Hypocretin/Orexin excites hypocretin neurons via a local glutamate neuron-A potential mechanism for orchestrating the hypothalamic arousal system.
Neurons that release hypocretin/orexin modulate sleep, arousal, and energy homeostasis; the absence of hypocretin results in narcolepsy. Here we present data on the physiological characteristics of these cells, identified with GFP in transgenic mouse brain slices. Hypocretin-1 and -2 depolarized hypocretin neurons by 15mV and evoked an increase in spike frequency (+366% from a 1-3 Hz baseline). The mechanism for this appears to be hypocretin-mediated excitation of local glutamatergic neurons that regulate hypocretin neuron activity, in part by presynaptic facilitation of glutamate release. This represents a possible mechanism for orchestrating the output of the diffuse hypothalamic arousal system. No direct effect of hypocretin on membrane properties of hypocretin cells was detected. Norepinephrine and serotonin, transmitters of other arousal systems, decreased spike frequency and evoked outward currents, whereas acetylcholine and histamine had little effect.
Li
Ying
Y
Department of Neurosurgery, Yale University, New Haven, CT 06520, USA.
Gao
Xiao Bing
XB
Sakurai
Takeshi
T
van den Pol
Anthony N
AN
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005246:Feedback / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D017930:Genes, Reporter / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D051379:Mice; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000068797:Orexins; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D018755:GABA Agonists; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D009479:Neuropeptides; D000068797:Orexins; D026941:Sodium Channel Blockers; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid