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

Panayiotis Tsokas, Changchi Hsieh, Yudong Yao, Edith Lesburguères, Emma Jane Claire Wallace, Andrew Tcherepanov, Desingarao Jothianandan, Benjamin Rush Hartley, Ling Pan, Bruno Rivard, Robert V. Farese, Mini P. Sajan, Peter John Bergold, Alejandro Iván Hernández, James E. Cottrell, Harel Z. Shouval, André Antonio Fenton, Todd Charlton Sacktor

Research output: Contribution to journalArticle

Abstract

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and longterm 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, PKCı/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 PKCą/Ĉ-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 PKCı/λ activation compensates for PKMζ loss in PKMζ-null mice.

Original languageEnglish (US)
Article numbere14846
JournaleLife
Volume5
Issue numberMAY2016
DOIs
StatePublished - May 17 2016

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Tsokas, P., Hsieh, C., Yao, Y., Lesburguères, E., Wallace, E. J. C., Tcherepanov, A., Jothianandan, D., Hartley, B. R., Pan, L., Rivard, B., Farese, R. V., Sajan, M. P., Bergold, P. J., Hernández, A. I., Cottrell, J. E., Shouval, H. Z., Fenton, A. A., & Sacktor, T. C. (2016). Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice. eLife, 5(MAY2016), [e14846]. https://doi.org/10.7554/eLife.14846