models and/or task parameters. Further, the use of brain-wide KO models precludes our understanding of Gadd45α in specific brain regions such as the hippocampus (HPC), which processes the spatial location of objects, or the perirhinal cortex (PRh), which has a larger role in object identity memory. Here, using a single object recognition task reliant on both the PRh and HPC - the object-in-place (OiP) task - we show that siRNA knockdown of Gadd45β or Gadd45γ, but not Gadd45α, within the dorsal HPC (dHPC) impaired long-term, but not short-term, OiP memory. Further, OiP learning induced an upregulation of Gadd45β mRNA in the dentate gyrus subregion of the dHPC. Within the PRh, siRNA knockdown of Gadd45α, but not Gadd45β or Gadd45γ, impaired long-term, but not short-term, OiP memory, with a concomitant increase in learning induced PRh Gadd45α mRNA. These results clarify previous discrepancies in the literature by demonstrating a clear necessity for Gadd45α in the PRh, but not the dHPC, for the consolidation of long-term object memories.