Multi-modal cell type atlases of somatosensory spinal cord neurons

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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.