Orexin-A infusion in the locus ceruleus triggers norepinephrine (NE) release and NE-induced long-term potentiation in the dentate gyrus.
The orexins (ORX-A/ORX-B) are neuroactive peptides known to have roles in feeding and sleep. Evidence of dense, excitatory projections of ORX-A neurons to the noradrenergic pontine nucleus, the locus ceruleus (LC), suggests ORX-A also participates in attention and memory. Activation of LC neurons by glutamate produces a beta-adrenergic receptor-mediated long-term potentiation (LTP) of the perforant path-evoked potential in the dentate gyrus, a target structure of the LC that has been implicated in memory. We asked whether ORX-A also activates norepinephrine (NE)-induced LTP by initiating NE release in the hippocampus. Here, we show that ORX-A infusion (0.25-25 fmol) into the LC produces a robust, beta-adrenergic receptor-dependent, long-lasting potentiation of the perforant path-evoked dentate gyrus population spike in the anesthetized rat. Pharmacological inactivation of the LC with an alpha2-adrenergic receptor agonist, before ORX-A infusion, prevents this potentiation. Analysis of NE concentrations in the hippocampus after ORX-A infusion into the LC reveals a transient, but robust, increase in NE release. Thus, this study demonstrates that the dense orexinergic projection to the LC promotes the induction of NE-LTP in the dentate gyrus. ORX-A modulation of LC activity may provide important support for the cognitive processes of attention and memory.
Department of Psychology, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B 3X9.
Susan G
SG
Walling
David J
DJ
Nutt
Margaret D
MD
Lalies
Carolyn W
CW
Harley
D000200:Action Potentials; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005071:Evoked Potentials; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology*; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation; D008297:Male; D017551:Microdialysis; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D011943:Receptors, Adrenergic, beta; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D009638:Norepinephrine