Document Detail

PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory.
MedLine Citation:
PMID:  23283174     Owner:  NLM     Status:  MEDLINE    
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.
Lenora J Volk; Julia L Bachman; Richard Johnson; Yilin Yu; Richard L Huganir
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-02
Journal Detail:
Title:  Nature     Volume:  493     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-17     Completed Date:  2013-03-04     Revised Date:  2014-10-10    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  420-3     Citation Subset:  IM    
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MeSH Terms
Avoidance Learning / drug effects,  physiology
Behavior, Animal / drug effects,  physiology
Conditioning, Classical
Hippocampus / drug effects,  physiology*
Isoenzymes / deficiency,  genetics,  metabolism
Lipopeptides / pharmacology
Long-Term Potentiation / drug effects,  genetics,  physiology
Memory, Long-Term / drug effects,  physiology*
Mice, Knockout
Neuronal Plasticity / genetics,  physiology*
Protein Kinase C / antagonists & inhibitors,  deficiency,  genetics,  metabolism*
Synapses / drug effects,  metabolism*
Synaptic Transmission / drug effects
Grant Support
NS36715/NS/NINDS NIH HHS; P30 NS050274/NS/NINDS NIH HHS; R01 NS036715/NS/NINDS NIH HHS; T32 EY017203/EY/NEI NIH HHS; T32 MH015330/MH/NIMH NIH HHS; T32MH15330/MH/NIMH NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Isoenzymes; 0/Lipopeptides; 0/myristoylated zeta-pseudosubstrate inhibitory peptide; EC Kinase C; EC kinase C zeta, mouse
Comment In:
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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