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Publication : Differential Coding of Itch and Pain by a Subpopulation of Primary Afferent Neurons.

First Author  Sharif B Year  2020
Journal  Neuron Volume  106
Issue  6 Pages  940-951.e4
PubMed ID  32298640 Mgi Jnum  J:296179
Mgi Id  MGI:6449450 Doi  10.1016/j.neuron.2020.03.021
Citation  Sharif B, et al. (2020) Differential Coding of Itch and Pain by a Subpopulation of Primary Afferent Neurons. Neuron 106(6):940-951.e4
abstractText  Itch and pain are distinct unpleasant sensations that can be triggered from the same receptive fields in the skin, raising the question of how pruriception and nociception are coded and discriminated. Here, we tested the multimodal capacity of peripheral first-order neurons, focusing on the genetically defined subpopulation of mouse C-fibers that express the chloroquine receptor MrgprA3. Using optogenetics, chemogenetics, and pharmacology, we assessed the behavioral effects of their selective stimulation in a wide variety of conditions. We show that metabotropic Gq-linked stimulation of these C-afferents, through activation of native MrgprA3 receptors or DREADDs, evokes stereotypical pruriceptive rather than nocifensive behaviors. In contrast, fast ionotropic stimulation of these same neurons through light-gated cation channels or native ATP-gated P2X3 channels predominantly evokes nocifensive rather than pruriceptive responses. We conclude that C-afferents display intrinsic multimodality, and we provide evidence that optogenetic and chemogenetic interventions on the same neuronal populations can drive distinct behavioral outputs.
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