Memory enhancement and formation by atypical PKM activity in Drosophila melanogaster

Nat Neurosci. 2002 Apr;5(4):316-24. doi: 10.1038/nn820.


Synaptic stimulation activates signal transduction pathways, producing persistently active protein kinases. PKMzeta is a truncated, persistently active isoform of atypical protein kinase C-zeta (aPKCzeta), which lacks the N-terminal pseudosubstrate regulatory domain. Using a Pavlovian olfactory learning task in Drosophila, we found that induction of the mouse aPKMzeta (MaPKMzeta) transgene enhanced memory. The enhancement required persistent kinase activity and was temporally specific, with optimal induction at 30 minutes after training. Induction also enhanced memory after massed training and corrected the memory defect of radish mutants, but did not improve memory produced by spaced training. The 'M' isoform of the Drosophila homolog of MaPKCzeta (DaPKM) was present and active in fly heads. Chelerythrine, an inhibitor of PKMzeta, and the induction of a dominant-negative MaPKMzeta transgene inhibited memory without affecting learning. Finally, induction of DaPKM after training also enhanced memory. These results show that atypical PKM is sufficient to enhance memory in Drosophila and suggest that it is necessary for normal memory maintenance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids
  • Animals
  • Animals, Genetically Modified
  • Avoidance Learning
  • Benzophenanthridines
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / physiology*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Head / physiology
  • Hot Temperature
  • Male
  • Memory / physiology*
  • Phenanthridines / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Smell / physiology
  • Tissue Extracts / chemistry
  • Tissue Extracts / metabolism


  • Alkaloids
  • Benzophenanthridines
  • Drosophila Proteins
  • Enzyme Inhibitors
  • Phenanthridines
  • Tissue Extracts
  • chelerythrine
  • Protein Kinase C