Compensation for PKMz in long term potentiation and spatial long term memory in mutant mice
PKMz is a persistently active PKC isoform proposed to maintain late LTP and long term memory. But late LTP and memory are maintained without PKMz in PKMz null mice. Two hypotheses can account for these findings. First, PKMz is unimportant for LTP or memory. Second, PKMz is essential for late LTP and long term memory in wild type mice, and PKMz null mice recruit compensatory mechanisms. We find that whereas PKMz persistently increases in LTP maintenance in wild type mice, PKCi/l, a gene product closely related to PKMz, persistently increases in LTP maintenance in PKMz null mice. Using a pharmacogenetic approach, we find PKMz antisense in hippocampus blocks late LTP and spatial long term memory in wild type mice, but not in PKMz null mice without the target mRNA. Conversely, a PKCi/l antagonist disrupts late LTP and spatial memory in PKMz null mice but not in wild type mice. Thus, whereas PKMz is essential for wild type LTP and long term memory, persistent PKCi/l activation compensates for PKMz loss in PKMz null mice. DOI: http:/dx.doi.org/10.7554/eLife.14846.001
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