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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

基本信息

批准号：
10743857
负责人：
Lingyong Li
金额：
$ 40.07万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-15 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10743857
关键词：
Multi modal cell type atlases

项目摘要

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.

项目总结/摘要这项建议的主要目标是分类体感神经元在一个更综合的方式，捕捉转录组，电生理学，和形态学特性的个别神经元中，脊髓背角（SDH）使用Patch-seq技术。SDH对于处理不同形式的感觉，如触摸、温度、化学物质、瘙痒和疼痛。SDH中的神经元是异质的，由绝大多数兴奋性和抑制性中间神经元组成，生理学和转录组学特性。SDH中的细胞类型分类提供了逻辑和理解细胞和回路如何支配躯体感觉的概念框架。尝试分类神经元包括形态学和/或电生理学特性，并且最近通过转录组学，功能.然而，将SDH中转录组学定义的细胞类型与它们的电生理/形态学联系起来，表型仍然是一个重大挑战。单细胞RNA测序与膜片钳技术联用记录（Patch-seq）是一种强大的方法，它使人们能够直接将转录组学特征与基因组学特征联系起来。给定神经元与相同神经元的表型，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，我们成功地利用了这一点，技术采集SDH神经元，获取神经元的内在放电特性，来自补丁神经元的形态学。在本提案中，我们将使用Patch-seq技术来分类躯体感觉神经元类型以更整合的方式通过捕获转录组，电生理，和小鼠SDH中单个神经元的形态学特性。我们提议的研究将弥补转录组学定义的细胞类型与细胞形态学/电生理学特性之间的联系 SDH中的躯体感觉神经元，这为说明SDH如何编码提供了关键的垫脚石并传递不同的感觉方式，以及SDH中感觉处理的中断如何导致慢性疼痛还很痒