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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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Anaesthetic level was comparable across state alternations.A) Individual (paired for animals across states by symbol) and overall averages of withdrawal latency across activated and deactivated states in response to a ramped infrared beam applied to the tail or hindpaw. Withdrawal latencies were comparable across states and neither the individual nor overall averages were significantly different.
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pone-0002004-g003: Anaesthetic level was comparable across state alternations.A) Individual (paired for animals across states by symbol) and overall averages of withdrawal latency across activated and deactivated states in response to a ramped infrared beam applied to the tail or hindpaw. Withdrawal latencies were comparable across states and neither the individual nor overall averages were significantly different.

Mentions: We also found that a behavioural assay of anaesthetic level was consistent across states. In initial experiments, we assessed withdrawal to sharp and consistent pressure applied on the hind paw pad within each state. Although we could find no differences using this technique we further (and more systematically) examined level of anaesthesia by directly measuring latency to withdrawal using a ramped heat tail-flick apparatus (see Methods section). Although the intensity of the infrared beam had to be maximized in order to elicit even a weak but measurable withdrawal response (consistent with a surgical plane of anaesthesia) a pair-wise t-test performed on temporally adjacent stimulation sets across all animals revealed no significant differences in withdrawal latency between activated and deactivated states (Figure 3, n = 10, p = 0.31). Thus, state alternations were not due to variations in anaesthetic level.


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)

Anaesthetic level was comparable across state alternations.A) Individual (paired for animals across states by symbol) and overall averages of withdrawal latency across activated and deactivated states in response to a ramped infrared beam applied to the tail or hindpaw. Withdrawal latencies were comparable across states and neither the individual nor overall averages were significantly different.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0002004-g003: Anaesthetic level was comparable across state alternations.A) Individual (paired for animals across states by symbol) and overall averages of withdrawal latency across activated and deactivated states in response to a ramped infrared beam applied to the tail or hindpaw. Withdrawal latencies were comparable across states and neither the individual nor overall averages were significantly different.
Mentions: We also found that a behavioural assay of anaesthetic level was consistent across states. In initial experiments, we assessed withdrawal to sharp and consistent pressure applied on the hind paw pad within each state. Although we could find no differences using this technique we further (and more systematically) examined level of anaesthesia by directly measuring latency to withdrawal using a ramped heat tail-flick apparatus (see Methods section). Although the intensity of the infrared beam had to be maximized in order to elicit even a weak but measurable withdrawal response (consistent with a surgical plane of anaesthesia) a pair-wise t-test performed on temporally adjacent stimulation sets across all animals revealed no significant differences in withdrawal latency between activated and deactivated states (Figure 3, n = 10, p = 0.31). Thus, state alternations were not due to variations in anaesthetic level.

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