The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5-HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potentials within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5-HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5-HT1A or 5-HT2A. We analyzed seven neural populations, including three defined by a molecular marker (putative glutamate, GABA or parvalbumin), and four defined by their projections to different downstream targets. First, we found that more than 70% of putative glutamatergic neurons, and only 30% of GABAergic neurons express the 5-HT1A. Second, within insular projection neurons, 5-HT1A is highly expressed (75–80%) in the populations targeting one sub-nuclei of the amygdala (central or basolateral), or targeting the rostral or caudal sections of the lateral hypothalamus (LH). Similarly, 70% of putative glutamatergic neurons and only 30% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in a majority of insula-amygdala and insula-LH projection neurons (73–82%). These observations suggest that most glutamatergic neurons can respond to 5-HT through 5-HT1A or 5-HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.

中文翻译：

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小鼠岛叶皮质分子和投影定义的神经元中血清素 1A 和 2A 受体的表达。

血清素 (5-HT) 系统是多种抗焦虑药的作用靶点，其中包括丁螺环酮，它是血清素 1A 受体 (5-HT1A) 的部分激动剂。同样，血清素 2A 受体 (5-HT2A) 的配体被证明可以改变焦虑水平。5-HT1A 和 2A 受体在大脑中广泛表达，但这些受体对焦虑产生影响的目标区域仍然未知。有趣的是，最近对人类和非人类灵长类动物的研究表明，岛叶皮质（岛叶）内的 5-HT1A 和 5-HT2A 结合电位与焦虑相关。作为定义岛叶中 5-HT 传递功能的第一步，我们量化了表达 5-HT1A 或 5-HT2A 的岛叶特定神经元群体的比例。我们分析了七个神经群体，包括三个由分子标记（推定的谷氨酸、GABA 或小白蛋白）定义的神经群体，以及四个由它们对不同下游目标的预测定义的神经群体。首先，我们发现超过 70% 的假定谷氨酸能神经元，而只有 30% 的 GABA 能神经元表达 5-HT1A。其次，在岛状投射神经元中，5-HT1A 在针对杏仁核（中央或基底外侧）的一个亚核或针对外侧下丘脑（LH）的头侧或尾侧部分的群体中高度表达（75-80％） 。同样，70% 的假定谷氨酸能神经元和仅 30% 的岛状 GABA 能神经元含有 5-HT2A。最后，5-HT2A 存在于大多数岛叶杏仁核和岛叶 LH 投射神经元中 (73-82%)。这些观察结果表明，大多数谷氨酸能神经元可以通过岛叶中的5-HT1A或5-HT2A对5-HT做出反应，并且5-HT直接影响有限数量的GABA能神经元。这项研究定义了岛叶皮质内 5-HT 系统的分子和神经解剖图，为识别选择性岛叶群体的血清素调节在焦虑中的潜在作用提供了基础知识。