Distribution of the major γ‐aminobutyric acid_A receptor subunits in the basal ganglia and associated limbic brain areas of the adult rat

Abstract

Within the basal ganglia, gamma-aminobutyric acid (GABA) exerts a fundamental role as neurotransmitter of local circuit and projection neurons. Its fast hyperpolarizing action is mediated through GABA(A) receptors. These ligand-gated chloride channels are assembled from five subunits, which derive from multiple genes. Using immunocytochemistry, we investigated the distribution of 12 major GABA(A) receptor subunits (alpha1-5, beta1-3, gamma1-3, and delta) in the basal ganglia and associated limbic brain areas of the rat. Immunoreactivity for an additional subunit (subunit alpha6) was not observed. The striatum, the nucleus accumbens, and the olfactory tubercle displayed strong, diffuse staining for the subunits alpha2, alpha4, beta3, and delta presumably located on dendrites of the principal medium spiny neurons. Subunit alpha1-, beta2-, and gamma2-immunoreactivities were apparently mostly restricted to interneurons of these areas. In contrast, the globus pallidus, the entopeduncular nucleus, the ventral pallidum, the subthalamic nucleus, and the substantia nigra pars reticulata revealed dense networks of presumable dendrites of resident projection neurons, which were darkly labeled for subunit alpha1-, beta2-, and gamma2-immunoreactivities. The globus pallidus, ventral pallidum, entopeduncular nucleus, and substantia nigra pars reticulata, all areas receiving innervations from the striatum, displayed strong subunit gamma1-immunoreactivity compared to other brain areas. In the substantia nigra pars compacta and in the ventral tegmental area, numerous presumptive dopaminergic neurons were labeled for subunits alpha3, gamma3, and/or delta. This highly heterogeneous distribution of individual GABA(A) receptor subunits suggests the existence of differently assembled, and presumably also functionally different, GABA(A) receptors within individual nuclei of the basal ganglia and associated limbic brain areas.

Loss of BDNF Signaling in D1R-Expressing NAc Neurons Enhances Morphine Reward by Reducing GABA Inhibition

“…Furthermore, we observed that D1-TrkB KO enhances Gabra2 levels, as opposed to reduced expression of many other GABA A R subunits and to the consequent reduction of sIPSCs, suggesting that the Gabra2 induction by reduced TrkB in morphine-treated D1-type MSNs might cancel out the effect of Gabra2 reduction by morphine. Rather, Gabra4, another GABA A R subunit of high abundance in NAc (Schwarzer et al, 2001;Wisden et al, 1992) that is decreased by morphine in NAc, particularly in D1-type MSNs, as well as by D1-TrkB KO or by itself in the present study, appears to be critical for morphine reward. A very recent report shows that Gabra4 deletion in D1-type MSNs increases cocaine CPP, but the deletion in D2-type MSNs does not (Maguire et al, 2014).…”

Effect of GABRA2 Genotype on Development of Incentive-Motivation Circuitry in a Sample Enriched for Alcoholism Risk

“…Inhibitory regulation of NAcc dopaminergic function comes from GABAergic influences (Steffensen et al, 1998). The GABRA2 gene is involved in encoding the a2 subunit of the g-aminobutyric acid A receptor (GABA A ), which is among the predominant receptor subtypes expressed in the NAcc (Schwarzer et al, 2001). GABRA2 gene deletion in a mouse model was found to reduce GABA A -mediated electrophysiological responses in the NAcc (Dixon et al, 2010).…”

Alcohol Modulation of Extra-synaptic Gamma-aminobutyric Acid Type A Receptors

“…The GABAARs are assembled from a pool of 19 subunits () (Rudolph and Mohler, 2006). The expression of the subunit genes is age-and region dependent (Wisden et al, 1992;Laurie et al, 1992a, b;Fritschy and Mohler, 1995;Schwarzer et al, 2001). The most abundant GABAARs in the mammalian brain seem to be the combination of 2 subunits with a subunit ratio of  (Ernst et al, 2003).…”