Distinct modes of dopamine and GABA release in a dual transmitter neuron.
Distinct modes of dopamine and GABA release in a dual transmitter neuron.
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DOI：
10.1523/jneurosci.4342-12.2013
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发表时间：
2013-01-30
期刊：
影响因子：
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通讯作者：
Westbrook GL
中科院分区：
文献类型：
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作者：
Borisovska M;Bensen AL;Chong G;Westbrook GL
我们现在知道，单个神经元含有多种神经递质的情况数量惊人。含有快速作用的神经递质（如谷氨酸或GABA）和调节性递质（如多巴胺）的神经元是一个特别有趣的例子，因为它们可能具有双重信号功能。嗅球中含有大量的GABA和多巴胺神经元，这些神经元与正常嗅觉和帕金森病有关。然而，它们被归类为非胞吐型的儿茶酚胺神经元，因为它们明显缺乏囊泡单胺转运体。因此，我们研究了多巴胺是如何储存和释放酪氨酸羟化酶阳性-GFP（TH+-GFP）小鼠肾小球周围神经元在体外。TH+细胞表达VMAT 2和VGAT，与多巴胺和GABA的囊泡储存一致。碳纤维电流分析法显示，释放多巴胺是量子和钙依赖性，但量子尺寸远小于预期的大致密的核心囊泡，这表明释放源于EM确定的小透明囊泡。TH+神经元的单个动作电位诱发短暂的GABA突触电流，而诱发的多巴胺释放是异步的，持续数十秒。我们的数据表明，多巴胺和GABA在这些双递质神经元中起着时间上不同的作用。
We now know of a surprising number of cases where single neurons contain multiple neurotransmitters. Neurons that contain a fast-acting neurotransmitter such as glutamate or GABA, and a modulatory transmitter such as dopamine are a particularly interesting case because they presumably serve dual signaling functions. The olfactory bulb contains a large population of GABA and dopamine-containing neurons, which have been implicated in normal olfaction as well as in Parkinson’s disease. Yet, they have been classified as non-exocytotic catecholamine neurons because of the apparent lack of vesicular monoamine transporters. Thus we examined how dopamine is stored and released from tyrosine-hydroxylase-positive-GFP (TH+-GFP) mouse periglomerular neurons in vitro. TH+ cells expressed both VMAT2 and VGAT, consistent with vesicular storage of both dopamine and GABA. Carbon fiber amperometry revealed that release of dopamine was quantal and calcium-dependent, but quantal size was much less than expected for large dense core vesicles, suggesting that release originated from EM-identified small clear vesicles. A single action potential in a TH+ neuron evoked a brief GABA synaptic current whereas evoked dopamine release was asynchronous, lasting for tens of seconds. Our data suggests that dopamine and GABA serve temporally distinct roles in these dual transmitter neurons.