Orexin neurons are necessary for the circadian control of REM sleep - PubMed (original) (raw)

Orexin neurons are necessary for the circadian control of REM sleep

Sandor Kantor et al. Sleep. 2009 Sep.

Abstract

Study objectives: The orexin-producing neurons are hypothesized to be essential for the circadian control of sleep/wake behavior, but it remains unknown whether these rhythms are mediated by the orexin peptides or by other signaling molecules released by these neurons such as glutamate or dynorphin. To determine the roles of these neurotransmitters, we examined the circadian rhythms of sleep/wake behavior in mice lacking the orexin neurons (ataxin-3 [Atx] mice) and mice lacking just the orexin neuropeptides (orexin knockout [KO] mice).

Design: We instrumented mice for recordings of sleep-wake behavior, locomotor activity (LMA), and body temperature (Tb) and recorded behavior after 6 days in constant darkness.

Results: The amplitude of the rapid eye movement (REM) sleep rhythm was substantially reduced in Atx mice but preserved in orexin KO mice. This blunted rhythm in Atx mice was caused by an increase in the amount of REM sleep during the subjective night (active period) due to more transitions into REM sleep and longer REM sleep episodes. In contrast, the circadian variations of Tb, LMA, Wake, non-REM sleep, and cataplexy were normal, suggesting that the circadian timekeeping system and other output pathways are intact in both Atx and KO mice.

Conclusions: These results indicate that the orexin neurons are necessary for the circadian suppression of REM sleep. Blunting of the REM sleep rhythm in Atx mice but not in orexin KO mice suggests that other signaling molecules such as dynorphin or glutamate may act in concert with orexins to suppress REM sleep during the active period.

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Figures

Figure 1

Figure 1

In constant darkness, the hourly amounts of Wake (A) and NREM sleep (B) are similar in Atx (n = 8) and WTAtx (n = 8) mice. However, Atx mice have more REM sleep (C) than their WTAtx littermates during the subjective night. Nearly all cataplexy (D) occurs during the subjective night in Atx mice. *P < 0.05 compared to WTAtx

Figure 2

Figure 2

Atx mice have little circadian variation in REM sleep rhythm, indicated by low circadian index (A) and a nocturnality ratio (B) close to 50%. In contrast, the circadian rhythms of Wake, NREM sleep, Tb and LMA are preserved in Atx mice. The circadian index is normalized to the mean circadian amplitude of WTAtx mice (100%). **P < 0.01 compared to WTAtx

Figure 3

Figure 3

During the subjective night, Atx mice have an increased amount of REM sleep as a percentage of total sleep time (TST) (A) demonstrating that more REM sleep in these mice is not a consequence of more sleep in general. The average REM sleep latencies were shorter in both Atx and orexin KO mice than in WT littermates (C, D). **P < 0.01 compared to WTAtx or WTKO.

Figure 4

Figure 4

In contrast to orexin KO mice (B, D), Atx mice have a generally higher probability of entering REM sleep (A) and have longer bouts of REM sleep (C) than their wild-type littermates during the subjective night (active period) suggesting that the orexin neurons may control the initiation and maintenance of REM sleep during the active period. *P < 0.05, **P < 0.01 compared to WTAtx or WTKO.

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