Htr2a-Expressing Cells in the Central Amygdala Control the Hierarchy between Innate and Learned Fear

• Published in: Cell Vol. 163; no. 5; pp. 1153 - 1164
• Main Authors: Isosaka, Tomoko, Matsuo, Tomohiko, Yamaguchi, Takashi, Funabiki, Kazuo, Nakanishi, Shigetada, Kobayakawa, Reiko, Kobayakawa, Ko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.11.2015
• Subjects: Amygdala - physiology; Animals; Fear - classification; Fear - physiology; Integrases; Male; Mice; Mice, Inbred C57BL; Neural Pathways; Periaqueductal Gray - physiology; Receptor, Serotonin, 5-HT2A - genetics; Receptor, Serotonin, 5-HT2A - metabolism; Smell
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2015.10.047

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. [Display omitted] •A hierarchical relationship exists between innate- and learned-fear responses•Innate but not learned-fear stimuli suppress the activity of CeA Htr2a+ cells•CeA Htr2a+ cell inhibition up/downregulates innate/learned freezing, respectively•CeA Htr2a+ cells act as a hierarchy generator prioritizing innate over learned fear The integration of innate and learned information processing is fundamental to controlling behavior. A population of serotonin 2A receptor-expressing cells in the central amygdala acts as a hierarchy generator by prioritizing innate over learned fear.