title: Tunicamycin impairs olfactory learning and synaptic plasticity in the olfactory bulb.
abstract: Tunicamycin (TM) induces endoplasmic reticulum (ER) stress and inhibits N-glycosylation in cells. ER stress is associated with neuronal death in neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, and most patients complain of the impairment of olfactory recognition. Here we examined the effects of TM on aversive olfactory learning and the underlying synaptic plasticity in the main olfactory bulb (MOB). Behavioral experiments demonstrated that the intrabulbar infusion of TM disabled aversive olfactory learning without affecting short-term memory. Histological analyses revealed that TM infusion upregulated C/EBP homologous protein (CHOP), a marker of ER stress, in the mitral and granule cell layers of MOB. Electrophysiological data indicated that TM inhibited tetanus-induced long-term potentiation (LTP) at the dendrodendritic excitatory synapse from mitral to granule cells. A low dose of TM (250nM) abolished the late phase of LTP, and a high dose (1μM) inhibited the early and late phases of LTP. Further, high-dose, but not low-dose, TM reduced the paired-pulse facilitation ratio, suggesting that the inhibitory effects of TM on LTP are partially mediated through the presynaptic machinery. Thus, our results support the hypothesis that TM-induced ER stress impairs olfactory learning by inhibiting synaptic plasticity via presynaptic and postsynaptic mechanisms in MOB.
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: Jia
authors.initials: J
authors.lastname: Tong
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan; Department of Occupational Health, Kochi Medical School, Nankoku, Kochi 783-8505, Japan. Electronic address: okutanif@kochi-u.ac.jp.
authors.forename: Fumino
authors.initials: F
authors.lastname: Okutani
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Murata
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Namba
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Kaba
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology; D005260:Female; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D007859:Learning Disabilities / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009830:Olfactory Bulb / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D055696:Olfactory Perception / Q000187:drug effects* / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D020318:Rats, Long-Evans; D046509:Tissue Culture Techniques; D051742:Transcription Factor CHOP / Q000378:metabolism; D014415:Tunicamycin / Q000633:toxicity*
chemical_list: C497251:Ddit3 protein, rat; D014415:Tunicamycin; D051742:Transcription Factor CHOP
keywords: C/EBP homologous protein; aversive olfactory learning; long-term potentiation; main olfactory bulb; paired-pulse facilitation; synaptic plasticity