title: The peptidergic control circuit for sighing.
abstract: Sighs are long, deep breaths expressing sadness, relief or exhaustion. Sighs also occur spontaneously every few minutes to reinflate alveoli, and sighing increases under hypoxia, stress, and certain psychiatric conditions. Here we use molecular, genetic, and pharmacologic approaches to identify a peptidergic sigh control circuit in murine brain. Small neural subpopulations in a key breathing control centre, the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG), express bombesin-like neuropeptide genes neuromedin B (Nmb) or gastrin-releasing peptide (Grp). These project to the preBötzinger Complex (preBötC), the respiratory rhythm generator, which expresses NMB and GRP receptors in overlapping subsets of ~200 neurons. Introducing either neuropeptide into preBötC or onto preBötC slices, induced sighing or in vitro sigh activity, whereas elimination or inhibition of either receptor reduced basal sighing, and inhibition of both abolished it. Ablating receptor-expressing neurons eliminated basal and hypoxia-induced sighing, but left breathing otherwise intact initially. We propose that these overlapping peptidergic pathways comprise the core of a sigh control circuit that integrates physiological and perhaps emotional input to transform normal breaths into sighs.
authors: Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, 94305.
authors: Peng
authors: P
authors: Li
authors: Systems Neurobiology Laboratory, Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095.
authors: Wiktor A
authors: WA
authors: Janczewski
authors: Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, 94305.
authors: Kevin
authors: K
authors: Yackle
authors: Systems Neurobiology Laboratory, Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095.
authors: Kaiwen
authors: K
authors: Kam
authors: Systems Neurobiology Laboratory, Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095.
authors: Silvia
authors: S
authors: Pagliardini
authors: Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, 94305.
authors: Mark A
authors: MA
authors: Krasnow
authors: Systems Neurobiology Laboratory, Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095.
authors: Jack L
authors: JL
authors: Feldman
mesh_terms: D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D004644:Emotions / Q000502:physiology; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018004:Receptors, Bombesin / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects; D012125:Respiratory Center / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology; D000076985:Saporins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D018004:Receptors, Bombesin; D054789:Ribosome Inactivating Proteins, Type 1; D019886:Gastrin-Releasing Peptide; D015287:Neurokinin B; C038393:neuromedin B; D000076985:Saporins; D001839:Bombesin