TY - JOUR
T1 - Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice
AU - Tsokas, Panayiotis
AU - Hsieh, Changchi
AU - Yao, Yudong
AU - Lesburguères, Edith
AU - Wallace, Emma Jane Claire
AU - Tcherepanov, Andrew
AU - Jothianandan, Desingarao
AU - Hartley, Benjamin Rush
AU - Pan, Ling
AU - Rivard, Bruno
AU - Farese, Robert V.
AU - Sajan, Mini P.
AU - Bergold, Peter John
AU - Hernández, Alejandro Iván
AU - Cottrell, James E.
AU - Shouval, Harel Z.
AU - Fenton, André Antonio
AU - Sacktor, Todd Charlton
N1 - Funding Information:
National Institute of Mental Health R37 MH057068 Todd Charlton Sacktor National Institute of Mental Health R01 MH53576 Todd Charlton Sacktor National Institute on Drug Abuse R01 DA034970 Harel Z Shouval Todd Charlton Sacktor Lightfighter Trust Todd Charlton Sacktor National Institute of Mental Health R01 MH084038 Andre Antonio Fenton National Institute of Mental Health R01 MH099128 Andre Antonio Fenton National Institute on Aging R01 AG043688 Andre Antonio Fenton National Science Foundation IOS-1146822 Andre Antonio Fenton.
Publisher Copyright:
© Tsokas et al.
PY - 2016/5/17
Y1 - 2016/5/17
N2 - PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and longterm 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, PKCı/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 PKCą/Ĉ-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 PKCı/λ activation compensates for PKMζ loss in PKMζ-null mice.
AB - PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and longterm 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, PKCı/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 PKCą/Ĉ-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 PKCı/λ activation compensates for PKMζ loss in PKMζ-null mice.
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U2 - 10.7554/eLife.14846
DO - 10.7554/eLife.14846
M3 - Article
C2 - 27187150
AN - SCOPUS:84971654955
SN - 2050-084X
VL - 5
JO - eLife
JF - eLife
IS - MAY2016
M1 - e14846
ER -