scholarly journals General Anaesthesia Shifts the Murine Circadian Clock in a Time-Dependant Fashion

2021 ◽  
Vol 3 (1) ◽  
pp. 87-97
Author(s):  
Nicola M. Ludin ◽  
Alma Orts-Sebastian ◽  
James F. Cheeseman ◽  
Janelle Chong ◽  
Alan F. Merry ◽  
...  
Keyword(s):  
Circadian Clock ◽  
General Anaesthesia ◽  
Wheel Running ◽  
Phase Shifts ◽  
Time Dependent ◽  
Suprachiasmatic Nuclei ◽  
Response Curves ◽  
Inhalational Anaesthetic ◽  
Locomotor Rhythms ◽  
Time Dependent Analysis

Following general anaesthesia (GA), patients frequently experience sleep disruption and fatigue, which has been hypothesized to result at least in part by GA affecting the circadian clock. Here, we provide the first comprehensive time-dependent analysis of the effects of the commonly administered inhalational anaesthetic, isoflurane, on the murine circadian clock, by analysing its effects on (a) behavioural locomotor rhythms and (b) PER2::LUC expression in the suprachiasmatic nuclei (SCN) of the mouse brain. Behavioural phase shifts elicited by exposure of mice (n = 80) to six hours of GA (2% isoflurane) were determined by recording wheel-running rhythms in constant conditions (DD). Phase shifts in PER2::LUC expression were determined by recording bioluminescence in organotypic SCN slices (n = 38) prior to and following GA exposure (2% isoflurane). Full phase response curves for the effects of GA on behaviour and PER2::LUC rhythms were constructed, which show that the effects of GA are highly time-dependent. Shifts in SCN PER2 expression were much larger than those of behaviour (c. 0.7 h behaviour vs. 7.5 h PER2::LUC). We discuss the implications of this work for understanding how GA affects the clock, and how it may inform the development of chronotherapeutic strategies to reduce GA-induced phase-shifting in patients.

scholarly journals The Effects of General Anaesthesia and Light on Behavioural Rhythms and GABAA Receptor Subunit Expression in the Mouse SCN

2021 ◽  
Vol 3 (3) ◽  
pp. 482-494
Author(s):  
Janelle Chong ◽  
James Frederick Cheeseman ◽  
Matthew D. M. Pawley ◽  
Andrea Kwakowsky ◽  
Guy R. Warman
Keyword(s):  
General Anaesthesia ◽  
Phase Shifts ◽  
Phase Shifting ◽  
Response Curves ◽  
Inhalational Anaesthetic ◽  
Subunit Expression ◽  
Locomotor Rhythms ◽  
Wheel Activity ◽  
Effect Of Light ◽  
Gabaar Subunit

General anaesthesia (GA) is known to affect the circadian clock. However, the mechanisms that underlie GA-induced shifting of the clock are less well understood. Activation of γ-aminobutyric acid (GABA)-type A receptors (GABAAR) in the suprachiasmatic nucleus (SCN) can phase shift the clock and thus GABA and its receptors represent a putative pathway via which GA exerts its effect on the clock. Here, we investigated the concurrent effects of the inhalational anaesthetic, isoflurane, and light, on mouse behavioural locomotor rhythms and on α1, β3, and γ2 GABAAR subunit expression in the SCN of the mouse brain. Behavioural phase shifts elicited by exposure of mice to four hours of GA (2% isoflurane) and light (400 lux) (n = 60) were determined by recording running wheel activity rhythms in constant conditions (DD). Full phase response curves for the effects of GA + light on behavioural rhythms show that phase shifts persist in anaesthetized mice exposed to light. Daily variation was detected in all three GABAAR subunits in LD 12:12. The γ2 subunit expression was significantly increased following GA in DD (compared to light alone) at times of large behavioural phase delays. We conclude that the phase shifting effect of light on the mouse clock is not blocked by GA administration, and that γ2 may potentially be involved in the phase shifting effect of GA on the clock. Further analysis of GABAAR subunit expression in the SCN will be necessary to confirm its role.

Entrainment of the master circadian clock by scheduled feeding

2004 ◽  
Vol 287 (3) ◽  
pp. R551-R555 ◽  
Author(s):  
Marina R. Castillo ◽  
Kelly J. Hochstetler ◽  
Ronald J. Tavernier ◽  
Dana M. Greene ◽  
Abel Bult-Ito
Keyword(s):  
Circadian Clock ◽  
Wheel Running ◽  
Expression Profiles ◽  
The Novel ◽  
Suprachiasmatic Nuclei ◽  
Behavioral Rhythms ◽  
Entrainment Process ◽  
Protein Expression Profiles ◽  
Access To Food ◽  
Constant Dark

The master circadian clock, located in the mammalian suprachiasmatic nuclei (SCN), generates and coordinates circadian rhythmicity, i.e., internal organization of physiological and behavioral rhythms that cycle with a near 24-h period. Light is the most powerful synchronizer of the SCN. Although other nonphotic cues also have the potential to influence the circadian clock, their effects can be masked by photic cues. The purpose of this study was to investigate the ability of scheduled feeding to entrain the SCN in the absence of photic cues in four lines of house mouse ( Mus domesticus). Mice were initially housed in 12:12-h light/dark cycle with ad libitum access to food for 6 h during the light period followed by 4–6 mo of constant dark under the same feeding schedule. Wheel running behavior suggested and circadian PER2 protein expression profiles in the SCN confirmed entrainment of the master circadian clock to the onset of food availability in 100% (49/49) of the line 2 mice in contrast to only 4% (1/24) in line 3 mice. Mice from line 1 and line 4 showed intermediate levels of entrainment, 57% (8/14) and 39% (7/18), respectively. The predictability of entrainment vs. nonentrainment in line 2 and line 3 and the novel entrainment process provide a powerful tool with which to further elucidate mechanisms involved in entrainment of the SCN by scheduled feeding.

Photoperiod differentially modulates photic and nonphotic phase response curves of hamsters

2004 ◽  
Vol 286 (3) ◽  
pp. R539-R546 ◽  
Author(s):  
J. A. Evans ◽  
J. A. Elliott ◽  
M. R. Gorman
Keyword(s):  
Wheel Running ◽  
Phase Response Curve ◽  
Phase Shifts ◽  
Phase Response ◽  
Cycle Phase ◽  
Phase Resetting ◽  
Response Curves ◽  
Syrian Hamsters ◽  
Light Pulses ◽  
Circadian Time

Circadian pacemakers respond to light pulses with phase adjustments that allow for daily synchronization to 24-h light-dark cycles. In Syrian hamsters, Mesocricetus auratus, light-induced phase shifts are larger after entrainment to short daylengths (e.g., 10 h light:14 h dark) vs. long daylengths (e.g., 14 h light:10 h dark). The present study assessed whether photoperiodic modulation of phase resetting magnitude extends to nonphotic perturbations of the circadian rhythm and, if so, whether the relationship parallels that of photic responses. Male Syrian hamsters, entrained for 31 days to either short or long daylengths, were transferred to novel wheel running cages for 2 h at times spanning the entire circadian cycle. Phase shifts induced by this stimulus varied with the circadian time of exposure, but the amplitude of the resulting phase response curve was not markedly influenced by photoperiod. Previously reported photoperiodic effects on photic phase resetting were verified under the current paradigm using 15-min light pulses. Photoperiodic modulation of phase resetting magnitude is input specific and may reflect alterations in the transmission of photic stimuli.

scholarly journals The cholinergic forebrain arousal system acts directly on the circadian pacemaker

2016 ◽  
Vol 113 (47) ◽  
pp. 13498-13503 ◽  
Author(s):  
Glenn R. Yamakawa ◽  
Priyoneel Basu ◽  
Filomeno Cortese ◽  
Johanna MacDonnell ◽  
Danica Whalley ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Basal Forebrain ◽  
Temporal Structure ◽  
Phase Shifts ◽  
Phase Shifting ◽  
Suprachiasmatic Nuclei ◽  
Functional Link ◽  
Substantia Innominata ◽  
Arousal System ◽  
Important System

Sleep and wake states are regulated by a variety of mechanisms. One such important system is the circadian clock, which provides temporal structure to sleep and wake. Conversely, changes in behavioral state, such as sleep deprivation (SD) or arousal, can phase shift the circadian clock. Here we demonstrate that the level of wakefulness is critical for this arousal resetting of the circadian clock. Specifically, drowsy animals with significant power in the 7- to 9-Hz band of their EEGs do not exhibit phase shifts in response to a mild SD procedure. We then show that treatments that both produce arousal and reset the phase of circadian clock activate (i.e., induce Fos expression in) the basal forebrain. Many of the activated cells are cholinergic. Using retrograde tract tracing, we demonstrate that cholinergic cells activated by these arousal procedures project to the circadian clock in the suprachiasmatic nuclei (SCN). We then demonstrate that arousal-induced phase shifts are blocked when animals are pretreated with atropine injections to the SCN, demonstrating that cholinergic activity at the SCN is necessary for arousal-induced phase shifting. Finally, we demonstrate that electrical stimulation of the substantia innominata of the basal forebrain phase shifts the circadian clock in a manner similar to that of our arousal procedures and that these shifts are also blocked by infusions of atropine to the SCN. These results establish a functional link between the major forebrain arousal center and the circadian system.

scholarly journals cGMP induces phase shifts of a mammalian circadian pacemaker at night, in antiphase to cAMP effects

1989 ◽  
Vol 86 (17) ◽  
pp. 6812-6815 ◽  
Author(s):  
R A Prosser ◽  
A J McArthur ◽  
M U Gillette
Keyword(s):  
Circadian Clock ◽  
Brain Slices ◽  
Phase Shifts ◽  
Suprachiasmatic Nuclei ◽  
Daily Cycle ◽  
Subjective Night ◽  
Camp And Cgmp ◽  
Diurnal Period ◽  
Nocturnal Period

The suprachiasmatic nuclei (SCN) of mammals contain a circadian clock that synchronizes behavioral and physiological rhythms to the daily cycle of light and darkness. We have been probing the biochemical substrates of this endogenous pacemaker by examining the ability of treatments affecting cyclic nucleotide-dependent pathways to induce changes in the phase of oscillation in electrical activity of rat SCN isolated in brain slices. Our previous work has shown that daytime treatments that stimulate cAMP-dependent pathways induce phase shifts of the SCN pacemaker in vitro but treatments during the subjective night are without effect. In this study we report that the phase of SCN oscillation is reset by treatments that stimulate cGMP-dependent pathways, but only during the subjective night. Thus, the nocturnal period of SCN sensitivity to cGMP is in antiphase to the diurnal period of sensitivity to cAMP. These results suggest that cAMP and cGMP affect the SCN pacemaker through separate biochemical pathways intrinsic to the SCN. These studies provide evidence that changing biochemical substrates within the SCN circadian clock may underlie some aspects of differential temporal sensitivity of mammals to resetting stimuli.

Serotonergic afferents mediate activity-dependent entrainment of the mouse circadian clock

1997 ◽  
Vol 273 (1) ◽  
pp. R265-R269 ◽  
Author(s):  
D. M. Edgar ◽  
M. S. Reid ◽  
W. C. Dement
Keyword(s):  
Circadian Clock ◽  
Wheel Running ◽  
Activity Levels ◽  
Suprachiasmatic Nuclei ◽  
Vigorous Exercise ◽  
Serotonin Content ◽  
Running Activity ◽  
Midbrain Raphe Nuclei ◽  
Activity Dependent

The circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus receives serotonergic afferents from the midbrain raphe nuclei, but the functional role of this projection is unclear. In rodents, locomotor activity increases serotonin content in the SCN, and serotonergic agonists phase shift the circadian clock in a manner closely similar to voluntary bouts of vigorous exercise, suggesting that serotonergic afferents could be part of the activity-dependent entrainment mechanism. We investigated this possibility by selectively lesioning serotonin terminals within and adjacent to the SCN by local microinjection of 5,7-dihydroxytryptamine in mice pretreated with desipramine. This treatment decreased serotonin content 96 +/- 1% and 5-hydroxyindole-3-acetic acid content below levels of detection (nearly 100%) but did not decrease norepinephrine content or neuropeptide Y immunoreactivity in the SCN. These lesions did not alter subsequent running activity levels, yet rendered mice unable to synchronize to a regularly scheduled 2-h wheel running paradigm that entrained sham-lesioned controls. Serotonin afferents are thus necessary for activity-dependent entrainment in the mouse.

Phase-shifting effects of acute increases in activity on circadian locomotor rhythms in hamsters

1991 ◽  
Vol 261 (5) ◽  
pp. R1109-R1117 ◽  
Author(s):  
C. R. Wickland ◽  
F. W. Turek
Keyword(s):  
Locomotor Activity ◽  
Circadian Clock ◽  
Phase Shifts ◽  
Phase Shifting ◽  
Running Wheel ◽  
Baseline Activity ◽  
Circadian Time ◽  
Activity State ◽  
Locomotor Rhythms ◽  
Running Wheels

Experiments were conducted in golden hamsters to examine the relationship between induced acute increases in locomotor activity and phase shifts in the circadian clock underlying the rhythm of activity. Injections of the short-acting benzodiazepine triazolam (TZ) 6 h before the onset of activity resulted in an acute increase in activity and a phase advance in the rhythm of activity; injections of TZ induced larger phase shifts in animals housed without running wheels than in those housed with wheels. Transfer to a cage with access to a running wheel for 1 h at different circadian times induced large phase advances (mean of 2 h) and small phase delays depending on the circadian time of transfer. Maximal mean phase advances resulted when animals were transferred to a cage with wheel 3 h before activity onset, and at this circadian time there was a significant correlation between the magnitude of the phase shift and the amount of increase over baseline activity for the first hour after transfer. These results indicate that access to a running wheel in animals housed without wheels can be a significant phase-shifting stimulus to the circadian clock and that the phase shifts induced by injection of TZ or transfer to a new cage with wheel are related to the activity state of the animal or to the amount of locomotor activity that is induced at particular times.

Neuropeptide Y phase advances the in vitro hamster circadian clock during the subjective day with no effect on phase during the subjective night

2000 ◽  
Vol 78 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Mary E Harrington ◽  
Kathryn M Schak
Keyword(s):  
Circadian Clock ◽  
Neuropeptide Y ◽  
Firing Rate ◽  
Phase Shifts ◽  
Suprachiasmatic Nuclei ◽  
Subjective Night ◽  
Circadian Change ◽  
Brain Slice Preparation ◽  
Spontaneous Firing Rate

The mammalian daily (circadian) clock is located in the suprachiasmatic nuclei of the hypothalamus. Clock function can be detected by the measurement of the circadian change in spontaneous firing rate of suprachiasmatic nuclei cells in a brain slice preparation in vitro. We investigated the effects of neuropeptide Y on this rhythm of firing rate in hamster suprachiasmatic nuclei neurons. Slices were prepared using standard techniques. On the 1st day in vitro, neuropeptide Y (200 ng/200 nL; 47 pmol) was applied as a microdrop to the suprachiasmatic nuclei region at various times. Spontaneous single-unit firing was measured for 6-12 h on the 2nd day in vitro. Peak firing rate in treated slices was compared with that of untreated control slices to measure phase shifts induced by the peptide. Neuropeptide Y induced phase advances of circa-3h when applied during the subjective day (ZT 2-10) but did not significantly alter phase when applied during the subjective night. The phase shifts to neuropeptide Y in the hamster tissue in vitro are similar in phase dependency and magnitude to shifts measured in vivo.Key words: circadian, neuropeptide Y, rhythm, suprachiasmatic.

Cycloheximide-induced phase shifting of circadian clock of Neurospora

1981 ◽  
Vol 241 (1) ◽  
pp. R31-R35 ◽  
Author(s):  
H. Nakashima ◽  
J. Perlman ◽  
J. F. Feldman
Keyword(s):  
Protein Synthesis ◽  
Circadian Clock ◽  
Response Curve ◽  
Phase Response Curve ◽  
Phase Shifts ◽  
Phase Shifting ◽  
Normal Operation ◽  
Circadian Cycle ◽  
Response Curves ◽  
Inhibition Of Protein Synthesis

Cycloheximide (CHX), an inhibitor of cytosolic (80S) protein synthesis in eucaryotes, causes phase shifts of the circadian clock of Neurospora crassa when administered as 4-h pulses to cultures in liquid medium. Differential effects of the pulses at different phases of the circadian cycle were observed and plotted as a phase-response curve (PRC). Nearly all phase shifts observed were phase advances, with maximum sensitivity in the middle of the subjective day. Inhibition of protein synthesis by CHX was the same at both phases of the cycle. The PRC was the same at 20 and 25 degrees C. Dose-response curves for the effects of CHX on phase shifting and inhibition of protein synthesis were determined and showed a striking parallel in the responses of these two phenomena to CHX. These results support the view that synthesis of one or more proteins at specific phases of the circadian cycle is necessary for the normal operation of the circadian clock of Neurospora.

A serotonin agonist phase-shifts the circadian clock in the suprachiasmatic nuclei in vitro

1990 ◽  
Vol 534 (1-2) ◽  
pp. 336-339 ◽  
Author(s):  
Rebecca A. Prosser ◽  
Joseph D. Miller ◽  
H. Craig Heller
Keyword(s):  
Circadian Clock ◽  
Phase Shifts ◽  
Suprachiasmatic Nuclei ◽  
Serotonin Agonist
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