Role of orexin input in the diurnal rhythm of locus coeruleus impulse activity

Brain Res. 2008 Aug 11:1224:43-52. doi: 10.1016/j.brainres.2008.05.060. Epub 2008 Jun 3.

Abstract

Activation of noradrenergic locus coeruleus (LC) neurons promotes wakefulness and behavioral arousal. In rats, LC neurons receive circadian inputs via a circuit that originates in the suprachiasmatic nucleus (SCN) and relays through the dorsomedial hypothalamus (DMH) to LC; this circuit input increases LC activity during the active period. DMH neurons expressing the peptide neurotransmitter orexin/hypocretin are ideally situated to act as a relay between SCN and LC due to their synaptic inputs from SCN and innervation of LC. Here, we examined the hypothesis that orexin is involved in transmitting circadian signals to LC using single-unit recordings of LC neurons in anesthetized rats maintained in 12:12 light-dark housing. We replicated earlier findings from this lab that LC neurons fire significantly faster on average during the active compared to rest periods. Local microinjection of an orexin antagonist, SB-334867-A attenuated the impulse activities of the fastest firing population of LC neurons during the active period. We also found that DMH orexin neurons project preferentially to LC and express a diurnal rhythm of activation that correlates with LC neuronal firing frequency. Therefore, we propose that DMH orexin neurons play a role in modulating the day-night differences of LC impulse activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Axons / metabolism
  • Axons / ultrastructure
  • Benzoxazoles / pharmacology
  • Circadian Rhythm / physiology*
  • Dorsomedial Hypothalamic Nucleus / cytology
  • Dorsomedial Hypothalamic Nucleus / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / pharmacology
  • Locus Coeruleus / cytology
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / metabolism*
  • Male
  • Microinjections
  • Naphthyridines
  • Neural Pathways / cytology
  • Neural Pathways / metabolism
  • Neuropeptides / metabolism*
  • Neuropeptides / pharmacology
  • Orexin Receptors
  • Orexins
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Receptors, Neuropeptide / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Urea / analogs & derivatives
  • Urea / pharmacology
  • Wakefulness / physiology

Substances

  • 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
  • Benzoxazoles
  • Intracellular Signaling Peptides and Proteins
  • Naphthyridines
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Urea