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Orexin\u2010A and orexin\u2010B bind with different affinities to two G\u2010protein\u2010coupled transmembrane receptors, orexin\u20101 and orexin\u20102 receptors (OR\u2010R1 and OR\u2010R2, respectively). Because of the similarities between the human and the swine brain, we have studied the pig to investigate the orexinergic system in the diencephalon, with special emphasis on the neuroanatomical projections to the epithalamic region. By using antibodies against orexin\u2010A and orexin\u2010B, immunoreactive large multipolar perikarya were detected in the hypothalamic periventricular and perifornical areas at the light and electron microscopic levels. In the region of the paraventricular nucleus, the orexinergic neurons extended all the way to the lateral hypothalamic area. Immunoreactive nerve fibers, often endowed with large varicosities, were found throughout the hypothalamus and the epithalamus. Some periventricular immunoreactive nerve fibers entered the epithalamic region and continued into the pineal stalk and parenchyma to disperse among the pinealocytes. Immunoelectron microscopy confirmed the presence of orexinergic nerve fibers in the pig pineal gland. After extraction of total mRNA from the hypothalamus and pineal gland, we performed RT\u2010PCR and nested PCR using primers specific for porcine orexin receptors. PCR products were sequenced, verifying the presence of both OR\u2010R1 and OR\u2010R2 in the tissues investigated. These findings, supported by previous studies on rodents, suggest a hypothalamic regulation of the pineal gland via central orexinergic nervous inputs. J. Comp. Neurol. 471:113\u2013127, 2004. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.20007","type":"journal-article","created":{"date-parts":[[2004,2,26]],"date-time":"2004-02-26T20:22:01Z","timestamp":1077826921000},"page":"113-127","source":"Crossref","is-referenced-by-count":28,"title":["Demonstration of an orexinergic central innervation of the pineal gland of the 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