title: mTOR is essential for corticosteroid effects on hippocampal AMPA receptor function and fear memory.
abstract: Glucocorticoid hormones, via activation of their receptors, promote memory consolidation, but the exact underlying mechanisms remain elusive. We examined how corticosterone regulates AMPA receptors (AMPARs), which are crucial for synaptic plasticity and memory formation. Combining a live imaging fluorescent recovery after photobleaching approach with the use of the pH-sensitive GFP-AMPAR tagging revealed that corticosterone enhances the AMPAR mobile fraction and increases synaptic trapping of AMPARs in hippocampal cells. In parallel, corticosterone-enhanced AMPAR-mediated synaptic transmission. Blocking the mammalian target of rapamycin (mTOR) pathway prevented the effects of corticosterone on both AMPAR trapping-but not on the mobile fraction-and synaptic transmission. Blocking the mTOR pathway also prevented the memory enhancing effects of corticosterone in a contextual fear-conditioning paradigm. We conclude that activation of the mTOR pathway is essential for the effects of corticosterone on synaptic trapping of AMPARs and, possibly as a consequence, fearful memory formation.
authors.affiliation: Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam 1098 XH, The Netherlands.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR-7275, University of Nice, Sophia Antipolis, Valbonne 06560, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cassé
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam 1098 XH, The Netherlands.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Xiong
authors.affiliation: Department of Neuroscience and Pharmacology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3508 AB, The Netherlands.
authors.forename: Marian
authors.initials: M
authors.lastname: Joëls
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR-7275, University of Nice, Sophia Antipolis, Valbonne 06560, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Martin
authors.affiliation: Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam 1098 XH, The Netherlands h.krugers@uva.nl.
authors.forename: Harm J
authors.initials: HJ
authors.lastname: Krugers
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000008:administration & dosage / Q000378:metabolism*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002491:Central Nervous System Agents; D018091:Receptors, AMPA; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D003345:Corticosterone