Xenon attenuates hippocampal long-term potentiation by diminishing synaptic and extrasynaptic N-methyl-D-aspartate receptor currents

Kratzer, Stephan; Mattusch, Corinna; Kochs, Eberhard; Eder, Matthias; Haseneder, Rainer; Rammes, Gerhard

doi:10.1097/aln.0b013e3182475d66

Cited by 21Neuroscience and Neuropharmacology ResearchAnesthesia and Neurotoxicity ResearchMemory and Neural Mechanisms

Xenon attenuates hippocampal long-term potentiation by diminishing synaptic and extrasynaptic N-methyl-D-aspartate receptor currents

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Kratzer, Stephan, Mattusch, Corinna, Kochs, Eberhard, Eder, Matthias, Haseneder, Rainer, Rammes, Gerhard·2012·Anesthesiology

DOI 10.1097/aln.0b013e3182475d66

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Abstract

BACKGROUND: The memory-blocking properties of general anesthetics are of high clinical relevance and scientific interest. The inhalational anesthetic xenon antagonizes N-methyl-D-aspartate (NMDA) receptors. It is unknown if xenon affects long-term potentiation (LTP), a cellular correlate for memory formation. In hippocampal brain slices, the authors investigated in area CA1 whether xenon affects LTP, NMDA receptor-mediated neurotransmission, and intracellular calcium concentrations. METHODS: In sagittal murine hippocampal brain slices, the authors investigated the effects of xenon on LTP by recording excitatory postsynaptic field potentials. Using fluorometric calcium imaging, the authors tested the influence of xenon on calcium influx during high-frequency stimulation. In addition, using the patch-clamp technique, the xenon effect on synaptic and extrasynaptic NMDA receptors and L-type calcium channels was examined. RESULTS: In the absence of xenon, high-frequency stimulation reliably induced LTP and potentiated field potential slopes to (mean ± SEM) 127.2 ± 5.8% (P < 0.001). In the presence of xenon, high-frequency stimulation induced only a short-term potentiation, and field potentials returned to baseline level after 15-20 min (105.9 ± 2.9%; P = 0.090). NMDA receptor-mediated excitatory postsynaptic currents were reduced reversibly by xenon to 65.9 ± 9.4% (P = 0.007) of control. When extrasynaptic receptors were activated, xenon decreased NMDA currents to 58.2 ± 5.8% (P < 0.001). Xenon reduced the increase in intracellular calcium during high-frequency stimulation without affecting L-type calcium channels. CONCLUSIONS: N-methyl-D-aspartate receptor activation is crucial for the induction of CA1 LTP. Thus, the depression of NMDA receptor-mediated neurotransmission presumably contributes to the blockade of LTP under xenon. Because LTP is assumed to be involved in learning and memory, its blockade might be a key mechanism for xenon's amnestic properties.

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Xenon reduces NMDA-induced synaptic currents and neuronal plasticity in brain areas involved in fear learning and memory, including the amygdala and hippocampus.
“This idea is supported by preclinical findings showing that xenon reduces NMDAinduced synaptic currents and neuronal plasticity in brain areas involved in fear learning and memory processes including the amygdala and hippocampus (Haseneder et al., 2008;Kratzer et al., 2012).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Kratzer et al., 2012

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Self-citation

Authors: Kratzer, S., Mattusch, C., Kochs, E., Eder, M., Haseneder, R., & Rammes, G.
Affiliations: Resident in Anesthesia.
Ph.D. Student.
Professor of Anesthesiology, Director and Chair.
Max Planck Institute of Psychiatry (DE)
Associate Professor.
TUM Klinikum (DE)
ORCID: Eder, Matthias
Haseneder, Rainer
Rammes, Gerhard
Venue: Anesthesiology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2012-03-01
Volume: 116
Issue: 3
Pages: 673-682
ISSN: 0003-3022 (ISSN-L)
DOI: 10.1097/aln.0b013e3182475d66
OpenAlex: W2039478530
Cited by: 21
References: 70
Citations by year: 2025: 2 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 2 · 2019: 3 · 2018: 1 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 1
FWCI: 0.66
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Anesthesiology (publishedVersion)
PubMed (publishedVersion)
mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
Funders: Deutsche Forschungsgemeinschaft
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: xenon, long-term potentiation, NMDA receptor, hippocampus, CA1, extrasynaptic receptors, intracellular calcium, L-type calcium channels, general anesthetics, amnesia, excitatory postsynaptic currents
MeSH terms: Animals, Hippocampus, Male, Mice, Inbred C57BL, Neural Inhibition, Organ Culture Techniques, Synapses, Xenon, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Mice

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Xenon attenuates hippocampal long-term potentiation by diminishing synaptic and extrasynaptic N-methyl-D-aspartate receptor currents

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