title: Prkcz null mice show normal learning and memory.
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.
authors.affiliation: Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, California 94608, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Lee
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Kanter
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Jana P
authors.initials: JP
authors.lastname: Lim
authors.forename: Mimi E
authors.initials: ME
authors.lastname: Zou
authors.forename: Chichen
authors.initials: C
authors.lastname: Qiu
authors.forename: Thomas
authors.initials: T
authors.lastname: McMahon
authors.forename: Jahan
authors.initials: J
authors.lastname: Dadgar
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Fischbach-Weiss
authors.forename: Robert O
authors.initials: RO
authors.lastname: Messing
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics; D001522:Behavior, Animal; D053119:Benzophenanthridines / Q000494:pharmacology; D003042:Cocaine; D003214:Conditioning, Classical; D003463:Cues; D005091:Exons / Q000235:genetics; D005239:Fear; D005260:Female; D017353:Gene Deletion; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D011493:Protein Kinase C / Q000032:analysis / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D000099221:Protein Kinase C zeta
chemical_list: D053119:Benzophenanthridines; D003042:Cocaine; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta; C016299:chelerythrine