Orexin-A projections to the caudal medulla and orexin-induced c-Fos expression, food intake, and autonomic function.
Orexin-expressing neurons in the hypothalamus project throughout the neuraxis and are involved in regulation of the sleep/wake cycle, food intake, and autonomic functions. Here we specifically analyze the anatomical organization of orexin projections to the dorsal vagal complex (DVC) and raphe pallidus and effects on ingestive behavior and autonomic functions of local orexin-A administration in nonanesthetized rats. Retrograde tracing experiments revealed that as many as 20% of hypothalamic orexin neurons project to the DVC, where they form straight varicose axon profiles, some of which are in close anatomical apposition with tyrosine hydroxylase (TH)-, glucagon-like peptide-1-, gamma-aminobutyric acid-, and nitric oxide synthase-immunoreactive neurons in a nonselective manner. Similar contacts were frequently observed with neurons of the nucleus of the solitary tract whose activation by gastrointestinal food stimuli was demonstrated by the expression of nuclear c-Fos immunoreactivity. Orexin-A administration to the fourth ventricle induced significant Fos-expression throughout the DVC compared with saline control injections, with about 20-25% of TH-ir neurons among the stimulated ones. Fourth ventricular orexin injections also significantly stimulated chow and water intake in nonfood-deprived rats. Direct bilateral injections of orexin into the DVC increased intake of palatable high-fat pellets. Orexin-ir fibers also innervated raphe pallidus. Fourth ventricular orexin-A (1 nmol) activated Fos expression in the raphe pallidus and C1/A1 catecholaminergic neurons in the ventral medulla and increased body temperature, heart rate, and locomotor activity. The results confirm that hypothalamomedullary orexin projections are involved in a variety of physiological functions, including ingestive behavior and sympathetic outflow.
Zheng
Huiyuan
H
Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808, USA.
Patterson
Laurel M
LM
Berthoud
Hans-Rudolf
HR
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D002772:Cholera Toxin / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D006339:Heart Rate / Q000187:drug effects; D007031:Hypothalamus / Q000033:anatomy & histology / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008845:Microinjections / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014630:Vagus Nerve / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D010446:Peptide Fragments; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D005680:gamma-Aminobutyric Acid; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002772:Cholera Toxin; D014446:Tyrosine 3-Monooxygenase