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Elife. 2016 May 17;5. pii: e14846. doi: 10.7554/eLife.14846.

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

Author information

1
Department of Physiology and Pharmacology, The Robert F Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, United States.
2
Department of Anesthesiology, State University of New York Downstate Medical Center, Brooklyn, United States.
3
Center for Neural Science, New York University, New York, United States.
4
Department of Internal Medicine, James A Haley Veterans Hospital, University of South Florida, Tampa, United States.
5
Department of Pathology, State University of New York Downstate Medical Center, Brooklyn, United States.
6
Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, Houston, United States.
7
Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, United States.

Abstract

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

KEYWORDS:

LTP; PKCiota/lambda; PKM-zeta; PKMzeta; atypical PKC; memory; mouse; neuroscience

PMID:
27187150
PMCID:
PMC4869915
DOI:
10.7554/eLife.14846
[Indexed for MEDLINE]
Free PMC Article

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