QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 5, 2008, 28(10):2495-2505; doi:10.1523/JNEUROSCI.4729-07.2008

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Hodges, M. R. Articles by Richerson, G. B. Search for Related Content PubMed PubMed Citation Articles by Hodges, M. R. Articles by Richerson, G. B.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons

Matthew R. Hodges,¹ Glenn J. Tattersall,² Michael B. Harris,³ Sean D. McEvoy,¹ Diana N. Richerson,¹ Evan S. Deneris,⁴ Randy L. Johnson,⁵ Zhou-Feng Chen,⁶ and George B. Richerson^1,7

¹Departments of Neurology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520, ²Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada L2S 3A1, ³Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska 99775, ⁴Department of Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106, ⁵Department of Biochemistry and Molecular Biology, University of Texas, Houston, Texas 77030, ⁶Departments of Anesthesiology, Psychiatry, Molecular Biology and Pharmacology, Washington University School of Medicine Pain Center, St. Louis, Missouri 63110, and ⁷Veterans Affairs Medical Center, West Haven, Connecticut 06516

Correspondence should be addressed to Dr. Matthew R. Hodges, Department of Neurology, LCI-704, Yale University School of Medicine, 15 York Street, P.O. Box 208018, New Haven, CT 06520-8018. Email: matthew.hodges{at}yale.edu

Serotonergic neurons project widely throughout the CNS and modulate many different brain functions. Particularly important, but controversial, are the contributions of serotonin (5-HT) neurons to respiratory and thermoregulatory control. To better define the roles of 5-HT neurons in breathing and thermoregulation, we took advantage of a unique conditional knock-out mouse in which Lmx1b is genetically deleted in Pet1-expressing cells (Lmx1b^f/f/p), resulting in near-complete absence of central 5-HT neurons. Here, we show that the hypercapnic ventilatory response in adult Lmx1b^f/f/p mice was decreased by 50% compared with wild-type mice, whereas baseline ventilation and the hypoxic ventilatory response were normal. In addition, Lmx1b^f/f/p mice rapidly became hypothermic when exposed to an ambient temperature of 4°C, decreasing core temperature to 30°C within 120 min. This failure of thermoregulation was caused by impaired shivering and nonshivering thermogenesis, whereas thermosensory perception and heat conservation were normal. Finally, intracerebroventricular infusion of 5-HT stimulated baseline ventilation, and rescued the blunted hypercapnic ventilatory response. These data identify a previously unrecognized role of 5-HT neurons in the CO₂ chemoreflex, whereby they enhance the response of the rest of the respiratory network to CO₂. We conclude that the proper function of the 5-HT system is particularly important under conditions of environmental stress and contributes significantly to the hypercapnic ventilatory response and thermoregulatory cold defense.

Key words: 5-HT; chemoreception; carbon dioxide; thermogenesis; respiratory control; temperature

---

Received Oct. 18, 2007; revised Jan. 21, 2008; accepted Jan. 21, 2008.

Correspondence should be addressed to Dr. Matthew R. Hodges, Department of Neurology, LCI-704, Yale University School of Medicine, 15 York Street, P.O. Box 208018, New Haven, CT 06520-8018. Email: matthew.hodges{at}yale.edu

This article has been cited by other articles:

				M. Tada, A. Kakita, Y. Toyoshima, O. Onodera, T. Ozawa, T. Morita, M. Nishizawa, and H. Takahashi Depletion of medullary serotonergic neurons in patients with multiple system atrophy who succumbed to sudden death Brain, July 1, 2009; 132(7): 1810 - 1819. [Abstract] [Full Text] [PDF]

				M. Kanamaru and I. Homma Dorsomedial medullary 5-HT2 receptors mediate immediate onset of initial hyperventilation, airway dilation, and ventilatory decline during hypoxia in mice Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2009; 297(1): R34 - R41. [Abstract] [Full Text] [PDF]

				N. Alenina, D. Kikic, M. Todiras, V. Mosienko, F. Qadri, R. Plehm, P. Boye, L. Vilianovitch, R. Sohr, K. Tenner, et al. Growth retardation and altered autonomic control in mice lacking brain serotonin PNAS, June 23, 2009; 106(25): 10332 - 10337. [Abstract] [Full Text] [PDF]

				J. T. Erickson and B. C. Sposato Autoresuscitation responses to hypoxia-induced apnea are delayed in newborn 5-HT-deficient Pet-1 homozygous mice J Appl Physiol, June 1, 2009; 106(6): 1785 - 1792. [Abstract] [Full Text] [PDF]

				J. C. Leiter Serotonin, gasping, autoresuscitation, and SIDS--a contrarian view J Appl Physiol, June 1, 2009; 106(6): 1761 - 1762. [Full Text] [PDF]

				K. J. Cummings, K. G. Commons, K. C. Fan, A. Li, and E. E. Nattie Severe spontaneous bradycardia associated with respiratory disruptions in rat pups with fewer brain stem 5-HT neurons Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2009; 296(6): R1783 - R1796. [Abstract] [Full Text] [PDF]

				S. B. G. Abbott, R. L. Stornetta, M. G. Fortuna, S. D. Depuy, G. H. West, T. E. Harris, and P. G. Guyenet Photostimulation of Retrotrapezoid Nucleus Phox2b-Expressing Neurons In Vivo Produces Long-Lasting Activation of Breathing in Rats J. Neurosci., May 6, 2009; 29(18): 5806 - 5819. [Abstract] [Full Text] [PDF]

				E. Nattie and A. Li Central chemoreception is a complex system function that involves multiple brain stem sites J Appl Physiol, April 1, 2009; 106(4): 1464 - 1466. [Full Text] [PDF]

				K. Ptak, T. Yamanishi, J. Aungst, L. S. Milescu, R. Zhang, G. B. Richerson, and J. C. Smith Raphe Neurons Stimulate Respiratory Circuit Activity by Multiple Mechanisms via Endogenously Released Serotonin and Substance P J. Neurosci., March 25, 2009; 29(12): 3720 - 3737. [Abstract] [Full Text] [PDF]

				K. C. Krueger and E. S. Deneris Serotonergic Transcription of Human FEV Reveals Direct GATA Factor Interactions and Fate of Pet-1-Deficient Serotonin Neuron Precursors J. Neurosci., November 26, 2008; 28(48): 12748 - 12758. [Abstract] [Full Text] [PDF]

				P. G. Guyenet The 2008 Carl Ludwig Lecture: retrotrapezoid nucleus, CO2 homeostasis, and breathing automaticity J Appl Physiol, August 1, 2008; 105(2): 404 - 416. [Abstract] [Full Text] [PDF]

				M. B. Dias, A. Li, and E. Nattie Focal CO2 dialysis in raphe obscurus does not stimulate ventilation but enhances the response to focal CO2 dialysis in the retrotrapezoid nucleus J Appl Physiol, July 1, 2008; 105(1): 83 - 90. [Abstract] [Full Text] [PDF]

				S. F. Morrison, K. Nakamura, and C. J. Madden Central control of thermogenesis in mammals Exp Physiol, July 1, 2008; 93(7): 773 - 797. [Abstract] [Full Text] [PDF]

				A. Li and E. Nattie Serotonin transporter knockout mice have a reduced ventilatory response to hypercapnia (predominantly in males) but not to hypoxia J. Physiol., May 1, 2008; 586(9): 2321 - 2329. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help