| Prkcz null mice show normal learning and memory. | |
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MedLine Citation:
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PMID: 23283171 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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 |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2013-01-02 |
Journal Detail:
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Title: Nature Volume: 493 ISSN: 1476-4687 ISO Abbreviation: Nature Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-01-17 Completed Date: 2013-03-04 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: England |
Other Details:
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Languages: eng Pagination: 416-9 Citation Subset: IM |
Affiliation:
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Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, California 94608, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anxiety / genetics Behavior, Animal Benzophenanthridines / pharmacology Cocaine Conditioning, Classical Cues Exons / genetics Fear Female Gene Deletion* Male Memory / physiology* Mice Protein Kinase C / analysis, deficiency*, genetics*, immunology |
| Grant Support | |
ID/Acronym/Agency:
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AA017072/AA/NIAAA NIH HHS; P50 AA017072/AA/NIAAA NIH HHS; //Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Benzophenanthridines; 50-36-2/Cocaine; E3B045W6X0/chelerythrine; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.13/protein kinase C zeta, mouse |
| Comments/Corrections | |
Comment In:
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Nature. 2013 Jan 17;493(7432):312-3
[PMID:
23283170
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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