TY - JOUR
T1 - Homeostatic plasticity of GABAergic synaptic transmission in mice lacking GAT1
AU - Xu, Yinfang
AU - Cai, Youqing
AU - Gong, Neng
AU - Chen, Chen
AU - Wu, Yuncheng
AU - Zhang-Nunes, Sandy
AU - Wang, Zhugang
AU - Xu, Tianle
AU - Fei, Jian
N1 - Funding Information:
Funded by: the National Natural Science Foundation of China (30370447); the Science and Technology Commission of Shanghai Municipality (06DZ19004, 06XD14014, 05DZ22915); and E-Institutes of Shanghai Municipal Education Commission (E03003).
Funding Information:
We thank Jun Chi for the animal care and Guiqi Qu for the experimental laboratorial affairs. This work was supported by grants from the National Natural Science Foundation of China (30370447, 30670438), the Science and Technology Commission of Shanghai Municipality (06DZ19004, 06XD14014, 54319939), and E-Institutes of Shanghai Municipal Education Commission (E03003).
PY - 2007/9/21
Y1 - 2007/9/21
N2 - 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 GAT1-/- mice. We hypothesized that homeostatic plasticity of GABAA 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 GAT1-/- mice decreased the sensitivity to some extent. These results confirmed our presumption about the down-regulation of phasic GABAergic transmission in the GAT1 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.
AB - 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 GAT1-/- mice. We hypothesized that homeostatic plasticity of GABAA 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 GAT1-/- mice decreased the sensitivity to some extent. These results confirmed our presumption about the down-regulation of phasic GABAergic transmission in the GAT1 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.
KW - GABA transporter
KW - Knockout
KW - Tiagabine
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U2 - 10.1016/j.bbrc.2007.07.042
DO - 10.1016/j.bbrc.2007.07.042
M3 - Article
C2 - 17655829
AN - SCOPUS:34547559353
SN - 0006-291X
VL - 361
SP - 499
EP - 504
JO - Biochemical and biophysical research communications
JF - Biochemical and biophysical research communications
IS - 2
ER -