Other
15 Authors
- Guo J,
- Challis RC,
- Song X,
- Ma M,
- Gradinaru V,
- Wu Q,
- Raabe T,
- Bhattarai J,
- Luo W,
- Beattie K,
- Gautam M,
- Liu Q,
- Cui L,
- Olson W,
- Cranfill SL
| First Author | Cui L | Year | 2022 |
| Journal | Neuron | Volume | 110 |
| Issue | 5 | Pages | 809-823.e5 |
| PubMed ID | 34986325 | Mgi Jnum | J:325013 |
| Mgi Id | MGI:7282313 | Doi | 10.1016/j.neuron.2021.12.007 |
| Citation | Cui L, et al. (2022) Glutamate in primary afferents is required for itch transmission. Neuron 110(5):809-823.e5 |
| abstractText | 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. |
