Modulation of isolated N-methyl-D-aspartate receptor response under hyperbaric conditions

Amir Mor, Yoram Grossman

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

In humans, hyperbaric pressure induces the high-pressure neurological syndrome (HPNS). HPNS is characterized by tremor, sleep disorders, electroencephalographic changes, and impairment of cognitive and motor performances. In animals, higher pressures result in convulsions and death. An increased N-methyl-d-aspartate receptor (NMDAR) response has been implicated with HPNS. We studied high-pressure effects on pharmacologically isolated NMDAR field excitatory postsynaptic potentials (fEPSPs). Hippocampal coronal brain slices from male Sprague-Dawley rats were prepared, constantly superfused with physiological solutions, gas-saturated at normobaric pressure and compressed up to 10.1 MPa with helium. fEPSPs were recorded from the dendritic layer of CA1 pyramidal neurones. High pressure significantly increased the single fEPSP delay, maximal initial slope, amplitude, decay time and time integral (elevated Na+ and Ca2+ influx) despite the known general decrease in glutamatergic synaptic release. The estimated negative and positive activation volumes (ΔV*) for various kinetic segments of the fEPSP suggest a complex response of the receptor to pressure. The NMDAR frequency response was tested by a train of five stimuli. At 50-100 Hz, high pressure did not increase the fEPSPs' frequency-dependent depression and the train's time integral remained unchanged. At 25 Hz, pressure induced a larger frequency-dependent depression and significantly increased the time integral. Our results provide, for the first time, direct information on the isolated brain NMDAR response under hyperbaric conditions. These observations may explain some increase in the excitability of single normal glutametergic fEPSPs and their frequency responses.

Original languageEnglish
Pages (from-to)3453-3462
Number of pages10
JournalEuropean Journal of Neuroscience
Volume24
Issue number12
DOIs
StatePublished - 1 Dec 2006

Keywords

  • Excitability
  • HPNS
  • Hippocampus
  • Neurotoxicity
  • Rat
  • fEPSP

ASJC Scopus subject areas

  • General Neuroscience

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