Glutamate in primary afferents is required for itch transmission.

Autor:	Cui L; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Guo J; Department of Anesthesiology, Center for the Study of Itch, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA., Cranfill SL; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Gautam M; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Bhattarai J; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Olson W; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Beattie K; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Challis RC; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Wu Q; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Song X; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Raabe T; Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Gradinaru V; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Ma M; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Liu Q; Department of Anesthesiology, Center for the Study of Itch, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA. Electronic address: qinliu@wustl.edu., Luo W; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: luow@pennmedicine.upenn.edu.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2022 Mar 02; Vol. 110 (5), pp. 809-823.e5. Date of Electronic Publication: 2022 Jan 04.
DOI:	10.1016/j.neuron.2021.12.007
Abstrakt:	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. Competing Interests: Declaration of interests V.G. is a member of the Neuron Advisory Board. V.G. is also a cofounder and board member of Capsida Biotherapeutics, a fully integrated AAV engineering and gene therapy company. The other authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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