Glutamate in primary afferents is required for itch transmission.
Glutamate in primary afferents is required for itch transmission.
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DOI：
10.1016/j.neuron.2021.12.007
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发表时间：
2022-03-02
期刊：
影响因子：
16.2
通讯作者：
Luo W
中科院分区：
文献类型：
--
作者：
Cui L;Guo J;Cranfill SL;Gautam M;Bhattarai J;Olson W;Beattie K;Challis RC;Wu Q;Song X;Raabe T;Gradinaru V;Ma M;Liu Q;Luo W
谷氨酸或瘙痒选择性神经递质是否被用来授予瘙痒特异性仍在争论中。我们专注于表达MRGPRA3的初级传入神经元中对瘙痒有选择性的群体，这些初级传入神经元高表达Vlec2和神经肽NMB(NMB)来研究这个问题。对MRGPRA3+传入的光遗传刺激会触发抓挠和其他与瘙痒相关的回避行为。结合光遗传学、脊髓切片记录、Vher2条件性基因敲除小鼠和行为学分析，我们发现谷氨酸是MRGPRA3+传入细胞传递瘙痒所必需的。我们进一步证明，MRGPRA3+传入神经元与NMBR+和NMBR-神经元形成单突触联系，NMB和谷氨酸共同作用可以增强NMBR+脊髓DH神经元的活动。此外，氯喹引起的划痕还需要MRGPRA3+传入神经元和NMBR+DH神经元中的NMB。总之，我们的结果建立了一个新的模型，在这个模型中，谷氨酸是瘙痒传递的初级传入中必不可少的神经递质，而NMB信号增强了它的活性。崔等人。证明在MRGPRA3+初级传入神经中，谷氨酸是瘙痒传递所必需的，它也使用神经肽NMB来增强信号转导。由于谷氨酸和NMB广泛存在于初级传入神经中，这表明不同的神经递质不是赋予瘙痒模式特异性所必需的。
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 express 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. Cui et al. demonstrate that glutamate is required for itch transmission in MRGPRA3+ primary afferents, which also use the neuropeptide NMB to enhance signaling. Since both glutamate and Nmb are broadly available in primary afferents, this suggests that distinct neurotransmitters are not necessary to confer itch modality specificity.
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影响因子：
16.2
作者：
Cui, Lian;Miao, Xuerong;Liang, Lingli;Abdus-Saboor, Ishmail;Olson, William;Fleming, Michael S.;Ma, Minghong;Tao, Yuan-Xiang;Luo, Wenqin
通讯作者：
Luo, Wenqin
影响因子：
4.6
作者：
Dong, Peter;Guo, Changxiong;Luo, Wenqin
通讯作者：
Luo, Wenqin
DOI：
10.1073/pnas.1013602108
发表时间：
2011-04-05
影响因子：
11.1
作者：
Lagerstrom, Malin C.;Rogoz, Katarzyna;Kullander, Klas
通讯作者：
Kullander, Klas
DOI：
10.1523/jneurosci.6451-10.2011
发表时间：
2011-03-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cavanaugh DJ;Chesler AT;Jackson AC;Sigal YM;Yamanaka H;Grant R;O'Donnell D;Nicoll RA;Shah NM;Julius D;Basbaum AI
通讯作者：
Basbaum AI
影响因子：
7.7
作者：
Fleming MS;Vysochan A;Paixão S;Niu J;Klein R;Savitt JM;Luo W
通讯作者：
Luo W