A mouse DRG genetic toolkit reveals morphological and physiological diversity of somatosensory neuron subtypes

Cell. 2024 Mar 14;187(6):1508-1526.e16. doi: 10.1016/j.cell.2024.02.006. Epub 2024 Mar 4.

Abstract

Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from the periphery to the CNS has been challenging with existing tools. Here, we develop and curate a mouse genetic toolkit that allows for interrogating the properties and functions of distinct cutaneous targeting DRG neuron subtypes. These tools have enabled a broad morphological analysis, which revealed distinct cutaneous axon arborization areas and branching patterns of the transcriptionally distinct DRG neuron subtypes. Moreover, in vivo physiological analysis revealed that each subtype has a distinct threshold and range of responses to mechanical and/or thermal stimuli. These findings support a model in which morphologically and physiologically distinct cutaneous DRG sensory neuron subtypes tile mechanical and thermal stimulus space to collectively encode a wide range of natural stimuli.

Keywords: dorsal root ganglion; genetic tools; mechanosensation; population code; somatosensation; sparse labeling; thermosensation; transcriptional heterogeneity.

MeSH terms

  • Animals
  • Ganglia, Spinal* / cytology
  • Mice
  • Sensory Receptor Cells* / cytology
  • Single-Cell Gene Expression Analysis*
  • Skin / innervation