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Memory enhancement and formation by atypical PKM activity in Drosophila melanogaster

Nature Neuroscience volume 5, pages 316324 (2002) | Download Citation

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Abstract

Synaptic stimulation activates signal transduction pathways, producing persistently active protein kinases. PKMζ is a truncated, persistently active isoform of atypical protein kinase C-ζ (aPKCζ), which lacks the N-terminal pseudosubstrate regulatory domain. Using a Pavlovian olfactory learning task in Drosophila, we found that induction of the mouse aPKMζ (MaPKMζ) 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 MaPKCζ (DaPKM) was present and active in fly heads. Chelerythrine, an inhibitor of PKMζ, and the induction of a dominant-negative MaPKMζ 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.

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Acknowledgements

E.A.D. is a postdoctoral fellow (fellowship no. PF-99-342-01-DDC) of the American Cancer Society. M.K.T. is a Fulbright/CONACYT fellow. A. Romanelli and J. Blenis provided the K281W mutant clone. We thank K. Svoboda, J. Dubnau and members of the Yin and Tully laboratories for comments on the manuscript.

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  1. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA

    • Eric A. Drier
    • , Marcela K. Tello
    • , Maureen Cowan
    • , Priscilla Wu
    •  & Jerry C.P. Yin
  2. Graduate Program in Genetics, SUNY Stony Brook, Stony Brook, New York 11794, USA

    • Marcela K. Tello
  3. Laboratory of Molecular Neuroscience, Departments of Physiology, Pharmacology and Neurology, Box 29, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, USA

    • Nancy Blace
    •  & Todd Charlton Sacktor

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The authors declare no competing financial interests.

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Correspondence to Jerry C.P. Yin.

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https://doi.org/10.1038/nn820

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