Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
Int J Oral Sci. 2023 Sep 25;15(1):45. doi: 10.1038/s41368-023-00246-z.
Dental primary afferent (DPA) neurons and proprioceptive mesencephalic trigeminal nucleus (MTN) neurons, located in the trigeminal ganglion and the brainstem, respectively, are essential for controlling masticatory functions. Despite extensive transcriptomic studies on various somatosensory neurons, there is still a lack of knowledge about the molecular identities of these populations due to technical challenges in their circuit-validated isolation. Here, we employed high-depth single-cell RNA sequencing (scRNA-seq) in combination with retrograde tracing in mice to identify intrinsic transcriptional features of DPA and MTN neurons. Our transcriptome analysis revealed five major types of DPA neurons with cell type-specific gene enrichment, some of which exhibit unique mechano-nociceptive properties capable of transmitting nociception in response to innocuous mechanical stimuli in the teeth. Furthermore, we discovered cellular heterogeneity within MTN neurons that potentially contribute to their responsiveness to mechanical stretch in the masseter muscle spindles. Additionally, DPA and MTN neurons represented sensory compartments with distinct molecular profiles characterized by various ion channels, receptors, neuropeptides, and mechanoreceptors. Together, our study provides new biological insights regarding the highly specialized mechanosensory functions of DPA and MTN neurons in pain and proprioception.
口腔初级传入 (DPA) 神经元和本体感觉脑桥三叉神经核 (MTN) 神经元分别位于三叉神经节和脑干中，对于控制咀嚼功能至关重要。尽管对各种躯体感觉神经元进行了广泛的转录组研究，但由于其回路验证分离的技术挑战，这些群体的分子特征仍然知之甚少。在这里，我们在小鼠中采用高深度单细胞 RNA 测序 (scRNA-seq) 结合逆行追踪来鉴定 DPA 和 MTN 神经元的内在转录特征。我们的转录组分析揭示了具有细胞类型特异性基因富集的五种主要类型的 DPA 神经元，其中一些表现出独特的机械伤害感受特性，能够在牙齿受到无害机械刺激时传递伤害感受。此外，我们发现 MTN 神经元内存在细胞异质性，这可能有助于它们对咀嚼肌梭内机械拉伸的反应。此外，DPA 和 MTN 神经元代表了具有不同分子特征的感觉隔室，其特征是各种离子通道、受体、神经肽和机械感受器。总之，我们的研究提供了关于 DPA 和 MTN 神经元在疼痛和本体感觉中高度专业化的机械感觉功能的新生物学见解。
