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

Abstract

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.

Postoperative cognitive dysfunction: spotlight on light, circadian rhythms, and sleep

“…General anesthesia has profound effects on the neurotransmitter systems, primarily those mediated by GABA, that regulate the circadian clock. Anesthetic agents such as isoflurane have been shown to exert a phase-shifting effect on the clock by activating SCN GABA receptors ( Chong et al, 2021 ). Furthermore, anesthesia alters the expression of several core clock genes, notably PER2 .…”

Metabolic cues impact non‐oscillatory intergeniculate leaflet and ventral lateral geniculate nucleus: standard versus high‐fat diet comparative study

“…This combination of anaesthetics was selected so as to maintain a stable surgical plane and thereby reduce the modulating influence of the general brain state on the LGN neuronal activity (Jeczmien‐Lazur et al., 2019). This was based on previous reports that suggested that deep anaesthesia may shift the phase of internal circadian timekeeping (Chong et al., 2021; Ludin et al., 2021; Prudian et al., 1997). Although the exact mixture of anaesthetics we used has not yet been tested for its hypothetical effects on the circadian clock, it is known that other general anaesthetics with similar effects (e.g.…”

“…Although the exact mixture of anaesthetics we used has not yet been tested for its hypothetical effects on the circadian clock, it is known that other general anaesthetics with similar effects (e.g. isoflurane, ether, halothane, or ketamine administered in combination with benzodiazepines) differentially affect circadian rhythms in rodents (Bellet et al., 2011; Chong et al., 2021; Ludin et al., 2021; Mihara et al., 2012; Prudian et al., 1997; Rebuelto et al., 2004). Moreover, our observations show that even minimal changes in the slow‐wave activity amplitude may affect the level of neuronal activity, and that, in turn, could influence the amplitude of the responses.…”