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Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin
- Source :
- The Journal of neuroscience : the official journal of the Society for Neuroscience. 18(19)
- Publication Year :
- 1998
-
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.
- Subjects :
- Patch-Clamp Techniques
Lateral hypothalamus
Molecular Sequence Data
Presynaptic Terminals
Glutamic Acid
Tetrodotoxin
Biology
Article
Membrane Potentials
SB-334867
Postsynaptic potential
Arcuate nucleus
mental disorders
medicine
Animals
Amino Acid Sequence
Axon
Enzyme Inhibitors
Evoked Potentials
Cells, Cultured
gamma-Aminobutyric Acid
Fluorescent Dyes
Neurons
Neurotransmitter Agents
Orexins
Dose-Response Relationship, Drug
General Neuroscience
Neuropeptides
Glutamate receptor
Arcuate Nucleus of Hypothalamus
Intracellular Signaling Peptides and Proteins
Feeding Behavior
Neurosecretory Systems
Orexin receptor
Electric Stimulation
Orexin
medicine.anatomical_structure
nervous system
Thapsigargin
Calcium
Carrier Proteins
Fura-2
Neuroscience
Cadmium
Signal Transduction
Subjects
Details
- ISSN :
- 02706474
- Volume :
- 18
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Accession number :
- edsair.doi.dedup.....743bf15ac0f2945be88e149e49690664