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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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Transition phase between activated and deactivated patterns was characterized by cortical spindling across both natural sleep and urethane anaesthesia.A) An expanded example of a cortical spindle oscillation recorded during natural sleep (left) and a similar pattern recorded at the same electrode during the transition phase under urethane anaesthesia (right). B) Superimposed spectral plots of cortical EEG taken during activated, transition and deactivated states in a urethane-anaesthetized animal. Note the spectral peak in the transition spectra centered at ∼8 Hz (spindle frequency). C) Superimposed spectrographic power at low (0 to 2 Hz: black) and spindle (7 to 10 Hz: red) frequencies (top panel), and the simultaneous occurrence and duration of spindles across the evolution of all state alternations for one full experiment (bottom panel). Note the augmented presence of spindling activity at the transition points between activated and deactivated patterns. D) Average (across all experiments) of the cross correlation function between 1 Hz and spindle (7–9 Hz) spectrographic power (n = 5; standardized cycle in degrees). The temporal relationship of spindling to slow oscillatory activity at 1 Hz patterns showed a consistent lag of approximately half a period length (∼180 degrees).
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pone-0002004-g005: Transition phase between activated and deactivated patterns was characterized by cortical spindling across both natural sleep and urethane anaesthesia.A) An expanded example of a cortical spindle oscillation recorded during natural sleep (left) and a similar pattern recorded at the same electrode during the transition phase under urethane anaesthesia (right). B) Superimposed spectral plots of cortical EEG taken during activated, transition and deactivated states in a urethane-anaesthetized animal. Note the spectral peak in the transition spectra centered at ∼8 Hz (spindle frequency). C) Superimposed spectrographic power at low (0 to 2 Hz: black) and spindle (7 to 10 Hz: red) frequencies (top panel), and the simultaneous occurrence and duration of spindles across the evolution of all state alternations for one full experiment (bottom panel). Note the augmented presence of spindling activity at the transition points between activated and deactivated patterns. D) Average (across all experiments) of the cross correlation function between 1 Hz and spindle (7–9 Hz) spectrographic power (n = 5; standardized cycle in degrees). The temporal relationship of spindling to slow oscillatory activity at 1 Hz patterns showed a consistent lag of approximately half a period length (∼180 degrees).

Mentions: In addition, another electrographic similarity was apparent during the transition period between activated and deactivated patterns across both sleep and urethane anaesthesia. During this period, the cortical EEG traces showed spindle activity, often with a characteristic K-complex-like spike followed by an envelope of high frequency (7–15 Hz) oscillations lasting longer than 0.5 s. As shown in Figure 5A, these events were remarkably similar across both natural sleep and urethane anaesthesia as recorded in the same animals. In fact, during urethane anaesthesia, spindle frequencies were a consistent facet of the transition period as demonstrated by a spectral peak in the 7–10 Hz range (Figure 5B). In long-duration recordings under urethane, spindle events were more probable and of higher duration in the intervening period between activated and deactivated states (Figure 5C). As well, increases in spindle frequency power (bandwidth 7–10 Hz, average: 8.2±0.4 Hz, n = 5) consistently led increases in 1 Hz (i.e. slow oscillation) power at an average lag of 170 degrees (i.e. at approximately the half-cycle point) with respect to the rhythmic activated-deactivated state alternation (Figure 5C,D).


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)

Transition phase between activated and deactivated patterns was characterized by cortical spindling across both natural sleep and urethane anaesthesia.A) An expanded example of a cortical spindle oscillation recorded during natural sleep (left) and a similar pattern recorded at the same electrode during the transition phase under urethane anaesthesia (right). B) Superimposed spectral plots of cortical EEG taken during activated, transition and deactivated states in a urethane-anaesthetized animal. Note the spectral peak in the transition spectra centered at ∼8 Hz (spindle frequency). C) Superimposed spectrographic power at low (0 to 2 Hz: black) and spindle (7 to 10 Hz: red) frequencies (top panel), and the simultaneous occurrence and duration of spindles across the evolution of all state alternations for one full experiment (bottom panel). Note the augmented presence of spindling activity at the transition points between activated and deactivated patterns. D) Average (across all experiments) of the cross correlation function between 1 Hz and spindle (7–9 Hz) spectrographic power (n = 5; standardized cycle in degrees). The temporal relationship of spindling to slow oscillatory activity at 1 Hz patterns showed a consistent lag of approximately half a period length (∼180 degrees).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0002004-g005: Transition phase between activated and deactivated patterns was characterized by cortical spindling across both natural sleep and urethane anaesthesia.A) An expanded example of a cortical spindle oscillation recorded during natural sleep (left) and a similar pattern recorded at the same electrode during the transition phase under urethane anaesthesia (right). B) Superimposed spectral plots of cortical EEG taken during activated, transition and deactivated states in a urethane-anaesthetized animal. Note the spectral peak in the transition spectra centered at ∼8 Hz (spindle frequency). C) Superimposed spectrographic power at low (0 to 2 Hz: black) and spindle (7 to 10 Hz: red) frequencies (top panel), and the simultaneous occurrence and duration of spindles across the evolution of all state alternations for one full experiment (bottom panel). Note the augmented presence of spindling activity at the transition points between activated and deactivated patterns. D) Average (across all experiments) of the cross correlation function between 1 Hz and spindle (7–9 Hz) spectrographic power (n = 5; standardized cycle in degrees). The temporal relationship of spindling to slow oscillatory activity at 1 Hz patterns showed a consistent lag of approximately half a period length (∼180 degrees).
Mentions: In addition, another electrographic similarity was apparent during the transition period between activated and deactivated patterns across both sleep and urethane anaesthesia. During this period, the cortical EEG traces showed spindle activity, often with a characteristic K-complex-like spike followed by an envelope of high frequency (7–15 Hz) oscillations lasting longer than 0.5 s. As shown in Figure 5A, these events were remarkably similar across both natural sleep and urethane anaesthesia as recorded in the same animals. In fact, during urethane anaesthesia, spindle frequencies were a consistent facet of the transition period as demonstrated by a spectral peak in the 7–10 Hz range (Figure 5B). In long-duration recordings under urethane, spindle events were more probable and of higher duration in the intervening period between activated and deactivated states (Figure 5C). As well, increases in spindle frequency power (bandwidth 7–10 Hz, average: 8.2±0.4 Hz, n = 5) consistently led increases in 1 Hz (i.e. slow oscillation) power at an average lag of 170 degrees (i.e. at approximately the half-cycle point) with respect to the rhythmic activated-deactivated state alternation (Figure 5C,D).

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