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

Elife. 2016 May 17;5:e14846. doi: 10.7554/eLife.14846.

Abstract

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.

Keywords: LTP; PKCiota/lambda; PKM-zeta; PKMzeta; atypical PKC; memory; mouse; neuroscience.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Hippocampus / physiology*
  • Long-Term Potentiation*
  • Memory, Long-Term*
  • Mice
  • Mice, Knockout
  • Pharmacogenetics
  • Protein Kinase C / metabolism*
  • Spatial Memory

Substances

  • protein kinase C zeta
  • Protein Kinase C