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Methodologies
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Presynaptic and postsynaptic
actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin
- Title
- Presynaptic and postsynaptic
actions and modulation of neuroendocrine neurons by a new hypothalamic peptide,
hypocretin/orexin.
- Author
- van den Pol AN; Gao XB; Obrietan K; Kilduff TS;
Belousov AB
- Source
- J Neurosci, 18(19):7962-71 1998 Oct 1
- Abstract
- A new orexigenic peptide called hypocretin (orexin) has recently been described in
neurons of the lateral hypothalamus and perifornical area. The medial and lateral hypothalamus have been
loosely called satiety and feeding centers of the brain, respectively. Approximately one-third of all
medial and lateral hypothalamic neurons tested, but not hippocampal neurons, show a striking nanomolar
sensitivity to hypocretin. As studied with calcium digital imaging with fura-2, hypocretin raises
cytoplasmic calcium via a mechanism based on G-protein enhancement of calcium influx through plasma
membrane channels. The peptide has a potent effect at both presynaptic and postsynaptic receptors. Most
synaptic activity in hypothalamic circuits is attributable to axonal release of GABA or glutamate. With
whole-cell patch-clamp recording, we show that hypocretin, acting directly at axon terminals, can increase
the release of each of these amino acid transmitters. Two hypocretin peptides, hypocretin-1 and
hypocretin-2, are coded by a single gene; neurons that respond to one peptide also respond to the other. In
addition to its effect on feeding, we find that this peptide also regulates the synaptic activity of
physiologically identified neuroendocrine neurons studied in hypothalamic slices containing the arcuate
nucleus, suggesting a second function of hypocretin in hormone regulation. The widespread distribution of
hypocretin axons, coupled with the strong response to the peptide at both presynaptic and postsynaptic
sites, suggests that the peptide probably modulates a variety of hypothalamic regulatory systems and could
regulate the axonal input to these regions presynaptically.
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