Accumbens dopamine D2 receptors increase motivation by decreasing inhibitory transmission to the ventral pallidum.
Accumbens dopamine D2 receptors increase motivation by decreasing inhibitory transmission to the ventral pallidum.
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DOI：
10.1038/s41467-018-03272-2
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发表时间：
2018-03-14
影响因子：
16.6
通讯作者：
Kellendonk C
中科院分区：
文献类型：
--
作者：
Gallo EF;Meszaros J;Sherman JD;Chohan MO;Teboul E;Choi CS;Moore H;Javitch JA;Kellendonk C
多巴胺D2受体（D2Rs）在延髓核（NAc）的调节动机行为，但潜在的神经生物学机制尚未解决。在这里，我们表明，选择性上调D2Rs在成人NAc的间接途径增强了工作的食物的意愿。脑切片中的机制研究表明，D2R上调减弱了间接通路的两个主要输出投射的抑制性传递，即到腹侧苍白球（VP）的经典长距离投射，以及到直接通路中等多刺神经元的局部侧支。在体内生理学证实，减少间接途径抑制性传输到VP，和VP的间接途径终端的抑制足以提高动机。相反，D2R在间接途径中的上调不会解除体内直接途径的神经元活性。这些数据表明，腹侧纹状体投射神经元中的D2Rs通过减弱腹侧苍白球的典型输出来促进动机。多巴胺D2受体在丘脑核的活性与动机性反应的调节有关。在这里，作者表明，在腹侧纹状体投射神经元中特异性D2受体的过表达通过减少对腹侧苍白球神经元的抑制性传递而导致工作意愿的增加。
Dopamine D2 receptors (D2Rs) in the nucleus accumbens (NAc) regulate motivated behavior, but the underlying neurobiological mechanisms remain unresolved. Here, we show that selective upregulation of D2Rs in the indirect pathway of the adult NAc enhances the willingness to work for food. Mechanistic studies in brain slices reveal that D2R upregulation attenuates inhibitory transmission at two main output projections of the indirect pathway, the classical long-range projections to the ventral pallidum (VP), as well as local collaterals to direct pathway medium spiny neurons. In vivo physiology confirms the reduction in indirect pathway inhibitory transmission to the VP, and inhibition of indirect pathway terminals to VP is sufficient to enhance motivation. In contrast, D2R upregulation in the indirect pathway does not disinhibit neuronal activity of the direct pathway in vivo. These data suggest that D2Rs in ventral striatal projection neurons promote motivation by weakening the canonical output to the ventral pallidum. Dopamine D2 receptor activity in the nucleus accumbens is associated with regulation of motivated responding. Here the authors show that overexpression of D2 receptors specifically in ventral striatal projection neurons leads to an increase in the willingness to work by reducing inhibitory transmission to ventral pallidal neurons.
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DOI：
10.1523/jneurosci.3833-10.2011
发表时间：
2011-01-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
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影响因子：
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影响因子：
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作者：
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