Multi-modal cell type atlases of somatosensory spinal cord neurons

体感脊髓神经元多模态细胞类型图谱

• 批准号: 10508739
• 负责人: Lingyong Li
• 金额: $ 0.64万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10508739
• 关键词: Atlases; Cells; Cellular Morphology; Chemicals; Classification; Code; Coupled; Data; Data Collection; Data Set; Electrophysiology (science); Esthesia; Exhibits; Gene Expression Profile; Heterogeneity; Individual; Interneurons; Label; Link; Location; Logistics; Maps; Modality; Morphology; Mus; Neurons; Pain; Pattern; Phenotype; Physiological; Posterior Horn Cells; Property; Pruritus; Sampling; Sensory; Shapes; Spinal; Spinal Cord; Techniques; Temperature; Touch sensation; base; cell type; chronic itch; chronic pain; dorsal horn; droplet sequencing; electrical property; excitatory neuron; inhibitory neuron; multimodal data; multimodality; novel; patch clamp; patch sequencing; single-cell RNA sequencing; somatosensory; transcriptome; transcriptomics

PROJECT SUMMARY/ABSTRACT The major objective of this proposal is to classify somatosensory neurons in a more integrated manner by capturing the transcriptomic, electrophysiological, and morphological properties of individual neurons in the spinal dorsal horn (SDH) using the Patch-seq technique. The SDH is critical for processing distinct modalities of sensation, such as touch, temperature, chemical, itch, and pain. Neurons in SDH are heterogenous and composed of a vast majority of excitatory and inhibitory interneurons that exhibit a wide range of morphological, physiological, and transcriptomic properties. Cell-type classification in the SDH provides a logistical and conceptual framework for understanding how cells and circuits govern somatic sensation. Attempts to classify neurons include morphological and/or electrophysiological properties, and more recently by transcriptomic features. However, linking transcriptomically defined cell types in SDH to their electrophysiological/morphological phenotypes remains a major challenge. The single-cell RNA-sequencing (scRNA-seq) coupled with patch clamp recording (Patch-seq) is a powerful approach that enables one to directly relate the transcriptomic features of a given neuron to the phenotypes of the same neuron, e.g., the neuron’s precise location, morphology, electrophysiological properties, and the functions. In the preliminary study, we have successfully used this technique to sample SDH neurons and acquired the neuron’s intrinsic firing properties and reconstructed morphology from patched neurons. In this proposal, we will use the Patch-seq technique to classify somatosensory neuron types in a more integrated manner by capturing the transcriptomic, electrophysiological, and morphological properties of individual neurons in mouse SDH. Our proposed study will bridge the missing link between transcriptomically defined cell types and morphological/electrophysiological properties of somatosensory neurons in the SDH, which provide a critical stepping-stone for illustrating how the SDH codes and relays distinct sensory modalities and how disruption of sensory processing in the SDH causes chronic pain and itch.

项目摘要/摘要 该提案的主要目的是通过更整合的方式对体感神经元进行分类 捕获单个神经元在 使用斑块ze技术，脊柱背角（SDH）。 SDH对于处理不同的方式至关重要 感觉，例如触摸，温度，化学，瘙痒和疼痛。 SDH中的神经元是异质的， 由绝大多数兴奋和抑制性中间神经元组成，它们表现出广泛的形态学， 生理和转录特性。 SDH中的细胞类型分类提供了后勤和 了解细胞和电路如何控制躯体感觉的概念框架。尝试分类 神经元包括形态学和/或电生理特性，最近通过转录组 特征。但是，将SDH中的转录定义细胞类型链接到其电生理/形态学 表型仍然是一个主要挑战。单细胞RNA-sequencing（SCRNA-SEQ）与斑块夹 录制（patch-seq）是一种强大的方法，使人们能够直接关联一个的转录组特征 给予对同一神经元的表型的神经元，例如神经元的精度位置，形态， 电生理特性和功能。在初步研究中，我们已经成功使用了 采样SDH神经元并获得神经元的内在触发和重建的技术 神经元的形态。在此提案中，我们将使用补丁式技术进行分类 通过捕获转录组，电生理学，以更整合的方式进行体感神经元类型 小鼠SDH中单个神经元的形态特性。我们提出的研究将弥合失踪的 转录定义的细胞类型与形态/电生理特性之间的联系 SDH中的体感神经元，该神经元提供了一个关键的垫脚石，用于说明SDH代码如何 并继电器不同的感觉方式以及SDH中感觉处理的破坏会导致慢性疼痛 和痒。