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Mrgprd-expressing polymodal nociceptive neurons innervate most known classes of substantia gelatinosa neurons.

The Mas-related G-protein-coupled receptor D (Mrgprd) marks a distinct subset of sensory neurons that transmit polymodal nociceptive information from the skin epidermis to the substantia gelatinosa (SG, lamina II) of the spinal cord. Moreover, Mrgprd-expressing (Mrgprd(+)) neurons are required for the full expression of mechanical but not thermal nociception. While such anatomical and functional specificity suggests Mrgprd(+) neurons might synapse with specific postsynaptic targets in the SG, precisely how Mrgprd(+) neurons interface with spinal circuits is currently unknown. To study circuit connectivity, we genetically targeted the light-activated ion channel Channelrhodopsin-2-Venus (ChR2-Venus) to the Mrgprd locus. In these knock-in mice, ChR2-Venus was localized to nonpeptidergic Mrgprd(+) neurons and axons, while peptidergic CGRP(+) neurons were not significantly labeled. Dissociated Mrgprd(+) DRG neurons from mice expressing one or two copies of ChR2-Venus could be activated in vitro as evidenced by light-evoked currents and action potentials. In addition, illumination of Mrgprd-ChR2-Venus(+) axon terminals in spinal cord slices evoked EPSCs in half of all SG neurons. Within this subset, Mrgprd(+) neurons were monosynaptically connected to most known classes of SG neurons, including radial, tonic central, transient central, vertical, and antenna cells. This cellular diversity ruled out the possibility that Mrgprd(+) neurons innervate a dedicated class of SG neuron. Our findings set broad constraints on the types of spinal neurons that process afferent input from Mrgprd(+) polymodal nociceptors.

Pubmed ID: 19846708


  • Wang H
  • Zylka MJ


The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

October 21, 2009

Associated Grants

  • Agency: NINDS NIH HHS, Id: P30NS045892
  • Agency: NINDS NIH HHS, Id: R01 NS060725
  • Agency: NINDS NIH HHS, Id: R01 NS060725-01
  • Agency: NINDS NIH HHS, Id: R01 NS060725-02
  • Agency: NINDS NIH HHS, Id: R01 NS060725-03
  • Agency: NINDS NIH HHS, Id: R01 NS060725-04
  • Agency: NINDS NIH HHS, Id: R01NS060725

Mesh Terms

  • Animals
  • Biophysics
  • Calcitonin Gene-Related Peptide
  • Cells, Cultured
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials
  • Ganglia, Spinal
  • Green Fluorescent Proteins
  • In Vitro Techniques
  • Lectins
  • Membrane Potentials
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Net
  • Nociceptors
  • Patch-Clamp Techniques
  • Photic Stimulation
  • Receptors, G-Protein-Coupled
  • Rhodopsin
  • Sensory Receptor Cells
  • Substantia Gelatinosa