Calcium-dependent subthreshold oscillations determine bursting activity induced by N-methyl-D-aspartate in rat subthalamic neurons in vitro

Zi Tao Zhu, Adam Munhall, Ke Zhong Shen, Steven W. Johnson

Research output: Contribution to journalArticle

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Abstract

We used whole-cell patch recordings in current clamp to investigate the ionic dependence of burst firing induced by N-methyl-D-aspartate (NMDA) in neurons of the subthalamic nucleus (STN) in slices of rat brain. NMDA (20 μM) converted single-spike firing to burst firing in 87% of STN neurons tested. NMDA-induced bursting was blocked by AP5 (50 μM), and was not mimicked by the non-NMDA receptor agonist AMPA (0.6 μM). Tetrodotoxin (1 μM) converted bursts to oscillations of membrane potential, which were most robust when oscillations ranged between -50 and -70 mV. The NMDA bursts were blocked by an elevated extracellular concentration of Mg2+, but superfusate containing no added Mg2+ either reduced or increased burst firing, depending upon the amount of intracellular current injection. Block of K + conductances by apamin and tetraethylammonium prolonged burst duration, but iberiotoxin had no effect. NMDA-induced burst firing and membrane oscillations were completely blocked by superfusate containing no added Ca 2+, and they were significantly reduced when patch pipettes contained BAPTA. Selective antagonists for T-type (mibefradil, 10 μM), L-type (nifedipine, 3 μM), and N-type (ω-conotoxin GVIA, 1 μM) Ca2+ channels had no effect on NMDA burst firing. Superfusate containing a low concentration of Na+ (20 mM) completely abolished NMDA-induced burst firing. Flufenamic acid (10 μM), which blocks current mediated by Ca2+-activated nonselective cation channels (I CAN), reversibly abolished NMDA-depended bursting. These results are consistent with the hypothesis that NMDA-induced burst firing in STN neurons requires activation of either an ICAN or a Na+-Ca 2+ exchanger.

Original languageEnglish (US)
Pages (from-to)1296-1304
Number of pages9
JournalEuropean Journal of Neuroscience
Volume19
Issue number5
DOIs
StatePublished - Mar 1 2004

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Keywords

  • Brain slice
  • Burst firing
  • Firing pattern
  • Subthalamic nucleus
  • Whole-cell recording

ASJC Scopus subject areas

  • Neuroscience(all)

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