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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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Physiological correlates of EEG state changes were similar across naturally sleeping and urethane-anaesthetized conditions.A) Simultaneous recordings of hippocampal field activity and neck EMG in naturally sleeping (left panel) and urethane anaesthetized (right panel) conditions in the same animal. Declines in EMG tone with transitions from nREM to REM sleep were also apparent under urethane anaesthesia with transitions from deactivated to activated EEG patterns. B) The average percentage loss of EMG amplitude across these transitions was consistent and significantly different across both natural sleep and urethane anaesthesia in the same animals. C) Simultaneous extraction of cortical spectrographic power at 1 Hz (top panel), heart rate (middle panel) and respiration rate (lower panel) demonstrating concomitant fluctuations. Increases in both heart and respiration rates appeared during the lowest EEG power readings (i.e. the activated state). As well, during the activated state, the peak frequency of respiratory cycle tended to show greater variation. D) Fluctuations in heart (top) and respiration rates (bottom) were rhythmically correlated with state changes as shown in the cross correlation of these variables to cortical power at 1 Hz. E) Summary data across experiments showing significant increases in both heart (top) and respiration rates (bottom) when comparing the activated to the deactivated state.
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pone-0002004-g007: Physiological correlates of EEG state changes were similar across naturally sleeping and urethane-anaesthetized conditions.A) Simultaneous recordings of hippocampal field activity and neck EMG in naturally sleeping (left panel) and urethane anaesthetized (right panel) conditions in the same animal. Declines in EMG tone with transitions from nREM to REM sleep were also apparent under urethane anaesthesia with transitions from deactivated to activated EEG patterns. B) The average percentage loss of EMG amplitude across these transitions was consistent and significantly different across both natural sleep and urethane anaesthesia in the same animals. C) Simultaneous extraction of cortical spectrographic power at 1 Hz (top panel), heart rate (middle panel) and respiration rate (lower panel) demonstrating concomitant fluctuations. Increases in both heart and respiration rates appeared during the lowest EEG power readings (i.e. the activated state). As well, during the activated state, the peak frequency of respiratory cycle tended to show greater variation. D) Fluctuations in heart (top) and respiration rates (bottom) were rhythmically correlated with state changes as shown in the cross correlation of these variables to cortical power at 1 Hz. E) Summary data across experiments showing significant increases in both heart (top) and respiration rates (bottom) when comparing the activated to the deactivated state.

Mentions: Our EMG recordings during urethane, however, did show changes consistent with natural sleep. In 3 of the 5 animals that had functional EMG recordings during natural sleep, we observed similar and significant (all pair-wise comparisons significant at p<0.01) decreases in EMG tone during transitions from deactivated to activated states during subsequent recordings during urethane (Figure 7A, B). The average decline across deactivated to activated states was 21.2±6.1%, during natural sleep as compared to 11.8±3.0% under urethane. This was despite the fact that urethane is known to induce muscular atonia itself [22], which was supported in our experiments by significantly lower average peak-to-peak values of EMG during urethane (1.36±0.55 mV) as compared to sleep (2.67±1.06 mV: one-tailed pair-wise t-test, p = 0.04, n = 5),, Consistent with a depression of EMG tone generally, the decline under urethane was smaller than that in natural sleep although this difference was not statistically significant (p = 0.09). In the remaining two animals, there was no change in the EMG tone under urethane across states but this failure may have reflected a floor effect due to a general depression of muscular tone. None of our animals demonstrated phasic events characterized by large muscular twitches during the activated state.


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)

Physiological correlates of EEG state changes were similar across naturally sleeping and urethane-anaesthetized conditions.A) Simultaneous recordings of hippocampal field activity and neck EMG in naturally sleeping (left panel) and urethane anaesthetized (right panel) conditions in the same animal. Declines in EMG tone with transitions from nREM to REM sleep were also apparent under urethane anaesthesia with transitions from deactivated to activated EEG patterns. B) The average percentage loss of EMG amplitude across these transitions was consistent and significantly different across both natural sleep and urethane anaesthesia in the same animals. C) Simultaneous extraction of cortical spectrographic power at 1 Hz (top panel), heart rate (middle panel) and respiration rate (lower panel) demonstrating concomitant fluctuations. Increases in both heart and respiration rates appeared during the lowest EEG power readings (i.e. the activated state). As well, during the activated state, the peak frequency of respiratory cycle tended to show greater variation. D) Fluctuations in heart (top) and respiration rates (bottom) were rhythmically correlated with state changes as shown in the cross correlation of these variables to cortical power at 1 Hz. E) Summary data across experiments showing significant increases in both heart (top) and respiration rates (bottom) when comparing the activated to the deactivated state.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2289875&req=5

pone-0002004-g007: Physiological correlates of EEG state changes were similar across naturally sleeping and urethane-anaesthetized conditions.A) Simultaneous recordings of hippocampal field activity and neck EMG in naturally sleeping (left panel) and urethane anaesthetized (right panel) conditions in the same animal. Declines in EMG tone with transitions from nREM to REM sleep were also apparent under urethane anaesthesia with transitions from deactivated to activated EEG patterns. B) The average percentage loss of EMG amplitude across these transitions was consistent and significantly different across both natural sleep and urethane anaesthesia in the same animals. C) Simultaneous extraction of cortical spectrographic power at 1 Hz (top panel), heart rate (middle panel) and respiration rate (lower panel) demonstrating concomitant fluctuations. Increases in both heart and respiration rates appeared during the lowest EEG power readings (i.e. the activated state). As well, during the activated state, the peak frequency of respiratory cycle tended to show greater variation. D) Fluctuations in heart (top) and respiration rates (bottom) were rhythmically correlated with state changes as shown in the cross correlation of these variables to cortical power at 1 Hz. E) Summary data across experiments showing significant increases in both heart (top) and respiration rates (bottom) when comparing the activated to the deactivated state.
Mentions: Our EMG recordings during urethane, however, did show changes consistent with natural sleep. In 3 of the 5 animals that had functional EMG recordings during natural sleep, we observed similar and significant (all pair-wise comparisons significant at p<0.01) decreases in EMG tone during transitions from deactivated to activated states during subsequent recordings during urethane (Figure 7A, B). The average decline across deactivated to activated states was 21.2±6.1%, during natural sleep as compared to 11.8±3.0% under urethane. This was despite the fact that urethane is known to induce muscular atonia itself [22], which was supported in our experiments by significantly lower average peak-to-peak values of EMG during urethane (1.36±0.55 mV) as compared to sleep (2.67±1.06 mV: one-tailed pair-wise t-test, p = 0.04, n = 5),, Consistent with a depression of EMG tone generally, the decline under urethane was smaller than that in natural sleep although this difference was not statistically significant (p = 0.09). In the remaining two animals, there was no change in the EMG tone under urethane across states but this failure may have reflected a floor effect due to a general depression of muscular tone. None of our animals demonstrated phasic events characterized by large muscular twitches during the activated state.

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