Persistently increased hippocampal PKMζ expression correlates with spatial long term memory maintenance

Abstract

The constitutively active, atypical protein kinase C isoform PKMζ has been strongly implicated in the maintenance of long‐term memory (LTM) in various animal models (Sacktor TC, Mol Brain 18;5(1): 31 [2012]). PKMζ is also involved in spatial LTM, and its necessity for maintaining memory has been demonstrated days and even weeks after memory formation (Pastalkova E, et al., Science 313(5790): 1141–1144 [2006]). Here, we show that PKMζ expression is significantly increased in the hippocampus after memory formation, specifically in the stratum radiatum, stratum lacunosum‐moleculare, and CA1 pyramidal cell layers. Adult male wild‐type mice received 4 active place avoidance training trials, at 1 hour intervals, for 2 consecutive days. Their retention was tested 1 month later. Their brains were harvested, fixed in 4% paraformaldehyde, and sectioned into 40 μM slices. PKMζ localization was analyzed using immunohistochemistry (IHC) and confocal microscopy. Western blots of hippocampal homogenates were also performed. We show that PKMζ levels increased in the aforementioned areas, compared to unconditioned animals. Additionally, the level of PKMζ expression by Western blot and IHC correlates with LTM performance. Thus, we argue that PKMζ protein is a physical substrate of the engram and is responsible for the maintenance of LTM.Grant Funding Source: NIH Grant R01DA034970