Glutamate in primary afferents is required for itch transmission

Lian Cui, Jeff Guo, Suna L. Cranfill, Mayank Gautam, Janardhan Bhattarai, William Olson, Katherine Beattie, Rosemary C. Challis, Qinxue Wu, Xue Song, Tobias Raabe, Viviana Gradinaru, Minghong Ma, Qin Liu, Wenqin Luo

Research output: Contribution to journalArticlepeer-review

Abstract

Whether glutamate or itch-selective neurotransmitters are used to confer itch specificity is still under debate. We focused on an itch-selective population of primary afferents expressing MRGPRA3, which highly expresses Vglut2 and the neuropeptide neuromedin B (Nmb), to investigate this question. Optogenetic stimulation of MRGPRA3+ afferents triggers scratching and other itch-related avoidance behaviors. Using a combination of optogenetics, spinal cord slice recordings, Vglut2 conditional knockout mice, and behavior assays, we showed that glutamate is essential for MRGPRA3+ afferents to transmit itch. We further demonstrated that MRGPRA3+ afferents form monosynaptic connections with both NMBR+ and NMBR neurons and that NMB and glutamate together can enhance the activity of NMBR+ spinal DH neurons. Moreover, Nmb in MRGPRA3+ afferents and NMBR+ DH neurons are required for chloroquine-induced scratching. Together, our results establish a new model in which glutamate is an essential neurotransmitter in primary afferents for itch transmission, whereas NMB signaling enhances its activities.

Original languageEnglish
Pages (from-to)809-823.e5
JournalNeuron
Volume110
Issue number5
DOIs
StatePublished - Mar 2 2022

Keywords

  • MRGPRA3+ afferents
  • NMB
  • VGLUT2
  • behavior assays
  • glutamate
  • high-speed imaging
  • itch-selective neurotransmitter
  • optogenetic stimulation
  • spinal cord slice recordings

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