1. Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice
- Author
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Panayiotis Tsokas, Changchi Hsieh, Yudong Yao, Edith Lesburguères, Emma Jane Claire Wallace, Andrew Tcherepanov, Desingarao Jothianandan, Benjamin Rush Hartley, Ling Pan, Bruno Rivard, Robert V Farese, Mini P Sajan, Peter John Bergold, Alejandro Iván Hernández, James E Cottrell, Harel Z Shouval, André Antonio Fenton, and Todd Charlton Sacktor
- Subjects
atypical PKC ,memory ,PKM-zeta ,LTP ,PKMzeta ,PKCiota/lambda ,Medicine ,Science ,Biology (General) ,QH301-705.5 - 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.
- Published
- 2016
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