Qi Lijun, Iskols Michael, Shi David, Reddy Pranav, Walker Christopher, Lezgiyeva Karina, Voisin Tiphaine, Pawlak Mathias, Kuchroo Vijay K, Chiu Isaac, Ginty David D, Sharma Nikhil
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115.
Department of Molecular Pharmacology and Therapeutics, Department of Systems Biology, Columbia University, New York, NY.
bioRxiv. 2023 Apr 23:2023.04.22.537932. doi: 10.1101/2023.04.22.537932.
Mechanical and thermal stimuli acting on the skin are detected by morphologically and physiologically distinct sensory neurons of the dorsal root ganglia (DRG). Achieving a holistic view of how this diverse neuronal population relays sensory information from the skin to the central nervous system (CNS) has been challenging with existing tools. Here, we used transcriptomic datasets of the mouse DRG to guide development and curation of a genetic toolkit to interrogate transcriptionally defined DRG neuron subtypes. Morphological analysis revealed unique cutaneous axon arborization areas and branching patterns of each subtype. Physiological analysis showed that subtypes exhibit distinct thresholds and ranges of responses to mechanical and/or thermal stimuli. The somatosensory neuron toolbox thus enables comprehensive phenotyping of most principal sensory neuron subtypes. Moreover, our findings support a population coding scheme in which the activation thresholds of morphologically and physiologically distinct cutaneous DRG neuron subtypes tile multiple dimensions of stimulus space.
作用于皮肤的机械和热刺激由背根神经节(DRG)中形态和生理上不同的感觉神经元检测。利用现有工具全面了解这一多样化的神经元群体如何将感觉信息从皮肤传递到中枢神经系统(CNS)一直具有挑战性。在这里,我们使用小鼠DRG的转录组数据集来指导一个基因工具包的开发和管理,以研究转录定义的DRG神经元亚型。形态学分析揭示了每个亚型独特的皮肤轴突分支区域和分支模式。生理学分析表明,各亚型对机械和/或热刺激表现出不同的阈值和反应范围。因此,体感神经元工具箱能够对大多数主要感觉神经元亚型进行全面的表型分析。此外,我们的研究结果支持一种群体编码方案,即形态和生理上不同的皮肤DRG神经元亚型的激活阈值在刺激空间的多个维度上分布。