Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice

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; Todd Charlton Sacktor

doi:10.7554/eLife.14846

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice

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, Todd Charlton Sacktor

Neural Science

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	e14846
Journal	eLife
Volume	5
Issue number	MAY2016
DOIs	https://doi.org/10.7554/eLife.14846
State	Published - May 17 2016

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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Tsokas, P., Hsieh, C., Yao, Y., Lesburguères, E., Wallace, E. J. C., Tcherepanov, A., Jothianandan, D., Hartley, B. R., Pan, L., Rivard, B., Farese, R. V., Sajan, M. P., Bergold, P. J., Hernández, A. I., Cottrell, J. E., Shouval, H. Z., Fenton, A. A., & Sacktor, T. C. (2016). Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice. eLife, 5(MAY2016), Article e14846. https://doi.org/10.7554/eLife.14846

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, TC 2016, 'Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice', eLife, vol. 5, no. MAY2016, e14846. https://doi.org/10.7554/eLife.14846

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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 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 PKC{\c a}/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.",

author = "Panayiotis Tsokas and Changchi Hsieh and Yudong Yao and Edith Lesburgu{\`e}res and Wallace, {Emma Jane Claire} and Andrew Tcherepanov and Desingarao Jothianandan and Hartley, {Benjamin Rush} and Ling Pan and Bruno Rivard and Farese, {Robert V.} and Sajan, {Mini P.} and Bergold, {Peter John} and Hern{\'a}ndez, {Alejandro Iv{\'a}n} and Cottrell, {James E.} and Shouval, {Harel Z.} and Fenton, {Andr{\'e} Antonio} and Sacktor, {Todd Charlton}",

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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

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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Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice

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