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 这项建议的主要目标是以更综合的方式对躯体感觉神经元进行分类，方法是 捕获单个神经元的转录、电生理和形态特性 脊髓背角(SDH)使用Patch-Seq技术。SDH对于处理不同模式的 感觉，如触摸、温度、化学物质、瘙痒和疼痛。SDH中的神经元是异质的，并且 由绝大多数兴奋性和抑制性中间神经元组成，它们表现出广泛的形态， 生理和转录特性。SDH中的小区类型分类提供了一种后勤和 理解细胞和回路如何支配躯体感觉的概念框架。试图将 神经元包括形态和/或电生理特性，最近通过转录切割 功能。然而，将SDH中转录定义的细胞类型与它们的电生理/形态联系起来 表型仍然是一个重大挑战。膜片钳结合的单细胞RNA测序技术 记录(Patch-seq)是一种功能强大的方法，它使人们能够直接关联 给定的神经元与同一神经元的表型相同，例如神经元的精确位置、形态、 电生理特性和功能。在初步研究中，我们成功地使用了这一点 采样SDH神经元并获取神经元的固有放电特性并进行重建的技术 打补丁的神经元的形态。在本提案中，我们将使用Patch-Seq技术来分类 通过捕获转录、电生理、 以及小鼠SDH中单个神经元的形态特征。我们提出的研究将弥补这一缺失 在转录定义的细胞类型和形态/电生理特性之间的联系 SDH中的体感神经元，它们为阐明SDH如何编码提供了关键的踏脚石 并传递不同的感觉模式以及SDH中感觉处理的中断如何导致慢性疼痛 而且很痒。