Stay Awake to Sync Brain's Master Clock to External Time
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Material below summarizes the article Sleep Deprivation and Caffeine Treatment Potentiate Photic Resetting of the Master Circadian Clock in a Diurnal Rodent, published on April 19, 2017, in JNeurosci and authored by Pawan Kumar Jha, Hanan Bouâouda, Sylviane Gourmelen, Stephanie Dumont, Fanny Fuchs, Yannick Goumon, Patrice Bourgin, Andries Kalsbeek, and Etienne Challet.
The states of being awake and falling asleep are regulated by interaction of wake and sleep promoting areas in the mammalian brain.
The master clock in the suprachiasmatic nucleus (SCN) of the hypothalamus provides a temporal pattern of sleep and wake that — like many other behavioral and physiological rhythms — is oppositely phased between nocturnal (night active) and diurnal (day active) animals.
The SCN primarily uses environmental light, perceived through the retina, to synchronize endogenous circadian rhythms with the 24-hour light/dark cycle of the outside world. The light responsiveness of SCN is similar in both nocturnal and diurnal species.
Studies in nocturnal animals have shown that arousing stimuli independent of light induce phase advances and attenuate light induced phase shifts. In diurnal species, including humans, the circadian responses of the master clock to these arousing stimuli remain largely unknown.
Since the wake and sleep periods are inverted between nocturnal and diurnal species but SCN neurons are largely active during daytime in both categories of mammals, we asked the following questions: Can behavioral arousal reset the SCN clock in diurnal animals? If yes, how does their timing affect SCN phase and photic resetting?
To address these questions, we used gentle handling and caffeine treatment as non-photic stimuli to induce arousal in the diurnal grass rat, Arvicanthis ansorgei.
First, we assessed the magnitude of sleep loss and arousal during sleep deprivation induced by gentle handling and caffeine treatment in early and late night by extensive monitoring of sleep and wake status of the animals. Handling and caffeine treatment significantly increased the time spent awake in early and late night.
Studies in nocturnal rats, mice, and hamsters indicate sleep deprivation and enhanced locomotion in the middle of the sleeping period (middle of the light period for nocturnal species) induce maximal phase advances of locomotor activity rhythm: animals begin and end activity much sooner than the usual activity onset and offset respectively. Caffeine did not induce a phase-shift, but did attenuate phase-shifts induced by sleep deprivation.
In diurnal grass rats, we found sleep deprivation in the early night induces phase-delays of wheel-running activity, and caffeine alone does not induce any phase-shift. These results indicate clock resetting by sleep deprivation in nocturnal and diurnal species depends upon their phase of sleep/wake cycle.
Sleep deprivation and caffeine treatment in nocturnal animals reduces the phase-shifting capacity of light. We tested this effect in diurnal species by exposing the animals to light pulses right after sleep deprivation and caffeine treatment in constant dark conditions.
Our data suggest sleep deprivation and caffeine treatment increase light-induced phase shifts. These findings reveal that, contrary to nocturnal species, behavioral arousal potentiates photic resetting in diurnal grass rat.
Marc Cuesta and others have shown enhanced light resetting of the SCN clock after serotoninergic activation in diurnal grass rats. This led us to hypothesize a role of serotonin in the observed effects of arousal on photic resetting.
We analyzed the levels of serotonin in the SCN and midbrain of sleep-deprived and caffeine-treated animals. Our data shows no change of serotonin levels after sleep deprivation in SCN and midbrain. However, caffeine treatment increased midbrain serotonin levels, indicating a possible role for serotonin in the caffeine-mediated effect on light resetting.
Next, we used c-Fos as a marker of neuronal activation to study the cellular mechanism of the photic and arousing stimuli in the SCN. Sleep deprivation in the early night increased the light-induced c-Fos induction, while caffeine treatment similarly enhanced it in the early and late night. These findings contrast to earlier studies in the nocturnal rodents in which arousing stimuli reduce the c-Fos expression induced by light.
We also aimed to identify the cell types in the SCN involved in the response to behavioral arousal. Results of our double immunolabeling experiment indicate that behavioral arousal activates calbindin-containing cells in the SCN of the diurnal grass rats.
In the present study, we showed prevention of sleep in the early hours of the rest period delays the clock and that arousal induced by both sleep deprivation and caffeine treatment speed up the phase resetting effects of light in the diurnal grass rats in contrast to previous studies in nocturnal rodents. These findings strengthen the notion that behavioral arousal modulates the master clock differently in nocturnal and diurnal species to maintain their respective temporal niche.
The understanding of neural circuits involved in arousal mediated regulation of circadian clock remains to be established. Further investigation of how wake-promoting molecules like caffeine modulate circadian rhythms in time-of-day dependent manner could be helpful to chronotherapies and other biomedical applications.
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Sleep Deprivation and Caffeine Treatment Potentiate Photic Resetting of the Master Circadian Clock in a Diurnal Rodent. Pawan Kumar Jha, Hanan Bouâouda, Sylviane Gourmelen, Stephanie Dumont, Fanny Fuchs, Yannick Goumon, Patrice Bourgin, Andries Kalsbeek, Etienne Challet. JNeurosci Apr 2017, 37 (16) 4343-4358; DOI: https://doi.org/10.1523/JNEUROSCI.3241-16.2017