title: Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.
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.
authors.affiliation: 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.|Department of Anesthesiology, State University of New York Downstate Medical Center, Brooklyn, United States.
authors.forename: Panayiotis
authors.identifier: 0000-0002-1679-8980
authors.initials: P
authors.lastname: Tsokas
authors.affiliation: 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.
authors.forename: Changchi
authors.identifier: 0000-0003-0488-1565
authors.initials: C
authors.lastname: Hsieh
authors.affiliation: 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.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Center for Neural Science, New York University, New York, United States.
authors.forename: Edith
authors.initials: E
authors.lastname: Lesburguères
authors.affiliation: 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.
authors.forename: Emma Jane Claire
authors.initials: EJC
authors.lastname: Wallace
authors.affiliation: 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.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tcherepanov
authors.affiliation: 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.
authors.forename: Desingarao
authors.initials: D
authors.lastname: Jothianandan
authors.affiliation: 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.
authors.forename: Benjamin Rush
authors.initials: BR
authors.lastname: Hartley
authors.affiliation: 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.
authors.forename: Ling
authors.initials: L
authors.lastname: Pan
authors.affiliation: 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.
authors.forename: Bruno
authors.initials: B
authors.lastname: Rivard
authors.affiliation: Department of Internal Medicine, James A Haley Veterans Hospital, University of South Florida, Tampa, United States.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Farese
authors.affiliation: Department of Internal Medicine, James A Haley Veterans Hospital, University of South Florida, Tampa, United States.
authors.forename: Mini P
authors.initials: MP
authors.lastname: Sajan
authors.affiliation: 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.
authors.forename: Peter John
authors.initials: PJ
authors.lastname: Bergold
authors.affiliation: Department of Pathology, State University of New York Downstate Medical Center, Brooklyn, United States.
authors.forename: Alejandro Iván
authors.initials: AI
authors.lastname: Hernández
authors.affiliation: Department of Anesthesiology, State University of New York Downstate Medical Center, Brooklyn, United States.
authors.forename: James E
authors.initials: JE
authors.lastname: Cottrell
authors.affiliation: Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, Houston, United States.
authors.forename: Harel Z
authors.initials: HZ
authors.lastname: Shouval
authors.affiliation: 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.|Center for Neural Science, New York University, New York, United States.
authors.forename: André Antonio
authors.identifier: 0000-0002-5063-1156
authors.initials: AA
authors.lastname: Fenton
authors.affiliation: 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.|Department of Anesthesiology, State University of New York Downstate Medical Center, Brooklyn, United States.|Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, United States.
authors.forename: Todd Charlton
authors.identifier: 0000-0002-8625-8701
authors.initials: TC
authors.lastname: Sacktor
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation; D057567:Memory, Long-Term; D051379:Mice; D018345:Mice, Knockout; D010597:Pharmacogenetics; D011493:Protein Kinase C / Q000378:metabolism*; D065852:Spatial Memory; D000099221:Protein Kinase C zeta
chemical_list: D011493:Protein Kinase C; D000099221:Protein Kinase C zeta
keywords: LTP; PKCiota/lambda; PKM-zeta; PKMzeta; atypical PKC; memory; mouse; neuroscience