title: Histone acetylation in the olfactory bulb of young rats facilitates aversive olfactory learning and synaptic plasticity.
abstract: Epigenetic mechanisms play an important role in memory formation and synaptic plasticity. Specifically, histone-associated heterochromatin undergoes changes in structure during the early stages of long-term memory formation. In keeping with the classical conditioning paradigm, young rats have been shown to exhibit aversion to an odor stimulus initially presented during foot shock. We previously showed that synaptic plasticity at the dendrodendritic synapses between mitral and granule cells in the olfactory bulb (OB) underlies this aversive olfactory learning. However, the epigenetic mechanisms involved are not well characterized. Therefore, we examined whether intrabulbar infusion of trichostatin A (TSA), a histone deacetylase inhibitor, facilitates olfactory learning in young rats. TSA infusion during odor-shock training enhanced a conditioned odor aversion in a dose-dependent manner and prolonged the learned aversion. Western blot and immunohistochemical analyses showed that the level of histone H4 acetylation significantly increased until 4 h after odor-shock training in both mitral and granule cells in the OB, whereas histone H3 acetylation returned to the control level at 2 h after the training. We also obtained evidence that TSA infusion elevated acetylation of histone H4 or H3. Furthermore, in vitro electrophysiological analysis using slices of the OB revealed that application of TSA significantly enhanced the long-term potentiation induced in synaptic transmission from mitral to granule cells at dendrodendritic synapses. Taken together, these results provide evidence that histone H4 and H3 acetylation in the OB is an epigenetic mechanism associated with aversive olfactory learning in young rats.
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan. Electronic address: okutanif@kochi-u.ac.jp.
authors.forename: F
authors.initials: F
authors.lastname: Okutani
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Murata
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Namba
authors.affiliation: Department of Physiology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kaba
mesh_terms: D000107:Acetylation; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D044127:Epigenesis, Genetic; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009830:Olfactory Bulb / Q000187:drug effects / Q000502:physiology*; D055696:Olfactory Perception / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D020318:Rats, Long-Evans; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A