Brainstem node for loss of consciousness due to GABAA receptor-active anesthetics

Minert, Anne; Devor, Marshall

doi:10.1016/j.expneurol.2015.10.001

Cited by 36 publications

(20 citation statements)

References 35 publications

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“…To investigate different responses to intravenous anesthetics in mice during different developmental periods, we used LORR analysis to examine the hypnotic actions of propofol and ketamine in developmental mice [ 9 , 21 ]. The LORR EC 50 of propofol decreased with the development of mice (Figure 1A and 1B , EC 50 : 13.66 ± 0.20 mg/kg for P14 mice, 12.35 ± 0.19 mg/kg for P21 mice, 10.80 ± 0.17 mg/kg for P28 mice and 9.73 ± 0.20 mg/kg for P35 mice, n=10, F=167.9, P <0.001 using one-way ANOVA).…”

Section: Resultsmentioning

confidence: 99%

“…Hypnosis was established as a loss-of-righting reflex (LORR) and a scale of righting reflex. We defined mice rapid forceful righting within 10 s and when placed on side as a negative LORR while no righting attempts within 10 s after completion of the injection and that persisted for at least10 s thereafter as a positive LORR [ 9 , 10 , 21 ].…”

Section: Methodsmentioning

confidence: 99%

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HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice

Gao

Shi

et al. 2018

Oncotarget

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It is widely accepted that the induction dose of anesthetics is higher in infants than in adults, although the relevant molecular mechanism remains elusive. We previously showed neuronal hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to hypnotic actions of propofol and ketamine. Interestingly, the expression of HCN channels in neocortex significantly changes during postnatal periods. Thus, we postulated that changes in HCN channels expression might contribute to sensitivity to intravenous anesthetics. Here we showed the EC50 for propofol- and ketamine-induced loss-of-righting reflex (LORR) was significantly lower for P35 than for P14 mice. Cerebrospinal fluid concentrations of propofol and ketamine were significantly higher in P14 mice than in P35 mice, with similar propofol- and ketamine-induced anesthesia at the LORR EC50. Western blotting indicated that the expression of HCN channels in neocortex changed significantly from P14 to P35 mice. In addition, the amplitude of HCN currents in the neocortical layer 5 pyramidal neurons and the inhibition of propofol and ketamine on HCN currents dramatically increased with development. Logistic regression analysis indicated that the changes of HCN channels were correlated with the age-related differences of propofol- and ketamine-induced anesthesia. These data reveal that the change of HCN channels expression with postnatal development may contribute to sensitivity to the hypnotic actions of propofol and ketamine in mice.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice

Gao

Shi

et al. 2018

Oncotarget

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“…But why did lidocaine fail to induce anaesthesia? A related paradox is the failure of MPTA lesions to induce coma (Minert & Devor, ).…”

Section: Discussionmentioning

confidence: 99%

“…The current hypothesis builds on this model in two ways: (1) it explains how anaesthetics administered unilaterally suppress aRAS function bilaterally; and (2) it provides a specific locus for anaesthetic action and also a mechanism for suppression given that delivering anaesthetics direct to individual RAS nuclei, or to their putative master controller in the VLPO, does not induce anaesthesia (Lu et al ., ; Devor & Zalkind, ; Lydic & Baghdoyan, ; Leung et al ., ; McCarren et al ., ). Indeed, absent the MPTA, delivery of PB at normal clinical doses to the entire aRAS, or the entire brain, is insufficient to induce anaesthesia (Minert & Devor, ).…”

Section: Discussionmentioning

confidence: 99%

Model of anaesthetic induction by unilateral intracerebral microinjection of GABAergic agonists

Devor

Zalkind

Fishman

et al. 2016

Eur J of Neuroscience

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General anaesthetic agents induce loss of consciousness coupled with suppression of movement, analgesia and amnesia. Although these diverse functions are mediated by neural structures located in wide-ranging parts of the neuraxis, anaesthesia can be induced rapidly and reversibly by bilateral microinjection of minute quantities of γ-aminobutyric acid (GABA)A -R agonists at a small, focal locus in the mesopontine tegmentum (MPTA). State switching under these circumstances is presumably executed by dedicated neural pathways and does not require widespread distribution of the anaesthetic agent itself, the classical assumption regarding anaesthetic induction. Here it was asked whether these pathways serve each hemisphere independently, or whether there is bilateral redundancy such that the MPTA on each side is capable of anaesthetizing the entire brain. Either of two GABAA -R ligands were microinjected unilaterally into the MPTA in awake rats, the barbiturate modulator pentobarbital and the direct receptor agonist muscimol. Both agents, microinjected on either side, induced clinical anaesthesia, including bilateral atonia, bilateral analgesia and bilateral changes in cortical activity. The latter was monitored using c-fos expression and electroencephalography. This action, however, was not simply a consequence of suppressing spike activity in MPTA neurons, as unilateral (or bilateral) microinjection of the local anaesthetic lidocaine at the same locus failed to induce anaesthesia. A model of the state-switching circuitry that accounts for the bilateral action of unilateral microinjection and also for the observation that inactivation with lidocaine is not equivalent to inhibition with GABAA -R agonists was proposed. This is a step in defining the overall switching circuitry that underlies anaesthesia.

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“…Based on such mental interactions among individuals, social psychology studies the influences exercised by some individuals on the thoughts, feelings, and behaviors of others (25). Such interpersonal influences induce specific mental phenomena and experiences like attitude, persuasion, social/ political influences, social cognition, etc.…”

Section: Conscious Representation Of Social Data In the Form Of Mentamentioning

confidence: 99%

The mind-body problem; three equations and one solution represented by immaterial-material data

Motofei¹,

Rowland²

2018

JMMS

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To cite this article: Motofei IG, Rowland Dl. The mind-body problem; three equations and one solution represented by immaterial-material data. AbstractHuman life occurs within a complex bio-psycho-social milieu, a heterogeneous system that is integrated by multiple bidirectional interrelations existing between the abstract-intangible ideas and physical-chemical support of environment. The mind is thus placed between the abstract ideas/ concepts and neurobiological brain that is further connected to environment. In other words, the mind acts as an interface between the immaterial (abstract/ intangible) data and material (biological) support. The science is unable to conceives and explains an interaction between the immaterial and material domains (to understand nature of the mind), this question generating in literature the mind-body problem.We have published in the past a succession of articles related to the mind-body problem, in order to demonstrate the fact that this question is actually a false issue. The phenomenon of immaterial-material interaction is impossible to be explained because it never occurs, which means that there is no need to explain the immaterial-material interaction. Our mind implies only a temporal association between the immaterial data and material support, this dynamic interrelation being presented and argued here as a solution to the mind-body problem.The limited psycho-biologic approach of the mind-body problem is expanded here to a more comprehensive and feasible bio-psycho-social perspective, generating thus three distinct (biopsychological, bio-social, and psycho-social) equations. These three equations can be solved through a solution represented by a dynamic cerebral system (two distinct and interconnected subunits of the brain) which presumably could have the capability of receiving and processing abstract data through association (with no interaction) between immaterial and material data.

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Brainstem node for loss of consciousness due to GABAA receptor-active anesthetics

Cited by 36 publications

References 35 publications

HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice

HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice

Model of anaesthetic induction by unilateral intracerebral microinjection of GABAergic agonists

The mind-body problem; three equations and one solution represented by immaterial-material data

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