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Persistent increases of PKMζ correlate with the retention and duration of spatial long‐term memory (728.11)
Author(s) -
Hartley Benjamin,
Hsieh Changchi,
Tsokas Paniyotas,
Serrano Peter,
Fenton Andre,
Marquez Samuel,
Sacktor Todd
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.728.11
Subject(s) - hippocampal formation , neuroscience , hippocampus , long term memory , endogeny , psychology , medicine , cognition
PKMζ is a constitutively active and brain‐specific atypical PKC isoform that plays an important role during long‐term memory (LTM) storage. Overexpressing PKMζ enhances LTM, and inhibiting PKMζ by overexpressing a dominant negative version of PKMζ or injecting ζ inhibitory peptide (ZIP) disrupts LTM, even very long‐term spatial memory 1 month post‐training. Here we examined endogenous PKMζ expression at different time points after short‐ or long‐term memory and correlated the amount of expressed PKMζ with LTM retention. Adult male Long‐Evans rats and C57BL/6J mice were trained by massed and spaced active place avoidance, respectively. Massed training consisted of eight 10‐min‐shock trials with 10 min inter‐trial interval (ITI), and spaced training consisted of three 30‐min‐shock trials with 120 min ITI. Quantitative immunoblotting showed that dorsal hippocampal PKMζ increased by the end of the massed training phase, and 1 day after both massed and spaced training, compared to animals that had not received shock when placed in the apparatus. The increase in PKMζ remained at least 30 days after the spaced training. Thus, the PKMζ level significantly correlated with 1 day LTM, but not with the number of shocks during the training. No PKMζ increase was detected after either short‐term memory training or 1 day after the administration of the tethered shocks in which animals received the same number and timing of shocks as the avoidance‐training group, but without association with spatial information. No long‐term contextual fear conditioned behaviors, such as freezing, or locomotor activity change was observed in the shock‐training group. Immunohistochemistry demonstrated that the increased PKMζ after the spatial training localized in the strata pyramidale, radiatum, and lacunosum‐moleculare in CA1 region at both 1 day and 1 month posttraining. These results support the hypothesis that persistently increased hippocampal PKMζ might be the molecular mechanism of the spatial LTM storage. Grant Funding Source : NIH Grant R01 MH053576