mRNA translation in astrocytes controls hippocampal long-term synaptic plasticity and memory

Vijendra Sharm; Mauricio M. Oliveira; Rapita Sood; Abdessattar Khlaifia; Danning Lou; Mehdi Hooshmandi; Tzu Yu Hung; Niaz Mahmood; Maya Reeves; David Ho-Tieng; Noah Cohen; Po Chieh Cheng; Mir Munir A. Rahim; Masha Prager-Khoutorsky; Randal J. Kaufman; Kobi Rosenblum; Jean Claude Lacaille; Arkady Khoutorsky; Eric Klann; Nahum Sonenberg

doi:10.1073/pnas.2308671120

mRNA translation in astrocytes controls hippocampal long-term synaptic plasticity and memory

Vijendra Sharm, Mauricio M. Oliveira, Rapita Sood, Abdessattar Khlaifia, Danning Lou, Mehdi Hooshmandi, Tzu Yu Hung, Niaz Mahmood, Maya Reeves, David Ho-Tieng, Noah Cohen, Po Chieh Cheng, Mir Munir A. Rahim, Masha Prager-Khoutorsky, Randal J. Kaufman, Kobi Rosenblum, Jean Claude Lacaille, Arkady Khoutorsky, Eric Klann, Nahum Sonenberg

Department of Neurobiology

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

Abstract

Activation of neuronal protein synthesis upon learning is critical for the formation of long-term memory. Here, we report that learning in the contextual fear conditioning paradigm engenders a decrease in eIF2α (eukaryotic translation initiation factor 2) phosphorylation in astrocytes in the hippocampal CA1 region, which promotes protein synthesis. Genetic reduction of eIF2α phosphorylation in hippocampal astrocytes enhanced contextual and spatial memory and lowered the threshold for the induction of long-lasting plasticity by modulating synaptic transmission. Thus, learning-induced dephosphorylation of eIF2α in astrocytes bolsters hippocampal synaptic plasticity and consolidation of long-term memories.

Original language	English
Article number	e2308671120
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	120
Issue number	49
DOIs	https://doi.org/10.1073/pnas.2308671120
State	Published - 2023

Bibliographical note

Publisher Copyright:
© 2023 the Author(s).

Keywords

astrocytes
integrated stress response
learning and memory
protein synthesis
synaptic plasticity
Hippocampus/physiology
Protein Biosynthesis
Memory, Long-Term/physiology
Astrocytes
Long-Term Potentiation/physiology
CA1 Region, Hippocampal
Neuronal Plasticity/genetics

ASJC Scopus subject areas

General

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10.1073/pnas.2308671120

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Sharm, V., Oliveira, M. M., Sood, R., Khlaifia, A., Lou, D., Hooshmandi, M., Hung, T. Y., Mahmood, N., Reeves, M., Ho-Tieng, D., Cohen, N., Cheng, P. C., Rahim, M. M. A., Prager-Khoutorsky, M., Kaufman, R. J., Rosenblum, K., Lacaille, J. C., Khoutorsky, A., Klann, E., & Sonenberg, N. (2023). mRNA translation in astrocytes controls hippocampal long-term synaptic plasticity and memory. Proceedings of the National Academy of Sciences of the United States of America, 120(49), Article e2308671120. https://doi.org/10.1073/pnas.2308671120

@article{021a4832d8d64105bc6e71673628a124,

title = "mRNA translation in astrocytes controls hippocampal long-term synaptic plasticity and memory",

abstract = "Activation of neuronal protein synthesis upon learning is critical for the formation of long-term memory. Here, we report that learning in the contextual fear conditioning paradigm engenders a decrease in eIF2α (eukaryotic translation initiation factor 2) phosphorylation in astrocytes in the hippocampal CA1 region, which promotes protein synthesis. Genetic reduction of eIF2α phosphorylation in hippocampal astrocytes enhanced contextual and spatial memory and lowered the threshold for the induction of long-lasting plasticity by modulating synaptic transmission. Thus, learning-induced dephosphorylation of eIF2α in astrocytes bolsters hippocampal synaptic plasticity and consolidation of long-term memories.",

keywords = "astrocytes, integrated stress response, learning and memory, protein synthesis, synaptic plasticity, Hippocampus/physiology, Protein Biosynthesis, Memory, Long-Term/physiology, Astrocytes, Long-Term Potentiation/physiology, CA1 Region, Hippocampal, Neuronal Plasticity/genetics",

author = "Vijendra Sharm and Oliveira, {Mauricio M.} and Rapita Sood and Abdessattar Khlaifia and Danning Lou and Mehdi Hooshmandi and Hung, {Tzu Yu} and Niaz Mahmood and Maya Reeves and David Ho-Tieng and Noah Cohen and Cheng, {Po Chieh} and Rahim, {Mir Munir A.} and Masha Prager-Khoutorsky and Kaufman, {Randal J.} and Kobi Rosenblum and Lacaille, {Jean Claude} and Arkady Khoutorsky and Eric Klann and Nahum Sonenberg",

note = "Publisher Copyright: {\textcopyright} 2023 the Author(s).",

year = "2023",

doi = "10.1073/pnas.2308671120",

language = "English",

volume = "120",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

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Sharm, V, Oliveira, MM, Sood, R, Khlaifia, A, Lou, D, Hooshmandi, M, Hung, TY, Mahmood, N, Reeves, M, Ho-Tieng, D, Cohen, N, Cheng, PC, Rahim, MMA, Prager-Khoutorsky, M, Kaufman, RJ, Rosenblum, K, Lacaille, JC, Khoutorsky, A, Klann, E & Sonenberg, N 2023, 'mRNA translation in astrocytes controls hippocampal long-term synaptic plasticity and memory', Proceedings of the National Academy of Sciences of the United States of America, vol. 120, no. 49, e2308671120. https://doi.org/10.1073/pnas.2308671120

TY - JOUR

T1 - mRNA translation in astrocytes controls hippocampal long-term synaptic plasticity and memory

AU - Sharm, Vijendra

AU - Oliveira, Mauricio M.

AU - Sood, Rapita

AU - Khlaifia, Abdessattar

AU - Lou, Danning

AU - Hooshmandi, Mehdi

AU - Hung, Tzu Yu

AU - Mahmood, Niaz

AU - Reeves, Maya

AU - Ho-Tieng, David

AU - Cohen, Noah

AU - Cheng, Po Chieh

AU - Rahim, Mir Munir A.

AU - Prager-Khoutorsky, Masha

AU - Kaufman, Randal J.

AU - Rosenblum, Kobi

AU - Lacaille, Jean Claude

AU - Khoutorsky, Arkady

AU - Klann, Eric

AU - Sonenberg, Nahum

PY - 2023

Y1 - 2023

N2 - Activation of neuronal protein synthesis upon learning is critical for the formation of long-term memory. Here, we report that learning in the contextual fear conditioning paradigm engenders a decrease in eIF2α (eukaryotic translation initiation factor 2) phosphorylation in astrocytes in the hippocampal CA1 region, which promotes protein synthesis. Genetic reduction of eIF2α phosphorylation in hippocampal astrocytes enhanced contextual and spatial memory and lowered the threshold for the induction of long-lasting plasticity by modulating synaptic transmission. Thus, learning-induced dephosphorylation of eIF2α in astrocytes bolsters hippocampal synaptic plasticity and consolidation of long-term memories.

AB - Activation of neuronal protein synthesis upon learning is critical for the formation of long-term memory. Here, we report that learning in the contextual fear conditioning paradigm engenders a decrease in eIF2α (eukaryotic translation initiation factor 2) phosphorylation in astrocytes in the hippocampal CA1 region, which promotes protein synthesis. Genetic reduction of eIF2α phosphorylation in hippocampal astrocytes enhanced contextual and spatial memory and lowered the threshold for the induction of long-lasting plasticity by modulating synaptic transmission. Thus, learning-induced dephosphorylation of eIF2α in astrocytes bolsters hippocampal synaptic plasticity and consolidation of long-term memories.

KW - astrocytes

KW - integrated stress response

KW - learning and memory

KW - protein synthesis

KW - synaptic plasticity

KW - Hippocampus/physiology

KW - Protein Biosynthesis

KW - Memory, Long-Term/physiology

KW - Astrocytes

KW - Long-Term Potentiation/physiology

KW - CA1 Region, Hippocampal

KW - Neuronal Plasticity/genetics

UR - http://www.scopus.com/inward/record.url?scp=85178497643&partnerID=8YFLogxK

U2 - 10.1073/pnas.2308671120

DO - 10.1073/pnas.2308671120

M3 - Article

C2 - 38015848

AN - SCOPUS:85178497643

SN - 0027-8424

VL - 120

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 49

M1 - e2308671120

ER -

mRNA translation in astrocytes controls hippocampal long-term synaptic plasticity and memory

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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