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. 2002 Jul 1;22(13):5282-6.
doi: 10.1523/JNEUROSCI.22-13-05282.2002.

Release of hypocretin (orexin) during waking and sleep states

Lyudmila I Kiyashchenko  1 , Boris Y Mileykovskiy, Nigel Maidment, Hoa A Lam, Ming-Fung Wu, Joshi John, John Peever, Jerome M Siegel
Affiliations

Release of hypocretin (orexin) during waking and sleep states

Lyudmila I Kiyashchenko et al. J Neurosci. .

Abstract

Hypocretin (Hcrt or orexin) somas are located in the hypothalamus and project widely to forebrain and brainstem regions, densely innervating monoaminergic and cholinergic cells. Loss of Hcrt function results in the sleep disorder narcolepsy. However, the normal pattern of Hcrt release across the sleep-wake cycle is unknown. We monitored Hcrt-1 release in the basal forebrain, perifornical hypothalamus, and locus ceruleus (LC) across the sleep-wake cycle using microdialysis in freely moving cats and a sensitive solid phase radioimmunoassay. We found that the peptide concentration in dialysates from the hypothalamus was significantly higher during active waking (AW) than during slow-wave sleep (SWS). Moreover, Hcrt-1 release was significantly higher during rapid eye movement (REM) sleep than during SWS in the hypothalamus and basal forebrain. We did not detect a significant difference in release across sleep-waking states in the LC, perhaps because recovered levels of the peptide were lower at this site. Because there was a trend toward higher levels of Hcrt-1 release during AW compared with quiet waking (QW) in our 10 min dialysis samples, we compared Hcrt-1 levels in CSF in 2 hr AW and QW periods. Hcrt-1 release into CSF was 67% higher during AW than during QW. Elevated levels of Hcrt during REM sleep and AW are consistent with a role for Hcrt in the central programming of motor activity.

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Figures

Fig. 1.
Fig. 1.
Sleep-cycle release of Hcrt. A–C, Location of the tips of dialysis probes in the HYP, BF, and LC.CI, Internal capsule; CO, optic chasm;f, fornix; LH, lateral hypothalamus.D–F, Hcrt levels across the sleep–waking states in the HYP, BF, and LC. Sleep-state values differ as a function of state (HYP,p < 0.003, F = 4.7, df = 3254; BF, p < 0.03, F = 3.2, df = 3133). Tukey's test; *p < 0.05; **p < 0.02; ***p < 0.002. Hcrt release is maximal during AW and REM sleep and minimal during SWS and QW in the HYP and BF.
Fig. 2.
Fig. 2.
Hypnogram (A) and Hcrt levels (B) in the HYP across the sleep cycle. Circles indicate points at which dialysate was taken. Hcrt levels are maximal after long AW and REM sleep periods and minimal after SWS periods.
Fig. 3.
Fig. 3.
Concentrations of Hcrt-1 in the CSF during AW and QW. Left, Actigraph readings reflect greater levels of head movement during active waking. Right, Hcrt levels are significantly higher in CSF taken after a 2 hr AW period than after a 2 hr QW period. **p < 0.02;t = 3.4; df = 5.
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