title: Xenon attenuates hippocampal long-term potentiation by diminishing synaptic and extrasynaptic N-methyl-D-aspartate receptor currents.
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.
authors.affiliation: Department of Anesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. skratzer@mpipsykl.mpg.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Kratzer
authors.forename: Corinna
authors.initials: C
authors.lastname: Mattusch
authors.forename: Eberhard
authors.initials: E
authors.lastname: Kochs
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.forename: Rainer
authors.initials: R
authors.lastname: Haseneder
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rammes
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014978:Xenon / Q000494:pharmacology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D014978:Xenon