Rui Chen, Xiang Xu, Xin-Yue Wang, Wen-Bin Jia, De-Shan Zhao, Na Liu, Zhen Pang, Xiao-Qing Liu, Yan Zhang
{"title":"外侧缰核调节瘙痒感和情绪。","authors":"Rui Chen, Xiang Xu, Xin-Yue Wang, Wen-Bin Jia, De-Shan Zhao, Na Liu, Zhen Pang, Xiao-Qing Liu, Yan Zhang","doi":"10.1186/s13041-023-01045-7","DOIUrl":null,"url":null,"abstract":"<p><p>Itch is a complex aversive sensory and emotional experience. As a most upsetting symptom in many dermatological and systemic diseases, it lacks efficient treatments. The lateral habenula nucleus (LHb) encodes negative emotions in the epithalamus and has been implicated in pain and analgesia. Nevertheless, the role of the lateral habenula nucleus in the pruritic sensation and emotion remains elusive. Here we defined the crucial role of glutamatergic neurons within the lateral habenula nucleus (Glu<sup>LHb</sup>) in itch modulation in mice. We established histamine-dependent and histamine-independent models of acute pruritus, as well as the acetone-ether-water (AEW) model of chronic pruritus. We first assessed the effects of pruritogen injection on neural activation in both medial and lateral divisions of LHb in vitro. We then demonstrated that the population activity of Glu<sup>LHb</sup> neurons was increased during the acute itch and chronic itch-induced scratching behaviors in vivo. In addition, electrophysiological data showed that the excitability of Glu<sup>LHb</sup> neurons was enhanced by chronic itch. Chemogenetic suppression of Glu<sup>LHb</sup> neurons disrupted both acute and chronic itch-evoked scratching behaviors. Furthermore, itch-induced conditioned place aversion (CPA) was abolished by Glu<sup>LHb</sup> neuronal inhibition. Finally, we dissected the LHb upstream brain regions. Together, these findings reveal the involvement of LHb in processing both the sensational and emotional components of pruritus and may shed new insights into itch therapy.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"16 1","pages":"54"},"PeriodicalIF":3.3000,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303242/pdf/","citationCount":"0","resultStr":"{\"title\":\"The lateral habenula nucleus regulates pruritic sensation and emotion.\",\"authors\":\"Rui Chen, Xiang Xu, Xin-Yue Wang, Wen-Bin Jia, De-Shan Zhao, Na Liu, Zhen Pang, Xiao-Qing Liu, Yan Zhang\",\"doi\":\"10.1186/s13041-023-01045-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Itch is a complex aversive sensory and emotional experience. As a most upsetting symptom in many dermatological and systemic diseases, it lacks efficient treatments. The lateral habenula nucleus (LHb) encodes negative emotions in the epithalamus and has been implicated in pain and analgesia. Nevertheless, the role of the lateral habenula nucleus in the pruritic sensation and emotion remains elusive. Here we defined the crucial role of glutamatergic neurons within the lateral habenula nucleus (Glu<sup>LHb</sup>) in itch modulation in mice. We established histamine-dependent and histamine-independent models of acute pruritus, as well as the acetone-ether-water (AEW) model of chronic pruritus. We first assessed the effects of pruritogen injection on neural activation in both medial and lateral divisions of LHb in vitro. We then demonstrated that the population activity of Glu<sup>LHb</sup> neurons was increased during the acute itch and chronic itch-induced scratching behaviors in vivo. In addition, electrophysiological data showed that the excitability of Glu<sup>LHb</sup> neurons was enhanced by chronic itch. Chemogenetic suppression of Glu<sup>LHb</sup> neurons disrupted both acute and chronic itch-evoked scratching behaviors. Furthermore, itch-induced conditioned place aversion (CPA) was abolished by Glu<sup>LHb</sup> neuronal inhibition. Finally, we dissected the LHb upstream brain regions. Together, these findings reveal the involvement of LHb in processing both the sensational and emotional components of pruritus and may shed new insights into itch therapy.</p>\",\"PeriodicalId\":18851,\"journal\":{\"name\":\"Molecular Brain\",\"volume\":\"16 1\",\"pages\":\"54\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2023-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303242/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Brain\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13041-023-01045-7\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Brain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13041-023-01045-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
The lateral habenula nucleus regulates pruritic sensation and emotion.
Itch is a complex aversive sensory and emotional experience. As a most upsetting symptom in many dermatological and systemic diseases, it lacks efficient treatments. The lateral habenula nucleus (LHb) encodes negative emotions in the epithalamus and has been implicated in pain and analgesia. Nevertheless, the role of the lateral habenula nucleus in the pruritic sensation and emotion remains elusive. Here we defined the crucial role of glutamatergic neurons within the lateral habenula nucleus (GluLHb) in itch modulation in mice. We established histamine-dependent and histamine-independent models of acute pruritus, as well as the acetone-ether-water (AEW) model of chronic pruritus. We first assessed the effects of pruritogen injection on neural activation in both medial and lateral divisions of LHb in vitro. We then demonstrated that the population activity of GluLHb neurons was increased during the acute itch and chronic itch-induced scratching behaviors in vivo. In addition, electrophysiological data showed that the excitability of GluLHb neurons was enhanced by chronic itch. Chemogenetic suppression of GluLHb neurons disrupted both acute and chronic itch-evoked scratching behaviors. Furthermore, itch-induced conditioned place aversion (CPA) was abolished by GluLHb neuronal inhibition. Finally, we dissected the LHb upstream brain regions. Together, these findings reveal the involvement of LHb in processing both the sensational and emotional components of pruritus and may shed new insights into itch therapy.
期刊介绍:
Molecular Brain is an open access, peer-reviewed journal that considers manuscripts on all aspects of studies on the nervous system at the molecular, cellular, and systems level providing a forum for scientists to communicate their findings.
Molecular brain research is a rapidly expanding research field in which integrative approaches at the genetic, molecular, cellular and synaptic levels yield key information about the physiological and pathological brain. These studies involve the use of a wide range of modern techniques in molecular biology, genomics, proteomics, imaging and electrophysiology.