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 Physiology and Pharmacology, The Robert F Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, United States
Yudong Yao
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
Edith Lesburguères
Center for Neural Science, New York University, New York, United States
Emma Jane Claire Wallace
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
Andrew Tcherepanov
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
Desingarao Jothianandan
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
Benjamin Rush Hartley
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
Ling Pan
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
Bruno Rivard
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
Robert V Farese
Department of Internal Medicine, James A Haley Veterans Hospital, University of South Florida, Tampa, United States
Mini P Sajan
Department of Internal Medicine, James A Haley Veterans Hospital, University of South Florida, Tampa, United States
Peter John Bergold
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
Alejandro Iván Hernández
Department of Pathology, State University of New York Downstate Medical Center, Brooklyn, United States
James E Cottrell
Department of Anesthesiology, State University of New York Downstate Medical Center, Brooklyn, United States
Harel Z Shouval
Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, Houston, United States
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
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
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.
