l-Glutamate excitation of A10 dopamine neurons is preferentially mediated by activation of NMDA receptors: extra- and intracellular electrophysiological studies in brain slices

Ting Wang, Edward D French

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58 Citations (Scopus)

Abstract

The aim of the present study was to assess the effects of l-glutamate (l-GLU) on the neurophysiology of ventral tegmental A10 dopamine neurons in rat midbrain slices using extracellular and intracellular recording methods. l-Glutamate perfusion of 10-100 μM concentrations produced dose-dependent increases in firing rate, with no changes in pattern of firing, while higher concentrations led to a loss of activity reminiscent of depolarization inactivation. The extracellular changes were relfected by the pronounced membrane depolarizations observed through intracellular recordings. The effects of low doses (≦ 30 μM) of l-GLU on firing rate and membrane potential were completely antagonized by co-perfusion with the noncompetitive NMDA blocker, phencyclidine, or the selective competitive NMDA receptor antagonist, CGS 19755, but not by the selective non-NMDA blocker NBQX. However, at concentrations of ≧ 300 μM l-GLU's effects could not be completely blocked without the presence of both CGS 19755 and NBQX. Moreover, the magnitude of l-GLU-induced depolarizations became attenuated at membrane potentials more negative than -70 mV. These results suggest that in physiological-like conditions that low extracellular levels of glutamate excite midbrain dopamine neurons via a preferential activation of NMDA receptors, and that only at higher concentrations of l-GLU are non-NMDA receptors brought into play.

Original languageEnglish (US)
Pages (from-to)299-306
Number of pages8
JournalBrain Research
Volume627
Issue number2
DOIs
StatePublished - Nov 12 1993

Fingerprint

Dopaminergic Neurons
antineoplaston A10
N-Methyl-D-Aspartate Receptors
Glutamic Acid
selfotel
Brain
Mesencephalon
Membrane Potentials
Perfusion
Phencyclidine
Neurophysiology
N-Methylaspartate
Membranes

Keywords

  • Brain slice
  • Electrophysiology
  • Excitatory amino acid
  • l-Glutamate
  • N-Methyl-d-aspartite acid
  • Ventral tegmental area

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

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title = "l-Glutamate excitation of A10 dopamine neurons is preferentially mediated by activation of NMDA receptors: extra- and intracellular electrophysiological studies in brain slices",
abstract = "The aim of the present study was to assess the effects of l-glutamate (l-GLU) on the neurophysiology of ventral tegmental A10 dopamine neurons in rat midbrain slices using extracellular and intracellular recording methods. l-Glutamate perfusion of 10-100 μM concentrations produced dose-dependent increases in firing rate, with no changes in pattern of firing, while higher concentrations led to a loss of activity reminiscent of depolarization inactivation. The extracellular changes were relfected by the pronounced membrane depolarizations observed through intracellular recordings. The effects of low doses (≦ 30 μM) of l-GLU on firing rate and membrane potential were completely antagonized by co-perfusion with the noncompetitive NMDA blocker, phencyclidine, or the selective competitive NMDA receptor antagonist, CGS 19755, but not by the selective non-NMDA blocker NBQX. However, at concentrations of ≧ 300 μM l-GLU's effects could not be completely blocked without the presence of both CGS 19755 and NBQX. Moreover, the magnitude of l-GLU-induced depolarizations became attenuated at membrane potentials more negative than -70 mV. These results suggest that in physiological-like conditions that low extracellular levels of glutamate excite midbrain dopamine neurons via a preferential activation of NMDA receptors, and that only at higher concentrations of l-GLU are non-NMDA receptors brought into play.",
keywords = "Brain slice, Electrophysiology, Excitatory amino acid, l-Glutamate, N-Methyl-d-aspartite acid, Ventral tegmental area",
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T1 - l-Glutamate excitation of A10 dopamine neurons is preferentially mediated by activation of NMDA receptors

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AU - Wang, Ting

AU - French, Edward D

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N2 - The aim of the present study was to assess the effects of l-glutamate (l-GLU) on the neurophysiology of ventral tegmental A10 dopamine neurons in rat midbrain slices using extracellular and intracellular recording methods. l-Glutamate perfusion of 10-100 μM concentrations produced dose-dependent increases in firing rate, with no changes in pattern of firing, while higher concentrations led to a loss of activity reminiscent of depolarization inactivation. The extracellular changes were relfected by the pronounced membrane depolarizations observed through intracellular recordings. The effects of low doses (≦ 30 μM) of l-GLU on firing rate and membrane potential were completely antagonized by co-perfusion with the noncompetitive NMDA blocker, phencyclidine, or the selective competitive NMDA receptor antagonist, CGS 19755, but not by the selective non-NMDA blocker NBQX. However, at concentrations of ≧ 300 μM l-GLU's effects could not be completely blocked without the presence of both CGS 19755 and NBQX. Moreover, the magnitude of l-GLU-induced depolarizations became attenuated at membrane potentials more negative than -70 mV. These results suggest that in physiological-like conditions that low extracellular levels of glutamate excite midbrain dopamine neurons via a preferential activation of NMDA receptors, and that only at higher concentrations of l-GLU are non-NMDA receptors brought into play.

AB - The aim of the present study was to assess the effects of l-glutamate (l-GLU) on the neurophysiology of ventral tegmental A10 dopamine neurons in rat midbrain slices using extracellular and intracellular recording methods. l-Glutamate perfusion of 10-100 μM concentrations produced dose-dependent increases in firing rate, with no changes in pattern of firing, while higher concentrations led to a loss of activity reminiscent of depolarization inactivation. The extracellular changes were relfected by the pronounced membrane depolarizations observed through intracellular recordings. The effects of low doses (≦ 30 μM) of l-GLU on firing rate and membrane potential were completely antagonized by co-perfusion with the noncompetitive NMDA blocker, phencyclidine, or the selective competitive NMDA receptor antagonist, CGS 19755, but not by the selective non-NMDA blocker NBQX. However, at concentrations of ≧ 300 μM l-GLU's effects could not be completely blocked without the presence of both CGS 19755 and NBQX. Moreover, the magnitude of l-GLU-induced depolarizations became attenuated at membrane potentials more negative than -70 mV. These results suggest that in physiological-like conditions that low extracellular levels of glutamate excite midbrain dopamine neurons via a preferential activation of NMDA receptors, and that only at higher concentrations of l-GLU are non-NMDA receptors brought into play.

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KW - Electrophysiology

KW - Excitatory amino acid

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KW - N-Methyl-d-aspartite acid

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