Volatile Anesthetics Depress Glutamate Transmission Via Presynaptic Actions

MacIver, M Bruce; Mikulec, Anthony A.; Amagasu, Shanti; Monroe, Frances A.

doi:10.1097/00000542-199610000-00018

Cited by 178 publications

(102 citation statements)

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“…A possible explanation for why we did not find a significant effect for the LDAEP of the P2 component in our experiments is that the mean amplitude of the P2 component is lower in rats than in humans (Sambeth et al, 2003). Furthermore, anesthesia reduces the AEP amplitudes, probably through a concomitant inhibition of the excitatory postsynaptic potentials of cortical pyramidal cells (Maclver et al, 1996;Schwender et al, 1997;Thornton and Sharpe, 1998;Antunes et al, 2003). As the animals in our study were anesthetized, the amplitude of the P2 component might have been decreased to a level at which differences were not significantly measurable whereas the naturally higher N1 component still showed a pronounced LDAEP.…”

Section: Discussionmentioning

confidence: 52%

Loudness Dependence of Auditory Evoked Potentials as Indicator of Central Serotonergic Neurotransmission: Simultaneous Electrophysiological Recordings and In Vivo Microdialysis in the Rat Primary Auditory Cortex

Wutzler

Winter

Kitzrow

et al. 2008

Neuropsychopharmacol

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Serotonin released in synapsis is one of the key neurotransmitters in psychiatry and psychopharmacology. The loudness dependence of auditory evoked potentials (LDAEP) has been proposed as a marker for central serotonergic neurotransmission. Several findings in animals and humans support this hypothesis. However, the in vivo measurement of cortical extracellular serotonin levels has never been performed simultaneously with the recording of auditory evoked potentials. The interrelationship between low cortical serotonergic activity and strong LDAEP is yet to be proven. The auditory evoked potentials were recorded in the epidura above the primary auditory cortex of male Wistar rats whereas extracellular serotonin levels in the primary auditory cortex were measured by in vivo microdialysis before and after i.p. application of the selective serotonin reuptake inhibitor citalopram. At baseline, the correlation of coefficients between the LDAEP, especially of the N1 component, and extracellular serotonin levels in the primary auditory cortex was negative. The increase of serotonin levels after citalopram application was significantly related to a decrease of LDAEP of the N1 component (r ¼ À0.86, p ¼ 0.003). These data support the view that the LDAEP is closely modulated by cortical serotonergic activity. Thus, the LDAEP might serve as an inversely related marker of synaptically released serotonin in the CNS.

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Section: Discussionmentioning

confidence: 52%

Loudness Dependence of Auditory Evoked Potentials as Indicator of Central Serotonergic Neurotransmission: Simultaneous Electrophysiological Recordings and In Vivo Microdialysis in the Rat Primary Auditory Cortex

Wutzler

Winter

Kitzrow

et al. 2008

Neuropsychopharmacol

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“…This result may be explained by modulation of: (1) neurotransmitter release, (2) blockage of postsynaptic targets, and/or (3) glutamate uptake by glial cells. The first explanation receives support from findings indicating a reduced synaptic release of glutamate under isoflurane resulting from various presynaptic mechanisms (MacIver et al, 1996;Westphalen and Hemmings, 2003b;Wu et al, 2004). The most appealing target of presynaptic depression, found in the calyx of Held, appears to be a reduction in amplitude of action potentials invading the axon terminal, resulting in a 50% reduction of glutamate release (Wu et al, 2004).…”

Section: Discussionmentioning

confidence: 98%

Cortical Inhibition during Burst Suppression Induced with Isoflurane Anesthesia

Ferron¹,

Kroeger²,

Chever³

et al. 2009

J. Neurosci.

125

126

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Isoflurane is a widely used anesthetic which safely and reversibly induces deep coma and associated burst suppression (BS) electroencephalographic patterns. Here we investigate possible underlying causes for the state of cortical hyperexcitability which was recently shown to be one of the characteristics of BS. Our hypothesis was that cortical inhibition is diminished during isoflurane-induced BS. Experiments were performed in vivo using intracellular recordings of cortical neurons to assess their responsiveness to stimulations of connected thalamic nuclei. We demonstrate that during BS EPSPs were diminished by 44%, whereas inhibitory potentials were completely suppressed. This finding was supported by additional results indicating that a decrease in neuronal input resistance normally found during inhibitory responses under low isoflurane conditions was abolished in the BS condition. Moreover, removal of inhibition occasionally revealed excitatory components which were absent during recordings before the induction of BS. We also show that the absence of inhibition during BS is not caused by a blockage of GABA receptors, since iontophoretically applied GABA shows receptor availability. Moreover, the concentration of extracellular chloride was increased during BS, as would be expected after reduced flow of chloride through GABA A receptors. Also inhibitory responses were reinstated by selective blockage of glial glutamate transporters with dihydrokainate. These results suggest that the lack of inhibition during BS is caused by reduced excitation, probably resulting from increased glial uptake of glutamate stimulated by isoflurane, which creates a diminished activation of cortical interneurons. Thus cortical hyperexcitability during BS is favored by suppressed inhibition.

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“…Although we cannot rule out this possibility, various lines of evidence make a direct effect unlikely. First, the function of vertebrate GLR-1 homologs has been found to be only weakly inhibited by clinical concentrations of VAs (8,11,12,(59)(60)(61). Second, inhibition of GLR-1 activity by VAs could not explain the observed behavioral effects in C.…”

Section: Discussionmentioning

confidence: 98%

“…VA effects on ␥-aminobutyric acid type A (GABA A ) receptors, glycine receptors, two-pore domain K ϩ channels, and neuronal nicotinic receptors have received particular scrutiny because of potential roles in overall nervous system excitability (1)(2)(3)(4)(5). In addition, VAs substantially inhibit excitatory neurotransmitter release by an ill-defined molecular mechanism (6)(7)(8)(9)(10). N 2 O, on the other hand, has been much less studied.…”

mentioning

confidence: 99%

Nitrous oxide (N ₂ O) requires the N -methyl- d -aspartate receptor for its action in Caenorhabditis elegans

Nägele

Metz

Crowder

2004

Proc. Natl. Acad. Sci. U.S.A.

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Nitrous oxide (N2O, also known as laughing gas) and volatile anesthetics (VAs), the original and still most widely used general anesthetics, produce anesthesia by ill-defined mechanisms. Electrophysiological experiments in vertebrate neurons have suggested that N 2O and VAs may act by distinct mechanisms; N2O antagonizes the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, whereas VAs alter the function of a variety of other synaptic proteins. However, no genetic or pharmacological experiments have demonstrated that any of these in vitro actions are responsible for the behavioral effects of either class of anesthetics. By using genetic tools in Caenorhabditis elegans, we tested whether the action of N 2 O requires the NMDA receptor in vivo and whether its mechanism is shared by VAs. Distinct from the action of VAs, N 2O produced behavioral defects highly specific and characteristic of that produced by loss-of-function mutations in both NMDA and non-NMDA glutamate receptors. A null mutant of nmr-1, which encodes a C. elegans NMDA receptor, was completely resistant to the behavioral effects of N 2O, whereas a non-NMDA receptor-null mutant was normally sensitive. The N 2O-resistant nmr-1(null) mutant was not resistant to VAs. Likewise, VA-resistant mutants had wild-type sensitivity to N 2O. Thus, the behavioral effects of N 2O require the NMDA receptor NMR-1, consistent with the hypothesis formed from vertebrate electrophysiological data that a major target of N 2O is the NMDA receptor.

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Volatile Anesthetics Depress Glutamate Transmission Via Presynaptic Actions

Cited by 178 publications

References 50 publications

Loudness Dependence of Auditory Evoked Potentials as Indicator of Central Serotonergic Neurotransmission: Simultaneous Electrophysiological Recordings and In Vivo Microdialysis in the Rat Primary Auditory Cortex

Loudness Dependence of Auditory Evoked Potentials as Indicator of Central Serotonergic Neurotransmission: Simultaneous Electrophysiological Recordings and In Vivo Microdialysis in the Rat Primary Auditory Cortex

Cortical Inhibition during Burst Suppression Induced with Isoflurane Anesthesia

Nitrous oxide (N ₂ O) requires the N -methyl- d -aspartate receptor for its action in Caenorhabditis elegans

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Volatile Anesthetics Depress Glutamate Transmission Via Presynaptic Actions

Cited by 178 publications

References 50 publications

Loudness Dependence of Auditory Evoked Potentials as Indicator of Central Serotonergic Neurotransmission: Simultaneous Electrophysiological Recordings and In Vivo Microdialysis in the Rat Primary Auditory Cortex

Loudness Dependence of Auditory Evoked Potentials as Indicator of Central Serotonergic Neurotransmission: Simultaneous Electrophysiological Recordings and In Vivo Microdialysis in the Rat Primary Auditory Cortex

Cortical Inhibition during Burst Suppression Induced with Isoflurane Anesthesia

Nitrous oxide (N 2 O) requires the N -methyl- d -aspartate receptor for its action in Caenorhabditis elegans

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Product

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Nitrous oxide (N ₂ O) requires the N -methyl- d -aspartate receptor for its action in Caenorhabditis elegans