General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal

@article{Franks2008GeneralAF,
  title={General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal},
  author={Nicholas P. Franks},
  journal={Nature Reviews Neuroscience},
  year={2008},
  volume={9},
  pages={370-386}
}
  • N. Franks
  • Published 1 May 2008
  • Psychology, Medicine
  • Nature Reviews Neuroscience
The mechanisms through which general anaesthetics, an extremely diverse group of drugs, cause reversible loss of consciousness have been a long-standing mystery. Gradually, a relatively small number of important molecular targets have emerged, and how these drugs act at the molecular level is becoming clearer. Finding the link between these molecular studies and anaesthetic-induced loss of consciousness presents an enormous challenge, but comparisons with the features of natural sleep are… Expand

Figures and Topics from this paper

General anesthesia and ascending arousal pathways.
TLDR
The authors take an in vivo approach, studying the effects of histamine and histamine receptor antagonists on cortical (and hippocampal) recordings from anesthetized rats, and show that histamine infusion into this region speeds up emergence from isoflurane anesthesia. Expand
Sleep and general anesthesia
TLDR
There is growing evidence in this review that modulating wake-active neurotransmitter release can impact on anesthesia, supporting the idea that this point of convergence is at the level of the brain arousal systems. Expand
Sleep and Anesthesia Interactions: A Pharmacological Appraisal
TLDR
This review will highlight the relevant sleep architecture and systems and focus on studies over the past few years that implicate these sleep-related structures as targets of anesthetics, highlighting a promising area of investigation regarding the mechanisms of action. Expand
Linking sleep and general anesthesia mechanisms: this is no walkover.
TLDR
The link between physiological sleep and general anesthesia is defined and the observed functional modifications of brain activity during anesthesia and the known biochemical targets of hypnotic anesthetic agents are determined. Expand
Neurochemical Modulators of Sleep and Anesthetic States
TLDR
This chapter focuses on intravenous and volatile anesthetics that have been shown to alter endogenous neurotransmitters known to regulate states of Consciousness and Sleep-Related Neurotransmitters. Expand
Anaesthesia and sleep
TLDR
The mechanisms regulating the control of consciousness in both spontaneous sleep–wake behaviour and general anaesthesia remain poorly understood and need to be elucidated to build a unifying mechanism of consciousness control. Expand
Neurobiological Parallels, Overlaps, and Divergences of Sleep and Anesthesia
TLDR
Increasingly, the overlaps and divergences between components of sleep and specific anesthetic agents are offering insight into the neurochemical mechanisms and fundamental brain circuitry involved in the induction and maintenance of unconsciousness. Expand
A Common Neuroendocrine Substrate for Diverse General Anesthetics and Sleep
TLDR
A core ensemble of hypothalamic neurons in and near the supraoptic nucleus, consisting primarily of neuroendocrine cells, which are persistently and commonly activated by multiple classes of GA drugs are discovered, which identify a common neural substrate underlying diverse GA drugs and natural sleep and reveal a crucial role of the neuro endocrine system in regulating global brain states. Expand
Mechanisms of general anesthetic action: Focus on the cellular network
TLDR
Several lines of evidence suggest that disruption in brain network connectivity is important for anaesthesia-induced loss of consciousness and this is discussed in relation to morphological changes. Expand
The Neural Circuits Underlying General Anesthesia and Sleep.
TLDR
Modern neuroscience techniques that enable the manipulation of specific neural circuits have led to new insights into the neural circuitry underlying general anesthesia and sleep, and it is likely that each class of anesthetic drugs produces a distinct combination of subcortical and cortical effects that lead to unconsciousness. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 240 REFERENCES
Sleep, Anesthesiology, and the Neurobiology of Arousal State Control
TLDR
This review considers 40 yr of research regarding the cellular and molecular mechanisms contributing to arousal state control and provides overwhelming support for the view that decrements in vigilance can negatively impact performance. Expand
Molecular and neuronal substrates for general anaesthetics
TLDR
The neuronal systems that are thought to be involved in mediating clinically relevant actions of general anaesthetics are described and how the function of individual drug targets, in particular GABAA-receptor subtypes, can be revealed by genetic studies in vivo is discussed. Expand
Molecular and cellular mechanisms of general anaesthesia
TLDR
It is now clear that anaesthetics act directly on proteins rather than on lipids, with potentiation of postsynaptic inhibitory channel activity best fitting the pharmacological profile observed in general anaesthesia. Expand
Volatile general anaesthetics activate a novel neuronal K+ current
TLDR
It is reported that amongst a group of apparently identical molluscan neurons having endogenous firing activity, a single cell displays an unusual sensitivity to volatile agents (which, at surgical levels, completely inhibit its activity); it is shown that this sensitivity is due to a novel anaesthetic-activated K+ current, which is found in the sensitive cell but not in the surrounding insensitive cells. Expand
An essential role for orexins in emergence from general anesthesia
TLDR
It is concluded that there are important differences in the neural substrates mediating induction and emergence that support the concept that emergence depends, in part, on recruitment and stabilization of wake-active regions of brain. Expand
Neocortex is the major target of sedative concentrations of volatile anaesthetics: strong depression of firing rates and increase of GABAA receptor‐mediated inhibition
TLDR
These findings challenge the notion of predominantly subcortical effects of volatile anaesthetics and suggest that intracortical targets, among them neocortical GABAA receptors, mediate the sedative and hypnotic properties of volatile Anaesthetics. Expand
Serotonin and sleep.
  • R. Ursin
  • Medicine
  • Sleep medicine reviews
  • 2002
TLDR
Serotonergic activity may be accompanied by waking or sleep depending on the brain area and receptor type involved in the response, on the current behavioural state and on the concomitant agonism/antagonism of other neurotransmitter systems. Expand
Neural pathways associated with loss of consciousness caused by intracerebral microinjection of GABAA‐active anesthetics
TLDR
It is hypothesize that barbiturate anesthetics and related agents microinjected into the MPTA enhance the inhibitory response of local GABAA‐R‐bearing neurons to endogenous GABA released at baseline during wakefulness, ultimately leading to loss of consciousness. Expand
Distinct molecular targets for the central respiratory and cardiac actions of the general anesthetics etomidate and propofol
TLDR
Results show that both immobilization and respiratory depression are mediated by β3‐containing GABAA receptors, hypnosis by bothβ3‐and β2‐ containing GAB AA receptors, while the hypothermic, cardiac depressant, and sedative actions are largely independent of β3-containing GabAA receptors. Expand
What can in vivo electrophysiology in animal models tell us about mechanisms of anaesthesia?
TLDR
Animal experiments can be designed to take the questions about anaesthetic actions to the level of the living organism, as it is controversial which of the many effects of anaesthetics demonstrated in vitro are important for producing relevant in vivo effects. Expand
...
1
2
3
4
5
...