title: Biphasic activation of the mTOR pathway in the gustatory cortex is correlated with and necessary for taste learning.
abstract: Different forms of memories and synaptic plasticity require synthesis of new proteins at the time of acquisition or immediately after. We are interested in the role of translation regulation in the cortex, the brain structure assumed to store long-term memories. The mammalian target of rapamycin, mTOR (also known as FRAP and RAFT-1), is part of a key signal transduction mechanism known to regulate translation of specific subset of mRNAs and to affect learning and synaptic plasticity. We report here that novel taste learning induces two waves of mTOR activation in the gustatory cortex. Interestingly, the first wave can be identified both in synaptoneurosomal and cellular fractions, whereas the second wave is detected in the cellular fraction but not in the synaptic one. Inhibition of mTOR, specifically in the gustatory cortex, has two effects. First, biochemically, it modulates several known downstream proteins that control translation and reduces the expression of postsynaptic density-95 in vivo. Second, behaviorally, it attenuates long-term taste memory. The results suggest that the mTOR pathway in the cortex modulates both translation factor activity and protein expression, to enable normal taste memory consolidation.
authors.affiliation: Department of Neurobiology and Ethology, Faculty for Science, University of Haifa, Haifa 30905, Israel.
authors.forename: Katya
authors.initials: K
authors.lastname: Belelovsky
authors.forename: Hanoch
authors.initials: H
authors.lastname: Kaphzan
authors.forename: Alina
authors.initials: A
authors.lastname: Elkobi
authors.forename: Kobi
authors.initials: K
authors.lastname: Rosenblum
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002540:Cerebral Cortex / Q000502:physiology*; D003214:Conditioning, Classical; D000076122:Disks Large Homolog 4 Protein; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007858:Learning / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory / Q000502:physiology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D013649:Taste; D013997:Time Factors
chemical_list: D002070:Butadienes; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009570:Nitriles; C113580:U 0126; D011494:Protein Kinases; C546845:mTOR protein, rat; D019893:Ribosomal Protein S6 Kinases; C526901:Rps6kb1 protein, rat; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus