Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems

Journal of Neuroscience - Tập 18 Số 23 - Trang 9996-10015 - 1998
Christelle Peyron1, Devin K. Tighe1, Anthony N. van den Pol1,2, Luis de Lecea3, H. Craig Heller1, J. Gregor Sutcliffe3, Thomas S. Kilduff1
1Department of Biological Sciences, Stanford University, Stanford, California, 94305
2Department of Neurosurgery, Yale University, New Haven, Connecticut 06520
3Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, and

Tóm tắt

The novel neuropeptides called hypocretins (orexins) have recently been identified as being localized exclusively in cell bodies in a subregion of the tuberal part of the hypothalamus. The structure of the hypocretins, their accumulation in vesicles of axon terminals, and their excitatory effect on cultured hypothalamic neurons suggest that the hypocretins function in intercellular communication. To characterize these peptides further and to help understand what physiological functions they may serve, we undertook an immunohistochemical study to examine the distribution of preprohypocretin-immunoreactive neurons and fibers in the rat brain. Preprohypocretin-positive neurons were found in the perifornical nucleus and in the dorsal and lateral hypothalamic areas. These cells were distinct from those that express melanin-concentrating hormone. Although they represent a restricted group of cells, their projections were widely distributed in the brain. We observed labeled fibers throughout the hypothalamus. The densest extrahypothalamic projection was found in the locus coeruleus. Fibers were also seen in the septal nuclei, the bed nucleus of the stria terminalis, the paraventricular and reuniens nuclei of the thalamus, the zona incerta, the subthalamic nucleus, the central gray, the substantia nigra, the raphe nuclei, the parabrachial area, the medullary reticular formation, and the nucleus of the solitary tract. Less prominent projections were found in cortical regions, central and anterior amygdaloid nuclei, and the olfactory bulb. These results suggest that hypocretins are likely to have a role in physiological functions in addition to food intake such as regulation of blood pressure, the neuroendocrine system, body temperature, and the sleep–waking cycle.

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