Activation of the glutamatergic cingulate cortical-cortical connection facilitates pain in adult mice
Abstract The brain consists of the left and right cerebral hemispheres and both are connected by callosal projections. Less is known about the basic mechanism of this cortical-cortical connection and its functional importance. Here we investigate the cortical-cortical connection between the bilatera...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05589-1 |
| _version_ | 1797397848565743616 |
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| author | Xu-Hui Li Wantong Shi Qi-Yu Chen Shun Hao Hui-Hui Miao Zhuang Miao Fang Xu Guo-Qiang Bi Min Zhuo |
| author_facet | Xu-Hui Li Wantong Shi Qi-Yu Chen Shun Hao Hui-Hui Miao Zhuang Miao Fang Xu Guo-Qiang Bi Min Zhuo |
| author_sort | Xu-Hui Li |
| collection | DOAJ |
| description | Abstract The brain consists of the left and right cerebral hemispheres and both are connected by callosal projections. Less is known about the basic mechanism of this cortical-cortical connection and its functional importance. Here we investigate the cortical-cortical connection between the bilateral anterior cingulate cortex (ACC) by using the classic electrophysiological and optogenetic approach. We find that there is a direct synaptic projection from one side ACC to the contralateral ACC. Glutamate is the major excitatory transmitter for bilateral ACC connection, including projections to pyramidal cells in superficial (II/III) and deep (V/VI) layers of the ACC. Both AMPA and kainate receptors contribute to synaptic transmission. Repetitive stimulation of the projection also evoked postsynaptic Ca2+ influx in contralateral ACC pyramidal neurons. Behaviorally, light activation of the ACC-ACC connection facilitated behavioral withdrawal responses to mechanical stimuli and noxious heat. In an animal model of neuropathic pain, light inhibitory of ACC-ACC connection reduces both primary and secondary hyperalgesia. Our findings provide strong direct evidence for the excitatory or facilitatory contribution of ACC-ACC connection to pain perception, and this mechanism may provide therapeutic targets for future treatment of chronic pain and related emotional disorders. |
| first_indexed | 2024-03-09T01:16:06Z |
| format | Article |
| id | doaj.art-ecfb5715867942a293852372758b9ded |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-09T01:16:06Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-ecfb5715867942a293852372758b9ded2023-12-10T12:28:29ZengNature PortfolioCommunications Biology2399-36422023-12-016111810.1038/s42003-023-05589-1Activation of the glutamatergic cingulate cortical-cortical connection facilitates pain in adult miceXu-Hui Li0Wantong Shi1Qi-Yu Chen2Shun Hao3Hui-Hui Miao4Zhuang Miao5Fang Xu6Guo-Qiang Bi7Min Zhuo8Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi’an Jiaotong UniversityCenter for Neuron and Disease, Frontier Institute of Science and Technology, Xi’an Jiaotong UniversityInstitute of Brain Research, Qingdao International Academician ParkInstitute of Brain Research, Qingdao International Academician ParkDepartment of Physiology, Faculty of Medicine, University of TorontoDepartment of Physiology, Faculty of Medicine, University of TorontoCAS Key Laboratory of Brain Connectome and Manipulation, Interdisciplinary Center for Brain Information, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science Shenzhen Fundamental Research InstitutionsCAS Key Laboratory of Brain Connectome and Manipulation, Interdisciplinary Center for Brain Information, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science Shenzhen Fundamental Research InstitutionsCenter for Neuron and Disease, Frontier Institute of Science and Technology, Xi’an Jiaotong UniversityAbstract The brain consists of the left and right cerebral hemispheres and both are connected by callosal projections. Less is known about the basic mechanism of this cortical-cortical connection and its functional importance. Here we investigate the cortical-cortical connection between the bilateral anterior cingulate cortex (ACC) by using the classic electrophysiological and optogenetic approach. We find that there is a direct synaptic projection from one side ACC to the contralateral ACC. Glutamate is the major excitatory transmitter for bilateral ACC connection, including projections to pyramidal cells in superficial (II/III) and deep (V/VI) layers of the ACC. Both AMPA and kainate receptors contribute to synaptic transmission. Repetitive stimulation of the projection also evoked postsynaptic Ca2+ influx in contralateral ACC pyramidal neurons. Behaviorally, light activation of the ACC-ACC connection facilitated behavioral withdrawal responses to mechanical stimuli and noxious heat. In an animal model of neuropathic pain, light inhibitory of ACC-ACC connection reduces both primary and secondary hyperalgesia. Our findings provide strong direct evidence for the excitatory or facilitatory contribution of ACC-ACC connection to pain perception, and this mechanism may provide therapeutic targets for future treatment of chronic pain and related emotional disorders.https://doi.org/10.1038/s42003-023-05589-1 |
| spellingShingle | Xu-Hui Li Wantong Shi Qi-Yu Chen Shun Hao Hui-Hui Miao Zhuang Miao Fang Xu Guo-Qiang Bi Min Zhuo Activation of the glutamatergic cingulate cortical-cortical connection facilitates pain in adult mice Communications Biology |
| title | Activation of the glutamatergic cingulate cortical-cortical connection facilitates pain in adult mice |
| title_full | Activation of the glutamatergic cingulate cortical-cortical connection facilitates pain in adult mice |
| title_fullStr | Activation of the glutamatergic cingulate cortical-cortical connection facilitates pain in adult mice |
| title_full_unstemmed | Activation of the glutamatergic cingulate cortical-cortical connection facilitates pain in adult mice |
| title_short | Activation of the glutamatergic cingulate cortical-cortical connection facilitates pain in adult mice |
| title_sort | activation of the glutamatergic cingulate cortical cortical connection facilitates pain in adult mice |
| url | https://doi.org/10.1038/s42003-023-05589-1 |
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