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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

Raw and spectral characteristics of forebrain EEG during activated and deactivated states were similar across during natural sleep and urethane anaesthesia.A) Expanded neocortical and hippocampal EEG traces across natural sleep and urethane anaesthesia in the same animal showing examples of activated and deactivated patterns in both situations. Regardless of condition, activated and deactivated patterns were highly similar. B) Spectra of cortical and hippocampal EEG traces overlaid across conditions for the same electrographic patterns. Although the peak frequency of hippocampal theta power during REM was at a higher frequency (∼7 Hz) than during the activated state under urethane anaesthesia (∼4 Hz), all other spectra across conditions appear highly similar. Scatter plot of C) peak frequencies and D) power (right panel) for neocortical and hippocampal signals during the activated and deactivated state for each animal. Except for the peak frequency of hippocampal signals during activated patterns, there were no significant differences across natural sleep and urethane anaesthesia.
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pone-0002004-g004: Raw and spectral characteristics of forebrain EEG during activated and deactivated states were similar across during natural sleep and urethane anaesthesia.A) Expanded neocortical and hippocampal EEG traces across natural sleep and urethane anaesthesia in the same animal showing examples of activated and deactivated patterns in both situations. Regardless of condition, activated and deactivated patterns were highly similar. B) Spectra of cortical and hippocampal EEG traces overlaid across conditions for the same electrographic patterns. Although the peak frequency of hippocampal theta power during REM was at a higher frequency (∼7 Hz) than during the activated state under urethane anaesthesia (∼4 Hz), all other spectra across conditions appear highly similar. Scatter plot of C) peak frequencies and D) power (right panel) for neocortical and hippocampal signals during the activated and deactivated state for each animal. Except for the peak frequency of hippocampal signals during activated patterns, there were no significant differences across natural sleep and urethane anaesthesia.

Mentions: To directly evaluate the similarity of the two conditions, we performed recordings in naturally sleeping rats that were later anaesthetized with urethane (Figure 4). The raw electrographic characteristics of REM sleep were highly similar to those demonstrated in the activated state under urethane anaesthesia, with the cortex displaying low-voltage fast activity (LVFA) and the hippocampus eliciting a prominent theta rhythm. The spectral characteristics of both states, assessed by comparison of peak frequencies and power, were likewise similar although the peak frequency of theta was significantly higher on average in REM (6.4±1.2 Hz) than in the activated state during urethane (4.1±0.1 Hz, p = 0.001) (Figure 4A, B, C). Likewise, during slow-wave sleep and the deactivated state under urethane anaesthesia, both cortical and hippocampal traces were dominated by the slow oscillation [10] and spectra showed overlapping distributions without significant differences in either peak frequency or power across these conditions (Figure 4A, B, C).


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)

Raw and spectral characteristics of forebrain EEG during activated and deactivated states were similar across during natural sleep and urethane anaesthesia.A) Expanded neocortical and hippocampal EEG traces across natural sleep and urethane anaesthesia in the same animal showing examples of activated and deactivated patterns in both situations. Regardless of condition, activated and deactivated patterns were highly similar. B) Spectra of cortical and hippocampal EEG traces overlaid across conditions for the same electrographic patterns. Although the peak frequency of hippocampal theta power during REM was at a higher frequency (∼7 Hz) than during the activated state under urethane anaesthesia (∼4 Hz), all other spectra across conditions appear highly similar. Scatter plot of C) peak frequencies and D) power (right panel) for neocortical and hippocampal signals during the activated and deactivated state for each animal. Except for the peak frequency of hippocampal signals during activated patterns, there were no significant differences across natural sleep and urethane anaesthesia.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2289875&req=5

pone-0002004-g004: Raw and spectral characteristics of forebrain EEG during activated and deactivated states were similar across during natural sleep and urethane anaesthesia.A) Expanded neocortical and hippocampal EEG traces across natural sleep and urethane anaesthesia in the same animal showing examples of activated and deactivated patterns in both situations. Regardless of condition, activated and deactivated patterns were highly similar. B) Spectra of cortical and hippocampal EEG traces overlaid across conditions for the same electrographic patterns. Although the peak frequency of hippocampal theta power during REM was at a higher frequency (∼7 Hz) than during the activated state under urethane anaesthesia (∼4 Hz), all other spectra across conditions appear highly similar. Scatter plot of C) peak frequencies and D) power (right panel) for neocortical and hippocampal signals during the activated and deactivated state for each animal. Except for the peak frequency of hippocampal signals during activated patterns, there were no significant differences across natural sleep and urethane anaesthesia.
Mentions: To directly evaluate the similarity of the two conditions, we performed recordings in naturally sleeping rats that were later anaesthetized with urethane (Figure 4). The raw electrographic characteristics of REM sleep were highly similar to those demonstrated in the activated state under urethane anaesthesia, with the cortex displaying low-voltage fast activity (LVFA) and the hippocampus eliciting a prominent theta rhythm. The spectral characteristics of both states, assessed by comparison of peak frequencies and power, were likewise similar although the peak frequency of theta was significantly higher on average in REM (6.4±1.2 Hz) than in the activated state during urethane (4.1±0.1 Hz, p = 0.001) (Figure 4A, B, C). Likewise, during slow-wave sleep and the deactivated state under urethane anaesthesia, both cortical and hippocampal traces were dominated by the slow oscillation [10] and spectra showed overlapping distributions without significant differences in either peak frequency or power across these conditions (Figure 4A, B, C).

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