Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo.
Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo.
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DOI：
10.1016/j.neuron.2010.02.012
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发表时间：
2010-03-11
期刊：
影响因子：
16.2
通讯作者：
Edwards, Robert H.
中科院分区：
文献类型：
--
作者：
Hnasko, Thomas S.;Chuhma, Nao;Zhang, Hui;Goh, Germaine Y.;Sulzer, David;Palmiter, Richard D.;Rayport, Stephen;Edwards, Robert H.
腹侧被盖区（VTA）的多巴胺神经元在药物成瘾的动机系统中起着重要作用，最近的研究表明，它们也释放兴奋性神经递质谷氨酸。为了评估谷氨酸共同释放的生理作用，我们选择性地破坏多巴胺神经元中囊泡谷氨酸转运体2的表达。条件性敲除废除谷氨酸释放从中脑多巴胺神经元在文化和严重减少其兴奋性突触输出在中脑切片。基线运动行为不受影响，但可卡因对自发活动的刺激受损，显然是通过选择性减少腹侧被盖区神经元向腹侧纹状体投射中的多巴胺储存。谷氨酸共进入通过增加驱动囊泡单胺转运的pH梯度来促进单胺储存。值得注意的是，低浓度的谷氨酸酸化突触囊泡的速度比等摩尔的Cl-更慢，但程度更大，表明一种独特的突触前机制来调节量子大小。
Dopamine neurons in the ventral tegmental area (VTA) play an important role in the motivational systems underlying drug addiction, and recent work has suggested that they also release the excitatory neurotransmitter glutamate. To assess a physiological role for glutamate corelease, we disrupted the expression of vesicular glutamate transporter 2 selectively in dopamine neurons. The conditional knockout abolishes glutamate release from midbrain dopamine neurons in culture and severely reduces their excitatory synaptic output in mesoaccumbens slices. Baseline motor behavior is not affected, but stimulation of locomotor activity by cocaine is impaired, apparently through a selective reduction of dopamine stores in the projection of VTA neurons to ventral striatum. Glutamate co-entry promotes monoamine storage by increasing the pH gradient that drives vesicular monoamine transport. Remarkably, low concentrations of glutamate acidify synaptic vesicles more slowly but to a greater extent than equimolar Cl−, indicating a distinct, presynaptic mechanism to regulate quantal size.
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影响因子：
2.5
作者：
Gutiérrez, R
通讯作者：
Gutiérrez, R
影响因子：
16.2
作者：
Fon, EA;Pothos, EN;Edwards, RH
通讯作者：
Edwards, RH
影响因子：
5.3
作者：
Chuhma, N;Zhang, H;Rayport, S
通讯作者：
Rayport, S
影响因子：
64.8
作者：
Graves, Austin R.;Curran, Patricia K.;Mindell, Joseph A.
通讯作者：
Mindell, Joseph A.
DOI：
10.1073/pnas.93.11.5347
发表时间：
1996-05-28
影响因子：
11.1
作者：
Busch, AE;Schuster, A;Lang, F
通讯作者：
Lang, F