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

Research output: Contribution to journalArticlepeer-review


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 languageEnglish (US)
Article numbere2308671120
JournalProceedings of the National Academy of Sciences of the United States of America
StatePublished - 2023


  • astrocytes
  • integrated stress response
  • learning and memory
  • protein synthesis
  • synaptic plasticity

ASJC Scopus subject areas

  • General


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