Brain Circuit of Claustrophobia-like Behavior in Mice Identified by Upstream Tracing of Sighing
Peng Li,
Shi-Bin Li,
Xuenan Wang,
Chrystian D. Phillips,
Lindsay A. Schwarz,
Liqun Luo,
Luis de Lecea,
Mark A. Krasnow
Affiliations
Peng Li
Department of Biochemistry, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; Life Sciences Institute, Departments of Biologic and Materials Sciences and of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Corresponding author
Shi-Bin Li
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA
Xuenan Wang
Life Sciences Institute, Departments of Biologic and Materials Sciences and of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
Chrystian D. Phillips
Life Sciences Institute, Departments of Biologic and Materials Sciences and of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
Lindsay A. Schwarz
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
Liqun Luo
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
Luis de Lecea
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA
Mark A. Krasnow
Department of Biochemistry, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; Corresponding author
Summary: Emotions are distinct patterns of behavioral and physiological responses triggered by stimuli that induce different brain states. Elucidating the circuits is difficult because of challenges in interrogating emotional brain states and their complex outputs. Here, we leverage the recent discovery in mice of a neural circuit for sighing, a simple, quantifiable output of various emotions. We show that mouse confinement triggers sighing, and this “claustrophobic” sighing, but not accompanying tachypnea, requires the same medullary neuromedin B (Nmb)-expressing neurons as physiological sighing. Retrograde tracing from the Nmb neurons identified 12 forebrain centers providing presynaptic input, including hypocretin (Hcrt)-expressing lateral hypothalamic neurons. Confinement activates Hcrt neurons, and optogenetic activation induces sighing and tachypnea whereas pharmacologic inhibition suppresses both responses. The effect on sighing is mediated by HCRT directly on Nmbneurons. We propose that this HCRT-NMB neuropeptide relay circuit mediates claustrophobic sighing and that activated Hcrt neurons are a claustrophobia brain state that directly controls claustrophobic outputs.
