Dopamine Inhibition Differentially Controls Excitability of Substantia Nigra Dopamine Neuron Subpopulations through T-Type Calcium Channels
Dopamine Inhibition Differentially Controls Excitability of Substantia Nigra Dopamine Neuron Subpopulations through T-Type Calcium Channels
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DOI：
10.1523/jneurosci.0117-17.2017
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发表时间：
2017-03-29
影响因子：
5.3
通讯作者：
Khaliq, Zayd M.
中科院分区：
文献类型：
--
作者：
Evans, Rebekah C.;Zhu, Manhua;Khaliq, Zayd M.
虽然人们越来越重视腹侧被盖区多巴胺神经元之间的多样性，但关于黑质致密部(SNC)神经元之间的功能异质性却知之甚少。在这里，我们发现小鼠背侧层Calbindin阳性和腹侧层Calbindin阴性的SNC多巴胺能神经元包括不同的功能亚群，它们的树突钙信号、反弹兴奋和对多巴胺D2受体(D2)自身抑制的生理反应不同。虽然已知多巴胺可以抑制动作电位的反向传播，但我们的实验显示，在D2受体抑制的情况下，兴奋性反应和树突状钙信号意外增强。具体地说，多巴胺抑制和直接超极化能够产生低阈值去极化，这种去极化是以全有或无或分级的方式发生的，这是由于T型钙通道的招募。有趣的是，这些效应选择性地发生在黑质内钙结合蛋白阴性的多巴胺能神经元中。因此，在存在多巴胺抑制的情况下，Calbindin阳性和Calbindin阴性的SNC神经元在其钙通道组成和兴奋性输入的有效性方面存在本质上的差异。
While there is growing appreciation for diversity among ventral tegmental area dopamine neurons, much less is known regarding functional heterogeneity among the substantia nigra pars compacta (SNc) neurons. Here, we show that calbindin-positive dorsal tier and calbindin-negative ventral tier SNc dopaminergic neurons in mice comprise functionally distinct subpopulations distinguished by their dendritic calcium signaling, rebound excitation, and physiological responses to dopamine D2-receptor (D2) autoinhibition. While dopamine is known to inhibit action potential backpropagation, our experiments revealed an unexpected enhancement of excitatory responses and dendritic calcium signals in the presence of D2-receptor inhibition. Specifically, dopamine inhibition and direct hyperpolarization enabled the generation of low-threshold depolarizations that occurred in an all-or-none or graded manner, due to recruitment of T-type calcium channels. Interestingly, these effects occurred selectively in calbindin-negative dopaminergic neurons within the SNc. Thus, calbindin-positive and calbindin-negative SNc neurons differ substantially in their calcium channel composition and efficacy of excitatory inputs in the presence of dopamine inhibition.