PKMζ maintains spatial, instrumental, and classically conditioned long-term memories

Peter Serrano, Eugenia L. Friedman, Jana Kenney, Stephen M. Taubenfeld, Joshua M. Zimmerman, John Hanna, Cristina Alberini, Ann E. Kelley, Stephen Maren, Jerry W. Rudy, Jerry C P Yin, Todd C. Sacktor, Andre Fenton

Research output: Contribution to journalArticle

Abstract

How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMζ), an autonomously active atypical protein kinase C (PKC) isoform critical for the maintenance of long-term potentiation (LTP). PKMζ maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP) by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMζ activity. We then examined, using ZIP, the effect of PKMζ inhibition in dorsal hippocampus (DH) and basolateral amygdala (BLA) on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMζ inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMζ activity. Similarly, PKMζ inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMζ inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US) associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMζ inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMζ activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise, or procedural information.

Original languageEnglish (US)
Article numbere318
Pages (from-to)2698-2706
Number of pages9
JournalPLoS Biology
Volume6
Issue number12
DOIs
StatePublished - Dec 2008

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Long-Term Memory
protein kinases
Protein Kinases
Data storage equipment
fearfulness
Fear
amygdala
hippocampus
Hippocampus
conditioned behavior
Brain
peptides
Peptides
brain
Water
Long-Term Potentiation
neurophysiology
Protein Kinase Inhibitors
Neurosciences
Short-Term Memory

ASJC Scopus subject areas

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

Cite this

Serrano, P., Friedman, E. L., Kenney, J., Taubenfeld, S. M., Zimmerman, J. M., Hanna, J., ... Fenton, A. (2008). PKMζ maintains spatial, instrumental, and classically conditioned long-term memories. PLoS Biology, 6(12), 2698-2706. [e318]. https://doi.org/10.1371/journal.pbio.0060318

PKMζ maintains spatial, instrumental, and classically conditioned long-term memories. / Serrano, Peter; Friedman, Eugenia L.; Kenney, Jana; Taubenfeld, Stephen M.; Zimmerman, Joshua M.; Hanna, John; Alberini, Cristina; Kelley, Ann E.; Maren, Stephen; Rudy, Jerry W.; Yin, Jerry C P; Sacktor, Todd C.; Fenton, Andre.

In: PLoS Biology, Vol. 6, No. 12, e318, 12.2008, p. 2698-2706.

Research output: Contribution to journalArticle

Serrano, P, Friedman, EL, Kenney, J, Taubenfeld, SM, Zimmerman, JM, Hanna, J, Alberini, C, Kelley, AE, Maren, S, Rudy, JW, Yin, JCP, Sacktor, TC & Fenton, A 2008, 'PKMζ maintains spatial, instrumental, and classically conditioned long-term memories', PLoS Biology, vol. 6, no. 12, e318, pp. 2698-2706. https://doi.org/10.1371/journal.pbio.0060318
Serrano P, Friedman EL, Kenney J, Taubenfeld SM, Zimmerman JM, Hanna J et al. PKMζ maintains spatial, instrumental, and classically conditioned long-term memories. PLoS Biology. 2008 Dec;6(12):2698-2706. e318. https://doi.org/10.1371/journal.pbio.0060318
Serrano, Peter ; Friedman, Eugenia L. ; Kenney, Jana ; Taubenfeld, Stephen M. ; Zimmerman, Joshua M. ; Hanna, John ; Alberini, Cristina ; Kelley, Ann E. ; Maren, Stephen ; Rudy, Jerry W. ; Yin, Jerry C P ; Sacktor, Todd C. ; Fenton, Andre. / PKMζ maintains spatial, instrumental, and classically conditioned long-term memories. In: PLoS Biology. 2008 ; Vol. 6, No. 12. pp. 2698-2706.
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