Synaptic localization of GABA(A) receptor subunits in the substantia nigra of the rat: effects of quinolinic acid lesions of the striatum.
The inhibitory amino acid, gamma-aminobutyric acid (GABA), plays a critical role in the substantia nigra (SN) in health and disease. GABA transmission is controlled in part by the type(s) of GABA receptor expressed, their subunit composition and their location in relation to GABA release sites. In order to define the subcellular localization of GABA(A) receptors in the SN in normal and pathological conditions, sections of SN from control rats and rats that had received quinolinic acid lesions of the striatum were immunolabelled using the postembedding immunogold technique with antibodies against subunits of the GABA(A) receptor. Immunolabelling for alpha1, beta2/3 and gamma2 subunits was primarily located at symmetrical synapses. Double-labelling revealed that beta2/3 subunit-positive synapses were formed by terminals that were enriched in GABA. Colocalization of alpha1, beta2/3 and gamma2 subunits occurred at individual symmetrical synapses, some of which were identified as degenerating terminals derived from the striatum. In the SN ipsilateral to the striatal lesion there was a significant elevation of immunolabelling for beta2/3 subunits of the GABA(A) receptor at symmetrical synapses, but not of GluR2/3 subunits of the AMPA receptor at asymmetrical synapses. It was concluded that fast GABA(A)-mediated transmission occurs primarily at symmetrical synapses within the SN, that different receptor subunits coexist at individual synapses and that the upregulation of GABA(A) receptors following striatal lesions is expressed as increased receptor density at synapses. The upregulation of GABA(A) receptors in Huntington's disease and its models is thus likely to lead to an increased efficiency of transmission at intact GABAergic synapses in the SN and may partly underlie the motor abnormalities of this disorder.
Fujiyama
Fumino
F
MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, Oxford, OX1 3TH, UK.
Stephenson
F Anne
FA
Bolam
J Paul
JP
D000818:Animals; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006816:Huntington Disease / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009498:Neurotoxins / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism* / Q000648:ultrastructure; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D013570:Synaptic Membranes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D009498:Neurotoxins; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D017378:Quinolinic Acid