title: Laterodorsal tegmentum interneuron subtypes oppositely regulate olfactory cue-induced innate fear.
abstract: Innate fear has a critical role in survival of animals. Unlike conditioned fear, the neuronal circuitry underlying innate fear is largely unknown. We found that the laterodorsal tegmentum (LDT) and lateral habenula (LHb) are specifically activated by the mouse predator odorant trimethylthiazoline (TMT). Using optogenetics to selectively stimulate GABAergic neurons in the LDT immediately produced fear-like responses (freezing, accelerated heart rate and increased serum corticosterone), whereas prolonged stimulation caused anxiety-like behaviors. Notably, although selective stimulation of parvalbumin (PV)-positive interneurons similarly induced fear-like responses, stimulation of somatostatin-positive interneurons or inhibition of PV neurons in the LDT suppressed TMT-induced fear-like responses without affecting conditioned fear. Finally, activation of LHb glutamatergic inputs to LDT interneurons was sufficient to generate fear-like responses. Thus, the LHb-LDT pathway is important for regulating olfactory cue-induced innate fear. Our results provide a potential target for therapeutic intervention for anxiety disorder.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang School of Medicine, Hangzhou, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang School of Medicine, Hangzhou, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang School of Medicine, Hangzhou, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Xi
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang School of Medicine, Hangzhou, China.
authors.forename: Sijia
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Neurology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Benyan
authors.initials: B
authors.lastname: Luo
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems and State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang School of Medicine, Hangzhou, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang School of Medicine, Hangzhou, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Lou
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang School of Medicine, Hangzhou, China.
authors.forename: Yan-qin
authors.initials: YQ
authors.lastname: Yu
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems and State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Wuhan, China.|Wuhan National Laboratory for Optoelectronics, Wuhan, China.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang School of Medicine, Hangzhou, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang School of Medicine, Hangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000473:pathology; D001522:Behavior, Animal; D003213:Conditioning, Psychological; D003345:Corticosterone / Q000097:blood; D003463:Cues; D005239:Fear / Q000523:psychology*; D005971:Glutamates / Q000378:metabolism; D006339:Heart Rate; D066298:In Vitro Techniques; D007395:Interneurons; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009812:Odorants; D062308:Optogenetics; D010320:Parvalbumins / Q000378:metabolism; D011235:Predatory Behavior; D012903:Smell; D013681:Tegmentum Mesencephali / Q000166:cytology*
chemical_list: D005971:Glutamates; D010320:Parvalbumins; D003345:Corticosterone