The Journal of Neuroscience, October 21, 2009, 29(42):13202-13209; doi:10.1523/JNEUROSCI.3248-09.2009
Previous Article | Next Article 
Cellular/Molecular
Mrgprd-Expressing Polymodal Nociceptive Neurons Innervate Most Known Classes of Substantia Gelatinosa Neurons
Hong Wang and
Mark J. Zylka
Department of Cell and Molecular Physiology, University of North Carolina Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina 27599
Correspondence should be addressed to Mark J. Zylka, Department of Cell and Molecular Physiology, University of North Carolina Neuroscience Center, University of North Carolina, CB #7545, 115 Mason Farm Road, Chapel Hill, NC 27599. Email: zylka{at}med.unc.edu
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.
Received July 8, 2009;
revised Sept. 9, 2009;
accepted Sept. 10, 2009.
Correspondence should be addressed to Mark J. Zylka, Department of Cell and Molecular Physiology, University of North Carolina Neuroscience Center, University of North Carolina, CB #7545, 115 Mason Farm Road, Chapel Hill, NC 27599. Email: zylka{at}med.unc.edu