Urethane anaesthesia exhibits neurophysiological correlates of unconsciousness and is distinct from sleep

Abstract

Urethane is a general anesthetic widely used in animal research. It is unique among anesthetics because urethane anesthesia alternates between macroscopically distinct electrographic states: a slow-wave state that resembles NREM sleep (NREMure), and an activated state with features of both REM sleep and wakefulness (REMure). However, the relationship between urethane anesthesia and physiological sleep is still unclear. In this study, electroencephalography (EEG) and electromyography were recorded in chronically prepared rats during natural sleep-wake states and during urethane anesthesia. We subsequently analyzed the EEG signatures associated with the loss of consciousness and found that, in comparison to natural sleepwake states, the power, coherence, directed connectivity and complexity of brain oscillations are distinct during urethane. We also demonstrate that both urethane states have clear EEG signatures of general anesthesia. Thus, despite superficial similarities that have led others to conclude that urethane is a model of sleep, the electrocortical traits of depressed and activated states during urethane anesthesia differ from physiological sleep states.

Activity in developing prefrontal cortex is shaped by sleep and sensory experience

“…Thus, as is increasingly appreciated in adults ( Akeju and Brown, 2017 ; Mondino et al, 2022 ), anesthesia in infants is not a suitable proxy for natural sleep or sleep-related neural activity. Nor is it compatible with the goal of understanding brain–behavior relations in early development.…”

Electrophysiological characterization of medial preoptic neurons in lactating rats and its modulation by hypocretin-1

“…Gender, reproductive state, or slight differences in the recording site may account for the differences in the results. Mondino et al (2022) have recently described differences between NREMure and REMure states and the corresponding natural sleep states, through a detailed analysis of the EEG that included power, coherence, directionality, and complexity. Given these recent findings, it would be particularly relevant to carry out this characterization of mPOA neurons and the effect of HCRT in non-anesthetized animals.…”

“…Given the wake-promoting role of HCRT, we might expect that HCRT activates neurons that are wake-ON. Since these recordings were made under anesthesia, we cannot determine if the REMure-ON neurons were either wake-ON or REM-ON, although Mondino et al (2022) stated that the active state under urethane has more similarities to REM sleep than to wakefulness. On the other hand, from the total of neurons that HCRT decreased its activity, 8% were REMure-ON while 15% were NREMure-ON.…”

“…Under this anesthesia, there are spontaneous and rhythmic alternations between two different electroencephalographic patterns, a slow-wave state that resembles NREM sleep, and an active state with features of both REM sleep and wakefulness (Clement et al, 2008;Pagliardini et al, 2013;Mondino et al, 2022). Mondino et al (2022) named these urethane-induced states NREMure and REMure, respectively. In addition, we also evaluated the effect on neuronal activity of juxta-cellular administration of HCRT-1 in both lactating and virgin rats.…”

Electrophysiological characterization of medial preoptic neurons in lactating rats and its modulation by hypocretin-1

“…In the present report, as a first step to characterize the in vivo electrophysiology of the mPOA neurons in postpartum and virgin rats, we utilized urethane anesthesia as a proxy for the sleep-wake cycle. Under this anesthesia, there are spontaneous and rhythmic alternations between two different electroencephalographic patterns, a slow-wave state that resembles NREM sleep, and an active state with features of both REM sleep and wakefulness (Clement et al, 2008; Pagliardini et al, 2013; Mondino et al, 2022). Mondino et al (2022) named these urethane-induced states NREMure and REMure, respectively.…”