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Cyclic and sleep-like spontaneous alternations of brain state under urethane anaesthesia.

Clement EA, Richard A, Thwaites M, Ailon J, Peters S, Dickson CT - PLoS ONE (2008)

Bottom Line: Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame ( approximately 11 minute period).Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep.Our results suggest that urethane promotes a condition of behavioural unconsciousness that closely mimics the full spectrum of natural sleep.

View Article: PubMed Central - PubMed

Affiliation: Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada.

ABSTRACT

Background: Although the induction of behavioural unconsciousness during sleep and general anaesthesia has been shown to involve overlapping brain mechanisms, sleep involves cyclic fluctuations between different brain states known as active (paradoxical or rapid eye movement: REM) and quiet (slow-wave or non-REM: nREM) stages whereas commonly used general anaesthetics induce a unitary slow-wave brain state.

Methodology/principal findings: Long-duration, multi-site forebrain field recordings were performed in urethane-anaesthetized rats. A spontaneous and rhythmic alternation of brain state between activated and deactivated electroencephalographic (EEG) patterns was observed. Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame ( approximately 11 minute period). Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep. The brain mechanisms of state alternations under urethane also closely overlapped those of natural sleep in their sensitivity to cholinergic pharmacological agents and dependence upon activity in the basal forebrain nuclei that are the major source of forebrain acetylcholine. Lastly, stimulation of brainstem regions thought to pace state alternations in sleep transiently disrupted state alternations under urethane.

Conclusions/significance: Our results suggest that urethane promotes a condition of behavioural unconsciousness that closely mimics the full spectrum of natural sleep. The use of urethane anaesthesia as a model system will facilitate mechanistic studies into sleep-like brain states and their alternations. In addition, it could also be exploited as a tool for the discovery of new molecular targets that are designed to promote sleep without compromising state alternations.

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Related in: MedlinePlus

The timing of cyclic EEG state alternations was highly similar across naturally sleeping and urethane-anaesthetized conditions.A) Long-duration EEG traces during a continuous natural sleep episode (left panel) and subsequently from the same animal under urethane anaesthesia (right panel). Regular fluctuations between REM and nREM sleep stages were highly comparable in their timing to the state alternations later observed under urethane. Plotted on the same time scale underneath the raw traces is the respective spectrographic power at 1 Hz extracted from the cortical signals. These fluctuations demonstrated a similar rhythmicity across both conditions. B) Scatterplot representing period lengths of alternations for all animals under both naturally sleeping and urethane anaesthetized conditions. There was a remarkable similarity in the distribution and average length of alternations for each animal as well as for the overall average for natural sleeping and urethane anaesthetized conditions.
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pone-0002004-g006: The timing of cyclic EEG state alternations was highly similar across naturally sleeping and urethane-anaesthetized conditions.A) Long-duration EEG traces during a continuous natural sleep episode (left panel) and subsequently from the same animal under urethane anaesthesia (right panel). Regular fluctuations between REM and nREM sleep stages were highly comparable in their timing to the state alternations later observed under urethane. Plotted on the same time scale underneath the raw traces is the respective spectrographic power at 1 Hz extracted from the cortical signals. These fluctuations demonstrated a similar rhythmicity across both conditions. B) Scatterplot representing period lengths of alternations for all animals under both naturally sleeping and urethane anaesthetized conditions. There was a remarkable similarity in the distribution and average length of alternations for each animal as well as for the overall average for natural sleeping and urethane anaesthetized conditions.

Mentions: Not only were the electrographic aspects of individual states similar across natural sleep and urethane anaesthesia, but the average alternation period between these states was also highly comparable (Figure 6). The same animals recorded across conditions showed an average cycle length of 11.1±0.5 minutes in natural sleep and 11.3±0.6 minutes when later recorded under urethane anaesthesia (Figure 5B). This difference was not significant (n = 8, two-tailed pair-wise t-test, p = 0.73). Perhaps not surprisingly, however, there was significantly greater variance in cycle length during sleep as compared to urethane anaesthesia (19.3±2.3 s in natural sleep versus 7.2±0.6 s in urethane anaesthesia, n = 8, pair-wise t-test, p = 0.001). This could have reflected a stereotypy of alternations mechanisms under urethane or disturbances of sleep cycling by arousal into wakefulness, or both.


Cyclic and sleep-like spontaneous alternations of brain state under urethane anaesthesia.

Clement EA, Richard A, Thwaites M, Ailon J, Peters S, Dickson CT - PLoS ONE (2008)

The timing of cyclic EEG state alternations was highly similar across naturally sleeping and urethane-anaesthetized conditions.A) Long-duration EEG traces during a continuous natural sleep episode (left panel) and subsequently from the same animal under urethane anaesthesia (right panel). Regular fluctuations between REM and nREM sleep stages were highly comparable in their timing to the state alternations later observed under urethane. Plotted on the same time scale underneath the raw traces is the respective spectrographic power at 1 Hz extracted from the cortical signals. These fluctuations demonstrated a similar rhythmicity across both conditions. B) Scatterplot representing period lengths of alternations for all animals under both naturally sleeping and urethane anaesthetized conditions. There was a remarkable similarity in the distribution and average length of alternations for each animal as well as for the overall average for natural sleeping and urethane anaesthetized conditions.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2289875&req=5

pone-0002004-g006: The timing of cyclic EEG state alternations was highly similar across naturally sleeping and urethane-anaesthetized conditions.A) Long-duration EEG traces during a continuous natural sleep episode (left panel) and subsequently from the same animal under urethane anaesthesia (right panel). Regular fluctuations between REM and nREM sleep stages were highly comparable in their timing to the state alternations later observed under urethane. Plotted on the same time scale underneath the raw traces is the respective spectrographic power at 1 Hz extracted from the cortical signals. These fluctuations demonstrated a similar rhythmicity across both conditions. B) Scatterplot representing period lengths of alternations for all animals under both naturally sleeping and urethane anaesthetized conditions. There was a remarkable similarity in the distribution and average length of alternations for each animal as well as for the overall average for natural sleeping and urethane anaesthetized conditions.
Mentions: Not only were the electrographic aspects of individual states similar across natural sleep and urethane anaesthesia, but the average alternation period between these states was also highly comparable (Figure 6). The same animals recorded across conditions showed an average cycle length of 11.1±0.5 minutes in natural sleep and 11.3±0.6 minutes when later recorded under urethane anaesthesia (Figure 5B). This difference was not significant (n = 8, two-tailed pair-wise t-test, p = 0.73). Perhaps not surprisingly, however, there was significantly greater variance in cycle length during sleep as compared to urethane anaesthesia (19.3±2.3 s in natural sleep versus 7.2±0.6 s in urethane anaesthesia, n = 8, pair-wise t-test, p = 0.001). This could have reflected a stereotypy of alternations mechanisms under urethane or disturbances of sleep cycling by arousal into wakefulness, or both.

Bottom Line: Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame ( approximately 11 minute period).Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep.Our results suggest that urethane promotes a condition of behavioural unconsciousness that closely mimics the full spectrum of natural sleep.

View Article: PubMed Central - PubMed

Affiliation: Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada.

ABSTRACT

Background: Although the induction of behavioural unconsciousness during sleep and general anaesthesia has been shown to involve overlapping brain mechanisms, sleep involves cyclic fluctuations between different brain states known as active (paradoxical or rapid eye movement: REM) and quiet (slow-wave or non-REM: nREM) stages whereas commonly used general anaesthetics induce a unitary slow-wave brain state.

Methodology/principal findings: Long-duration, multi-site forebrain field recordings were performed in urethane-anaesthetized rats. A spontaneous and rhythmic alternation of brain state between activated and deactivated electroencephalographic (EEG) patterns was observed. Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame ( approximately 11 minute period). Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep. The brain mechanisms of state alternations under urethane also closely overlapped those of natural sleep in their sensitivity to cholinergic pharmacological agents and dependence upon activity in the basal forebrain nuclei that are the major source of forebrain acetylcholine. Lastly, stimulation of brainstem regions thought to pace state alternations in sleep transiently disrupted state alternations under urethane.

Conclusions/significance: Our results suggest that urethane promotes a condition of behavioural unconsciousness that closely mimics the full spectrum of natural sleep. The use of urethane anaesthesia as a model system will facilitate mechanistic studies into sleep-like brain states and their alternations. In addition, it could also be exploited as a tool for the discovery of new molecular targets that are designed to promote sleep without compromising state alternations.

Show MeSH
Related in: MedlinePlus