Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Neuroscience. 2019 Aug 10;413:45-63. doi: 10.1016/j.neuroscience.2019.06.021. Epub 2019 Jun 21.
Orofacial and somatic disgust reactions are observed in rats following intraoral infusion of not only bitter quinine (innate disgust) but also sweet saccharin previously paired with illness (learned disgust). It remains unclear, however, whether these innate and learned disgust reactions share a common neural basis and which brain regions, if any, host it. In addition, there is no established method to genetically access neurons whose firing is associated with disgust (disgust-associated neurons). Here, we examined the expression of cFos and Arc, two markers of neuronal activity, in the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) of male mice that showed innate disgust and mice that showed learned disgust. Furthermore, we used a targeted recombination in active populations (TRAP) method to genetically label the disgust-associated neurons in the IPAC with YFP. We found a significant increase of both cFos-positive neurons and Arc-positive neurons in the IPAC of mice that showed innate disgust and mice that showed learned disgust. In addition, TRAP following quinine infusion (Quinine-TRAP) resulted in significantly more YFP-positive neurons in the IPAC, compared to TRAP following water infusion. A significant number of the YFP-positive neurons following Quinine-TRAP were co-labeled with Arc following the second quinine infusion, confirming that Quinine-TRAP preferentially labeled quinine-activated neurons in the IPAC. Our results suggest that the IPAC activity is associated with both innate and learned disgust and that disgust-associated neurons in the IPAC are genetically accessible by TRAP.
口腔和躯体厌恶反应在大鼠中观察到，不仅在口腔内输注苦奎宁（先天厌恶）后，而且在先前与疾病（习得厌恶）配对的甜萨赫林后。然而，目前尚不清楚这些先天和习得的厌恶反应是否具有共同的神经基础，以及哪些大脑区域存在这种基础。此外，目前还没有一种既定的方法来遗传地获取与厌恶相关的神经元（厌恶相关神经元）。在这里，我们检查了雄性小鼠中前连合后肢间核（IPAC）中两种神经元活动标志物 cFos 和 Arc 的表达，这些小鼠表现出先天厌恶和习得厌恶。此外，我们使用靶向重组在活性群体（TRAP）方法将 IPAC 中的厌恶相关神经元用 YFP 进行基因标记。我们发现，无论是表现出先天厌恶的小鼠还是表现出习得厌恶的小鼠，其 IPAC 中的 cFos 阳性神经元和 Arc 阳性神经元数量均显著增加。此外，与水输注后相比，在奎宁输注（Quinine-TRAP）后，IPAC 中的 YFP 阳性神经元数量显著增加。在第二次奎宁输注后，Quinine-TRAP 后的大量 YFP 阳性神经元与 Arc 共标记，证实 Quinine-TRAP 优先标记 IPAC 中的奎宁激活神经元。我们的研究结果表明，IPAC 的活性与先天和习得的厌恶有关，并且 IPAC 中的厌恶相关神经元可以通过 TRAP 进行基因标记。
