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GABA(A) receptors: structure and function in the basal ganglia.

ABSTRACT: gamma-Aminobutyric acid type A (GABA(A)) receptors, the major inhibitory neurotransmitter receptors responsible for fast inhibition in the basal ganglia, belong to the superfamily of "cys-cys loop" ligand-gated ion channels. GABA(A) receptors form as pentameric assemblies of subunits, with a central Cl(-) permeable pore. On binding of two GABA molecules to the extracellular receptor domain, a conformational change is induced in the oligomer and Cl(-), in most adult neurons, moves into the cell leading to an inhibitory hyperpolarization. Nineteen mammalian subunit genes have been identified, each showing distinct regional and cell-type-specific expression. The combinatorial assembly of the subunits generates considerable functional diversity. Here we place the focus on GABA(A) receptor expression in the basal ganglia: striatum, globus pallidus, substantia nigra and subthalamic nucleus, where, in addition to the standard alpha1beta2/3gamma2 receptor subtype, significant levels of other subunits (alpha2, alpha3, alpha4, gamma1, gamma3 and delta) are expressed in some nuclei.

SUBMITTER: Goetz T

PROVIDER: S-EPMC2648504 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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GABA(A) receptors: structure and function in the basal ganglia.

Goetz T T Arslan A A Wisden W W Wulff P P

Progress in brain research 20070101

gamma-Aminobutyric acid type A (GABA(A)) receptors, the major inhibitory neurotransmitter receptors responsible for fast inhibition in the basal ganglia, belong to the superfamily of "cys-cys loop" ligand-gated ion channels. GABA(A) receptors form as pentameric assemblies of subunits, with a central Cl(-) permeable pore. On binding of two GABA molecules to the extracellular receptor domain, a conformational change is induced in the oligomer and Cl(-), in most adult neurons, moves into the cell l ...[more]

PMID: 17499107

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Project description:IntroductionNeonatal arterial ischemic stroke (NAIS) is a common model to study the impact of a unilateral early brain insult on developmental brain plasticity and the appearance of long-term outcomes. Motor difficulties that may arise are typically related to poor function of the affected (contra-lesioned) hand, but surprisingly also of the ipsilesional hand. Although many longitudinal studies after NAIS have shown that predicting the occurrence of gross motor difficulties is easier, accurately predicting hand motor function (for both hands) from morphometric MRI remains complicated. The hypothesis of an association between the structural organization of the basal ganglia (BG) and thalamus with hand motor function seems intuitive given their key role in sensorimotor function. Neuroimaging studies have frequently investigated these structures to evaluate the correlation between their volumes and motor function following early brain injury. However, the results have been controversial. We hypothesize the involvement of other structural parameters.MethodThe study involves 35 children (mean age 7.3 years, SD 0.4) with middle cerebral artery NAIS who underwent a structural T1-weighted 3D MRI and clinical examination to assess manual dexterity using the Box and Blocks Test (BBT). Graphs are used to represent high-level structural information of the BG and thalami (volumes, elongations, distances) measured from the MRI. A graph neural network (GNN) is proposed to predict children's hand motor function through a graph regression. To reduce the impact of external factors on motor function (such as behavior and cognition), we calculate a BBT score ratio for each child and hand.ResultsThe results indicate a significant correlation between the score ratios predicted by our method and the actual score ratios of both hands (p < 0.05), together with a relatively high accuracy of prediction (mean L1 distance < 0.03). The structural information seems to have a different influence on each hand's motor function. The affected hand's motor function is more correlated with the volume, while the 'unaffected' hand function is more correlated with the elongation of the structures. Experiments emphasize the importance of considering the whole macrostructural organization of the basal ganglia and thalami networks, rather than the volume alone, to predict hand motor function.ConclusionThere is a significant correlation between the structural characteristics of the basal ganglia/thalami and motor function in both hands. These results support the use of MRI macrostructural features of the basal ganglia and thalamus as an early biomarker for predicting motor function in both hands after early brain injury.

Project description:Background and objectiveRecent studies suggest perivascular spaces are a marker of small vessel disease, blood-brain barrier permeability, and inflammation, but little is known about their risk factors and associations with peripheral blood markers.Materials and methodsIn prospectively recruited patients with recent minor ischemic stroke, we investigated the influence of age, sex, hypertension, diabetes, and smoking on the severity of perivascular spaces in the basal ganglia seen on T2-weighted magnetic resonance imaging. We assessed plasma markers of endothelial function (von Willebrand factor, intracellular adhesion molecule-1), inflammation (interleukin-6, tumor necrosis factor-alpha, C-reactive protein), and thrombosis (fibrinogen, prothrombin fragments 1 + 2, thrombin-antithrombin complex, tissue plasminogen activator, D-dimer). We used a validated semi-automated method to measure basal ganglia perivascular spaces count and volume. We tested uni- and multivariable associations between blood markers and basal ganglia perivascular spaces count and volume.FindingsIn 100 patients (median age: 67 years, range: 37-92), on adjusted analysis, basal ganglia perivascular spaces count was associated with age (r = .117, P = .003) and hypertension (r = 2.225, P = .013). On multivariable linear regression, adjusted for age, sex, hypertension, smoking and diabetes, reduced von Willebrand factor was associated with increased basal ganglia perivascular spaces count (r = -.025, P = .032).ConclusionThe association of increased basal ganglia perivascular spaces count with reduced von Willebrand factor is novel. As von Willebrand factor may promote cerebral endothelial integrity, insufficient von Willebrand factor is consistent with dysfunctional cerebral endothelium and increased basal ganglia perivascular spaces in cerebral small vessel disease. Quantitative perivascular spaces measurement may increase sensitivity to detect cerebral endothelial dysfunction.

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GABA(A) receptors: structure and function in the basal ganglia.

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GABA(A) receptors: structure and function in the basal ganglia.

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