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

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.

2021 ◽  
Vol 3 (1) ◽  
pp. 87-97
Author(s):  
Nicola M. Ludin ◽  
Alma Orts-Sebastian ◽  
James F. Cheeseman ◽  
Janelle Chong ◽  
Alan F. Merry ◽  
...  

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.


1991 ◽  
Vol 261 (5) ◽  
pp. R1109-R1117 ◽  
Author(s):  
C. R. Wickland ◽  
F. W. Turek

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.


1982 ◽  
Vol 242 (3) ◽  
pp. R326-R332
Author(s):  
G. Corrent ◽  
A. Eskin ◽  
I. Kay

The finding that serotonin (5-HT) treatments as short as 1.5 h in duration produce phase shifts in a circadian rhythm from the isolated eye of Aplysia suggested that release of 5-HT was part of an ocular entrainment pathway. Since light cycles entrain this rhythm, we compared phase shifting by 5-HT and by light. The similarity in the shapes of the phase-response curves for 5-HT and light pulses indicates that 5-HT treatments are capable of entraining the rhythm. Also, "skeleton" 5-HT treatments phase shift as well as continuous 5-HT treatments. However, 5-HT does not appear to mediate the phase shifts produced by light, since 1) treatments that should block transmitter release do not change the phase shifts produced by light pulses; 2) the response curves of 5-HT and light pulses are displaced by 12 h relative to one another on the phase axis of the response curve; and 3) light-induced phase shifts are apparent almost immediately, whereas 5-HT-induced phase shifts become evident only about 24 h after 5-HT treatment. The eye appears to contain two independent entrainment pathways, one for light and one utilizing 5-HT.


1981 ◽  
Vol 241 (1) ◽  
pp. R31-R35 ◽  
Author(s):  
H. Nakashima ◽  
J. Perlman ◽  
J. F. Feldman

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.


1993 ◽  
Author(s):  
Eve Van Cauter ◽  
Jeppe Sturis ◽  
Maria M. Byrne ◽  
John D. Blackman ◽  
Neal H. Scherberg ◽  
...  

2000 ◽  
Vol 39 (4) ◽  
pp. 585 ◽  
Author(s):  
Xin Chen ◽  
Maureen Gramaglia ◽  
John A. Yeazell

1964 ◽  
Vol 54 (5A) ◽  
pp. 1459-1471
Author(s):  
S. K. Chakrabarty ◽  
G. C. Choudhury ◽  
S. N. Roy Choudhury

Abstract The general solution of the equations connecting the motion of the two coupled components in an electromagnetic seismograph has been obtained in another paper and it shows that the magnification of a seismograph depend on seven instrumental constants. Using these results, equations and curves have been derived in the present paper from which the Magnification as well as Phase shifts in the response of a seismograph and their variations with damping and coil inductance can be easily obtained. Based on these curves a number of magnification curves for different combinations, which are in operation at the different seismological stations of the world, have been derived. Suitable equations and curves have also been obtained which can be used for estimating the absolute Magnification of a Seismograph. An experimental method of obtaining the frequency response curves of seismographs in their operating condition has been described and the results obtained by this method has been given. It has been indicated how the results incorporated in the present paper can be used in the proper design of seismographs required for the different purposes.


Author(s):  
María Aguilar ◽  
E. Serrano ◽  
Vicente López ◽  
M. Carrascosa ◽  
F. Agulló-López

1983 ◽  
Vol 245 (1) ◽  
pp. R10-R17
Author(s):  
P. H. Gander ◽  
R. D. Lewis

The phase resetting action of light on the circadian rhythm of locomotor activity has been examined in wild-caught Polynesian rats (Rattus exulans). Phase-response curves to 4-, 8-, and 16-h light pulses have been derived. All three curves conform to the generalization that pulses occurring during late subjective day and early subjective night produce delays, whereas advances occur in response to pulses coinciding with the late subjective night and early subjective day. Weak (type 1) phase resetting is observed in response to 4-h pulses and perhaps 8-h pulses, whereas strong (type 0) resetting apparently occurs in response to 16-h pulses. These data evidently constitute the first report of strong phase resetting in mammalian circadian rhythms. The phase relationship between an entrained activity rhythm and the light-dark cycle is dependent on the photoperiod and, in 24-h cycles, on the period difference between the rhythm and the zeitgeber. In longer zeitgeber cycles, activity onset is delayed by a direct masking effect of light. A primarily nonparametric action of light in natural entrainment is consistent with these data and with field observations.


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