Activation of mammalian target of rapamycin signaling in spatial learning.
Novel protein synthesis is an essential element of various learning paradigms. Although pharmacological and genetic strategies have indicated the importance of translational activation in learning, the specific signaling pathways that are activated in the brain remain unclear. Here, we show that mammalian target of rapamycin (mTOR), a key serine/threonine protein kinase in translational control, is activated in hippocampus of the learning rat as revealed by in vitro kinase assay, Western blotting and immunohistochemistry. The substrates of mTOR, eukaryotic initiation factor 4E-binding protein (4EBP) and p70S6 kinase (p70S6K) are phosphorylated, and total protein synthesis is enhanced, in the learning hippocampus. Furthermore, the inhibition of mTOR by chronic infusion of rapamycin, a specific inhibitor of mTOR, into the ventricle retards the establishment of spatial learning. Thus, mTOR signaling is activated during learning, enhances translation, and plays a crucial role in the spatial learning.
Qi
Sihua
S
Department of Molecular Neurobiology, Brain Research Institute, Niigata University, 1, Asahimachi, Niigata 951-8585, Japan.
Mizuno
Makoto
M
Yonezawa
Kazuyoshi
K
Nawa
Hiroyuki
H
Takei
Nobuyuki
N
D000704:Analysis of Variance; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C546845:mTOR protein, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus