| PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory. | |
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MedLine Citation:
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PMID: 23283174 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Long-term potentiation (LTP), a well-characterized form of synaptic plasticity, has long been postulated as a cellular correlate of learning and memory. Although LTP can persist for long periods of time, the mechanisms underlying LTP maintenance, in the midst of ongoing protein turnover and synaptic activity, remain elusive. Sustained activation of the brain-specific protein kinase C (PKC) isoform protein kinase M-ζ (PKM-ζ) has been reported to be necessary for both LTP maintenance and long-term memory. Inhibiting PKM-ζ activity using a synthetic zeta inhibitory peptide (ZIP) based on the PKC-ζ pseudosubstrate sequence reverses established LTP in vitro and in vivo. More notably, infusion of ZIP eliminates memories for a growing list of experience-dependent behaviours, including active place avoidance, conditioned taste aversion, fear conditioning and spatial learning. However, most of the evidence supporting a role for PKM-ζ in LTP and memory relies heavily on pharmacological inhibition of PKM-ζ by ZIP. To further investigate the involvement of PKM-ζ in the maintenance of LTP and memory, we generated transgenic mice lacking PKC-ζ and PKM-ζ. We find that both conventional and conditional PKC-ζ/PKM-ζ knockout mice show normal synaptic transmission and LTP at Schaffer collateral-CA1 synapses, and have no deficits in several hippocampal-dependent learning and memory tasks. Notably, ZIP still reverses LTP in PKC-ζ/PKM-ζ knockout mice, indicating that the effects of ZIP are independent of PKM-ζ. |
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Authors:
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Lenora J Volk; Julia L Bachman; Richard Johnson; Yilin Yu; Richard L Huganir |
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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: 2013-04-01 |
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: 420-3 Citation Subset: IM |
Affiliation:
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Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Avoidance Learning / drug effects, physiology Behavior, Animal / drug effects, physiology Conditioning, Classical Fear Female Hippocampus / drug effects, physiology* Isoenzymes / deficiency, genetics, metabolism Lipopeptides / pharmacology Long-Term Potentiation / drug effects, genetics, physiology Male Memory, Long-Term / drug effects, physiology* Mice Mice, Knockout Neuronal Plasticity / genetics, physiology* Protein Kinase C / antagonists & inhibitors, deficiency, genetics, metabolism* Synapses / drug effects, metabolism* Synaptic Transmission / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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NS36715/NS/NINDS NIH HHS; T32MH15330/MH/NIMH NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Isoenzymes; 0/Lipopeptides; 0/myristoylated zeta-pseudosubstrate inhibitory peptide; 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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Nat Rev Neurosci. 2013 Mar;14(3):154
[PMID:
23340604
]
Nature. 2013 Jan 17;493(7432):312-3 [PMID: 23283170 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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