Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and...

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Published in:eLife 2016-05, Vol.5
Main Authors: Tsokas, Panayiotis, Hsieh, Changchi, Yao, Yudong, Lesburguères, Edith, Wallace, Emma Jane Claire, Tcherepanov, Andrew, Jothianandan, Desingarao, Hartley, Benjamin Rush, Pan, Ling, Rivard, Bruno, Farese, Robert V, Sajan, Mini P, Bergold, Peter John, Hernández, Alejandro Iván, Cottrell, James E, Shouval, Harel Z, Fenton, André Antonio, Sacktor, Todd Charlton
Format: Article
Language:English
Subjects:
Animals
Antisense RNA
atypical PKC
Hippocampus - physiology
Hypotheses
Kinases
Long term memory
Long-Term Potentiation
LTP
memory
Memory, Long-Term
Mice
Mice, Knockout
mRNA
Neuroscience
Neurosciences
Pharmacogenetics
Physiology
PKCiota/lambda
PKM-zeta
PKMzeta
Protein Kinase C - metabolism
Protein synthesis
Proteins
Rodents
Signal transduction
Spatial Memory
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Summary:PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.14846