Supraspinal facilitation of painful stimuli by glutamatergic innervation from the retrosplenial to the anterior cingulate cortex.
The anterior cingulate cortex (ACC) is recognized as a pivotal cortical region involved in the perception of pain. The retrosplenial cortex (RSC), located posterior to the ACC, is known to play a significant role in navigation and memory processes. Although the projections from the RSC to the ACC ha...
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3003011 |
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| author | Shun Hao Man Xue Qi-Yu Chen Jinjin Wan Yu-Jie Ma Wantong Shi Xuanying Chen Xu-Hui Li Jing-Shan Lu Fang Xu Guo-Qiang Bi Wucheng Tao Min Zhuo |
| author_facet | Shun Hao Man Xue Qi-Yu Chen Jinjin Wan Yu-Jie Ma Wantong Shi Xuanying Chen Xu-Hui Li Jing-Shan Lu Fang Xu Guo-Qiang Bi Wucheng Tao Min Zhuo |
| author_sort | Shun Hao |
| collection | DOAJ |
| description | The anterior cingulate cortex (ACC) is recognized as a pivotal cortical region involved in the perception of pain. The retrosplenial cortex (RSC), located posterior to the ACC, is known to play a significant role in navigation and memory processes. Although the projections from the RSC to the ACC have been found, the specifics of the synaptic connections and the functional implications of the RSC-ACC projections remain less understood. In this study, we employed a combination of whole-brain imaging, in vitro electrophysiology, and two-photon calcium imaging techniques to confirm the presence of direct excitatory glutamatergic projections from the RSC to the ACC in mice. This excitatory transmission is predominantly mediated by the postsynaptic AMPA receptors. Furthermore, the activation of the RSC-ACC projections through opto-/chemogenetics significantly facilitated the behavioral responses to both mechanical and thermal nociceptive stimuli in adult mice. Notably, this activation did not influence spinal nociceptive responses in the tail-flick test, nor did it affect anxiety-like or aversive behaviors. These findings indicate that the RSC-ACC glutamatergic pathway modulates nociceptive perception primarily at the supraspinal cortical level. We have identified a novel cortico-cortical facilitatory pathway that contributes to nociceptive processing in the cingulate cortex. The RSC-ACC pathway probably serves to integrate memory engrams with pain perception in both humans and animals. |
| format | Article |
| id | doaj-art-76368291ec3741829f4f5de31d3f8474 |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-76368291ec3741829f4f5de31d3f84742025-02-12T05:30:23ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852025-01-01231e300301110.1371/journal.pbio.3003011Supraspinal facilitation of painful stimuli by glutamatergic innervation from the retrosplenial to the anterior cingulate cortex.Shun HaoMan XueQi-Yu ChenJinjin WanYu-Jie MaWantong ShiXuanying ChenXu-Hui LiJing-Shan LuFang XuGuo-Qiang BiWucheng TaoMin ZhuoThe anterior cingulate cortex (ACC) is recognized as a pivotal cortical region involved in the perception of pain. The retrosplenial cortex (RSC), located posterior to the ACC, is known to play a significant role in navigation and memory processes. Although the projections from the RSC to the ACC have been found, the specifics of the synaptic connections and the functional implications of the RSC-ACC projections remain less understood. In this study, we employed a combination of whole-brain imaging, in vitro electrophysiology, and two-photon calcium imaging techniques to confirm the presence of direct excitatory glutamatergic projections from the RSC to the ACC in mice. This excitatory transmission is predominantly mediated by the postsynaptic AMPA receptors. Furthermore, the activation of the RSC-ACC projections through opto-/chemogenetics significantly facilitated the behavioral responses to both mechanical and thermal nociceptive stimuli in adult mice. Notably, this activation did not influence spinal nociceptive responses in the tail-flick test, nor did it affect anxiety-like or aversive behaviors. These findings indicate that the RSC-ACC glutamatergic pathway modulates nociceptive perception primarily at the supraspinal cortical level. We have identified a novel cortico-cortical facilitatory pathway that contributes to nociceptive processing in the cingulate cortex. The RSC-ACC pathway probably serves to integrate memory engrams with pain perception in both humans and animals.https://doi.org/10.1371/journal.pbio.3003011 |
| spellingShingle | Shun Hao Man Xue Qi-Yu Chen Jinjin Wan Yu-Jie Ma Wantong Shi Xuanying Chen Xu-Hui Li Jing-Shan Lu Fang Xu Guo-Qiang Bi Wucheng Tao Min Zhuo Supraspinal facilitation of painful stimuli by glutamatergic innervation from the retrosplenial to the anterior cingulate cortex. PLoS Biology |
| title | Supraspinal facilitation of painful stimuli by glutamatergic innervation from the retrosplenial to the anterior cingulate cortex. |
| title_full | Supraspinal facilitation of painful stimuli by glutamatergic innervation from the retrosplenial to the anterior cingulate cortex. |
| title_fullStr | Supraspinal facilitation of painful stimuli by glutamatergic innervation from the retrosplenial to the anterior cingulate cortex. |
| title_full_unstemmed | Supraspinal facilitation of painful stimuli by glutamatergic innervation from the retrosplenial to the anterior cingulate cortex. |
| title_short | Supraspinal facilitation of painful stimuli by glutamatergic innervation from the retrosplenial to the anterior cingulate cortex. |
| title_sort | supraspinal facilitation of painful stimuli by glutamatergic innervation from the retrosplenial to the anterior cingulate cortex |
| url | https://doi.org/10.1371/journal.pbio.3003011 |
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