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

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 hippoca...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2023-12, Vol.120 (49), p.e2308671120-e2308671120
Hauptverfasser: Sharma, Vijendra, Oliveira, Mauricio M, Sood, Rapita, Khlaifia, Abdessattar, Lou, Danning, Hooshmandi, Mehdi, Hung, Tzu-Yu, Mahmood, Niaz, Reeves, Maya, Ho-Tieng, David, Cohen, Noah, Cheng, Po-Chieh, Rahim, Mir Munir A, Prager-Khoutorsky, Masha, Kaufman, Randal J, Rosenblum, Kobi, Lacaille, Jean-Claude, Khoutorsky, Arkady, Klann, Eric, Sonenberg, Nahum
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Sprache:eng
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Zusammenfassung: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2308671120