The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus.
Long-lasting synaptic plasticity and memory requires mRNA translation, yet little is known as to how this process is regulated. To explore the role that the translation repressor 4E-BP2 plays in hippocampal long-term potentiation (LTP) and learning and memory, we examined 4E-BP2 knock-out mice. Interestingly, genetic elimination of 4E-BP2 converted early-phase LTP to late-phase LTP (L-LTP) in the Schaffer collateral pathway, likely as a result of increased eIF4F complex formation and translation initiation. A critical limit for activity-induced translation was revealed in the 4E-BP2 knock-out mice because L-LTP elicited by traditional stimulation paradigms was obstructed. Moreover, the 4E-BP2 knock-out mice also exhibited impaired spatial learning and memory and conditioned fear-associative memory deficits. These results suggest a crucial role for proper regulation of the eIF4F complex by 4E-BP2 during LTP and learning and memory in the mouse hippocampus.
Banko
Jessica L
JL
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA.
Poulin
Francis
F
Hou
Lingfei
L
DeMaria
Christine T
CT
Sonenberg
Nahum
N
Klann
Eric
E
D000818:Animals; D039562:Eukaryotic Initiation Factor-4F / Q000172:deficiency / Q000502:physiology*; D039642:Eukaryotic Initiation Factors / Q000172:deficiency / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000502:physiology
C491255:Eif4ebp2 protein, mouse; D039562:Eukaryotic Initiation Factor-4F; D039642:Eukaryotic Initiation Factors; D012097:Repressor Proteins