title: Bidirectional modulation of fear extinction by mediodorsal thalamic firing in mice.
abstract: The mediodorsal thalamic nucleus has been implicated in the control of memory processes. However, the underlying neural mechanism remains unclear. Here we provide evidence for bidirectional modulation of fear extinction by the mediodorsal thalamic nucleus. Mice with a knockout or mediodorsal thalamic nucleus-specific knockdown of phospholipase C β4 exhibited impaired fear extinction. Mutant mediodorsal thalamic nucleus neurons in slices showed enhanced burst firing accompanied by increased T-type Ca(2+) currents; blocking of T channels in vivo rescued the fear extinction. Tetrode recordings in freely moving mice revealed that, during extinction, the single-spike (tonic) frequency of mediodorsal thalamic nucleus neurons increased in wild-type mice, but was static in mutant mice. Furthermore, tonic-evoking microstimulations of the mediodorsal thalamic nucleus, contemporaneous with the extinction tones, rescued fear extinction in mutant mice and facilitated it in wild-type mice. In contrast, burst-evoking microstimulation suppressed extinction in wild-type mice, mimicking the mutation. These results suggest that the firing mode of the mediodorsal thalamic nucleus is critical for the modulation of fear extinction.
authors.affiliation: Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Sukchan
authors.initials: S
authors.lastname: Lee
authors.forename: Touqeer
authors.initials: T
authors.lastname: Ahmed
authors.forename: Soojung
authors.initials: S
authors.lastname: Lee
authors.forename: Huisu
authors.initials: H
authors.lastname: Kim
authors.forename: Sukwoo
authors.initials: S
authors.lastname: Choi
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Sang Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jeiwon
authors.initials: J
authors.lastname: Cho
authors.forename: Hee-Sup
authors.initials: HS
authors.lastname: Shin
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000200:Action Potentials / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000523:psychology; D001522:Behavior, Animal; D015220:Calcium Channels / Q000378:metabolism; D003213:Conditioning, Psychological / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004558:Electric Stimulation; D004569:Electroencephalography; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D054799:Phospholipase C beta / Q000172:deficiency / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics; D013788:Thalamus / Q000166:cytology*
chemical_list: D015220:Calcium Channels; D034741:RNA, Small Interfering; D054799:Phospholipase C beta; C518043:Plcb4 protein, mouse; D010751:Phosphopyruvate Hydratase