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

• Published in: Journal of neurochemistry Vol. 122; no. 5; pp. 900 - 910
• Main Authors: Rosas-Arellano, Abraham, Machuca-Parra, Arturo I., Reyes-Haro, Daniel, Miledi, Ricardo, Martínez-Torres, Ataúlfo
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2012
• Subjects: Animals; Astrocytes; bicuculline; Brain slice preparation; CACA; Calbindins; Calretinin; Dopamine D2 receptors; Drug Interactions; Electrophysiological recording; GABA Agents - pharmacology; gamma -Aminobutyric acid; gamma -Aminobutyric acid A receptors; gamma -Aminobutyric acid receptors; gamma-Aminobutyric Acid - pharmacology; Gene Expression Regulation - genetics; glia; Glial Fibrillary Acidic Protein - metabolism; Green Fluorescent Proteins - genetics; In Vitro Techniques; Interneurons; Ion channels (ligand-gated); medium spiny neurons; Membrane Potentials - drug effects; Membrane Potentials - genetics; Mice; Mice, Transgenic; Microscopy, Immunoelectron; Neostriatum; Neostriatum - cytology; Neuroglia - metabolism; Neuroglia - ultrastructure; Neurons - classification; Neurons - drug effects; Neurons - physiology; Neurons - ultrastructure; Neurotransmission; Patch-Clamp Techniques; Receptor mechanisms; Receptors, Dopamine D1 - genetics; Receptors, Dopamine D2 - genetics; Receptors, GABA-A - genetics; Receptors, GABA-A - metabolism; Retina; RNA, Messenger - metabolism; S100 Calcium Binding Protein G - metabolism; spiny neurons; TPMPA
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2011.07621.x

J. Neurochem. (2012) 122, 900–910.
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 D2 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.
GABAρ receptors in neurons and astrocytes of striatum 
GABA transmission plays a central role in the interneurons of the striatum. We aimed to investigate whether GABAρ receptors, which are bicuculline‐resistant and do not desensitize are expressed in this area. We found that GABAρ are present in calretinin neurons and astrocyes, and although the receptors are sensitive to TPMPA, they most likely form heteromeric complexes with other GABA subunits.