Dopamine D1 and D5 Receptors Are Localized to Discrete Populations of Interneurons in Primate Prefrontal Cortex
Dopamine D1 and D5 Receptors Are Localized to Discrete Populations of Interneurons in Primate Prefrontal Cortex
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DOI：
10.1093/cercor/bhn212
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发表时间：
2009-08-01
期刊：
影响因子：
3.7
通讯作者：
Muly, E. Chris
中科院分区：
文献类型：
--
作者：
Glausier, Jill R.;Khan, Zafar U.;Muly, E. Chris
工作记忆 (WM) 是一个核心认知过程，依赖于 D1 家族受体 (D1R) 和前额皮质 (PFC) 中抑制性中间神经元的激活。 D1R 由 D-1 和 D-5 亚型组成，D-5 对多巴胺的亲和力高出 10 倍。小白蛋白 (PV) 和钙视网膜蛋白 (CR) 是 2 个中间神经元群体，它们受 D1R 刺激的影响不同，并且具有离散的突触后靶标，因此 PV 中间神经元对锥体细胞提供强烈的抑制，而 CR 中间神经元则抑制其他中间神经元。 D1R 和中间神经元亚型的独特特性可能有助于 D1R 刺激和 WM 能力的“倒 U”关系。为了确定 D-1 和 D-5 在 PV 和 CR 中间神经元中的患病率，我们在猕猴第 9 区的 III 层进行了定量双标记免疫电子显微镜检查。我们发现 D-1 是 PV 中间神经元中主要的 D1R 亚型，主要存在于树突中。相比之下，D-5 是 CR 中间神经元中主要的 D1R 亚型，主要存在于树突中。将这些发现与之前发表的电生理学数据相结合，我们提出了一个电路模型作为框架，用于理解 D1R 的多巴胺刺激与 WM 表现之间的倒 U 关系。
Working memory (WM) is a core cognitive process that depends upon activation of D1 family receptors (D1R) and inhibitory interneurons in the prefrontal cortex (PFC). D1R are comprised of the D-1 and D-5 subtypes, and D-5 has a 10-fold higher affinity for dopamine. Parvalbumin (PV) and calretinin (CR) are 2 interneuron populations that are differentially affected by D1R stimulation and have discrete postsynaptic targets, such that PV interneurons provide strong inhibition to pyramidal cells, whereas CR interneurons inhibit other interneurons. The distinct properties of both the D1R and interneuron subtypes may contribute to the "inverted-U" relationship of D1R stimulation and WM ability. To determine the prevalence of D-1 and D-5 in PV and CR interneurons, we performed quantitative double-label immunoelectron microscopy in layer III of macaque area 9. We found that D-1 was the predominant D1R subtype in PV interneurons and was found mainly in dendrites. In contrast, D-5 was the predominant D1R subtype in CR interneurons and was found mainly in dendrites. Integrating these findings with previously published electrophysiological data, we propose a circuitry model as a framework for understanding the inverted-U relationship between dopamine stimulation of D1R and WM performance.