Synaptic localization of GABA_A receptor subunits in the substantia nigra of the rat: effects of quinolinic acid lesions of the striatum

Abstract

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.

Habenula-Induced Inhibition of Midbrain Dopamine Neurons Is Diminished by Lesions of the Rostromedial Tegmental Nucleus

“…rons and induce a pacemaker-like firing pattern similar to that observed in the present study (Grace and Bunney, 1980;Engberg et al, 1993). Therefore, a compensatory postsynaptic upregulation in the expression of GABA B receptors on DA neurons after loss of GABAergic input from the RMTg could explain the dramatic shift in the distribution of firing patterns between the sham and lesioned groups.…”

Glutamate and GABA receptors and transporters in the basal ganglia: What does their subsynaptic localization reveal about their function?

“…The freeze-substitution technique, nevertheless, has been instrumental for the localization of ionotropic GABA and glutamate receptors in various brain regions, including the basal ganglia (e.g. Nusser et al, 1994;Baude et al, 1995;Nusser et al, 1995a;Matsubara et al, 1996;Bernard et al, 1997;Ottersen and Landsend, 1997;Fujiyama et al, 2002;Wu et al, 2005).…”

“…The ultrastructural localization of some of the most prevalent subunits (α1, β2/3, γ2) has been analyzed using immunogold in rat striatum (Fujiyama et al, 2000), monkey and rat GP Charara et al, 2005), in rat SN (Fujiyama et al, 2002), as well as in the monkey STN , as detailed in Table 3.…”

“…6B). GABA A receptor α1, β2/3 and γ2 subunits are often co-localized and evenly distributed along synaptic specializations Fujiyama et al, 2000;Fujiyama et al, 2002;Galvan et al, 2004;Charara et al, 2005), suggesting that fast GABA A -mediated IPSPs, reported extensively in various basal ganglia structures (e. g. Kita et al, 1983;Nakanishi et al, 1985;Nakanishi et al, 1987;Kita and Kitai, 1991;Tepper et al, 1995;Paladini et al, 1999;Kita, 2001;Bevan et al, 2002;Hallworth and Bevan, 2005), are mostly mediated by synaptic GABA A receptors containing α1, β2/3 and γ2 subunits.…”

“…For the most part, GABA A -positive synapses are formed by terminals enriched in GABA (Fujiyama et al, 2000(Fujiyama et al, ,2002, but in the rat striatum, about half of these terminals present no detectable GABA levels (Fujiyama et al, 2000). These could represent non-GABAergic terminals associated with GABA A receptors, including dopaminergic and cholinergic boutons (Izzo and Bolam, 1988;Pickel and Chan, 1990;Smith et al, 1994).…”