Laterodorsal tegmentum interneuron subtypes oppositely regulate olfactory cue-induced innate fear

• Published in: Nature neuroscience Vol. 19; no. 2; pp. 283 - 289
• Main Authors: Yang, Hongbin, Yang, Junhua, Xi, Wang, Hao, Sijia, Luo, Benyan, He, Xiaobin, Zhu, Liya, Lou, Huifang, Yu, Yan-qin, Xu, Fuqiang, Duan, Shumin, Wang, Hao
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2016; Nature Publishing Group
• Subjects: 42; 631/378/1457/1601; 631/378/3920; 64; 64/110; 64/60; 9/74; Animal Genetics and Genomics; Animals; Anxiety; Anxiety Disorders - pathology; Behavior; Behavior, Animal; Behavioral Sciences; Biological Techniques; Biomedicine; Conditioning (Psychology); Corticosterone - blood; Cues; Fear; Fear & phobias; Fear - psychology; Glutamates - metabolism; Heart Rate; In Vitro Techniques; Interneurons; Laboratories; Male; Mice; Mice, Inbred C57BL; Neurobiology; Neurosciences; Odorants; Odors; Olfactory pathway; Optogenetics; Parvalbumins - metabolism; Physiological aspects; Predatory Behavior; Psychological aspects; Smell; Tegmentum Mesencephali - cytology; China
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.4208

Animals can fear specific objects with no previous experience. For example, naive mice are innately afraid of cats. Here the authors employed optogenet­ics and behavioral assays to determine the neural circuit mechanisms involved in mediating olfactory cue–induced innate fear in mice. 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.