Orexin a preferentially excites glucose-sensitive neurons in the lateral hypothalamus of the rat in vitro.
Falls in blood glucose induce hunger and initiate feeding. The lateral hypothalamic area (LHA) contains glucose-sensitive neurons (GSNs) and orexin neurons, both of which are stimulated by falling blood glucose and are implicated in hypoglycemia-induced feeding. We combined intracellular electrophysiological recording with fluorescein labeling of GSNs to determine their neuroanatomic and functional relationships with orexin neurons. Orexin A (1 micromol/l) caused a 500% increase (P < 0.01) in spontaneous firing rate and rapid and lasting depolarization that was tetrodotoxin-resistant and thus a direct postsynaptic effect. Orexin A altered the intrinsic neuronal properties of GSNs, consistent with increased excitability. Confocal microscopy showed that GSNs were intimately related to orexin neurons: orexin-immunoreactive axons were frequently entwined around GSN dendrites, establishing close and putatively synaptic contacts. Orexin-cell axons also passed in close proximity to glucose-responsive neurons, which are inhibited by low glucose, but orexin A caused smaller depolarization than on GSNs and only a 200% increase in spontaneous firing rate (P < 0.05 vs. GSN). We conclude that GSNs are specific target neurons for orexin A and suggest that they may mediate, at least in part, the acute appetite-stimulating effect of orexin A. Orexin neurons may regulate GSNs so as to control the onset and termination of hypoglycemia-induced feeding.
Liu
X H
XH
Diabetes and Endocrinology Research Group, Department of Medicine University of Liverpool, Liverpool, UK.
Morris
R
R
Spiller
D
D
White
M
M
Williams
G
G
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D004594:Electrophysiology; D005947:Glucose / Q000502:physiology*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D051381:Rats; D017208:Rats, Wistar
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D005947:Glucose