Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex
Serotonin (5-HT) is one of the major neuromodulators present in the mammalian brain and has been shown to play a role in multiple physiological processes. The mechanisms by which 5-HT modulates cortical network activity, however, are not yet fully understood. We investigated the effects of 5-HT on s...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/66960 |
| _version_ | 1811180965748277248 |
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| author | Roberto de Filippo Benjamin R Rost Alexander Stumpf Claire Cooper John J Tukker Christoph Harms Prateep Beed Dietmar Schmitz |
| author_facet | Roberto de Filippo Benjamin R Rost Alexander Stumpf Claire Cooper John J Tukker Christoph Harms Prateep Beed Dietmar Schmitz |
| author_sort | Roberto de Filippo |
| collection | DOAJ |
| description | Serotonin (5-HT) is one of the major neuromodulators present in the mammalian brain and has been shown to play a role in multiple physiological processes. The mechanisms by which 5-HT modulates cortical network activity, however, are not yet fully understood. We investigated the effects of 5-HT on slow oscillations (SOs), a synchronized cortical network activity universally present across species. SOs are observed during anesthesia and are considered to be the default cortical activity pattern. We discovered that (±)3,4-methylenedioxymethamphetamine (MDMA) and fenfluramine, two potent 5-HT releasers, inhibit SOs within the entorhinal cortex (EC) in anesthetized mice. Combining opto- and pharmacogenetic manipulations with in vitro electrophysiological recordings, we uncovered that somatostatin-expressing (Sst) interneurons activated by the 5-HT2A receptor (5-HT2AR) play an important role in the suppression of SOs. Since 5-HT2AR signaling is involved in the etiology of different psychiatric disorders and mediates the psychological effects of many psychoactive serotonergic drugs, we propose that the newly discovered link between Sst interneurons and 5-HT will contribute to our understanding of these complex topics. |
| first_indexed | 2024-04-11T09:12:06Z |
| format | Article |
| id | doaj.art-c1a9161b8a234b4aa3a326ef35059fd7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:12:06Z |
| publishDate | 2021-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c1a9161b8a234b4aa3a326ef35059fd72022-12-22T04:32:29ZengeLife Sciences Publications LtdeLife2050-084X2021-03-011010.7554/eLife.66960Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortexRoberto de Filippo0https://orcid.org/0000-0002-4085-9114Benjamin R Rost1Alexander Stumpf2Claire Cooper3John J Tukker4https://orcid.org/0000-0002-4394-199XChristoph Harms5https://orcid.org/0000-0002-2063-2860Prateep Beed6Dietmar Schmitz7https://orcid.org/0000-0003-2741-5241Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, Germany; Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Cluster of Excellence NeuroCure, Berlin, GermanyGerman Centre for Neurodegenerative Diseases (DZNE), Berlin, GermanyCharité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, GermanyCharité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, GermanyCharité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, Germany; German Centre for Neurodegenerative Diseases (DZNE), Berlin, GermanyCharité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Experimental Neurology, Berlin, Germany; Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Center for Stroke Research Berlin, Berlin, Germany; Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Einstein Center for Neurosciences Berlin, Berlin, GermanyCharité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, GermanyCharité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, Germany; Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Cluster of Excellence NeuroCure, Berlin, Germany; German Centre for Neurodegenerative Diseases (DZNE), Berlin, Germany; Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Einstein Center for Neurosciences Berlin, Berlin, GermanySerotonin (5-HT) is one of the major neuromodulators present in the mammalian brain and has been shown to play a role in multiple physiological processes. The mechanisms by which 5-HT modulates cortical network activity, however, are not yet fully understood. We investigated the effects of 5-HT on slow oscillations (SOs), a synchronized cortical network activity universally present across species. SOs are observed during anesthesia and are considered to be the default cortical activity pattern. We discovered that (±)3,4-methylenedioxymethamphetamine (MDMA) and fenfluramine, two potent 5-HT releasers, inhibit SOs within the entorhinal cortex (EC) in anesthetized mice. Combining opto- and pharmacogenetic manipulations with in vitro electrophysiological recordings, we uncovered that somatostatin-expressing (Sst) interneurons activated by the 5-HT2A receptor (5-HT2AR) play an important role in the suppression of SOs. Since 5-HT2AR signaling is involved in the etiology of different psychiatric disorders and mediates the psychological effects of many psychoactive serotonergic drugs, we propose that the newly discovered link between Sst interneurons and 5-HT will contribute to our understanding of these complex topics.https://elifesciences.org/articles/66960serotoninsomatostatin interneuronsslow oscillationsMDMAfenfluramine |
| spellingShingle | Roberto de Filippo Benjamin R Rost Alexander Stumpf Claire Cooper John J Tukker Christoph Harms Prateep Beed Dietmar Schmitz Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex eLife serotonin somatostatin interneurons slow oscillations MDMA fenfluramine |
| title | Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex |
| title_full | Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex |
| title_fullStr | Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex |
| title_full_unstemmed | Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex |
| title_short | Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex |
| title_sort | somatostatin interneurons activated by 5 ht2a receptor suppress slow oscillations in medial entorhinal cortex |
| topic | serotonin somatostatin interneurons slow oscillations MDMA fenfluramine |
| url | https://elifesciences.org/articles/66960 |
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