Tonic activation of group I mGluRs modulates inhibitory synaptic strength by regulating KCC2 activity

被引:34
作者
Banke, Tue G. [1 ]
Gegelashvili, Georgi [2 ,3 ]
机构
[1] Johnson & Johnson PRD, San Diego, CA 92121 USA
[2] Bispebjerg Hosp, Lab Mol Neurosci, Res Dept Stereol & Neurosci, DK-2400 Copenhagen NV, Denmark
[3] I Chavchavadze State Univ, Dept Life Sci, GE-0178 Tbilisi, Georgia
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2008年 / 586卷 / 20期
基金
美国国家科学基金会;
关键词
D O I
10.1113/jphysiol.2008.157024
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The furosemide-sensitive potassium-chloride cotransporter (KCC2) plays an important role in establishing the intracellular chloride concentration in many neurons within the central nervous system. Consequently, modulation of KCC2 function will regulate the reversal potential for synaptic GABAergic inputs, thus setting the strength of inhibitory transmission. We show that tonic activation of group I metabotropic glutamate receptors (mGluR1s) regulates inhibitory synaptic strength via modulation of KCC2 function in pyramidal neurons of the hippocampal CA3 area. Specifically, group I mGluRs signal via activation of a protein kinase C-dependent pathway to alter KCC2 activity, thereby altering the intracellular chloride concentration, and thus inhibitory synaptic input. This interaction between the glutamatergic and chloride transport systems highlights a novel homeostatic mechanism whereby ambient glutamate levels directly regulate the inhibitory synaptic tone by setting the activity level of KCC2. Thus, mGluRs are poised to play a pivotal role in providing a direct interplay between the excitatory and inhibitory systems in the hippocampus.
引用
收藏
页码:4925 / 4934
页数:10
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