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Impaired Respiratory and Body Temperature Control Upon Acute Serotonergic Neuron Inhibition

Science, 29 July 2011
Vol. 333, Issue 6042, p. 637-642
DOI: 10.1126/science.1205295

Impaired Respiratory and Body Temperature Control Upon Acute Serotonergic Neuron Inhibition

  1. Russell S. Ray1,*,
  2. Andrea E. Corcoran2,*,
  3. Rachael D. Brust1,*,
  4. Jun Chul Kim3,
  5. George B. Richerson4,
  6. Eugene Nattie2,
  7. Susan M. Dymecki1,
  1. 1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  2. 2Department of Physiology and Neurobiology, Dartmouth Medical School, Lebanon, NH 03756, USA.
  3. 3Department of Psychology, University of Toronto, Toronto, Ontario M5S 3G3, Canada.
  4. 4Department of Neurology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 2007 RCP, Iowa City, IA 52242, USA.
  1. To whom correspondence should be addressed. E-mail: dymecki{at}genetics.med.harvard.edu
  1. * These authors contributed equally to this work.

Abstract

Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved, but their constituent neurons are just beginning to be resolved. To query brain serotonergic neurons in homeostasis, we used a neuronal silencing tool, mouse RC::FPDi (based on the synthetic G protein–coupled receptor Di), designed for cell type–specific, ligand-inducible, and reversible suppression of action potential firing. In mice harboring Di-expressing serotonergic neurons, administration of the ligand clozapine-N-oxide (CNO) by systemic injection attenuated the chemoreflex that normally increases respiration in response to tissue carbon dioxide (CO2) elevation and acidosis. At the cellular level, CNO suppressed firing rate increases evoked by CO2 acidosis. Body thermoregulation at room temperature was also disrupted after CNO triggering of Di; core temperatures plummeted, then recovered. This work establishes that serotonergic neurons regulate life-sustaining respiratory and thermoregulatory networks, and demonstrates a noninvasive tool for mapping neuron function.

  • Received for publication 7 March 2011.
  • Accepted for publication 15 June 2011.

Citation:

R. S. Ray, A. E. Corcoran, R. D. Brust, J. C. Kim, G. B. Richerson, E. Nattie, and S. M. Dymecki, Impaired Respiratory and Body Temperature Control Upon Acute Serotonergic Neuron Inhibition. Science 333, 637-642 (2011).

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Principles of designing interpretable optogenetic behavior experiments
B. D. Allen, A. C. Singer, and E. S. Boyden
Learn. Mem. 22, 232-238 (18 March 2015)

HCN channels contribute to serotonergic modulation of ventral surface chemosensitive neurons and respiratory activity
V. E. Hawkins, J. M. Hawryluk, A. C. Takakura, A. V. Tzingounis, T. S. Moreira, and D. K. Mulkey
J. Neurophysiol. 113, 1195-1205 (15 February 2015)

Rational design of new NO and redox sensitivity into connexin26 hemichannels
L. Meigh, D. Cook, J. Zhang, and N. Dale
Open Biol 5, 140208-140208 (1 February 2015)

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R. T. R. Huckstepp, K. P. Cardoza, L. E. Henderson, and J. L. Feldman
J. Neurosci. 35, 1052-1067 (21 January 2015)

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P.-L. Ruffault, F. D'Autreaux, J. A. Hayes, M. Nomaksteinsky, S. Autran, T. Fujiyama, M. Hoshino, M. Hagglund, O. Kiehn, J.-F. Brunet et al.
elife 4, e07051-e07051 (1 January 2015)

DREADD: A Chemogenetic GPCR Signaling Platform
H. Zhu, and B. L. Roth
Int J Neuropsychopharmacol 18, pyu007-pyu007 (1 January 2015)

Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal
J. S. Park, B. Rhau, A. Hermann, K. A. McNally, C. Zhou, D. Gong, O. D. Weiner, B. R. Conklin, J. Onuffer, W. A. Lim et al.
Proc. Natl. Acad. Sci. USA 111, 5896-5901 (22 April 2014)

Medullary serotonin neurons are CO2 sensitive in situ
K. E. Iceman, G. B. Richerson, and M. B. Harris
J. Neurophysiol. 110, 2536-2544 (1 December 2013)

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H. Wildner, R. Das Gupta, D. Brohl, P. A. Heppenstall, H. U. Zeilhofer, and C. Birchmeier
J. Neurosci. 33, 7299-7307 (24 April 2013)

The Inhibition of Neurons in the Central Nervous Pathways for Thermoregulatory Cold Defense Induces a Suspended Animation State in the Rat
M. Cerri, M. Mastrotto, D. Tupone, D. Martelli, M. Luppi, E. Perez, G. Zamboni, and R. Amici
J. Neurosci. 33, 2984-2993 (13 February 2013)

HTR2 Receptors in a Songbird Premotor Cortical-Like Area Modulate Spectral Characteristics of Zebra Finch Song
W. E. Wood, T. K. Roseberry, and D. J. Perkel
J. Neurosci. 33, 2908-2915 (13 February 2013)

Allosteric Modulation of a Chemogenetically Modified G Protein-Coupled Receptor
A. Abdul-Ridha, J. R. Lane, P. M. Sexton, M. Canals, and A. Christopoulos
Mol. Pharmacol. 83, 521-530 (1 February 2013)

CO2 directly modulates connexin 26 by formation of carbamate bridges between subunits
L. Meigh, S. A. Greenhalgh, T. L. Rodgers, M. J. Cann, D. I. Roper, and N. Dale
elife 2, e01213-e01213 (1 January 2013)

KCNQ Channels Determine Serotonergic Modulation of Ventral Surface Chemoreceptors and Respiratory Drive
J. M. Hawryluk, T. S. Moreira, A. C. Takakura, I. C. Wenker, A. V. Tzingounis, and D. K. Mulkey
J. Neurosci. 32, 16943-16952 (21 November 2012)

Autonomous and nonautonomous roles of Hedgehog signaling in regulating limb muscle formation
J. K.-H. Hu, E. McGlinn, B. D. Harfe, G. Kardon, and C. J. Tabin
Genes Dev. 26, 2088-2102 (15 September 2012)

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Response to Comment on "Impaired Respiratory and Body Temperature Control Upon Acute Serotonergic Neuron Inhibition"
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K. G. Broadbelt, K. D. Rivera, D. S. Paterson, J. R. Duncan, F. L. Trachtenberg, J. A. Paulo, M. D. Stapels, N. S. Borenstein, R. A. Belliveau, E. A. Haas et al.
MCP 11, M111.009530-M111.009530 (1 January 2012)

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K. Nakamura, K. D. Rivera, D. S. Paterson, J. R. Duncan, F. L. Trachtenberg, J. A. Paulo, M. D. Stapels, N. S. Borenstein, R. A. Belliveau, E. A. Haas et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R1207-R1228 (1 November 2011)

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K. D. Rivera, D. S. Paterson, J. R. Duncan, F. L. Trachtenberg, J. A. Paulo, M. D. Stapels, N. S. Borenstein, R. A. Belliveau, E. A. Haas, C. Stanley et al.
DMM 4, 558-558 (1 September 2011)

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