Serotonin and psilocybin activate 5-HT1B receptors to suppress cortical signaling through the claustrum
Abstract Through its widespread reciprocal connections with the cerebral cortex, the claustrum is implicated in sleep and waking cortical network states. Yet, basic knowledge of neuromodulation in this structure is lacking. The claustrum is richly innervated by serotonergic fibers, expresses seroton...
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62980-8 |
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| author | Maxwell B. Madden Chloe Schaefgen Binita Vedak Jian Kwon Kiara S. Dresp Pedra Samuel H. Sheats Adam C. Puche Steffen B. E. Wolff Brian N. Mathur |
| author_facet | Maxwell B. Madden Chloe Schaefgen Binita Vedak Jian Kwon Kiara S. Dresp Pedra Samuel H. Sheats Adam C. Puche Steffen B. E. Wolff Brian N. Mathur |
| author_sort | Maxwell B. Madden |
| collection | DOAJ |
| description | Abstract Through its widespread reciprocal connections with the cerebral cortex, the claustrum is implicated in sleep and waking cortical network states. Yet, basic knowledge of neuromodulation in this structure is lacking. The claustrum is richly innervated by serotonergic fibers, expresses serotonin receptors, and is suggested to play a role in the ability of psilocybin, which is metabolized to the non-specific serotonin receptor agonist psilocin, to disrupt cortex-wide network states. We therefore addressed the possible role of serotonin, and the classic psychedelic psilocybin, in modulating cortical signaling through the claustrum. We show that serotonin activates 5-HT1B receptors on anterior cingulate cortex inputs – a primary driver of claustrum activity – to suppress signaling to parietal association cortex-projecting claustrum neurons. Additionally, we demonstrate that psilocybin injection also activates anterior cingulate cortex presynaptic 5-HT1B receptors to suppress cortical signaling through the claustrum. Thus, serotonin, via 5-HT1B, may provide gain-control of cortical input to the claustrum, a mechanism that may be directly targeted by psilocybin to modulate downstream cortical network states. |
| format | Article |
| id | doaj-art-e18e76ae2e6d46978a0d95bcecf0e7dd |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e18e76ae2e6d46978a0d95bcecf0e7dd2025-08-24T11:39:52ZengNature PortfolioNature Communications2041-17232025-08-0116111310.1038/s41467-025-62980-8Serotonin and psilocybin activate 5-HT1B receptors to suppress cortical signaling through the claustrumMaxwell B. Madden0Chloe Schaefgen1Binita Vedak2Jian Kwon3Kiara S. Dresp Pedra4Samuel H. Sheats5Adam C. Puche6Steffen B. E. Wolff7Brian N. Mathur8Department of Pharmacology and Physiology, School of Medicine, University of MarylandDepartment of Pharmacology and Physiology, School of Medicine, University of MarylandDepartment of Pharmacology and Physiology, School of Medicine, University of MarylandDepartment of Pharmacology and Physiology, School of Medicine, University of MarylandDepartment of Pharmacology and Physiology, School of Medicine, University of MarylandDepartment of Pharmacology and Physiology, School of Medicine, University of MarylandDepartment of Neurobiology, School of Medicine, University of MarylandDepartment of Pharmacology and Physiology, School of Medicine, University of MarylandDepartment of Pharmacology and Physiology, School of Medicine, University of MarylandAbstract Through its widespread reciprocal connections with the cerebral cortex, the claustrum is implicated in sleep and waking cortical network states. Yet, basic knowledge of neuromodulation in this structure is lacking. The claustrum is richly innervated by serotonergic fibers, expresses serotonin receptors, and is suggested to play a role in the ability of psilocybin, which is metabolized to the non-specific serotonin receptor agonist psilocin, to disrupt cortex-wide network states. We therefore addressed the possible role of serotonin, and the classic psychedelic psilocybin, in modulating cortical signaling through the claustrum. We show that serotonin activates 5-HT1B receptors on anterior cingulate cortex inputs – a primary driver of claustrum activity – to suppress signaling to parietal association cortex-projecting claustrum neurons. Additionally, we demonstrate that psilocybin injection also activates anterior cingulate cortex presynaptic 5-HT1B receptors to suppress cortical signaling through the claustrum. Thus, serotonin, via 5-HT1B, may provide gain-control of cortical input to the claustrum, a mechanism that may be directly targeted by psilocybin to modulate downstream cortical network states.https://doi.org/10.1038/s41467-025-62980-8 |
| spellingShingle | Maxwell B. Madden Chloe Schaefgen Binita Vedak Jian Kwon Kiara S. Dresp Pedra Samuel H. Sheats Adam C. Puche Steffen B. E. Wolff Brian N. Mathur Serotonin and psilocybin activate 5-HT1B receptors to suppress cortical signaling through the claustrum Nature Communications |
| title | Serotonin and psilocybin activate 5-HT1B receptors to suppress cortical signaling through the claustrum |
| title_full | Serotonin and psilocybin activate 5-HT1B receptors to suppress cortical signaling through the claustrum |
| title_fullStr | Serotonin and psilocybin activate 5-HT1B receptors to suppress cortical signaling through the claustrum |
| title_full_unstemmed | Serotonin and psilocybin activate 5-HT1B receptors to suppress cortical signaling through the claustrum |
| title_short | Serotonin and psilocybin activate 5-HT1B receptors to suppress cortical signaling through the claustrum |
| title_sort | serotonin and psilocybin activate 5 ht1b receptors to suppress cortical signaling through the claustrum |
| url | https://doi.org/10.1038/s41467-025-62980-8 |
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