期刊
NEURON
卷 110, 期 5, 页码 809-+出版社
CELL PRESS
DOI: 10.1016/j.neuron.2021.12.007
关键词
-
资金
- NIH [AI125743, AI163146, EY024704, NS083702, NS094224]
This study investigates the role of glutamate and neuropeptide neuromedin B (Nmb) in itch transmission. The results show that glutamate is essential for transmitting itch through MRGPRA3(+) afferents, while Nmb signaling enhances its activities.
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.
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