| First Author | Lee AM | Year | 2013 |
| Journal | Nature | Volume | 493 |
| Issue | 7432 | Pages | 416-9 |
| PubMed ID | 23283171 | Mgi Jnum | J:194398 |
| Mgi Id | MGI:5473727 | Doi | 10.1038/nature11803 |
| Citation | Lee AM, et al. (2013) Prkcz null mice show normal learning and memory. Nature 493(7432):416-9 |
| abstractText | Protein kinase M-zeta (PKM-zeta) 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-zeta in memory maintenance have used pharmacological PKM-zeta 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-zeta (PKC-zeta) and PKM-zeta (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-zeta, PKC-iota and PKC-zeta with similar inhibition constant (K(i)) values. Chelerythrine was a weak inhibitor of PKM-zeta (K(i) = 76 muM). Our findings show that absence of PKM-zeta does not impair learning and memory in mice, and that ZIP can erase reward memory even when PKM-zeta is not present. |
