Expression of GABAρ receptors in the neostriatum: localization in aspiny, medium spiny neurons and GFAP-positive cells

J Neurochem. 2012 Sep;122(5):900-10. doi: 10.1111/j.1471-4159.2011.07621.x. Epub 2012 Jan 23.

Abstract

GABAergic transmission in the neostriatum plays a central role in motor coordination, in which a plethora of GABA-A receptor subunits combine to modulate neural inhibition. GABAρ receptors were originally described in the mammalian retina. These receptors possess special electrophysiological and pharmacological properties, forming a characteristic class of ionotropic receptors. In previous studies, we suggested that GABAρ receptors are expressed in the neostriatum, and in this report we show that they are indeed present in all the calretinin-positive interneurons of the neostriatum. In addition, they are located in calbindin-positive interneurons and projection neurons that express the dopamine D(2) receptor. GABAρ receptors were also located in 30% of the glial fibrillary acidic protein-positive cells, and may therefore also contribute to gliotransmission. Quantitative reverse transcription-PCR suggested that the mRNAs of this receptor do not express as much as in the retina, and that GABAρ2 is more abundant than GABAρ1. Electrophysiological recordings in brain slices provided evidence of neurons expressing a cis-4-aminocrotonic acid-activated, 1,2,5,6-tetrahydropyridine-4-yl methylphosphinic acid-sensitive ionotropic GABA receptor, indicating the presence of functional GABAρ receptors in the neostriatum. Finally, electron-microscopy and immunogold located the receptors mainly in perisynaptic as well as in extrasynaptic sites. All these observations reinforce the importance of GABAρ receptors in the neostriatum and contribute to the diversity of inhibitory regulation in this area.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calbindins
  • Drug Interactions
  • GABA Agents / pharmacology
  • Gene Expression Regulation / genetics
  • Glial Fibrillary Acidic Protein / metabolism*
  • Green Fluorescent Proteins / genetics
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Mice
  • Mice, Transgenic
  • Microscopy, Immunoelectron
  • Neostriatum / cytology*
  • Neuroglia / metabolism*
  • Neuroglia / ultrastructure
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Patch-Clamp Techniques
  • RNA, Messenger / metabolism
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D2 / genetics
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • S100 Calcium Binding Protein G / metabolism
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Calbindins
  • GABA Agents
  • Glial Fibrillary Acidic Protein
  • RNA, Messenger
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, GABA-A
  • S100 Calcium Binding Protein G
  • Green Fluorescent Proteins
  • gamma-Aminobutyric Acid