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. 2022 Dec 17;39(5):793–807. doi: 10.1007/s12264-022-00996-6

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — The ACC→VTA projection is required for chronic itch-induced scratching. A Experimental timeline for chemogenetic suppression of VTA-projecting ACC neurons in chronic itch. B Scheme for specific infection of VTA-projecting ACC neurons with hM4Di. C Histological verification of the viral infection. Scale bars, 200 μm (left) and 30 μm (right). D Chemogenetic inhibition of ACC neurons that project to VTA results in a significant decrease in DCP-evoked scratching behaviors. n = 11 or 12 mice; ***P <0.001; unpaired Student’s t test. E, F Total distance travelled (E) and average velocity (F) in the open field. No significant difference was detected between the two groups. n = 11 or 12 mice. G Experimental timeline for chemogenetic suppression of ACC-innervated VTA neurons in chronic itch. H Scheme for specific infection of ACC-recipient VTA neurons with hM4Di. I Histological verification of the viral infection. Scale bars, 200 μm (left) and 50 μm (right). J Chemogenetic inhibition of VTA neurons that receive inputs from the ACC strongly attenuates scratching behaviors in chronic itch. n = 9 or 8 mice; ***P <0.001; unpaired Student’s t test. K, L Total distance travelled (K) and average velocity (L) in the open field. No significant difference was detected between the two groups. n = 9 or 8 mice. M Experimental timeline for chemogenetic inhibition of the VTA→ACC projection. N Scheme for specific infection of ACC-projecting VTA neurons with hM4Di. O Chemogenetic inactivation of the VTA→ACC projection has no effect on DCP-evoked scratching behaviors. n = 5 mice per group; unpaired Student’s t test. Data are shown as the mean ± SEM.