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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 rhythmicity and periodicity of state alternations under urethane were not affected by moderate increases in anaesthetic dosage.A) Long duration raw cortical EEG traces demonstrating the electrographic effects of a moderate increase in the depth of urethane anaesthesia. Although the overall amplitude of the signal increased following the supplemental dose, state alternations (apparent as rhythmic changes in signal amplitude) were still observed. B) Spectrographic power at 1 Hz for the traces shown in A. Following the supplemental dose, power continued to fluctuate at a similar periodicity although there was an increase in the overall power in addition to the time spent in the deactivated state (and consequently a decrease in the time spent in the activated state). C) Autocorrelation of power values in B demonstrating similar rhythmicity before and after supplemental urethane administration. D) Individual (paired for animal across conditions by symbol and line) and overall averages demonstrating the consistency of alternation period duration before and after the supplemental doses of urethane across all experiments. Neither the individual nor the overall averages were significantly different.
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pone-0002004-g002: The rhythmicity and periodicity of state alternations under urethane were not affected by moderate increases in anaesthetic dosage.A) Long duration raw cortical EEG traces demonstrating the electrographic effects of a moderate increase in the depth of urethane anaesthesia. Although the overall amplitude of the signal increased following the supplemental dose, state alternations (apparent as rhythmic changes in signal amplitude) were still observed. B) Spectrographic power at 1 Hz for the traces shown in A. Following the supplemental dose, power continued to fluctuate at a similar periodicity although there was an increase in the overall power in addition to the time spent in the deactivated state (and consequently a decrease in the time spent in the activated state). C) Autocorrelation of power values in B demonstrating similar rhythmicity before and after supplemental urethane administration. D) Individual (paired for animal across conditions by symbol and line) and overall averages demonstrating the consistency of alternation period duration before and after the supplemental doses of urethane across all experiments. Neither the individual nor the overall averages were significantly different.

Mentions: Supplemental doses of urethane (ranging from 0.07 to 0.27 mg/kg), while decreasing the relative amount of time spent in the activated state (8.9±2% for every 0.1 mg/kg administered, n = 5), did not alter either the presence or the rhythmicity of state alternations per se (Figure 2). No significant differences were observed for the duration of alternation periods pre- and post-supplement in any individual experiment (p≥0.15) nor overall (p = 0.68). This suggests that the cyclicity of state alternations is not affected by the absolute concentration of urethane in the blood.


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 rhythmicity and periodicity of state alternations under urethane were not affected by moderate increases in anaesthetic dosage.A) Long duration raw cortical EEG traces demonstrating the electrographic effects of a moderate increase in the depth of urethane anaesthesia. Although the overall amplitude of the signal increased following the supplemental dose, state alternations (apparent as rhythmic changes in signal amplitude) were still observed. B) Spectrographic power at 1 Hz for the traces shown in A. Following the supplemental dose, power continued to fluctuate at a similar periodicity although there was an increase in the overall power in addition to the time spent in the deactivated state (and consequently a decrease in the time spent in the activated state). C) Autocorrelation of power values in B demonstrating similar rhythmicity before and after supplemental urethane administration. D) Individual (paired for animal across conditions by symbol and line) and overall averages demonstrating the consistency of alternation period duration before and after the supplemental doses of urethane across all experiments. Neither the individual nor the overall averages were significantly different.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2289875&req=5

pone-0002004-g002: The rhythmicity and periodicity of state alternations under urethane were not affected by moderate increases in anaesthetic dosage.A) Long duration raw cortical EEG traces demonstrating the electrographic effects of a moderate increase in the depth of urethane anaesthesia. Although the overall amplitude of the signal increased following the supplemental dose, state alternations (apparent as rhythmic changes in signal amplitude) were still observed. B) Spectrographic power at 1 Hz for the traces shown in A. Following the supplemental dose, power continued to fluctuate at a similar periodicity although there was an increase in the overall power in addition to the time spent in the deactivated state (and consequently a decrease in the time spent in the activated state). C) Autocorrelation of power values in B demonstrating similar rhythmicity before and after supplemental urethane administration. D) Individual (paired for animal across conditions by symbol and line) and overall averages demonstrating the consistency of alternation period duration before and after the supplemental doses of urethane across all experiments. Neither the individual nor the overall averages were significantly different.
Mentions: Supplemental doses of urethane (ranging from 0.07 to 0.27 mg/kg), while decreasing the relative amount of time spent in the activated state (8.9±2% for every 0.1 mg/kg administered, n = 5), did not alter either the presence or the rhythmicity of state alternations per se (Figure 2). No significant differences were observed for the duration of alternation periods pre- and post-supplement in any individual experiment (p≥0.15) nor overall (p = 0.68). This suggests that the cyclicity of state alternations is not affected by the absolute concentration of urethane in the blood.

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