Histochemistry and Cell Biology

, Volume 123, Issue 2, pp 147–156 | Cite as

Orexin inputs to caudal raphé neurons involved in thermal, cardiovascular, and gastrointestinal regulation

  • Hans-Rudolf BerthoudEmail author
  • Laurel M. Patterson
  • Gregory M. Sutton
  • Christopher Morrison
  • Huiyuan Zheng


Orexin-expressing neurons in the lateral hypothalamus with their wide projections throughout the brain are important for the regulation of sleep and wakefulness, ingestive behavior, and the coordination of these behaviors in the environmental context. To further identify downstream effector targets of the orexin system, we examined in detail orexin-A innervation of the caudal raphé nuclei in the medulla, known to harbor sympathetic preganglionic motor neurons involved in thermal, cardiovascular, and gastrointestinal regulation. All three components of the caudal raphé nuclei, raphé pallidus, raphé obscurus, and parapyramidal nucleus, are innervated by orexin-A-immunoreactive fibers. Using confocal microscopy, we demonstrate close anatomical appositions between varicose orexin-A immunoreactive axon profiles and sympathetic premotor neurons identified with either a transneuronal retrograde pseudorabies virus tracer injected into the interscapular brown fat pads, or with in situ hybridization of pro-TRH mRNA. Furthermore, orexin-A injected into the fourth ventricle induced c-Fos expression in the raphé pallidus and parapyramidal nucleus. These findings suggest that orexin neurons in the hypothalamus can modulate brown fat thermogenesis, cardiovascular, and gastrointestinal functions by acting directly on neurons in the caudal raphé nuclei, and support the idea that orexin’s simultaneous stimulation of food intake and sympathetic activity might have evolved as a mechanism to stay alert while foraging.


Orexin-A Raphé pallidus Raphé obscurus Parapyramidal nucleus Sympathetic premotor neurons Brown adipose tissue TRH 



The authors would like to thank Irina Stoyanova, Michele Corkern, and Amy Whittington for their excellent technical help. This research was partially supported by The Community Foundation of Southwestern Michigan and the National Institute of Diabetes and Digestive and Kidney Diseases, Grant DK 47348.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Hans-Rudolf Berthoud
    • 1
    Email author
  • Laurel M. Patterson
    • 1
  • Gregory M. Sutton
    • 1
  • Christopher Morrison
    • 1
  • Huiyuan Zheng
    • 1
  1. 1.Neurobiology of Nutrition Laboratory, Pennington Biomedical Research CenterLouisiana State UniversityBaton RougeUSA

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