Prkcz null mice show normal learning and memory

Anna M. Lee, Benjamin R. Kanter, Dan Wang, Jana P. Lim, Mimi E. Zou, Chichen Qiu, Thomas McMahon, Jahan Dadgar, Sarah C. Fischbach-Weiss, Robert O. Messing

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

Protein kinase M-ζ (PKM-ζ) is a constitutively active form of atypical protein kinase C that is exclusively expressed in the brain and implicated in the maintenance of long-term memory. Most studies that support a role for PKM-ζ in memory maintenance have used pharmacological PKM-ζ inhibitors such as the myristoylated zeta inhibitory peptide (ZIP) or chelerythrine. Here we use a genetic approach and target exon 9 of the Prkcz gene to generate mice that lack both protein kinase C-ζ (PKC-ζ) and PKM-ζ (Prkcz-/-mice). Prkcz-/-mice showed normal behaviour in a cage environment and in baseline tests of motor function and sensory perception, but displayed reduced anxiety-like behaviour. Notably, Prkcz-/-mice did not show deficits in learning or memory in tests of cued fear conditioning, novel object recognition, object location recognition, conditioned place preference for cocaine, or motor learning, when compared with wild-type littermates. ZIP injection into the nucleus accumbens reduced expression of cocaine-conditioned place preference in Prkcz-/-mice. In vitro, ZIP and scrambled ZIP inhibited PKM-ζ, PKC-ι and PKC-ζ with similar inhibition constant (K i) values. Chelerythrine was a weak inhibitor of PKM-ζ (K i = 76 μM). Our findings show that absence of PKM-ζ does not impair learning and memory in mice, and that ZIP can erase reward memory even when PKM-ζ is not present.

Original languageEnglish (US)
Pages (from-to)416-419
Number of pages4
JournalNature
Volume493
Issue number7432
DOIs
StatePublished - Jan 17 2013

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Protein Kinase C
Learning
Peptides
Cocaine
Long-Term Memory
Nucleus Accumbens
Protein Kinase Inhibitors
Reward
Fear
Exons
Anxiety
Maintenance
Pharmacology
Injections
Brain
Genes

Cite this

Lee, A. M., Kanter, B. R., Wang, D., Lim, J. P., Zou, M. E., Qiu, C., ... Messing, R. O. (2013). Prkcz null mice show normal learning and memory. Nature, 493(7432), 416-419. https://doi.org/10.1038/nature11803

Prkcz null mice show normal learning and memory. / Lee, Anna M.; Kanter, Benjamin R.; Wang, Dan; Lim, Jana P.; Zou, Mimi E.; Qiu, Chichen; McMahon, Thomas; Dadgar, Jahan; Fischbach-Weiss, Sarah C.; Messing, Robert O.

In: Nature, Vol. 493, No. 7432, 17.01.2013, p. 416-419.

Research output: Contribution to journalArticle

Lee, AM, Kanter, BR, Wang, D, Lim, JP, Zou, ME, Qiu, C, McMahon, T, Dadgar, J, Fischbach-Weiss, SC & Messing, RO 2013, 'Prkcz null mice show normal learning and memory', Nature, vol. 493, no. 7432, pp. 416-419. https://doi.org/10.1038/nature11803
Lee AM, Kanter BR, Wang D, Lim JP, Zou ME, Qiu C et al. Prkcz null mice show normal learning and memory. Nature. 2013 Jan 17;493(7432):416-419. https://doi.org/10.1038/nature11803
Lee, Anna M. ; Kanter, Benjamin R. ; Wang, Dan ; Lim, Jana P. ; Zou, Mimi E. ; Qiu, Chichen ; McMahon, Thomas ; Dadgar, Jahan ; Fischbach-Weiss, Sarah C. ; Messing, Robert O. / Prkcz null mice show normal learning and memory. In: Nature. 2013 ; Vol. 493, No. 7432. pp. 416-419.
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