Qi Lijun, Iskols Michael, Shi David, Reddy Pranav, Walker Christopher, Lezgiyeva Karina, Voisin Tiphaine, Pawlak Mathias, Kuchroo Vijay K, Chiu Isaac M, Ginty David D, Sharma Nikhil
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
Department of Molecular Pharmacology and Therapeutics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.
Cell. 2024 Mar 14;187(6):1508-1526.e16. doi: 10.1016/j.cell.2024.02.006. Epub 2024 Mar 4.
Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from the periphery to the CNS has been challenging with existing tools. Here, we develop and curate a mouse genetic toolkit that allows for interrogating the properties and functions of distinct cutaneous targeting DRG neuron subtypes. These tools have enabled a broad morphological analysis, which revealed distinct cutaneous axon arborization areas and branching patterns of the transcriptionally distinct DRG neuron subtypes. Moreover, in vivo physiological analysis revealed that each subtype has a distinct threshold and range of responses to mechanical and/or thermal stimuli. These findings support a model in which morphologically and physiologically distinct cutaneous DRG sensory neuron subtypes tile mechanical and thermal stimulus space to collectively encode a wide range of natural stimuli.
背根神经节(DRG)体感神经元可检测作用于身体的机械、热和化学刺激。利用现有工具全面了解不同的DRG神经元亚型如何将神经信号从外周传递到中枢神经系统一直具有挑战性。在此,我们开发并整理了一个小鼠基因工具包,可用于探究不同的皮肤靶向DRG神经元亚型的特性和功能。这些工具实现了广泛的形态学分析,揭示了转录上不同的DRG神经元亚型具有不同的皮肤轴突分支区域和分支模式。此外,体内生理学分析表明,每个亚型对机械和/或热刺激都有不同的阈值和反应范围。这些发现支持了一种模型,即形态学和生理学上不同的皮肤DRG感觉神经元亚型划分机械和热刺激空间,以共同编码广泛的自然刺激。