PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.

How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta), an autonomously active atypical protein kinase C (PKC) isoform crit...

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Autores principales: Peter Serrano, Eugenia L Friedman, Jana Kenney, Stephen M Taubenfeld, Joshua M Zimmerman, John Hanna, Cristina Alberini, Ann E Kelley, Stephen Maren, Jerry W Rudy, Jerry C P Yin, Todd C Sacktor, André A Fenton
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Publicado: Public Library of Science (PLoS) 2008
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Acceso en línea:https://doaj.org/article/1bfbe7a0f11e48f285b78ebd5198a9c3
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spelling oai:doaj.org-article:1bfbe7a0f11e48f285b78ebd5198a9c32021-11-25T05:33:53ZPKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.1544-91731545-788510.1371/journal.pbio.0060318https://doaj.org/article/1bfbe7a0f11e48f285b78ebd5198a9c32008-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19108606/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta), an autonomously active atypical protein kinase C (PKC) isoform critical for the maintenance of long-term potentiation (LTP). PKMzeta maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP) by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH) and basolateral amygdala (BLA) on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMzeta activity. Similarly, PKMzeta inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMzeta inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US) associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise, or procedural information.Peter SerranoEugenia L FriedmanJana KenneyStephen M TaubenfeldJoshua M ZimmermanJohn HannaCristina AlberiniAnn E KelleyStephen MarenJerry W RudyJerry C P YinTodd C SacktorAndré A FentonPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 6, Iss 12, Pp 2698-2706 (2008)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle Biology (General)
QH301-705.5
Peter Serrano
Eugenia L Friedman
Jana Kenney
Stephen M Taubenfeld
Joshua M Zimmerman
John Hanna
Cristina Alberini
Ann E Kelley
Stephen Maren
Jerry W Rudy
Jerry C P Yin
Todd C Sacktor
André A Fenton
PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.
description How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta), an autonomously active atypical protein kinase C (PKC) isoform critical for the maintenance of long-term potentiation (LTP). PKMzeta maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP) by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH) and basolateral amygdala (BLA) on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMzeta activity. Similarly, PKMzeta inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMzeta inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US) associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise, or procedural information.
format article
author Peter Serrano
Eugenia L Friedman
Jana Kenney
Stephen M Taubenfeld
Joshua M Zimmerman
John Hanna
Cristina Alberini
Ann E Kelley
Stephen Maren
Jerry W Rudy
Jerry C P Yin
Todd C Sacktor
André A Fenton
author_facet Peter Serrano
Eugenia L Friedman
Jana Kenney
Stephen M Taubenfeld
Joshua M Zimmerman
John Hanna
Cristina Alberini
Ann E Kelley
Stephen Maren
Jerry W Rudy
Jerry C P Yin
Todd C Sacktor
André A Fenton
author_sort Peter Serrano
title PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.
title_short PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.
title_full PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.
title_fullStr PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.
title_full_unstemmed PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories.
title_sort pkmzeta maintains spatial, instrumental, and classically conditioned long-term memories.
publisher Public Library of Science (PLoS)
publishDate 2008
url https://doaj.org/article/1bfbe7a0f11e48f285b78ebd5198a9c3
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