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.
journal_name
Elifejournal_title
eLifeauthors
Tsokas P,Hsieh C,Yao Y,Lesburguères E,Wallace EJC,Tcherepanov A,Jothianandan D,Hartley BR,Pan L,Rivard B,Farese RV,Sajan MP,Bergold PJ,Hernández AI,Cottrell JE,Shouval HZ,Fenton AA,Sacktor TCdoi
10.7554/eLife.14846subject
Has Abstractpub_date
2016-05-17 00:00:00issn
2050-084Xjournal_volume
5pub_type
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