Neuronal Glutamate Transporters Regulate Glial Excitatory Transmission

被引:20
作者
Tsai, Ming-Chi [1 ,2 ]
Tanaka, Kohichi [3 ,4 ]
Overstreet-Wadiche, Linda [1 ,2 ]
Wadiche, Jacques I. [1 ,2 ]
机构
[1] Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA
[2] Univ Alabama, Evelyn McKnight Brain Inst, Birmingham, AL 35294 USA
[3] Tokyo Med & Dent Univ, Sch Biomed Sci, Bunkyo Ku, Tokyo 1138510, Japan
[4] Tokyo Med & Dent Univ, Med Res Inst, Bunkyo Ku, Tokyo 1138510, Japan
基金
美国国家卫生研究院;
关键词
CEREBELLAR PURKINJE-CELLS; SYNAPTICALLY RELEASED GLUTAMATE; MULTIVESICULAR RELEASE; CHLORIDE CHANNEL; RAT CEREBELLUM; GABA SYNTHESIS; MICE LACKING; TIME-COURSE; RECEPTOR; ACTIVATION;
D O I
10.1523/JNEUROSCI.5232-11.2012
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the CNS, excitatory amino acid transporters (EAATs) localized to neurons and glia terminate the actions of synaptically released glutamate. Whereas glial transporters are primarily responsible for maintaining low ambient levels of extracellular glutamate, neuronal transporters have additional roles in shaping excitatory synaptic transmission. Here we test the hypothesis that the expression level of the Purkinje cell (PC)-specific transporter, EAAT4, near parallel fiber (PF) release sites controls the extrasynaptic glutamate concentration transient following synaptic stimulation. Expression of EAAT4 follows a parasagittal banding pattern that allows us to compare regions of high and low EAAT4-expressing PCs. Using EAAT4 promoter-driven eGFP reporter mice together with pharmacology and genetic deletion, we show that the level of neuronal transporter expression influences extrasynaptic transmission from PFs to adjacent Bergmann glia (BG). Surprisingly, a twofold difference in functional EAAT4 levels is sufficient to alter signaling to BG, although EAAT4 may only be responsible for removing a fraction of released glutamate. These results demonstrate that physiological regulation of neuronal transporter expression can alter extrasynaptic neuroglial signaling.
引用
收藏
页码:1528 / 1535
页数:8
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