title: Htr2a-Expressing Cells in the Central Amygdala Control the Hierarchy between Innate and Learned Fear.
abstract: Fear is induced by innate and learned mechanisms involving separate pathways. Here, we used an olfactory-mediated innate-fear versus learned-fear paradigm to investigate how these pathways are integrated. Notably, prior presentation of innate-fear stimuli inhibited learned-freezing response, but not vice versa. Whole-brain mapping and pharmacological screening indicated that serotonin-2A receptor (Htr2a)-expressing cells in the central amygdala (CeA) control both innate and learned freezing, but in opposing directions. In vivo fiber photometry analyses in freely moving mice indicated that innate but not learned-fear stimuli suppressed the activity of Htr2a-expressing CeA cells. Artificial inactivation of these cells upregulated innate-freezing response and downregulated learned-freezing response. Thus, Htr2a-expressing CeA cells serve as a hierarchy generator, prioritizing innate fear over learned fear.
authors.affiliation: Institute of Biomedical Science, Kansai Medical University, Osaka 573-1010, Japan; Department of Functional Neuroscience, Osaka Bioscience Institute, Osaka 565-0874, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Isosaka
authors.affiliation: Institute of Biomedical Science, Kansai Medical University, Osaka 573-1010, Japan; Department of Functional Neuroscience, Osaka Bioscience Institute, Osaka 565-0874, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Matsuo
authors.affiliation: Department of Systems Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Systems Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Funabiki
authors.affiliation: Department of Systems Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan.
authors.forename: Shigetada
authors.initials: S
authors.lastname: Nakanishi
authors.affiliation: Institute of Biomedical Science, Kansai Medical University, Osaka 573-1010, Japan; Department of Functional Neuroscience, Osaka Bioscience Institute, Osaka 565-0874, Japan. Electronic address: kobayakr@hirakata.kmu.ac.jp.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kobayakawa
authors.affiliation: Institute of Biomedical Science, Kansai Medical University, Osaka 573-1010, Japan; Department of Functional Neuroscience, Osaka Bioscience Institute, Osaka 565-0874, Japan. Electronic address: kobayakk@hirakata.kmu.ac.jp.
authors.forename: Ko
authors.initials: K
authors.lastname: Kobayakawa
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D005239:Fear / Q000145:classification / Q000502:physiology*; D019426:Integrases; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways; D010487:Periaqueductal Gray / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism*; D012903:Smell
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; C045073:Cre recombinase; D019426:Integrases