화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.361, No.2, 499-504, 2007
Homeostatic plasticity of GABAergic synaptic transmission in mice lacking GAT1
GABA transporter-1 (GAT1) plays a key role in GABA reuptake, and deletion of GAT1 leads to a largely increased GABA-induced tonic conductance in the GATI-1- mice. We hypothesized that homeostatic plasticity of GABA(A) receptor-mediated inhibition takes place to balance the increased tonic inhibition and maintains stability of the nervous system. In this study, we employed the loss of righting reflex assay and compared the behavioral difference of three animal models, mice with acute, partial, and permanent GAT1 deficiency, to confirm our hypothesis. Our data demonstrated that both acute and partial block of GAT1 increased the sensitivity of mice to GABAergic sedative/hypnotic drugs, whereas permanent GAT1 dysfunction in the GATI-1- mice decreased the sensitivity to some extent. These results confirmed our presumption about the down-regulation of phasic GABAergic transmission in the GATI knockout mice. Moreover, electrophysiological measurements performed on slices from motor cortex suggested that it was the reduced GABA release, but not change of postsynaptic GABA receptors, which led to the down-regulation of phasic inhibition in GAT1(-/-) mice. (c) 2007 Elsevier Inc. All rights reserved.