Identification of GABAA receptor subunit variants in midbrain dopaminergic neurons

J Neurochem. 2004 Apr;89(1):7-14. doi: 10.1111/j.1471-4159.2004.02271.x.

Abstract

Modulation of the activity of dopamine (DA)-producing neurons by GABA plays an important role in the control of DA-mediated brain functions. Ionotropic GABA(A) receptors exist as heteropentametric structures assembling different subunits composed of various subtypes. However, the expression pattern of these subunits in DA neurons in the ventral midbrain has not been fully defined. In the present study, we investigated the subunit composition of GABA(A) receptors in DA neurons in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA). We isolated DA neurons from the ventral midbrain of transgenic mice that express green fluorescent protein under the control of the tyrosine hydroxylase (TH) gene promoter and analyzed expression of various GABA(A) receptor subunits in single cells by using the reverse transcription-polymerase chain reaction. This analysis showed the presence of the transcripts encoding alpha2, alpha3, alpha4, beta1, beta3 and gamma2 subunits in the isolated DA neurons. Double fluorescence in situ hybridization with probes for TH and GABA(A) receptor subunit mRNAs revealed the expression of these six subunits in the majority of DA neurons in the SNc and the VTA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Separation
  • Dopamine / metabolism*
  • Green Fluorescent Proteins
  • Heterozygote
  • In Situ Hybridization
  • Luminescent Proteins / biosynthesis
  • Luminescent Proteins / genetics
  • Mesencephalon / cytology
  • Mesencephalon / metabolism*
  • Mice
  • Mice, Transgenic
  • Neurons / cytology
  • Neurons / metabolism*
  • Promoter Regions, Genetic / genetics
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • RNA, Messenger / biosynthesis
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Substantia Nigra / cytology
  • Substantia Nigra / metabolism
  • Tyrosine 3-Monooxygenase / genetics
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / metabolism

Substances

  • Luminescent Proteins
  • Protein Subunits
  • RNA, Messenger
  • Receptors, GABA-A
  • Green Fluorescent Proteins
  • Tyrosine 3-Monooxygenase
  • Dopamine