scholarly journals PDF neuron firing phase-shifts key circadian activity neurons in Drosophila

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Fang Guo ◽  
Isadora Cerullo ◽  
Xiao Chen ◽  
Michael Rosbash

Our experiments address two long-standing models for the function of the Drosophila brain circadian network: a dual oscillator model, which emphasizes the primacy of PDF-containing neurons, and a cell-autonomous model for circadian phase adjustment. We identify five different circadian (E) neurons that are a major source of rhythmicity and locomotor activity. Brief firing of PDF cells at different times of day generates a phase response curve (PRC), which mimics a light-mediated PRC and requires PDF receptor expression in the five E neurons. Firing also resembles light by causing TIM degradation in downstream neurons. Unlike light however, firing-mediated phase-shifting is CRY-independent and exploits the E3 ligase component CUL-3 in the early night to degrade TIM. Our results suggest that PDF neurons integrate light information and then modulate the phase of E cell oscillations and behavioral rhythms. The results also explain how fly brain rhythms persist in constant darkness and without CRY.

1982 ◽  
Vol 243 (3) ◽  
pp. R373-R378 ◽  
Author(s):  
N. D. Horseman ◽  
C. F. Ehret

Intraperitoneal temperatures were monitored by radiotelemetry to observe the thermoregulatory rhythm of male laboratory rats (Rattus norvegicus albinus) Rats received single injections of dexamethasone (as dexamethasone sodium phosphate) during constant darkness (0.1 lx) with food freely available or no food available. No phase shifts occurred following saline injection or dexamethasone at 1 mg/kg body wt. Depending on the phase of injection relative to the circadian cycle, dexamethasone at 10 mg/kg caused thermoregulatory peaks to be either delayed or advanced on the 4th and 5th day after injection. There was an insensitive interval which corresponded to subjective day. Phase shifts induced by dexamethasone during ad libitum feeding were of less magnitude than those induced during starvation. The determination of phase-shifting parameters (i.e., a phase-response curve) for hormonal substances represents a rigorous and broadly applicable technique for determining endogenous mechanisms for circadian phase control and entrainment.


2008 ◽  
Vol 28 (12) ◽  
pp. 4080-4092 ◽  
Author(s):  
Ayumu Nakashima ◽  
Takeshi Kawamoto ◽  
Kiyomasa K. Honda ◽  
Taichi Ueshima ◽  
Mitsuhide Noshiro ◽  
...  

ABSTRACT DEC1 suppresses CLOCK/BMAL1-enhanced promoter activity, but its role in the circadian system of mammals remains unclear. Here we examined the effect of Dec1 overexpression or deficiency on circadian gene expression triggered with 50% serum. Overexpression of Dec1 delayed the phase of clock genes such as Dec1, Dec2, Per1, and Dbp that contain E boxes in their regulatory regions, whereas it had little effect on the circadian phase of Per2 and Cry1 carrying CACGTT E′ boxes. In contrast, Dec1 deficiency advanced the phase of the E-box-containing clock genes but not that of the E′-box-containing clock genes. Accordingly, DEC1 showed strong binding and transrepression on the E box, but not on the E′ box, in chromatin immunoprecipitation, electrophoretic mobility shift, and luciferase reporter assays. Dec1 −/− mice showed behavioral rhythms with slightly but significantly longer circadian periods under conditions of constant darkness and faster reentrainment to a 6-h phase-advanced shift of a light-dark cycle. Knockdown of Dec2 with small interfering RNA advanced the phase of Dec1 and Dbp expression, and double knockdown of Dec1 and Dec2 had much stronger effects on the expression of the E-box-containing clock genes. These findings suggest that DEC1, along with DEC2, plays a role in the finer regulation and robustness of the molecular clock.


1986 ◽  
Vol 250 (1) ◽  
pp. R5-R17
Author(s):  
D. P. Lotshaw ◽  
J. W. Jacklet

The effects of the protein synthesis inhibitors anisomycin and puromycin were measured on protein synthesis and phase shifting of the circadian rhythm in the isolated Aplysia eye. Anisomycin pulses induce phase delays proportional in magnitude to the duration and percentage of protein synthesis inhibition. The phase-response curve to anisomycin pulses consisted of delays induced throughout the subjective night. Delays were maximal between circadian times (CT) 18 and CT 2; pulses initiated between CT 2 and CT 12 did not phase shift. Puromycin induced phase delays and advances. Delays were proportional to the duration and percentage of protein synthesis inhibition, occurring with increasing magnitude throughout the subjective night (CT 12-2). Peptidyl-puromycin formation may contribute to the magnitude of the delay. Advances, occurring between CT 2 and CT 8, required a greater drug concentration and pulse duration than delays and appeared to result from an effect other than protein synthesis inhibition. Our results support the hypothesis of a phase-dependent requirement for protein synthesis during the subjective night in this circadian clock.


2006 ◽  
Vol 290 (3) ◽  
pp. R785-R792 ◽  
Author(s):  
M. M. Canal ◽  
H. D. Piggins

Circadian rhythms of animals are reset by exposure to light as well as dark; however, although the parameters of photic entrainment are well characterized, the phase-shifting actions of dark pulses are poorly understood. Here, we determined the tonic and phasic effects of short (0.25 h), moderate (3 h), and long (6–9 h) duration dark pulses on the wheel-running rhythms of hamsters in constant light. Moderate- and long-duration dark pulses phase dependently reset behavioral rhythms, and the magnitude of these phase shifts increased as a function of the duration of the dark pulse. In contrast, the 0.25-h dark pulses failed to evoke consistent effects at any circadian phase tested. Interestingly, moderate- and long-dark pulses elevated locomotor activity (wheel-running) on the day of treatment. This induced wheel-running was highly correlated with phase shift magnitude when the pulse was given during the subjective day. This, together with the finding that animals pulsed during the subjective day are behaviorally active throughout the pulse, suggests that both locomotor activity and behavioral activation play an important role in the phase-resetting actions of dark pulses. We also found that the robustness of the wheel-running rhythm was weakened, and the amount of wheel-running decreased on the days after exposure to dark pulses; these effects were dependent on pulse duration. In summary, similarly to light, the resetting actions of dark pulses are dependent on both circadian phase and stimulus duration. However, dark pulses appear more complex stimuli, with both photic and nonphotic resetting properties.


1975 ◽  
Vol 30 (3-4) ◽  
pp. 240-244 ◽  
Author(s):  
Ursula Hamm ◽  
M Aroli ◽  
K Chandrashekaran ◽  
W Olfgang Engelmann

Abstract The phase shifting action of low temperature pulses of 6 °C and 2 h duration administered to the various phases of the Drosophila pseudoobscura circadian rhythm and the action of light pulses given 30 min after the beginning of these low temperature pulses have been investigated. The phase response curve obtained from experiments with light pulses during low temperature cannot be ex­ plained on the basis of a straightforward and sequential phase shifting of the oscillation by the various transitions in the pulses. The response curve, after the slight phase shifting action of the temperature pulses is corrected for, resembles the standard phase response curve 4 for light pulses (at 20 °C) in its wave form but not in its time course. Our curve is shifted in time in a manner that indicates that the light pulses accompanying the low temperature pulses arrived at phase points 1.5 h later than the actual phases at which they were given. We attribute this delay to a slowing down of the information that is apparently transmitted by a process that is temperature dependent.


1982 ◽  
Vol 242 (1) ◽  
pp. R44-R50 ◽  
Author(s):  
G. B. Ellis ◽  
R. E. McKlveen ◽  
F. W. Turek

We compared the effects of light pulses in constant darkness (DD) and dark pulses in constant light (LL) on the free-running rhythm of locomotor activity in male golden hamsters. Light pulses yielded advances, delays, or no change in the rhythm of activity. These data conform to a typical phase-response curve; this curve was unaffected by pinealectomy. Dark pulses occurring either late in the subjective night or early in the subjective day had little effect. In contrast, dark pulses occurring either late in the subjective day or early in the subjective night altered the rhythm in one of three ways: advance of the rhythm; splitting into two components; or induction of a new component, in phase with the pulse. Because dark pulses in LL perturb the circadian system in a different manner than do light pulses in DD, they may have value in identifying heretofore unknown aspects of circadian systems. As such, the use of dark pulses to perturb circadian rhythmicity will be a useful tool in examining the formal properties of circadian systems.


2003 ◽  
Vol 284 (3) ◽  
pp. R714-R724 ◽  
Author(s):  
Orfeu M. Buxton ◽  
Calvin W. Lee ◽  
Mireille L'Hermite-Balériaux ◽  
Fred W. Turek ◽  
Eve Van Cauter

To examine the immediate phase-shifting effects of high-intensity exercise of a practical duration (1 h) on human circadian phase, five groups of healthy men 20–30 yr of age participated in studies involving no exercise or exposure to morning, afternoon, evening, or nocturnal exercise. Except during scheduled sleep/dark and exercise periods, subjects remained under modified constant routine conditions allowing a sleep period and including constant posture, knowledge of clock time, and exposure to dim light intensities averaging (±SD) 42 ± 19 lx. The nocturnal onset of plasma melatonin secretion was used as a marker of circadian phase. A phase response curve was used to summarize the phase-shifting effects of exercise as a function of the timing of exercise. A significant effect of time of day on circadian phase shifts was observed ( P < 0.004). Over the interval from the melatonin onset before exercise to the first onset after exercise, circadian phase was significantly advanced in the evening exercise group by 30 ± 15 min (SE) compared with the phase delays observed in the no-exercise group (−25 ± 14 min, P < 0.05). Phase shifts in response to evening exercise exposure were attenuated on the second day after exercise exposure and no longer significantly different from phase shifts observed in the absence of exercise. Unanticipated transient elevations of melatonin levels were observed in response to nocturnal exercise and in some evening exercise subjects. Taken together with the results from previous studies in humans and diurnal rodents, the current results suggest that 1) a longer duration of exercise exposure and/or repeated daily exposure to exercise may be necessary for reliable phase-shifting of the human circadian system and that 2) early evening exercise of high intensity may induce phase advances relevant for nonphotic entrainment of the human circadian system.


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