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

Vijendra SharmaMauricio M OliveiraRapita SoodAbdessattar KhlaifiaDanning LouMehdi HooshmandiTzu-Yu HungNiaz MahmoodMaya ReevesDavid Ho-TiengNoah CohenPo-Chieh ChengMir Munir A RahimMasha Prager-KhoutorskyAlexandre Rosa CamposKobi RosenblumJean-Claude LacailleArkady KhoutorskyEric KlannNahum Sonenberg
Published in: Proceedings of the National Academy of Sciences of the United States of America (2023)
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.
Keyphrases
  • cerebral ischemia
  • working memory
  • protein kinase
  • signaling pathway
  • subarachnoid hemorrhage
  • gene expression
  • blood brain barrier
  • oxidative stress
  • prefrontal cortex